Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles.

PubMed

Asati, Atul; Santra, Santimukul; Kaittanis, Charalambos; Perez, J Manuel

2010-09-28

Cerium oxide nanoparticles (nanoceria) have shown great potential as antioxidant and radioprotective agents for applications in cancer therapy. Recently, various polymer-coated nanoceria preparations have been developed to improve their aqueous solubility and allow for surface functionalization of these nanoparticles. However, the interaction of polymer-coated nanoceria with cells, their uptake mechanism, and subcellular localization are poorly understood. Herein, we engineered polymer-coated cerium oxide nanoparticles with different surface charges (positive, negative, and neutral) and studied their internalization and toxicity in normal and cancer cell lines. The results showed that nanoceria with a positive or neutral charge enters most of the cell lines studied, while nanoceria with a negative charge internalizes mostly in the cancer cell lines. Moreover, upon entry into the cells, nanoceria is localized to different cell compartments (e.g., cytoplasm and lysosomes) depending on the nanoparticle's surface charge. The internalization and subcellular localization of nanoceria plays a key role in the nanoparticles' cytotoxicity profile, exhibiting significant toxicity when they localize in the lysosomes of the cancer cells. In contrast, minimal toxicity is observed when they localize into the cytoplasm or do not enter the cells. Taken together, these results indicate that the differential surface-charge-dependent localization of nanoceria in normal and cancer cells plays a critical role in the nanoparticles' toxicity profile.

A special issue on reviews in biomedical applications of nanomaterials, tissue engineering, stem cells, bioimaging, and toxicity.

PubMed

Nalwa, Hari Singh

2014-10-01

This second special issue of the Journal of Biomedical Nanotechnology in a series contains another 30 state-of-the-art reviews focused on the biomedical applications of nanomaterials, biosensors, bone tissue engineering, MRI and bioimaging, single-cell detection, stem cells, endothelial progenitor cells, toxicity and biosafety of nanodrugs, nanoparticle-based new therapeutic approaches for cancer, hepatic and cardiovascular disease.

A novel approach reveals that zinc oxide nanoparticles are bioavailable and toxic after dietary exposures

USGS Publications Warehouse

Croteau, M.-N.; Dybowska, A.D.; Luoma, S.N.; Valsami-Jones, E.

2011-01-01

If engineered nanomaterials are released into the environment, some are likely to end up associated with the food of animals due to aggregation and sorption processes. However, few studies have considered dietary exposure of nanomaterials. Here we show that zinc (Zn) from isotopically modified 67ZnO particles is efficiently assimilated by freshwater snails when ingested with food. The 67Zn from nano-sized 67ZnO appears as bioavailable as 67Zn internalized by diatoms. Apparent agglomeration of the zinc oxide (ZnO) particles did not reduce bioavailability, nor preclude toxicity. In the diet, ZnO nanoparticles damage digestion: snails ate less, defecated less and inefficiently processed the ingested food when exposed to high concentrations of ZnO. It was not clear whether the toxicity was due to the high Zn dose achieved with nanoparticles or to the ZnO nanoparticles themselves. Further study of exposure from nanoparticles in food would greatly benefit assessment of ecological and human health risks. ?? 2011 Informa UK, Ltd.

Impact of engineered zinc oxide nanoparticles on the energy budgets of Mytilus galloprovincialis

NASA Astrophysics Data System (ADS)

Muller, Erik B.; Hanna, Shannon K.; Lenihan, Hunter S.; Miller, Robert J.; Nisbet, Roger M.

2014-11-01

This paper characterizes the sublethal impact of engineered ZnO nanoparticles on the individual performance of the marine mussel Mytilus galloprovincialis within the context of Dynamic Energy Budget theory, thereby allowing an integrated evaluation of the impact of multiple stressors on various endpoints. Data include measurements of the impact of ZnO nanoparticles on body burden, feeding, respiration, shell length, biomass, and mortality of mussels kept in laboratory tanks for over 100 days. ZnO nanoparticles in the environment impair the mussels' feeding rate (EC50 for the maximum feeding rate is 1.5 mg ZnO nanoparticles L- 1). Zn accumulated in tissue increases respiration (EC50 for the respiration rate is 0.9 mg environmental ZnO nanoparticles L- 1 with the body burden having reached its ultimate level), indicating that maintenance processes are more affected by ZnO nanoparticles than feeding. The feeding regime constrained growth and biomass production to the extent that the impact of ZnO nanoparticles on these processes was undetectable, yet the remaining measurements allowed the estimation of the toxicity parameters. The toxicity representation, combined with the DEB model, allowed the calculation of the effect of the nanoparticles on the expected lifetime production of reproductive matter. EC50 for the expected lifetime production of reproductive matter is less than 0.25 mg ZnO nanoparticles L- 1, indicating that that the ecological impact of ZnO nanoparticle exposure is stronger than its impact on individual physiological rates.

Fate and Transport of Zinc Oxide Nanoparticles in Porous Media in the Presence of Naturally Occurring Organic Ligands

EPA Science Inventory

The potential toxicity of nanoscale particles has received considerable attention, but there is little knowledge in the literature relating to the fate and transport of engineered nanoparticles in the environment. In this present study, column experiments were performed to asses...

Effects of Natural Organic Matter on Stability, Transport and Deposition of Engineered Nano-particles in Porous Media

EPA Science Inventory

The interaction of nano-particles and organic substances, like natural organic matter, could have significant influence on the fate, transport and bioavailability of toxic substances. Natural organic matter (NOM) is a mixture of chemically complex polyelectrolytes with varying m...

Toxicity Assessment of Silica Coated Iron Oxide Nanoparticles and Biocompatibility Improvement by Surface Engineering

PubMed Central

Malvindi, Maria Ada; De Matteis, Valeria; Galeone, Antonio; Brunetti, Virgilio; Anyfantis, George C.; Athanassiou, Athanassia; Cingolani, Roberto; Pompa, Pier Paolo

2014-01-01

We have studied in vitro toxicity of iron oxide nanoparticles (NPs) coated with a thin silica shell (Fe3O4/SiO2 NPs) on A549 and HeLa cells. We compared bare and surface passivated Fe3O4/SiO2 NPs to evaluate the effects of the coating on the particle stability and toxicity. NPs cytotoxicity was investigated by cell viability, membrane integrity, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) assays, and their genotoxicity by comet assay. Our results show that NPs surface passivation reduces the oxidative stress and alteration of iron homeostasis and, consequently, the overall toxicity, despite bare and passivated NPs show similar cell internalization efficiency. We found that the higher toxicity of bare NPs is due to their stronger in-situ degradation, with larger intracellular release of iron ions, as compared to surface passivated NPs. Our results indicate that surface engineering of Fe3O4/SiO2 NPs plays a key role in improving particles stability in biological environments reducing both cytotoxic and genotoxic effects. PMID:24465736

Implication of oxidative stress in size-dependent toxicity of silica nanoparticles in kidney cells.

PubMed

Passagne, Isabelle; Morille, Marie; Rousset, Marine; Pujalté, Igor; L'azou, Béatrice

2012-09-28

Silica nanoparticles (nano-SiO(2)) are one of the most popular nanomaterials used in industrial manufacturing, synthesis, engineering and medicine. While inhalation of nanoparticles causes pulmonary damage, nano-SiO(2) can be transported into the blood and deposit in target organs where they exert potential toxic effects. Kidney is considered as such a secondary target organ. However, toxicological information of their effect on renal cells and the mechanisms involved remain sparse. In the present study, the cytotoxicity of nano-SiO(2) of different sizes was investigated on two renal proximal tubular cell lines (human HK-2 and porcine LLC-PK(1)). The molecular pathways involved were studied with a focus on the involvement of oxidative stress. Nanoparticle characterization was performed (primary nanoparticle size, surface area, dispersion) in order to investigate a potential relationship between their physical properties and their toxic effects. Firstly, evidence of particle internalization was obtained by transmission electron microscopy and conventional flux cytometry techniques. The use of specific inhibitors of endocytosis pathways showed an internalization process by macropinocytosis and clathrin-mediated endocytosis for 100 nm nano-SiO(2) nanoparticles. These nanoparticles were localized in vesicles. Toxicity was size- and time-dependent (24h, 48 h, 72 h). Indeed, it increased as nanoparticles became smaller. Secondly, analysis of oxidative stress based on the assessment of ROS (reactive oxygen species) production (DHE, dihydroethidium) or lipid peroxidation (MDA, malondialdehyde) clearly demonstrated the involvement of oxidative stress in the toxicity of 20 nm nano-SiO(2). The induction of antioxidant enzymes (catalase, GSTpi, thioredoxin reductase) could explain their lesser toxicity with 100 nm nano-SiO(2). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Metal nanoparticles in diesel exhaust derived by in-cylinder melting of detached engine fragments

NASA Astrophysics Data System (ADS)

Liati, Anthi; Pandurangi, Sushant Sunil; Boulouchos, Konstantinos; Schreiber, Daniel; Arroyo Rojas Dasilva, Yadira

2015-01-01

A wide range of environmental and health effects are linked to combustion-generated pollutants related to traffic. Nanoparticles, in particular, are a major concern for humans since they can be inhaled and have potentially toxic effects. The variability and sources of combustion-related nanoparticle pollutants remain inadequately investigated. Here we report the presence of ca. 5-100 nm large Fe3O4 nanoparticles, in form of agglomerates, in diesel exhaust. The mode of occurrence of these nanoparticles, in combination with their chemical composition matching that of steel indicate that they derive by melting of engine fragments in the combustion chamber and subsequent crystallization during cooling. To evaluate this hypothesis, we applied CFD simulations of material transport in the cylinder of a diesel engine, assuming detachment of steel fragments from various sites of the cylinder. The CFD results show that fragments ≤20 μm in size dislodged from the piston surface or from the fuel nozzle interior can be indeed transported to such hot areas of the combustion chamber where they can melt. The simulation results concur with the experimental observations and point out that metal nanoparticle formation by in-cylinder melting of engine fragments can occur in diesel engines. The present study proposes a hitherto neglected formation mechanism of metal nanoparticle emissions from internal combustion engines raising possible environmental and health concerns, especially in urban areas.

Widespread Nanoparticle-Assay Interference: Implications for Nanotoxicity Testing

PubMed Central

Ong, Kimberly J.; MacCormack, Tyson J.; Clark, Rhett J.; Ede, James D.; Ortega, Van A.; Felix, Lindsey C.; Dang, Michael K. M.; Ma, Guibin; Fenniri, Hicham; Veinot, Jonathan G. C.; Goss, Greg G.

2014-01-01

The evaluation of engineered nanomaterial safety has been hindered by conflicting reports demonstrating differential degrees of toxicity with the same nanoparticles. The unique properties of these materials increase the likelihood that they will interfere with analytical techniques, which may contribute to this phenomenon. We tested the potential for: 1) nanoparticle intrinsic fluorescence/absorbance, 2) interactions between nanoparticles and assay components, and 3) the effects of adding both nanoparticles and analytes to an assay, to interfere with the accurate assessment of toxicity. Silicon, cadmium selenide, titanium dioxide, and helical rosette nanotubes each affected at least one of the six assays tested, resulting in either substantial over- or under-estimations of toxicity. Simulation of realistic assay conditions revealed that interference could not be predicted solely by interactions between nanoparticles and assay components. Moreover, the nature and degree of interference cannot be predicted solely based on our current understanding of nanomaterial behaviour. A literature survey indicated that ca. 95% of papers from 2010 using biochemical techniques to assess nanotoxicity did not account for potential interference of nanoparticles, and this number had not substantially improved in 2012. We provide guidance on avoiding and/or controlling for such interference to improve the accuracy of nanotoxicity assessments. PMID:24618833

Si-based Nanoparticles: a biocompatibility study

NASA Astrophysics Data System (ADS)

Rivolta, I.; Lettiero, B.; Panariti, A.; D'Amato, R.; Maurice, V.; Falconieri, M.; Herlein, N.; Borsella, E.; Miserocchi, G.

2010-10-01

Exposure to silicon nanoparticles (Si-NPs) may occur in professional working conditions or for people undergoing a diagnostic screening test. Despite the fact that silicon is known as a non-toxic material, in the first case the risk is mostly related to the inhalation of nanoparticles, thus the most likely route of entry is across the lung alveolar epithelium. In the case of diagnostic imaging, nanoparticles are usually injected intravenously and Si-NPs could impact on the endothelial wall. In our study we investigated the interaction between selected Si-based NPs and an epithelial lung cell line. Our data showed that, despite the overall silicon biocompatibility, however accurate studies of the potential toxicity induced by the nanostructure and engineered surface characteristics need to be accurately investigated before Si nanoparticles can be safely used for in vivo applications as bio-imaging, cell staining and drug delivery.

Tangential Flow Filtration of Colloidal Silver Nanoparticles: A "Green" Laboratory Experiment for Chemistry and Engineering Students

ERIC Educational Resources Information Center

Dorney, Kevin M.; Baker, Joshua D.; Edwards, Michelle L.; Kanel, Sushil R.; O'Malley, Matthew; Pavel Sizemore, Ioana E.

2014-01-01

Numerous nanoparticle (NP) fabrication methodologies employ "bottom-up" syntheses, which may result in heterogeneous mixtures of NPs or may require toxic capping agents to reduce NP polydispersity. Tangential flow filtration (TFF) is an alternative "green" technique for the purification, concentration, and size-selection of…

Synthesis and optimization of chitosan nanoparticles: Potential applications in nanomedicine and biomedical engineering.

PubMed

Ghadi, Arezou; Mahjoub, Soleiman; Tabandeh, Fatemeh; Talebnia, Farid

2014-01-01

Chitosan nanoparticles have become of great interest for nanomedicine, biomedical engineering and development of new therapeutic drug release systems with improved bioavailability, increased specificity and sensitivity, and reduced pharmacological toxicity. The aim of the present study was to synthesis and optimize of the chitosan nanoparticles for industrial and biomedical applications. Fe3O4 was synthesized and optimized as magnetic core nanoparticles and then chitosan covered this magnetic core. The size and morphology of the nano-magnetic chitosan was analyzed by scanning electron microscope (SEM). Topography and size distribution of the nanoparticles were shown with two-dimensional and three-dimensional images of atomic force microscopy (AFM). The nanoparticles were analyzed using transmission electron microscopy (TEM). The chitosan nanoparticles prepared in the experiment exhibited white powder shape. The SEM micrographs of the nano-magnetic chitosan showed that they were approximately uniform spheres. The unmodified chitosan nanoparticles composed of clusters of nanoparticles with sizes ranging from 10 nm to 80 nm. AFM provides a three-dimensional surface profile. The TEM image showed physical aggregation of the chitosan nanoparticles. The results show that a novel chitosan nanoparticle was successfully synthesized and characterized. It seems that this nanoparticle like the other chitosan nano particles has potential applications for nanomedicine, biomedical engineering, industrial and pharmaceutical fields.

The concept of bio-corona in modulating the toxicity of engineered nanomaterials (ENM)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westmeier, Dana; Stauber, Roland H.; Docter, Dominic, E-mail: docter@uni-mainz.de

Besides the wide use of engineered nanomaterials (ENM) in technical products, their application spectrum in biotechnology and biomedicine is steadily increasing. In complex physiological environments the physico-chemical properties and the behavior of nanoparticles (NPs) are challenging to characterize. Biomolecules rapidly adsorb to the nanomaterial, leading to the formation of the protein/biomolecule corona, which critically affects the nanomaterials' (patho)biological and technical identities. This formation can trigger an immune response and affect nanoparticles' toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the (protein)corona-nanoparticle interaction and discuss how the corona modulates both cytotoxicity and the immunemore » response as well as to improve the efficacy of targeted delivery of nanocarriers. - Highlights: • “Nanotoxicology” has emerged an autonomous field with an explosive growth. • Nanomaterials adsorb (bio)molecules forming the so-called (bio)molecule corona. • (Fine-)tune of the corona composition could enable new possibilities in nanomedicine.« less

The potential of TiO2 nanoparticles as carriers for cadmium uptake in Lumbriculus variegatus and Daphnia magna.

PubMed

Hartmann, Nanna B; Legros, Samuel; Von der Kammer, Frank; Hofmann, Thilo; Baun, Anders

2012-08-15

The use of engineered nanoparticles (e.g. in industrial applications and consumer products) is increasing. Consequently, these particles will be released into the aquatic environment. Through aggregation/agglomeration and sedimentation, sediments are expected ultimately to be sinks for nanoparticles. Both in the water phase and in the sediments engineered nanoparticles will mix and interact with other environmental pollutants, including metals. In this study the toxicity of cadmium to two freshwater organisms, water column crustacean Daphnia magna and sediment oligochaete Lumbriculus variegatus, was investigated both in the absence and presence of titanium dioxide (TiO(2)) nanoparticles (P25 Evonic Degussa, d: 30 nm). The uptake of cadmium in sub-lethal concentrations was also studied in the absence and presence of 2 mg/L TiO(2) nanoparticles. Formation of larger nanoparticles aggregates/agglomerates was observed and sizes varied depending on media composition (358±13 nm in US EPA moderately hard synthetic freshwater and 1218±7 nm in Elendt M7). TiO(2) nanoparticles are potential carriers for cadmium and it was found that 25% and 6% of the total cadmium mass in the test system for L. variegatus and D. magna tests were associated to suspended TiO(2) particles, respectively. μXRF (micro X-ray fluorescence) analysis confirmed the uptake of TiO(2) in the gut of D. magna. For L. variegatus μXRF analysis indicated attachment of TiO(2) nanoparticles to the organism surface as well as a discrete distribution within the organisms. Though exact localisation in this organism was more difficult to assess, the uptake seems to be within the coelomic cavity. Results show that the overall body burden and toxicity of cadmium to L. variegatus was unchanged by addition of TiO(2) nanoparticles, showing that cadmium adsorption to TiO(2) nanoparticles did not affect overall bioavailability. Despite facilitated uptake of cadmium by TiO(2) nanoparticles in D. magna, resulting in increased total cadmium body burden, no change in toxicity was observed. Copyright © 2012 Elsevier B.V. All rights reserved.

Exposure assessment and risk management of engineered nanoparticles: Investigation in semiconductor wafer processing

NASA Astrophysics Data System (ADS)

Shepard, Michele N.

Engineered nanomaterials (ENMs) are currently used in hundreds of commercial products and industrial processes, with more applications being investigated. Nanomaterials have unique properties that differ from bulk materials. While these properties may enable technological advancements, the potential risks of ENMs to people and the environment are not yet fully understood. Certain low solubility nanoparticles are more toxic than their bulk material, such that existing occupational exposure limits may not be sufficiently protective for workers. Risk assessments are currently challenging due to gaps in data on the numerous emerging materials and applications as well as method uncertainties and limitations. Chemical mechanical planarization (CMP) processes with engineered nanoparticle abrasives are used for research and commercial manufacturing applications in the semiconductor and related industries. Despite growing use, no published studies addressed occupational exposures to nanoparticles associated with CMP or risk assessment and management practices for these scenarios. Additional studies are needed to evaluate potential sources of workplace exposure or emission, as well as to help test and refine assessment methods. This research was conducted to: identify the lifecycle stages and potential exposure sources for ENMs in CMP processes; characterize worker exposure; determine recommended engineering controls and compare risk assessment models. The study included workplace air and surface sampling and an evaluation of qualitative risk banding approaches. Exposure assessment results indicated the potential for worker contact with ENMs on workplace surfaces but did not identify nanoparticles readily dispersed in air during work tasks. Some increases in respirable particle concentrations were identified, but not consistently. Measured aerosol concentrations by number and mass were well below current reference values for poorly soluble low toxicity nanoparticles. From application and evaluation of qualitative risk assessment approaches, differences in control banding models and results were identified, although output generally agreed with conclusions from air sampling as to whether an upgrade in site engineering controls was recommended. This research helped to improve understanding of potential worker exposures to ENMs in CMP processes, as well as the methods for risk assessment and management of metal oxide nanoparticles in occupational environments.

Applications of Bacterial Magnetic Nanoparticles in Nanobiotechnology.

PubMed

Chen, Chuanfang; Wang, Pingping; Li, Linlin

2016-03-01

The bacterial magnetic nanoparticle (BMP) has been well researched in nanobiotechnology as a new magnetic crystal. The BMPs are extracted from magnetotactic bacteria and under precise biological control. Compared with engineered magnetic nanoparticles synthesized by chemical approaches, BMPs have the properties of large production, monodispersity, high crystallinity, and close-to-bulk magnetization, which enable BMPs to be the highly promising magnetic nanoparticles for nanobiotechnology. In this paper, we review the biomedical applications of BMPs in magnetic hyperthermia, drug treatment with tumour and bioseparation. In addition, the biodistribution and toxicity are also reviewed.

Rationally engineered polymeric cisplatin nanoparticle for improved antitumor efficacy

PubMed Central

Paraskar, Abhimanyu; Soni, Shivani; Basu, Sudipta; Chitra, J; Amarasiriwardena; Lupoli, Nicola; Srivats, Shyam; Roy, Rituparna Sinha; Sengupta, Shiladitya

2011-01-01

The use of cisplatin, a first line chemotherapy for most cancers, is dose-limited due to nephrotoxicity. While, this toxicity can be addressed through nanotechnology, previous attempts at engineering cisplatin nanoparticles have been limited by the impact on the potency of cisplatin. Here we report the rational engineering of a novel cisplatin nanoparticle by harnessing a novel polyethylene glycol-functionalized poly-isobutylene-maleic acid (PEG-PIMA) co-polymer, which can complex with cis-platinum (II) through a monocarboxylato and a coordinate bond. We show that this complex self-assembles into a nanoparticle, and exhibit an IC50 = 0.77 ± 0.11μM comparable to that of free cisplatin (IC50 = 0.44 ± 0.09 μM). The nanoparticles are internalized into the endolysosomal compartment of cancer cells, and releases cisplatin in a pH-dependent manner. Furthermore, the nanoparticles exhibited significantly improved antitumor efficacy in a 4T1 breast cancer model in vivo with limited nephrotoxicity, which can be explained by preferential biodistribution in the tumor with reduced kidney concentrations. Our results suggest that the PEG-PIMA-cisplatin nanoparticle can emerge as an attractive solution to the challenges in cisplatin chemotherapy. PMID:21576779

Reduced Silver Nanoparticle Phytotoxicity in Crambe abyssinica with Enhanced Glutathione Production by Overexpressing Bacterial y-Glutamylcysteine Synthase

Treesearch

Chuanxin Ma; Sudesh Chhikara; Rakesh Minocha; Stephanie Long; Craig Musante; Jason C. White; Baoshan Xing; Om Parkash Dhankher

2015-01-01

Silver nanoparticles (Ag NPs) are widely used in consumer products, and their release has raised serious concerns about the risk of their exposure to the environment and to human health. However, biochemical mechanisms by which plants counteract NP toxicity are largely unknown. We have previously engineered Crambe abyssinica plants expressing the...

Transport and retention of zinc oxide nanoparticles in porous media: Effects of natural organic matter versus natural organic ligands at circumneutral pH

EPA Science Inventory

The potential toxicity of nanoparticles (NPs) has received considerable attention, but there is little knowledge relating to the fate and transport of engineered ZnO NPs in the environment. Column experiments were performed at pH 7.3–7.6 to generate effluent concentrations and re...

An improved, non-functionalized route to plasmonic nanoparticle based cellular probing through osmolyte mediation (Conference Presentation)

NASA Astrophysics Data System (ADS)

Siddhanta, Soumik; Barman, Ishan

2017-02-01

Engineering nanostructured probes for ultra-sensitive detection of specific molecular species, our research seeks to capture the complex changes in cells and tissues that can predict disease progression in an individual. While such nanoparticle-based platforms are rapidly gaining a foothold in cancer diagnostics, one of the most concerning factors is the vulnerability of cells to the interaction with functional nanoparticles thereby raising the specter of systemic toxicity. The nanoparticles end up damaging the cells and disrupting cellular functions thereby impeding their imaging aim. Furthermore, PEGylation, and similar routes, force a tradeoff between desired nanoparticle properties (recognition, uptake, and reduced toxicity) and sensitivity of plasmon-enhanced spectroscopic sensing methods, such as surface-enhanced Raman spectroscopy (SERS) where the proximal presence of noble metal NP and the organic molecule of interest is key. In this work, we report a trehalose-mediated, non-surface functionalized route for cell-nanoparticle interactions that maintains cell viability while allowing selective interaction of the nanoparticle with the cell surface receptors and subsequent internalization. Through careful electron microscopy of nanoparticle-prostate cancer cells interactions, we elucidated that there exists a dynamic equilibrium between "free" cytosolic diffusion of the nanoparticles and endocytosis through vesicle formation - and trehalose tilts the scale in favor of the latter to mask the toxic effects of the nanoparticles. The precise molecular interpretation of this behavior was further probed through SERS, which directly points towards the protein stabilization properties of trehalose mediation during interaction of the nanoparticles with the plasma membrane components.

Mitochondrial dysfunction and loss of glutamate uptake in primary astrocytes exposed to titanium dioxide nanoparticles

NASA Astrophysics Data System (ADS)

Wilson, Christina L.; Natarajan, Vaishaali; Hayward, Stephen L.; Khalimonchuk, Oleh; Kidambi, Srivatsan

2015-11-01

Titanium dioxide (TiO2) nanoparticles are currently the second most produced engineered nanomaterial in the world with vast usage in consumer products leading to recurrent human exposure. Animal studies indicate significant nanoparticle accumulation in the brain while cellular toxicity studies demonstrate negative effects on neuronal cell viability and function. However, the toxicological effects of nanoparticles on astrocytes, the most abundant cells in the brain, have not been extensively investigated. Therefore, we determined the sub-toxic effect of three different TiO2 nanoparticles (rutile, anatase and commercially available P25 TiO2 nanoparticles) on primary rat cortical astrocytes. We evaluated some events related to astrocyte functions and mitochondrial dysregulation: (1) glutamate uptake; (2) redox signaling mechanisms by measuring ROS production; (3) the expression patterns of dynamin-related proteins (DRPs) and mitofusins 1 and 2, whose expression is central to mitochondrial dynamics; and (4) mitochondrial morphology by MitoTracker® Red CMXRos staining. Anatase, rutile and P25 were found to have LC50 values of 88.22 +/- 10.56 ppm, 136.0 +/- 31.73 ppm and 62.37 +/- 9.06 ppm respectively indicating nanoparticle specific toxicity. All three TiO2 nanoparticles induced a significant loss in glutamate uptake indicative of a loss in vital astrocyte function. TiO2 nanoparticles also induced an increase in reactive oxygen species generation, and a decrease in mitochondrial membrane potential, suggesting mitochondrial damage. TiO2 nanoparticle exposure altered expression patterns of DRPs at low concentrations (25 ppm) and apoptotic fission at high concentrations (100 ppm). TiO2 nanoparticle exposure also resulted in changes to mitochondrial morphology confirmed by mitochondrial staining. Collectively, our data provide compelling evidence that TiO2 nanoparticle exposure has potential implications in astrocyte-mediated neurological dysfunction.Titanium dioxide (TiO2) nanoparticles are currently the second most produced engineered nanomaterial in the world with vast usage in consumer products leading to recurrent human exposure. Animal studies indicate significant nanoparticle accumulation in the brain while cellular toxicity studies demonstrate negative effects on neuronal cell viability and function. However, the toxicological effects of nanoparticles on astrocytes, the most abundant cells in the brain, have not been extensively investigated. Therefore, we determined the sub-toxic effect of three different TiO2 nanoparticles (rutile, anatase and commercially available P25 TiO2 nanoparticles) on primary rat cortical astrocytes. We evaluated some events related to astrocyte functions and mitochondrial dysregulation: (1) glutamate uptake; (2) redox signaling mechanisms by measuring ROS production; (3) the expression patterns of dynamin-related proteins (DRPs) and mitofusins 1 and 2, whose expression is central to mitochondrial dynamics; and (4) mitochondrial morphology by MitoTracker® Red CMXRos staining. Anatase, rutile and P25 were found to have LC50 values of 88.22 +/- 10.56 ppm, 136.0 +/- 31.73 ppm and 62.37 +/- 9.06 ppm respectively indicating nanoparticle specific toxicity. All three TiO2 nanoparticles induced a significant loss in glutamate uptake indicative of a loss in vital astrocyte function. TiO2 nanoparticles also induced an increase in reactive oxygen species generation, and a decrease in mitochondrial membrane potential, suggesting mitochondrial damage. TiO2 nanoparticle exposure altered expression patterns of DRPs at low concentrations (25 ppm) and apoptotic fission at high concentrations (100 ppm). TiO2 nanoparticle exposure also resulted in changes to mitochondrial morphology confirmed by mitochondrial staining. Collectively, our data provide compelling evidence that TiO2 nanoparticle exposure has potential implications in astrocyte-mediated neurological dysfunction. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03646a

Cyborg cells: functionalisation of living cells with polymers and nanomaterials.

PubMed

Fakhrullin, Rawil F; Zamaleeva, Alsu I; Minullina, Renata T; Konnova, Svetlana A; Paunov, Vesselin N

2012-06-07

Living cells interfaced with a range of polyelectrolyte coatings, magnetic and noble metal nanoparticles, hard mineral shells and other complex nanomaterials can perform functions often completely different from their original specialisation. Such "cyborg cells" are already finding a range of novel applications in areas like whole cell biosensors, bioelectronics, toxicity microscreening, tissue engineering, cell implant protection and bioanalytical chemistry. In this tutorial review, we describe the development of novel methods for functionalisation of cells with polymers and nanoparticles and comment on future advances in this technology in the light of other literature approaches. We review recent studies on the cell viability and function upon direct deposition of nanoparticles, coating with polyelectrolytes, polymer assisted assembly of nanomaterials and hard shells on the cell surface. The cell toxicity issues are considered for many practical applications in terms of possible adverse effects of the deposited polymers, polyelectrolytes and nanoparticles on the cell surface.

A Review on the Respiratory System Toxicity of Carbon Nanoparticles.

PubMed

Pacurari, Maricica; Lowe, Kristine; Tchounwou, Paul B; Kafoury, Ramzi

2016-03-15

The respiratory system represents the main gateway for nanoparticles' entry into the human body. Although there is a myriad of engineered nanoparticles, carbon nanoparticles/nanotubes (CNPs/CNTs) have received much attention mainly due to their light weight, very high surface area, durability, and their diverse applications. Since their discovery and manufacture over two decades ago, much has been learned about nanoparticles' interactions with diverse biological system models. In particular, the respiratory system has been of great interest because various natural and man-made fibrous particles are known to be responsible for chronic and debilitating lung diseases. In this review, we present up-to-date the literature regarding the effects of CNTs or carbon nanofibers (CNFs) on the human respiratory system with respect to respiratory toxicity pathways and associated pathologies. This article is intended to emphasize the potentially dangerous effects to the human respiratory system if inadequate measures are used in the manufacture, handling, and preparation and applications of CNP or CNP-based products.

Differential genomic effects of six different TiO2 nanomaterials on human liver HepG2 cells

EPA Science Inventory

Engineered nanoparticles are reported to cause liver toxicity in vivo. To better assess the mechanism of the in vivo liver toxicity, we used the human hepatocarcinoma cells (HepG2) as a model system. Human HepG2 cells were exposed to 6 TiO2 nanomaterials (with dry primary partic...

Evaluation of the role of oxidative stress, inflammation and apoptosis in the pulmonary and the hepatic toxicity induced by cerium oxide nanoparticles following intratracheal instillation in male Sprague-Dawley rats

NASA Astrophysics Data System (ADS)

Nalabotu, Siva Krishna

The field of nanotechnology is rapidly progressing with potential applications in the automobile, healthcare, electronics, cosmetics, textiles, information technology, and environmental sectors. Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. With increased applications of nanotechnology, there are increased chances of exposure to manufactured nanomaterials. Recent reports on the toxicity of engineered nanomaterials have given scientific and regulatory agencies concerns over the safety of nanomaterials. Specifically, the Organization for Economic Co-operation and Development (OECD) has identified fourteen high priority nanomaterials for study. Cerium oxide (CeO2) nanoparticles are one among the high priority group. Recent data suggest that CeO2 nanoparticles may be toxic to lung cell lines in vitro and lung tissues in vivo. Other work has proposed that oxidative stress may play an important role in the toxicity; however, the exact mechanism of the toxicity, has to our knowledge, not been investigated. Similarly, it is not clear whether CeO2 nanoparticles exhibit systemic toxicity. Here, we investigate whether pulmonary exposure to CeO2 nanoparticles is associated with oxidative stress, inflammation and apoptosis in the lungs and liver of adult male Sprague-Dawley rats. Our data suggest that the intratracheal instillation of CeO2 nanoparticles can cause an increased lung weight to body weight ratio. Changes in lung weights were associated with the accumulation of cerium in the lungs, elevations in serum inflammatory markers, an increased Bax to Bcl-2 ratio, elevated caspase-3 protein levels, increased phosphorylation of p38-MAPK and diminished phosphorylation of ERK1/2-MAPK. Our findings from the study evaluating the possible translocation of CeO2 nanoparticles from the lungs to the liver suggest that CeO 2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio and decreased serum triglyceride levels. Consistent with these data, rats exposed to CeO2 nanoparticles also exhibited reductions in liver weight and dose dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation and the accumulation of granular material in the hepatocytes. In a follow-up study, we next examined if CeO2 deposition in the liver is characterized by increased oxidative stress and apoptosis. Our data demonstrate that increased cerium in the liver is associated with increased oxidative stress and apoptosis as assessed from hydroethidium staining, the analysis of lipid peroxidation, and TUNEL staining. In addition, increased cerium concentration in the liver was associated with an increased Bax to Bcl-2 ratio, elevated caspase-9 and elevated caspase-3 protein levels. Taken together, these data suggest that exposure to CeO 2 nanoparticles is associated with increased oxidative stress and cellular apoptosis in the lungs. It is also evident that CeO2 nanoparticles can translocate to liver and induce hepatic damage. The hepatic damage induced by CeO2 nanoparticles is associated with increased oxidative stress and apoptosis in the liver.

Endotoxin contamination: a key element in the interpretation of nanosafety studies.

PubMed

Li, Yang; Boraschi, Diana

2016-02-01

The study of toxicity and potential risks of engineered nanoparticles is of particular importance in nanomedicine. Endotoxin, a common contaminant of bacterial origin, has biological effects that can mask the true biological effects of nanoparticles, if its presence is overlooked. In this review, we report the features of nanoparticle contamination by endotoxin, and the different biological effects of endotoxin-contaminated nanoparticles. We will describe different methods for endotoxin detection applied to nanoparticles, and discuss their pros and cons. Eventually, we describe various methods for eliminating endotoxin contamination in nanoparticles. Although there is no universal technique for efficiently removing endotoxin from nanoparticles, specific solutions can be found case by case, which can allow us to perform nanosafety studies in biologically relevant conditions.

Short-term exposure to gold nanoparticle suspension impairs swimming behavior in a widespread calanoid copepod.

PubMed

Michalec, François-Gaël; Holzner, Markus; Barras, Alexandre; Lacoste, Anne-Sophie; Brunet, Loïc; Lee, Jae-Seong; Slomianny, Christian; Boukherroub, Rabah; Souissi, Sami

2017-09-01

Calanoid copepods play an important role in the functioning of marine and brackish ecosystems. Information is scarce on the behavioral toxicity of engineered nanoparticles to these abundant planktonic organisms. We assessed the effects of short-term exposure to nonfunctionalized gold nanoparticles on the swimming behavior of the widespread estuarine copepod Eurytemora affinis. By means of three-dimensional particle tracking velocimetry, we reconstructed the trajectories of males, ovigerous and non-ovigerous females. We quantified changes in their swimming activity and in the kinematics and geometrical properties of their motion, three important descriptors of the motility patterns of zooplankters. In females, exposure to gold nanoparticles in suspension (11.4 μg L -1 ) for 30 min caused depressed activity and lower velocity and acceleration, whereas the same exposure caused minimal effects in males. This response differs clearly from the hyperactive behavior that is commonly observed in zooplankters exposed to pollutants, and from the generally lower sensitivity of female copepods to toxicants. Accumulation of gold nanoparticles on the external appendages was not observed, precluding mechanical effects. Only very few nanoparticles appeared sporadically in the inner part of the gut in some samples, either as aggregates or as isolated nanoparticles, which does not suggest systemic toxicity resulting from pronounced ingestion. Hence, the precise mechanisms underlying the behavioral toxicity observed here remain to be elucidated. These results demonstrate that gold nanoparticles can induce marked behavioral alterations at very low concentration and short exposure duration. They illustrate the applicability of swimming behavior as a suitable and sensitive endpoint for investigating the toxicity of nanomaterials present in estuarine and marine environments. Changes in swimming behavior may impair the ability of planktonic copepods to interact with their environment and with other organisms, with possible impacts on population dynamics and community structure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans

PubMed Central

Zanon, Tyler; Kappell, Anthony D.; Petrella, Lisa N.; Andersen, Erik C.; Hristova, Krassimira R.

2016-01-01

Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nanoparticles and copper sulfate on C. elegans toxicological endpoints to elucidate their biological effects. Several toxicological endpoints were analyzed in C. elegans, including nematode reproduction, feeding behavior, and average body length. We examined three wild C. elegans isolates together with the Bristol N2 laboratory strain to explore the influence of different genotypic backgrounds on the physiological response to copper challenge. All strains exhibited greater sensitivity to copper oxide nanoparticles compared to copper sulfate, as indicated by reduction of average body length and feeding behavior. Reproduction was significantly reduced only at the highest copper dose, though still more pronounced with copper oxide nanoparticles compared to copper sulfate treatment. Furthermore, we investigated the effects of copper oxide nanoparticles and copper sulfate on neurons, cells with known vulnerability to heavy metal toxicity. Degeneration of dopaminergic neurons was observed in up to 10% of the population after copper oxide nanoparticle exposure. Additionally, mutants in the divalent-metal transporters, smf-1 or smf-2, showed increased tolerance to copper exposure, implicating both transporters in copper-induced neurodegeneration. These results highlight the complex nature of CuO nanoparticle toxicity, in which a nanoparticle-specific effect was observed in some traits (average body length, feeding behavior) and a copper ion specific effect was observed for other traits (neurodegeneration, response to stress). PMID:27911941

Biodegradable luminescent porous silicon nanoparticles for in vivo applications

PubMed Central

Park, Ji-Ho; Gu, Luo; von Maltzahn, Geoffrey; Ruoslahti, Erkki; Bhatia, Sangeeta N.; Sailor, Michael J.

2011-01-01

Nanomaterials that can circulate in the body hold great potential to diagnose and treat disease1–4. For such applications, it is important that the nanomaterials be harmlessly eliminated from the body in a reasonable period of time after they carry out their diagnostic or therapeutic function. Despite efforts to improve their targeting efficiency, significant quantities of systemically administered nanomaterials are cleared by the mononuclear phagocytic system before finding their targets, increasing the likelihood of unintended acute or chronic toxicity. However, there has been little effort to engineer the self-destruction of errant nanoparticles into non-toxic, systemically eliminated products. Here, we present luminescent porous silicon nanoparticles (LPSiNPs) that can carry a drug payload and of which the intrinsic near-infrared photoluminescence enables monitoring of both accumulation and degradation in vivo. Furthermore, in contrast to most optically active nanomaterials (carbon nanotubes, gold nanoparticles and quantum dots), LPSiNPs self-destruct in a mouse model into renally cleared components in a relatively short period of time with no evidence of toxicity. As a preliminary in vivo application, we demonstrate tumour imaging using dextran-coated LPSiNPs (D-LPSiNPs). These results demonstrate a new type of multifunctional nanostructure with a low-toxicity degradation pathway for in vivo applications. PMID:19234444

Surface Defects on Plate-Shaped Silver Nanoparticles Contribute to Its Hazard Potential in a Fish Gill Cell Line and Zebrafish Embyos

PubMed Central

George, Saji; Lin, Sijie; Ji, Zhaoxia; Thomas, Courtney; Li, LinJiang; Mecklenburg, Mathew; Meng, Huan; Wang, Xiang; Zhang, Haiyuan; Xia, Tian; Lin, Shuo; Hohman, J. Nathan; Zink, Jeffrey I.; Weiss, Paul; Nel, André E.

2014-01-01

We investigated and compared nano-size Ag spheres, plates, and wires in a fish gill epithelial cell line (RT-W1) and in zebrafish embryos to understand the mechanism of toxicity of an engineered nanomaterial raising considerable environmental concern. While most of the Ag nanoparticles induced N-acetyl cysteine sensitive toxic oxidative stress effects in RT-W1, Ag nanoplates were considerably more toxic than other particle shapes. Interestingly, while Ag ion shedding and bioavailability failed to explain the high toxicity of the nanoplates, cellular injury required direct particle contact, resulting in cell membrane lysis in RT-W1 as well as red blood cells (RBC). Ag nanoplates were also considerably more toxic in zebrafish embryos in spite of their lesser ability to shed Ag into the exposure medium. In order to elucidate the “surface reactivity” of Ag nanoplates, high-resolution transmission electron microscopy was performed and demonstrated a high level of crystal defects (stacking faults and point defects) on the nanoplate surfaces. Surface coating with cysteine was used to passivate the surface defects and demonstrated a reduction of toxicity in RT-W1 cells, RBC, and zebrafish embryos. This study demonstrates the important role of crystal defects in contributing to Ag nanoparticle toxicity in addition to the established roles of Ag ion shed from spherical nanoparticles. The excellent correlation between the in vitro and in vivo toxicological assessment illustrates the utility of using a fish cell line in parallel with zebrafish embryos to perform a predictive environmental toxicological paradigm. PMID:22482460

Release of Metal Impurities from Carbon Nanomaterials Influences Aquatic Toxicity

DTIC Science & Technology

2009-01-01

nanoparticles were more acutely toxic to zebrafish than could be explained by dissolution alone. Derfus et al. (12) reported that oxidation of CdSe...extracts that are generated during some nanomanufacturing processes (21). Metals-laden wastes are of particular concern given the known toxicological ...that researchers continue to evaluate the toxicological behavior of engineered nanomaterials, our results emphasize the need for studies to evaluate

Distinct toxic interactions of TiO2 nanoparticles with four coexisting organochlorine contaminants on algae.

PubMed

Zhang, Shuai; Deng, Rui; Lin, Daohui; Wu, Fengchang

Engineered nanoparticles are increasingly discharged into the environment. After discharge, these nanoparticles can interact with co-existing organic contaminants, resulting in a phenomena referred to as 'joint toxicity'. This study evaluated joint toxicities of TiO 2 nanoparticles (TiO 2 NPs) with four different (atrazine, hexachlorobenzene, pentachlorobenzene, and 3,3',4,4'-tetrachlorobiphenyl) organochlorine contaminants (OCs) toward algae (Chlorella pyrenoidosa). The potential mechanisms underlying the joint toxicity were discussed, including TiO 2 NPs-OC interactions, effects of TiO 2 NPs and OCs on biophysicochemical properties of algae and effects of TiO 2 NPs and OCs on each other's bioaccumulation in algae. The results indicate that coexposure led to a synergistic effect on the joint toxicity for TiO 2 NPs-atrazine, antagonistic effect for TiO 2 NPs-hexachlorobenzene and TiO 2 NPs-3,3',4,4'-tetrachlorobiphenyl, and an additive effect for TiO 2 NPs-pentachlorobenzene. There was nearly no adsorption of OCs by TiO 2 NPs, and the physicochemical properties of TiO 2 NPs were largely unaltered by the presence of OCs. However, both OCs and NPs affected the biophysicochemical properties of algal cells and thereby influenced the cell surface binding and/or internalization. TiO 2 NPs significantly increased the bioaccumulation of each OC. However, with the exception of atrazine, the bioaccumulation of TiO 2 NPs decreased when used with each OC. The distinct joint toxicity outcomes were a result of the balance between the increased toxicities of OCs (increased bioaccumulations) and the altered toxicity of TiO 2 NPs (bioaccumulation can either increase or decrease). These results can significantly improve our understanding of the potential environmental risks associated with NPs.

Vitro Pulmonary Toxicity of Metal Oxide Nanoparticles

EPA Science Inventory

The diversity of engineered-nanomaterials and their applications as well as potential unknown health effects of these novel materials are significant challenges to assessing the health risks of nanotechnology. An integrated multi-tier testing strategy (www.epa.gov/nanoscience/) ...

Untangling the biological effects of cerium oxide nanoparticles: the role of surface valence states

PubMed Central

Pulido-Reyes, Gerardo; Rodea-Palomares, Ismael; Das, Soumen; Sakthivel, Tamil Selvan; Leganes, Francisco; Rosal, Roberto; Seal, Sudipta; Fernández-Piñas, Francisca

2015-01-01

Cerium oxide nanoparticles (nanoceria; CNPs) have been found to have both pro-oxidant and anti-oxidant effects on different cell systems or organisms. In order to untangle the mechanisms which underlie the biological activity of nanoceria, we have studied the effect of five different CNPs on a model relevant aquatic microorganism. Neither shape, concentration, synthesis method, surface charge (ζ-potential), nor nominal size had any influence in the observed biological activity. The main driver of toxicity was found to be the percentage of surface content of Ce3+ sites: CNP1 (58%) and CNP5 (40%) were found to be toxic whereas CNP2 (28%), CNP3 (36%) and CNP4 (26%) were found to be non-toxic. The colloidal stability and redox chemistry of the most and least toxic CNPs, CNP1 and CNP2, respectively, were modified by incubation with iron and phosphate buffers. Blocking surface Ce3+ sites of the most toxic CNP, CNP1, with phosphate treatment reverted toxicity and stimulated growth. Colloidal destabilization with Fe treatment only increased toxicity of CNP1. The results of this study are relevant in the understanding of the main drivers of biological activity of nanoceria and to define global descriptors of engineered nanoparticles (ENPs) bioactivity which may be useful in safer-by-design strategies of nanomaterials. PMID:26489858

Antibacterial properties and toxicity from metallic nanomaterials

PubMed Central

Vimbela, Gina V; Ngo, Sang M; Fraze, Carolyn; Yang, Lei; Stout, David A

2017-01-01

The era of antibiotic resistance is a cause of increasing concern as bacteria continue to develop adaptive countermeasures against current antibiotics at an alarming rate. In recent years, studies have reported nanoparticles as a promising alternative to antibacterial reagents because of their exhibited antibacterial activity in several biomedical applications, including drug and gene delivery, tissue engineering, and imaging. Moreover, nanomaterial research has led to reports of a possible relationship between the morphological characteristics of a nanomaterial and the magnitude of its delivered toxicity. However, conventional synthesis of nanoparticles requires harsh chemicals and costly energy consumption. Additionally, the exact relationship between toxicity and morphology of nanomaterials has not been well established. Here, we review the recent advancements in synthesis techniques for silver, gold, copper, titanium, zinc oxide, and magnesium oxide nanomaterials and composites, with a focus on the toxicity exhibited by nanomaterials of multidimensions. This article highlights the benefits of selecting each material or metal-based composite for certain applications while also addressing possible setbacks and the toxic effects of the nanomaterials on the environment. PMID:28579779

Nanoparticles of volcanic ash as a carrier for toxic elements on the global scale.

PubMed

Ermolin, Mikhail S; Fedotov, Petr S; Malik, Natalia A; Karandashev, Vasily K

2018-06-01

At present, there is concern about engineered nanoparticles in the environment, whereas natural nanoparticles (NPs) and their impact are often neglected. In our paper, we demonstrate the important role of nanoparticles of volcanic ash in transport of toxic elements on a global scale. A single volcanic eruption can eject millions of tons of ash. NPs of volcanic ash reach the upper troposphere and the stratosphere and may "travel" around the world for years affecting human health, environment, and even climate. So far, there is a gap in exposure assessment of volcanic ash NPs since their chemical composition remains largely unknown. Here we show for the first time that volcanic ash NPs can serve as an important carrier for potentially toxic elements. The concentrations of Ni, Zn, Cd, Ag, Sn, Se, Te, Hg, Tl, Pb, Bi in volcanic ash NPs (<100 nm) were found to be 10-500 times higher than total contents of these elements in bulk samples. This is valid for volcanoes from different regions of the world (Kamchatka, Far East of Russia and Andes, Chile). The work opens a new door into studies on biogeochemical impact of volcanic ash. Copyright © 2018 Elsevier Ltd. All rights reserved.

The potential risks of nanomaterials: a review carried out for ECETOC

PubMed Central

Borm, Paul JA; Robbins, David; Haubold, Stephan; Kuhlbusch, Thomas; Fissan, Heinz; Donaldson, Ken; Schins, Roel; Stone, Vicki; Kreyling, Wolfgang; Lademann, Jurgen; Krutmann, Jean; Warheit, David; Oberdorster, Eva

2006-01-01

During the last few years, research on toxicologically relevant properties of engineered nanoparticles has increased tremendously. A number of international research projects and additional activities are ongoing in the EU and the US, nourishing the expectation that more relevant technical and toxicological data will be published. Their widespread use allows for potential exposure to engineered nanoparticles during the whole lifecycle of a variety of products. When looking at possible exposure routes for manufactured Nanoparticles, inhalation, dermal and oral exposure are the most obvious, depending on the type of product in which Nanoparticles are used. This review shows that (1) Nanoparticles can deposit in the respiratory tract after inhalation. For a number of nanoparticles, oxidative stress-related inflammatory reactions have been observed. Tumour-related effects have only been observed in rats, and might be related to overload conditions. There are also a few reports that indicate uptake of nanoparticles in the brain via the olfactory epithelium. Nanoparticle translocation into the systemic circulation may occur after inhalation but conflicting evidence is present on the extent of translocation. These findings urge the need for additional studies to further elucidate these findings and to characterize the physiological impact. (2) There is currently little evidence from skin penetration studies that dermal applications of metal oxide nanoparticles used in sunscreens lead to systemic exposure. However, the question has been raised whether the usual testing with healthy, intact skin will be sufficient. (3) Uptake of nanoparticles in the gastrointestinal tract after oral uptake is a known phenomenon, of which use is intentionally made in the design of food and pharmacological components. Finally, this review indicates that only few specific nanoparticles have been investigated in a limited number of test systems and extrapolation of this data to other materials is not possible. Air pollution studies have generated indirect evidence for the role of combustion derived nanoparticles (CDNP) in driving adverse health effects in susceptible groups. Experimental studies with some bulk nanoparticles (carbon black, titanium dioxide, iron oxides) that have been used for decades suggest various adverse effects. However, engineered nanomaterials with new chemical and physical properties are being produced constantly and the toxicity of these is unknown. Therefore, despite the existing database on nanoparticles, no blanket statements about human toxicity can be given at this time. In addition, limited ecotoxicological data for nanomaterials precludes a systematic assessment of the impact of Nanoparticles on ecosystems. PMID:16907977

Toxicity of silver and gold nanoparticles on marine microalgae.

PubMed

Moreno-Garrido, Ignacio; Pérez, Sara; Blasco, Julián

2015-10-01

The increased use of nanomaterials in several novel industrial applications during the last decade has led to a rise in concerns about the potential toxic effects of released engineered nanoparticles (NPs) into the environment, as their potential toxicity to aquatic organisms is just beginning to be recognised. Toxicity of metallic nanoparticles to aquatic organisms, including microalgae, seems to be related to their physical and chemical properties, as well as their behaviour in the aquatic media where processes of dissolution, aggregation and agglomeration can occur. Although the production of these particles has increased considerably in recent years, data on their toxicity on microalgae, especially those belonging to marine or estuarine environments remain scarce and scattered. The literature shows a wide variation of results on toxicity, mainly due to the different methodology used in bioassays involving microalgae. These can range for up to EC50 data, in the case of AgNPs, representing five orders of magnitude. The importance of initial cellular density is also addressed in the text, as well as the need for keeping test conditions as close as possible to environmental conditions, in order to increase their environmental relevance. This review focuses on the fate and toxicity of silver, gold, and gold-silver alloy nanoparticles on microalgae, as key organisms in aquatic ecosystems. It is prompted by their increased production and use, and taking into account that oceans and estuaries are the final sink for those NPs. The design of bioassays and further research in the field of microalgae nanoecotoxicology is discussed, with a brief survey on newly developed technology of green (algae mediated) production of Ag, Au and Ag-Au bimetallic NPs, as well as some final considerations about future research on this field. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization and preliminary toxicity assay of nano-titanium dioxide additive in sugar-coated chewing gum.

PubMed

Chen, Xin-Xin; Cheng, Bin; Yang, Yi-Xin; Cao, Aoneng; Liu, Jia-Hui; Du, Li-Jing; Liu, Yuanfang; Zhao, Yuliang; Wang, Haifang

2013-05-27

Nanotechnology shows great potential for producing food with higher quality and better taste through including new additives, improving nutrient delivery, and using better packaging. However, lack of investigations on safety issues of nanofood has resulted in public fears. How to characterize engineered nanomaterials in food and assess the toxicity and health impact of nanofood remains a big challenge. Herein, a facile and highly reliable separation method of TiO2 particles from food products (focusing on sugar-coated chewing gum) is reported, and the first comprehensive characterization study on food nanoparticles by multiple qualitative and quantitative methods is provided. The detailed information on nanoparticles in gum includes chemical composition, morphology, size distribution, crystalline phase, particle and mass concentration, surface charge, and aggregation state. Surprisingly, the results show that the number of food products containing nano-TiO2 (<200 nm) is much larger than known, and consumers have already often been exposed to engineered nanoparticles in daily life. Over 93% of TiO2 in gum is nano-TiO2 , and it is unexpectedly easy to come out and be swallowed by a person who chews gum. Preliminary cytotoxicity assays show that the gum nano-TiO2 particles are relatively safe for gastrointestinal cells within 24 h even at a concentration of 200 μg mL(-1) . This comprehensive study demonstrates accurate physicochemical property, exposure, and cytotoxicity information on engineered nanoparticles in food, which is a prerequisite for the successful safety assessment of nanofood products. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Natural inorganic nanoparticles--formation, fate, and toxicity in the environment.

PubMed

Sharma, Virender K; Filip, Jan; Zboril, Radek; Varma, Rajender S

2015-12-07

The synthesis, stability, and toxicity of engineered metal nanoparticles (ENPs) have been extensively studied during the past two decades. In contrast, research on the formation, fate, and ecological effects of naturally-occurring nanoparticles (NNPs) has become a focus of attention only recently. The natural existence of metal nanoparticles and their oxides/sulfides in waters, wastewaters, ore deposits, mining regions, and hydrothermal vents, as exemplified by the formation of nanoparticles containing silver and gold (AgNPs and AuNPs), Fe, Mn, pyrite (FeS2), Ag2S, CuS, CdS, and ZnS, is dictated largely by environmental conditions (temperature, pH, oxic/anoxic, light, and concentration and characteristics of natural organic matter (NOM)). Examples include the formation of nanoparticles containing pyrite, Cu and Zn-containing pyrite, and iron in hydrothermal vent black smoker emissions. Metal sulfide nanoparticles can be formed directly from their precursor ions or indirectly by sulfide ion-assisted transformation of the corresponding metal oxides under anaerobic conditions. This tutorial focuses on the formation mechanisms, fate, and toxicity of natural metal nanoparticles. Natural waters containing Ag(I) and Au(III) ions in the presence of NOM generate AgNPs and AuNPs under thermal, non-thermal, and photochemical conditions. These processes are significantly accelerated by existing redox species of iron (Fe(II)/Fe(III)). NOM, metal-NOM complexes, and reactive oxygen species (ROS) such as O2˙(-), ˙OH, and H2O2 are largely responsible for the natural occurrence of nanoparticles. AgNPs and AuNPs emanating from Ag(I)/Au(III)-NOM reactions are stable for several months, thus indicating their potential to be transported over long distances from their point of origin. However, endogenous cations present in natural waters can destabilize the nanoparticles, with divalent cations (e.g., Ca(2+), Mg(2+)) being more influential than their monovalent equivalents (e.g., Na(+), K(+)). The toxicity of NNPs may differ from that of ENPs because of differences in the coatings on the nanoparticle surfaces. An example of this phenomenon is presented and is briefly discussed.

Peptide-directed self-assembly of functionalized polymeric nanoparticles. Part II: effects of nanoparticle composition on assembly behavior and multiple drug loading ability.

PubMed

Xiang, Xu; Ding, Xiaochu; Moser, Trevor; Gao, Qi; Shokuhfar, Tolou; Heiden, Patricia A

2015-04-01

Peptide-functionalized polymeric nanoparticles were designed and self-assembled into continuous nanoparticle fibers and three-dimensional scaffolds via ionic complementary peptide interaction. Different nanoparticle compositions can be designed to be appropriate for each desired drug, so that the release of each drug is individually controlled and the simultaneous sustainable release of multiple drugs is achieved in a single scaffold. A self-assembled scaffold membrane was incubated with NIH3T3 fibroblast cells in a culture dish that demonstrated non-toxicity and non-inhibition on cell proliferation. This type of nanoparticle scaffold combines the advantages of peptide self-assembly and the versatility of polymeric nanoparticle controlled release systems for tissue engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The effects of size and surface modification of amorphous silica particles on biodistribution and liver metabolism in mice

NASA Astrophysics Data System (ADS)

Lu, Xiaoyan; Ji, Cai; Jin, Tingting; Fan, Xiaohui

2015-05-01

Engineered nanoparticles, with unconventional properties, are promising platforms for biomedical applications. Since they may interact with a wide variety of biomolecules, it is critical to understand the impact of the physicochemical properties of engineered nanoparticles on biological systems. In this study, the effects of particle size and surface modification alone or in combination of amorphous silica particles (SPs) on biological responses were determined using a suite of general toxicological assessments and metabonomics analysis in mice model. Our results suggested that amino or carboxyl surface modification mitigated the liver toxicity of plain-surface SPs. 30 nm SPs with amino surface modification were found to be the most toxic SPs among all the surface-modified SP treatments at the same dosage. When treatment dose was increased, submicro-sized SPs with amino or carboxyl surface modification also induced liver toxicity. Biodistribution studies suggested that 70 nm SPs were mainly accumulated in liver and spleen regardless of surface modifications. Interestingly, these two organs exhibited different uptake trends. Furthermore, metabonomics studies indicated that surface modification plays a more dominant role to affect the liver metabolism than particle size.

Nanoparticle interactions with co-existing contaminants: joint toxicity, bioaccumulation and risk.

PubMed

Deng, Rui; Lin, Daohui; Zhu, Lizhong; Majumdar, Sanghamitra; White, Jason C; Gardea-Torresdey, Jorge L; Xing, Baoshan

2017-06-01

With their growing production and application, engineered nanoparticles (NPs) are increasingly discharged into the environment. The released NPs can potentially interact with pre-existing contaminants, leading to biological effects (bioaccumulation and/or toxicity) that are poorly understood. Most studies on NPs focus on single analyte exposure; the existing literature on joint toxicity of NPs and co-existing contaminants is rather limited but beginning to develop rapidly. This is the first review paper evaluating the current state of knowledge regarding the joint effects of NPs and co-contaminants. Here, we review: (1) methods for investigating and evaluating joint effects of NPs and co-contaminants; (2) simultaneous toxicities from NPs co-exposed with organic contaminants, metal/metalloid ions, dissolved organic matter (DOM), inorganic ligands and additional NPs; and (3) the influence of NPs co-exposure on the bioaccumulation of organic contaminants and heavy metal ions, as well as the influence of contaminants on NPs bioaccumulation. In addition, future research needs are discussed so as to better understand risk associated with NPs-contaminant co-exposure.

Implications of handling practices on the ecotoxic profile of alumina nanoparticles towards the bacteria Vibrio fischeri.

PubMed

Tsiridis, Vasilios; Petala, Maria; Koukiotis, Chris; Darakas, Efthymios

2017-01-02

The complex nature and behavior of Engineered Nanomaterials (ENMs) has led to adoption of customized experimental ecotoxicity practices that are prone to possible artefacts in the inherent toxic properties of ENMs. In addition, the lack of standardized handling procedures for the ecotoxicity testing of ENMs prevents the development of experimental protocols for regulatory purposes. In this study, a suite of techniques for dispersion of ENMs was adopted and tested for two types of surface-modified alumina nanoparticles-one hydrophobic and one hydrophilic-towards the bacteria, Vibrio fischeri. The effect of certain handling practices on the observed ecotoxic effects on V. fischeri was examined. The overall goal was to evaluate by what means the handling practices of ENMs may affect the obtained toxicity results. It was realized that the toxicity of the hydrophilic and hydrophobic ENMs was mainly affected by the centrifugation and the salinity of the tested dispersions, respectively. It is more likely that both aluminium and coating substance contributed to the overall toxicity. Toxicity results are discussed with regard to generic physicochemical characteristics of the dispersions.

Cd2+ Toxicity to a Green Alga Chlamydomonas reinhardtii as Influenced by Its Adsorption on TiO2 Engineered Nanoparticles

PubMed Central

Yang, Wei-Wan; Miao, Ai-Jun; Yang, Liu-Yan

2012-01-01

In the present study, Cd2+ adsorption on polyacrylate-coated TiO2 engineered nanoparticles (TiO2-ENs) and its effect on the bioavailability as well as toxicity of Cd2+ to a green alga Chlamydomonas reinhardtii were investigated. TiO2-ENs could be well dispersed in the experimental medium and their pHpzc is approximately 2. There was a quick adsorption of Cd2+ on TiO2-ENs and a steady state was reached within 30 min. A pseudo-first order kinetics was found for the time-related changes in the amount of Cd2+ complexed with TiO2-ENs. At equilibrium, Cd2+ adsorption followed the Langmuir isotherm with the maximum binding capacity 31.9, 177.1, and 242.2 mg/g when the TiO2-EN concentration was 1, 10, and 100 mg/l, respectively. On the other hand, Cd2+ toxicity was alleviated in the presence of TiO2-ENs. Algal growth was less suppressed in treatments with comparable total Cd2+ concentration but more TiO2-ENs. However, such toxicity difference disappeared and all the data points could be fitted to a single Logistic dose-response curve when cell growth inhibition was plotted against the free Cd2+ concentration. No detectable amount of TiO2-ENs was found to be associated with the algal cells. Therefore, TiO2-ENs could reduce the free Cd2+ concentration in the toxicity media, which further lowered its bioavailability and toxicity to C. reinhardtii. PMID:22403644

Characterization of silver nanoparticles using flow-field flow fractionation interfaced to inductively coupled plasma mass spectrometry.

PubMed

Poda, A R; Bednar, A J; Kennedy, A J; Harmon, A; Hull, M; Mitrano, D M; Ranville, J F; Steevens, J

2011-07-08

The ability to detect and identify the physiochemical form of contaminants in the environment is important for degradation, fate and transport, and toxicity studies. This is particularly true of nanomaterials that exist as discrete particles rather than dissolved or sorbed contaminant molecules in the environment. Nanoparticles will tend to agglomerate or dissolve, based on solution chemistry, which will drastically affect their environmental properties. The current study investigates the use of field flow fractionation (FFF) interfaced to inductively coupled plasma-mass spectrometry (ICP-MS) as a sensitive and selective method for detection and characterization of silver nanoparticles. Transmission electron microscopy (TEM) is used to verify the morphology and primary particle size and size distribution of precisely engineered silver nanoparticles. Subsequently, the hydrodynamic size measurements by FFF are compared to dynamic light scattering (DLS) to verify the accuracy of the size determination. Additionally, the sensitivity of the ICP-MS detector is demonstrated by fractionation of μg/L concentrations of mixed silver nanoparticle standards. The technique has been applied to nanoparticle suspensions prior to use in toxicity studies, and post-exposure biological tissue analysis. Silver nanoparticles extracted from tissues of the sediment-dwelling, freshwater oligochaete Lumbriculus variegatus increased in size from approximately 31-46nm, indicating a significant change in the nanoparticle characteristics during exposure. Published by Elsevier B.V.

Targeted polymeric nanoparticles for cancer gene therapy

PubMed Central

Kim, Jayoung; Wilson, David R.; Zamboni, Camila G.; Green, Jordan J.

2015-01-01

In this article, advances in designing polymeric nanoparticles for targeted cancer gene therapy are reviewed. Characterization and evaluation of biomaterials, targeting ligands, and transcriptional elements are each discussed. Advances in biomaterials have driven improvements to nanoparticle stability and tissue targeting, conjugation of ligands to the surface of polymeric nanoparticles enable binding to specific cancer cells, and the design of transcriptional elements has enabled selective DNA expression specific to the cancer cells. Together, these features have improved the performance of polymeric nanoparticles as targeted non-viral gene delivery vectors to treat cancer. As polymeric nanoparticles can be designed to be biodegradable, non-toxic, and to have reduced immunogenicity and tumorigenicity compared to viral platforms, they have significant potential for clinical use. Results of polymeric gene therapy in clinical trials and future directions for the engineering of nanoparticle systems for targeted cancer gene therapy are also presented. PMID:26061296

TiO2, SiO2 and ZrO2 Nanoparticles Synergistically Provoke Cellular Oxidative Damage in Freshwater Microalgae

PubMed Central

Liu, Yinghan; Ye, Nan; Fang, Hao; Wang, Degao

2018-01-01

Metal-based nanoparticles (NPs) are the most widely used engineered nanomaterials. The individual toxicities of metal-based NPs have been plentifully studied. However, the mixture toxicity of multiple NP systems (n ≥ 3) remains much less understood. Herein, the toxicity of titanium dioxide (TiO2) nanoparticles (NPs), silicon dioxide (SiO2) NPs and zirconium dioxide (ZrO2) NPs to unicellular freshwater algae Scenedesmus obliquus was investigated individually and in binary and ternary combination. Results show that the ternary combination systems of TiO2, SiO2 and ZrO2 NPs at a mixture concentration of 1 mg/L significantly enhanced mitochondrial membrane potential and intracellular reactive oxygen species level in the algae. Moreover, the ternary NP systems remarkably increased the activity of the antioxidant defense enzymes superoxide dismutase and catalase, together with an increase in lipid peroxidation products and small molecule metabolites. Furthermore, the observation of superficial structures of S. obliquus revealed obvious oxidative damage induced by the ternary mixtures. Taken together, the ternary NP systems exerted more severe oxidative stress in the algae than the individual and the binary NP systems. Thus, our findings highlight the importance of the assessment of the synergistic toxicity of multi-nanomaterial systems. PMID:29419775

Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity

NASA Astrophysics Data System (ADS)

Harper, Bryan; Thomas, Dennis; Chikkagoudar, Satish; Baker, Nathan; Tang, Kaizhi; Heredia-Langner, Alejandro; Lins, Roberto; Harper, Stacey

2015-06-01

The integration of rapid assays, large datasets, informatics, and modeling can overcome current barriers in understanding nanomaterial structure-toxicity relationships by providing a weight-of-the-evidence mechanism to generate hazard rankings for nanomaterials. Here, we present the use of a rapid, low-cost assay to perform screening-level toxicity evaluations of nanomaterials in vivo. Calculated EZ Metric scores, a combined measure of morbidity and mortality in developing embryonic zebrafish, were established at realistic exposure levels and used to develop a hazard ranking of diverse nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both the core composition and outermost surface chemistry of nanomaterials. The resulting clusters guided the development of a surface chemistry-based model of gold nanoparticle toxicity. Our findings suggest that risk assessments based on the size and core composition of nanomaterials alone may be wholly inappropriate, especially when considering complex engineered nanomaterials. Research should continue to focus on methodologies for determining nanomaterial hazard based on multiple sub-lethal responses following realistic, low-dose exposures, thus increasing the availability of quantitative measures of nanomaterial hazard to support the development of nanoparticle structure-activity relationships.

Copper Nanoparticle Induced Cytotoxicity to Nitrifying Bacteria in Wastewater Treatment: A Mechanistic Copper Speciation Study by X-ray Absorption Spectroscopy

EPA Science Inventory

With the inclusion of engineered nanomaterials in industrial processes and consumer products, wastewater treatments plants (WWTPs) will serve as a major sink for these emerging contaminants. Previous research has demonstrated that nanomaterials are potentially toxic to microbial ...

General linear model-predicted and observed toxicity of three organo-coated silver nanoparticles: Impacts of particle size, surface charge and dose

EPA Science Inventory

Intrinsic to the myriad of nano-enabled products are atomic-size multifunctional engineered nanomaterials, which upon release contaminate the environments, raising considerable health and safety concerns. Despite global research efforts, mechanism underlying nanotoxicity has rema...

New insight into artifactual phenomena during in vitro toxicity assessment of engineered nanoparticles: study of TNF-α adsorption on alumina oxide nanoparticle.

PubMed

Pailleux, Mélanie; Boudard, Delphine; Pourchez, Jérémie; Forest, Valérie; Grosseau, Philippe; Cottier, Michèle

2013-04-01

Biomolecules can be adsorbed on nanoparticles (NPs) and degraded during in vitro toxicity assays. These artifactual phenomena could lead to misinterpretation of biological activity, such as false-negative results. To avoid possible underestimation of cytokine release after contact between NP and cells, we propose a methodology to account for these artifactual phenomena and lead to accurate measurements. We focused on the pro-inflammatory cytokine tumor necrosis factor TNF-α. We studied well-characterized boehmite engineered NP [aluminum oxide hydroxide, AlO(OH)]. The rate of TNF-α degradation and its adsorption (on boehmite and on the walls of wells) were determined in cell-free conditions by adding a known TNF-α concentration (1500 pg/ml) under various experimental conditions. After a 24-h incubation, we quantified that 7 wt.% of the initial TNF-α was degraded over time, 6 wt.% adsorbed on the walls of 96-well plates, and 13 wt.% adsorbed on the boehmite surface. Finally, boehmite NP were incubated with murine macrophages (RAW 264.7 cell line). The release of TNF-α was assessed for boehmite NP and the experimental data were corrected considering the artifactual phenomena, which accounted for about 20-30% of the total. Copyright © 2013 Elsevier Ltd. All rights reserved.

Environmental impact of engineered carbon nanoparticles: from releases to effects on the aquatic biota.

PubMed

Mottier, Antoine; Mouchet, Florence; Pinelli, Éric; Gauthier, Laury; Flahaut, Emmanuel

2017-08-01

Nano-ecotoxicology is an emerging science which aims to assess the environmental effect of nanotechnologies. The development of this particular aspect of ecotoxicology was made necessary in order to evaluate the potential impact of recently produced and used materials: nanoparticles (NPs). Among all the types of NPs, carbon nanoparticles (CNPs) especially draw attention giving the increasing number of applications and integration into consumer products. However the potential impacts of CNPs in the environment remain poorly known. This review aims to point out the critical issues and aspects that will govern the toxicity of CNPs in the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nanoparticles: Health Effects—Pros and Cons

PubMed Central

Gwinn, Maureen R.; Vallyathan, Val

2006-01-01

With the advent of nanotechnology, the prospects for using engineered nanomaterials with diameters of < 100 nm in industrial applications, medical imaging, disease diagnoses, drug delivery, cancer treatment, gene therapy, and other areas have progressed rapidly. The potential for nanoparticles (NPs) in these areas is infinite, with novel new applications constantly being explored. The possible toxic health effects of these NPs associated with human exposure are unknown. Many fine particles generally considered “nuisance dusts” are likely to acquire unique surface properties when engineered to nanosize and may exhibit toxic biological effects. Consequently, the nuisance dust may be transported to distant sites and could induce adverse health effects. In addition the beneficial uses of NPs in drug delivery, cancer treatment, and gene therapy may cause unintentional human exposure. Because of our lack of knowledge about the health effects associated with NP exposure, we have an ethical duty to take precautionary measures regarding their use. In this review we highlight the possible toxic human health effects that can result from exposure to ultrafine particles (UFPs) generated by anthropogenic activities and their cardiopulmonary outcomes. The comparability of engineered NPs to UFPs suggests that the human health effects are likely to be similar. Therefore, it is prudent to elucidate their toxicologic effect to minimize occupational and environmental exposure. Highlighting the human health outcomes caused by UFPs is not intended to give a lesser importance to either the unprecedented technologic and industrial rewards of the nanotechnology or their beneficial human uses. PMID:17185269

Nanoparticles: health effects--pros and cons.

PubMed

Gwinn, Maureen R; Vallyathan, Val

2006-12-01

With the advent of nanotechnology, the prospects for using engineered nanomaterials with diameters of < 100 nm in industrial applications, medical imaging, disease diagnoses, drug delivery, cancer treatment, gene therapy, and other areas have progressed rapidly. The potential for nanoparticles (NPs) in these areas is infinite, with novel new applications constantly being explored. The possible toxic health effects of these NPs associated with human exposure are unknown. Many fine particles generally considered "nuisance dusts" are likely to acquire unique surface properties when engineered to nanosize and may exhibit toxic biological effects. Consequently, the nuisance dust may be transported to distant sites and could induce adverse health effects. In addition the beneficial uses of NPs in drug delivery, cancer treatment, and gene therapy may cause unintentional human exposure. Because of our lack of knowledge about the health effects associated with NP exposure, we have an ethical duty to take precautionary measures regarding their use. In this review we highlight the possible toxic human health effects that can result from exposure to ultrafine particles (UFPs) generated by anthropogenic activities and their cardiopulmonary outcomes. The comparability of engineered NPs to UFPs suggests that the human health effects are likely to be similar. Therefore, it is prudent to elucidate their toxicologic effect to minimize occupational and environmental exposure. Highlighting the human health outcomes caused by UFPs is not intended to give a lesser importance to either the unprecedented technologic and industrial rewards of the nanotechnology or their beneficial human uses.

Platinum nanoparticles: a non-toxic, effective and thermally stable alternative plasmonic material for cancer therapy and bioengineering.

PubMed

Samadi, Akbar; Klingberg, Henrik; Jauffred, Liselotte; Kjær, Andreas; Bendix, Poul Martin; Oddershede, Lene B

2018-05-17

Absorption of near infrared (NIR) light by metallic nanoparticles can cause extreme heating and is of interest for instance in cancer treatment since NIR light has a relatively large penetration depth into biological tissue. Here, we quantify the extraordinary thermoplasmonic properties of platinum nanoparticles and demonstrate their efficiency in photothermal cancer therapy. Although platinum nanoparticles are extensively used for catalysis, they are much overlooked in a biological context. Via direct measurements based on a biological matrix we show that individual irradiated platinum nanoparticles with diameters of 50-70 nm can easily reach surface temperatures up to 900 K. In contrast to gold nanoshells, which are often used for photothermal purposes, we demonstrate that the platinum particles remain stable at these extreme temperatures. The experiments are paralleled by finite element modeling confirming the experimental results and establishing a theoretical understanding of the particles' thermoplasmonic properties. At extreme temperatures it is likely that a vapor layer will form around the plasmonic particle, and we show this scenario to be consistent with direct measurements and simulations. Viability studies demonstrate that platinum nanoparticles themselves are non-toxic at therapeutically relevant concentrations, however, upon laser irradiation we show that they efficiently kill human cancer cells. Therefore, platinum nanoparticles are highly promising candidates for thermoplasmonic applications in the life sciences, in nano-medicine, and for bio-medical engineering.

Toxic effect of Cr(VI) in presence of n-TiO2 and n-Al2O3 particles towards freshwater microalgae.

PubMed

Dalai, Swayamprava; Pakrashi, Sunandan; Bhuvaneshwari, M; Iswarya, V; Chandrasekaran, N; Mukherjee, Amitava

2014-01-01

The reactivity and toxicity of the soluble toxicants in the presence of the engineered nanomaterials is not well explored. In this study, the probable effects of TiO2 and Al2O3 nanoparticles (n-TiO2, n-Al2O3) on the toxicity of Cr(VI) were assessed with the dominant freshwater algae, Scenedesmus obliquus, in a low range of exposure concentrations (0.05, 0.5 and 1μg/mL). In the presence of 0.05μg/mL n-TiO2, the toxicity of Cr(VI) decreased considerably, which was presumably due to the Cr(VI) adsorption on the nanoparticle surface leading to its aggregation and precipitation. The elevated n-TiO2 concentrations (0.5 and 1μg/mL) did not significantly influence Cr(VI) bio-availability, and a dose dependent toxicity of Cr(VI) was observed. On the other hand, n-Al2O3 did not have any significant effect on the Cr(VI) toxicity. The microscopic observations presented additional information on the morphological changes of the algal cells in the presence of the binary toxicants. The generation of reactive oxygen species (ROS) suggested contribution of oxidative stress on toxicity and LDH release confirmed membrane permeability of algal cells upon stress. Copyright © 2013 Elsevier B.V. All rights reserved.

Water chemistry controlled aggregation and photo-transformation of silver nanoparticles in environmental waters.

PubMed

Yin, Yongguang; Yang, Xiaoya; Zhou, Xiaoxia; Wang, Weidong; Yu, Sujuan; Liu, Jingfu; Jiang, Guibin

2015-08-01

The inevitable release of engineered silver nanoparticles (AgNPs) into aquatic environments has drawn great concerns about its environmental toxicity and safety. Although aggregation and transformation play crucial roles in the transport and toxicity of AgNPs, how the water chemistry of environmental waters influences the aggregation and transformation of engineered AgNPs is still not well understood. In this study, the aggregation of polyvinylpyrrolidone (PVP) coated AgNPs was investigated in eight typical environmental water samples (with different ionic strengths, hardness, and dissolved organic matter (DOM) concentrations) by using UV-visible spectroscopy and dynamic light scattering. Raman spectroscopy was applied to probe the interaction of DOM with the surface of AgNPs. Further, the photo-transformation and morphology changes of AgNPs in environmental waters were studied by UV-visible spectroscopy, inductively coupled plasma mass spectrometry, and transmission electron microscopy. The results suggested that both electrolytes (especially Ca(2+) and Mg(2+)) and DOM in the surface waters are key parameters for AgNP aggregation, and sunlight could accelerate the morphology change, aggregation, and further sedimentation of AgNPs. This water chemistry controlled aggregation and photo-transformation should have significant environmental impacts on the transport and toxicity of AgNPs in the aquatic environments. Copyright © 2015. Published by Elsevier B.V.

Freshwater Sediment Characterization Factors of Copper Oxide Nanoparticles

NASA Astrophysics Data System (ADS)

Pu, Yubing; Laratte, Bertrand; Ionescu, Rodica Elena

2017-01-01

Wide use of engineered nanoparticles (ENPs) is likely to result in the eventually accumulation of ENPs in sediment. The benthic organisms living in sediments may suffer relatively high toxic effects of ENPs. This study has selected copper oxide nanoparticles (nano-CuO) as a research object. To consider the impacts of spatial heterogeneity on ENPs toxicity, the characterization factor (CF) derived from life cycle assessment (LCA) methodology is used as an indicator in this study. A nano-specific fate model has been used to calculate the freshwater sediment fate factor (FF) of nano-CuO. A literature survey of the nano-CuO toxicology values has been performed to calculate the effect factor (EF). Seventeen freshwater sediment CFs of nano-CuO are proposed as recommended values for subcontinental regions. The region most likely to be affected by nano-CuO is northern Australia (CF of 21.01·103 CTUe, comparative toxic units) and the least likely is northern Europe and northern Canada (CF of 8.55·103 CTUe). These sediment CFs for nano-CuO could be used in the future when evaluating the ecosystem impacts of products containing nano-CuO by LCA method.

Phytotoxicity of ZnO nanoparticles and the released Zn(II) ion to corn (Zea mays L.) and cucumber (Cucumis sativus L.) during germination.

PubMed

Zhang, Ruichang; Zhang, Haibo; Tu, Chen; Hu, Xuefeng; Li, Lianzhen; Luo, Yongming; Christie, Peter

2015-07-01

Toxicity of engineered nanoparticles on organisms is of concern worldwide due to their extensive use and unique properties. The impacts of ZnO nanoparticles (ZnO NPs) on seed germination and root elongation of corn (Zea mays L.) and cucumber (Cucumis sativus L.) were investigated in this study. The role of seed coats of corn in the mitigation toxicity of nanoparticles was also evaluated. ZnO NPs (1,000 mg L(-1)) reduced root length of corn and cucumber by 17 % (p < 0.05) and 51 % (p < 0.05), respectively, but exhibited no effects on germination. In comparison with Zn(2+), toxicity of ZnO NPs on the root elongation of corn could be attributed to the nanoparticulate ZnO, while released Zn ion from ZnO could solely contribute to the inhibition of root elongation of cucumber. Zn uptake in corn exposed to ZnO NPs during germination was much higher than that in corn exposed to Zn(2+), whereas Zn uptake in cucumber was significantly correlated with soluble Zn in suspension. It could be inferred that Zn was taken up by corn and cucumber mainly in the form of ZnO NPs and soluble Zn, respectively. Transmission electron microscope confirmed the uptake of ZnO NPs into root of corn. Although isolation of the seed coats might not be the principal factor that achieved avoidance from toxicity on germination, seed coats of corn were found to mitigate the toxicity of ZnO NPs on root elongation and prevent approximately half of the Zn from entering into root and endosperm.

Bacterial Interactions with CdSe Quantum Dots

NASA Astrophysics Data System (ADS)

Holden, P.; Nadeau, J. L.; Kumar, A.; Clarke, S.; Priester, J. H.; Stucky, G. D.

2007-12-01

Cadmium selenide quantum dots (QDs) are semiconductor nanoparticles that are manufactured for biomedical imaging, photovoltaics, and other applications. While metallic nanoparticles can be made biotically by bacteria and fungi, and thus occur in nature, the fate of either natural or engineered QDs and relationships to nanoparticle size, conjugate and biotic conditions are mostly unknown. Working with several different bacterial strains and QDs of different sizes and conjugate chemistries, including QDs synthesized by a Fusarium fungal strain, we show that QDs can enter cells through specfic receptor-mediated processes, that QDs are broken down by bacteria during cell association, and that toxicity to cells is much like that imposed by Cd(II) ions. The mechanisms of entry and toxicity are not fully understood, but preliminary evidence suggests that electron transfer between cells and QDs occurs. Also, cell membranes are compromised, indicating oxidative stress is occurring. Results with planktonic and biofilm bacteria are similar, but differently, biofilms tend to accumulate Cd(II) associated with QD treatments.

A Review on the Respiratory System Toxicity of Carbon Nanoparticles

PubMed Central

Pacurari, Maricica; Lowe, Kristine; Tchounwou, Paul B.; Kafoury, Ramzi

2016-01-01

The respiratory system represents the main gateway for nanoparticles’ entry into the human body. Although there is a myriad of engineered nanoparticles, carbon nanoparticles/nanotubes (CNPs/CNTs) have received much attention mainly due to their light weight, very high surface area, durability, and their diverse applications. Since their discovery and manufacture over two decades ago, much has been learned about nanoparticles’ interactions with diverse biological system models. In particular, the respiratory system has been of great interest because various natural and man-made fibrous particles are known to be responsible for chronic and debilitating lung diseases. In this review, we present up-to-date the literature regarding the effects of CNTs or carbon nanofibers (CNFs) on the human respiratory system with respect to respiratory toxicity pathways and associated pathologies. This article is intended to emphasize the potentially dangerous effects to the human respiratory system if inadequate measures are used in the manufacture, handling, and preparation and applications of CNP or CNP-based products. PMID:26999172

Online Coupling of Flow-Field Flow Fractionation and Single Particle Inductively Coupled Plasma-Mass Spectrometry: Characterization of Nanoparticle Surface Coating Thickness and Aggregation State

EPA Science Inventory

Surface coating thickness and aggregation state have strong influence on the environmental fate, transport, and toxicity of engineered nanomaterials. In this study, flow-field flow fractionation coupled on-line with single particle inductively coupled plasma-mass spectrometry i...

Nanomaterials and nanoparticles: sources and toxicity.

PubMed

Buzea, Cristina; Pacheco, Ivan I; Robbie, Kevin

2007-12-01

This review is presented as a common foundation for scientists interested in nanoparticles, their origin,activity, and biological toxicity. It is written with the goal of rationalizing and informing public health concerns related to this sometimes-strange new science of "nano," while raising awareness of nanomaterials' toxicity among scientists and manufacturers handling them.We show that humans have always been exposed to tiny particles via dust storms, volcanic ash, and other natural processes, and that our bodily systems are well adapted to protect us from these potentially harmful intruders. There ticuloendothelial system, in particular, actively neutralizes and eliminates foreign matter in the body,including viruses and nonbiological particles. Particles originating from human activities have existed for millennia, e.g., smoke from combustion and lint from garments, but the recent development of industry and combustion-based engine transportation has profoundly increased an thropogenic particulate pollution. Significantly, technological advancement has also changed the character of particulate pollution, increasing the proportion of nanometer-sized particles--"nanoparticles"--and expanding the variety of chemical compositions. Recent epidemiological studies have shown a strong correlation between particulate air pollution levels, respiratory and cardiovascular diseases, various cancers, and mortality. Adverse effects of nanoparticles on human health depend on individual factors such as genetics and existing disease, as well as exposure, and nanoparticle chemistry, size, shape,agglomeration state, and electromagnetic properties. Animal and human studies show that inhaled nanoparticles are less efficiently removed than larger particles by the macrophage clearance mechanisms in the lungs, causing lung damage, and that nanoparticles can translocate through the circulatory, lymphatic, and nervous systems to many tissues and organs, including the brain. The key to understanding the toxicity of nanoparticles is that their minute size, smaller than cells and cellular organelles, allows them to penetrate these basic biological structures, disrupting their normal function.Examples of toxic effects include tissue inflammation, and altered cellular redox balance toward oxidation, causing abnormal function or cell death. The manipulation of matter at the scale of atoms,"nanotechnology," is creating many new materials with characteristics not always easily predicted from current knowledge. Within the nearly limitless diversity of these materials, some happen to be toxic to biological systems, others are relatively benign, while others confer health benefits. Some of these materials have desirable characteristics for industrial applications, as nanostructured materials often exhibit beneficial properties, from UV absorbance in sunscreen to oil-less lubrication of motors.A rational science-based approach is needed to minimize harm caused by these materials, while supporting continued study and appropriate industrial development. As current knowledge of the toxicology of "bulk" materials may not suffice in reliably predicting toxic forms of nanoparticles,ongoing and expanded study of "nanotoxicity" will be necessary. For nanotechnologies with clearly associated health risks, intelligent design of materials and devices is needed to derive the benefits of these new technologies while limiting adverse health impacts. Human exposure to toxic nanoparticles can be reduced through identifying creation-exposure pathways of toxins, a study that may someday soon unravel the mysteries of diseases such as Parkinson's and Alzheimer's. Reduction in fossil fuel combustion would have a large impact on global human exposure to nanoparticles, as would limiting deforestation and desertification.While nanotoxicity is a relatively new concept to science, this review reveals the result of life's long history of evolution in the presence of nanoparticles, and how the human body, in particular, has adapted to defend itself against nanoparticulate intruders. 2007 American Vacuum Society.

Review on nanoparticles and nanostructured materials: history, sources, toxicity and regulations

PubMed Central

Jeevanandam, Jaison; Chan, Yen S; Dufresne, Alain

2018-01-01

Nanomaterials (NMs) have gained prominence in technological advancements due to their tunable physical, chemical and biological properties with enhanced performance over their bulk counterparts. NMs are categorized depending on their size, composition, shape, and origin. The ability to predict the unique properties of NMs increases the value of each classification. Due to increased growth of production of NMs and their industrial applications, issues relating to toxicity are inevitable. The aim of this review is to compare synthetic (engineered) and naturally occurring nanoparticles (NPs) and nanostructured materials (NSMs) to identify their nanoscale properties and to define the specific knowledge gaps related to the risk assessment of NPs and NSMs in the environment. The review presents an overview of the history and classifications of NMs and gives an overview of the various sources of NPs and NSMs, from natural to synthetic, and their toxic effects towards mammalian cells and tissue. Additionally, the types of toxic reactions associated with NPs and NSMs and the regulations implemented by different countries to reduce the associated risks are also discussed. PMID:29719757

Review on nanoparticles and nanostructured materials: history, sources, toxicity and regulations.

PubMed

Jeevanandam, Jaison; Barhoum, Ahmed; Chan, Yen S; Dufresne, Alain; Danquah, Michael K

2018-01-01

Nanomaterials (NMs) have gained prominence in technological advancements due to their tunable physical, chemical and biological properties with enhanced performance over their bulk counterparts. NMs are categorized depending on their size, composition, shape, and origin. The ability to predict the unique properties of NMs increases the value of each classification. Due to increased growth of production of NMs and their industrial applications, issues relating to toxicity are inevitable. The aim of this review is to compare synthetic (engineered) and naturally occurring nanoparticles (NPs) and nanostructured materials (NSMs) to identify their nanoscale properties and to define the specific knowledge gaps related to the risk assessment of NPs and NSMs in the environment. The review presents an overview of the history and classifications of NMs and gives an overview of the various sources of NPs and NSMs, from natural to synthetic, and their toxic effects towards mammalian cells and tissue. Additionally, the types of toxic reactions associated with NPs and NSMs and the regulations implemented by different countries to reduce the associated risks are also discussed.

Carbon nanotubes affect the toxicity of CuO nanoparticles to denitrification in marine sediments by altering cellular internalization of nanoparticle

PubMed Central

Zheng, Xiong; Su, Yinglong; Chen, Yinguang; Wan, Rui; Li, Mu; Huang, Haining; Li, Xu

2016-01-01

Denitrification is an important pathway for nitrate transformation in marine sediments, and this process has been observed to be negatively affected by engineered nanomaterials. However, previous studies only focused on the potential effect of a certain type of nanomaterial on microbial denitrification. Here we show that the toxicity of CuO nanoparticles (NPs) to denitrification in marine sediments is highly affected by the presence of carbon nanotubes (CNTs). It was found that the removal efficiency of total NOX−-N (NO3−-N and NO2−-N) in the presence of CuO NPs was only 62.3%, but it increased to 81.1% when CNTs appeared in this circumstance. Our data revealed that CuO NPs were more easily attached to CNTs rather than cell surface because of the lower energy barrier (3.5 versus 36.2 kT). Further studies confirmed that the presence of CNTs caused the formation of large, incompact, non-uniform dispersed, and more negatively charged CuO-CNTs heteroaggregates, and thus reduced the nanoparticle internalization by cells, leading to less toxicity to metabolism of carbon source, generation of reduction equivalent, and activities of nitrate reductase and nitrite reductase. These results indicate that assessing nanomaterial-induced risks in real circumstances needs to consider the “mixed” effects of nanomaterials. PMID:27279546

Monolayer coated gold nanoparticles for delivery applications

PubMed Central

Rana, Subinoy; Bajaj, Avinash; Mout, Rubul; Rotello, Vincent M.

2011-01-01

Gold nanoparticles (AuNPs) provide attractive vehicles for delivery of drugs, genetic materials, proteins, and small molecules. AuNPs feature low core toxicity coupled with the ability to parametrically control particle size and surface properties. In this review, we focus on engineering of the AuNP surface monolayer, highlighting recent advances in tuning monolayer structures for efficient delivery of drugs and biomolecules. This review covers two broad categories of particle functionalization, organic monolayers and biomolecule coatings, and discusses their applications in drug, DNA/RNA, protein and small molecule delivery. PMID:21925556

Polylactic acid (PLA) controlled delivery carriers for biomedical applications.

PubMed

Tyler, Betty; Gullotti, David; Mangraviti, Antonella; Utsuki, Tadanobu; Brem, Henry

2016-12-15

Polylactic acid (PLA) and its copolymers have a long history of safety in humans and an extensive range of applications. PLA is biocompatible, biodegradable by hydrolysis and enzymatic activity, has a large range of mechanical and physical properties that can be engineered appropriately to suit multiple applications, and has low immunogenicity. Formulations containing PLA have also been Food and Drug Administration (FDA)-approved for multiple applications making PLA suitable for expedited clinical translatability. These biomaterials can be fashioned into sutures, scaffolds, cell carriers, drug delivery systems, and a myriad of fabrications. PLA has been the focus of a multitude of preclinical and clinical testing. Three-dimensional printing has expanded the possibilities of biomedical engineering and has enabled the fabrication of a myriad of platforms for an extensive variety of applications. PLA has been widely used as temporary extracellular matrices in tissue engineering. At the other end of the spectrum, PLA's application as drug-loaded nanoparticle drug carriers, such as liposomes, polymeric nanoparticles, dendrimers, and micelles, can encapsulate otherwise toxic hydrophobic anti-tumor drugs and evade systemic toxicities. The clinical translation of these technologies from preclinical experimental settings is an ever-evolving field with incremental advancements. In this review, some of the biomedical applications of PLA and its copolymers are highlighted and briefly summarized. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Surface-Engineered Nanoparticle-Based Dispersants for Marine Oil Spills on the Model Organism Artemia franciscana

PubMed Central

2015-01-01

Fine particles are under active consideration as alternatives to chemical dispersants for large-scale petroleum spills. Fine carbon particles with engineered surface chemistry have been shown to stabilize oil-in-water emulsions, but the environmental impacts of large-scale particle introduction to the marine environment are unknown. Here we study the impact of surface-engineered carbon-black materials on brine shrimp (Artemia franciscana) as a model marine microcrustacean. Mortality was characterized at 50–1000 mg/L, and levels of heat shock protein 70 (hsp70) were characterized at sublethal particle concentrations (25–50 mg/L). Functionalized carbon black (CB) nanoparticles were found to be nontoxic at all concentrations, while hydrophobic (annealed) and as-produced CB induced adverse effects at high concentrations. CB was also shown to adsorb benzene, a model hydrocarbon representing the more soluble and toxic low-molecular weight aromatic fraction of petroleum, but the extent of adsorption was insufficient to mitigate benzene toxicity to Artemia in coexposure experiments. At lower benzene concentrations (25–75 mg/L), coexposure with annealed and as-produced CB increased hsp70 protein levels. This study suggests that surface functionalization for increased hydrophilicity can not only improve the performance of CB-based dispersants but also reduce their adverse environmental impacts on marine organisms. PMID:24823274

Interactions of metal-based engineered nanoparticles with aquatic higher plants: A review of the state of current knowledge.

PubMed

Thwala, Melusi; Klaine, Stephen J; Musee, Ndeke

2016-07-01

The rising potential for the release of engineered nanoparticles (ENPs) into aquatic environments requires evaluation of risks to protect ecological health. The present review examines knowledge pertaining to the interactions of metal-based ENPs with aquatic higher plants, identifies information gaps, and raises considerations for future research to advance knowledge on the subject. The discussion focuses on ENPs' bioaccessibility; uptake, adsorption, translocation, and bioaccumulation; and toxicity effects on aquatic higher plants. An information deficit surrounds the uptake of ENPs and associated dynamics, because the influence of ENP characteristics and water quality conditions has not been well documented. Dissolution appears to be a key mechanism driving bioaccumulation of ENPs, whereas nanoparticulates often adsorb to plant surfaces with minimal internalization. However, few reports document the internalization of ENPs by plants; thus, the role of nanoparticulates' internalization in bioaccumulation and toxicity remains unclear, requiring further investigation. The toxicities of metal-based ENPs mainly have been associated with dissolution as a predominant mechanism, although nano toxicity has also been reported. To advance knowledge in this domain, future investigations need to integrate the influence of ENP characteristics and water physicochemical parameters, as their interplay determines ENP bioaccessibility and influences their risk to health of aquatic higher plants. Furthermore, harmonization of test protocols is recommended for fast tracking the generation of comparable data. Environ Toxicol Chem 2016;35:1677-1694. © 2016 SETAC. © 2016 SETAC.

Effect of surfactant in mitigating cadmium oxide nanoparticle toxicity: Implications for mitigating cadmium toxicity in environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balmuri, Sricharani Rao

Cadmium (Cd), classified as human carcinogen, is an extremely toxic heavy metal pollutant, and there is an increasing environmental concern for cadmium exposure through anthropogenic sources including cigarette smoke. Though Cd based nanoparticles such as cadmium oxide (CdO) are being widely used in a variety of clinical and industrial applications, the toxicity of CdO nanoparticles has not been well characterized. Herein we report the toxicity of CdO nanoparticles employing zebrafish as a model. Two different CdO nanoparticles were prepared, calcination of Cd(OH){sub 2} without any organic molecule (CdO-1) and calcination of Cd-citrate coordination polymer (CdO-2), to evaluate and compare themore » toxicity of these two different CdO nanoparticles. Results show that zebrafish exposed to CdO-2 nanoparticles expressed reduced toxicity as judged by lower oxidative stress levels, rescue of liver carboxylesterases and reduction in metallothionein activity compared to CdO-1 nanoparticles. Histopathological observations also support our contention that CdO-1 nanoparticles showed higher toxicity relative to CdO-2 nanoparticles. The organic unit of Cd-citrate coordination polymer might have converted into carbon during calcination that might have covered the surface of CdO nanoparticles. This carbon surface coverage can control the release of Cd{sup 2+} ions in CdO-2 compared to non-covered CdO-1 nanoparticles and hence mitigate the toxicity in the case of CdO-2. This was supported by atomic absorption spectrophotometer analyses of Cd{sup 2+} ions release from CdO-1 and CdO-2 nanoparticles. Thus the present study clearly demonstrates the toxicity of CdO nanoparticles in an aquatic animal and also indicates that the toxicity could be substantially reduced by carbon coverage. This could have important implications in terms of anthropogenic release and environmental pollution caused by Cd and human exposure to Cd{sup 2+} from sources such as cigarette smoke. - Highlights: • Toxicity of CdO nanoparticles can be mitigated by the use of sodium citrate. • Sodium citrate covers the CdO surface and reduces Cd{sup 2+} ion release. • Use of sodium citrate reduces both biochemical and histopathological changes. • Sodium citrate can be a remediation strategy against CdO nanoparticles toxicity.« less

Bacterial toxicity comparison between nano- and micro-scaled oxide particles.

PubMed

Jiang, Wei; Mashayekhi, Hamid; Xing, Baoshan

2009-05-01

Toxicity of nano-scaled aluminum, silicon, titanium and zinc oxides to bacteria (Bacillus subtilis, Escherichia coli and Pseudomonas fluorescens) was examined and compared to that of their respective bulk (micro-scaled) counterparts. All nanoparticles but titanium oxide showed higher toxicity (at 20 mg/L) than their bulk counterparts. Toxicity of released metal ions was differentiated from that of the oxide particles. ZnO was the most toxic among the three nanoparticles, causing 100% mortality to the three tested bacteria. Al(2)O(3) nanoparticles had a mortality rate of 57% to B. subtilis, 36% to E. coli, and 70% to P. fluorescens. SiO(2) nanoparticles killed 40% of B. subtilis, 58% of E. coli, and 70% of P. fluorescens. TEM images showed attachment of nanoparticles to the bacteria, suggesting that the toxicity was affected by bacterial attachment. Bacterial responses to nanoparticles were different from their bulk counterparts; hence nanoparticle toxicity mechanisms need to be studied thoroughly.

Lipid-Based Nanoparticles as Pharmaceutical Drug Carriers: From Concepts to Clinic

PubMed Central

Puri, Anu; Loomis, Kristin; Smith, Brandon; Lee, Jae-Ho; Yavlovich, Amichai; Heldman, Eli; Blumenthal, Robert

2010-01-01

In recent years, various nanotechnology platforms in the area of medical biology, including both diagnostics and therapy, have gained remarkable attention. Moreover, research and development of engineered multifunctional nanoparticles as pharmaceutical drug carriers have spurred exponential growth in applications to medicine in the last decade. Design principles of these nanoparticles, including nano-emulsions, dendrimers, nano-gold, liposomes, drug-carrier conjugates, antibody-drug complexes, and magnetic nanoparticles, are primarily based on unique assemblies of synthetic, natural, or biological components, including but not limited to synthetic polymers, metal ions, oils, and lipids as their building blocks. However, the potential success of these particles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, drug loading efficiencies, drug release potential, and, most importantly, minimum toxicity of the carrier itself. Among these, lipid-based nanoparticles bear the advantage of being the least toxic for in vivo applications, and significant progress has been made in the area of DNA/RNA and drug delivery using lipid-based nanoassemblies. In this review, we will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery. We begin with a review of current activities in the field of liposomes (the so-called honorary nanoparticles), and challenging issues of targeting and triggering will be discussed in detail. We will further describe nanoparticles derived from a novel class of amphipathic lipids called bolaamphiphiles with unique lipid assembly features that have been recently examined as drug/DNA delivery vehicles. Finally, an overview of an emerging novel class of particles (based on lipid components other than phospholipids), solid lipid nanoparticles and nanostructured lipid carriers will be presented. We conclude with a few examples of clinically successful formulations of currently available lipid-based nanoparticles. PMID:20402623

Metal Nanoparticles as Targeted Carriers Circumventing the Blood-Brain Barrier.

PubMed

Sintov, A C; Velasco-Aguirre, C; Gallardo-Toledo, E; Araya, E; Kogan, M J

2016-01-01

Metal nanoparticles have been proposed as a carrier and a therapeutic agent in biomedical field because of their unique physiochemical properties. Due to these physicochemical properties, they can be used in different fields of biomedicine. In relation to this, plasmonic nanoparticles can be used for detection and photothermal destruction of tumor cells or toxic protein aggregates, and magnetic iron nanoparticles can be used for imaging and for hyperthermia of tumor cells. In addition, both therapy and imaging can be combined in one nanoparticle system, in a process called theranostics. Metal nanoparticles can be synthesized to modulate their size and shape, and conjugated with different ligands, which allow their application in drug delivery, diagnostics, and treatment of central nervous system diseases. This review is focused on the potential applications of metal nanoparticles and their capability to circumvent the blood-brain barrier (BBB). Although many articles have demonstrated delivery of metal nanoparticles to the brain by crossing the BBB after systemic administration, the percentage of the injected dose that reaches this organ is low in comparison to others, especially the liver and spleen. In connection with this drawback, we elaborate the architecture of the BBB and review possible mechanisms to cross this barrier by engineered nanoparticles. The potential uses of metal nanoparticles for treatment of disorders as well as related neurotoxicological considerations are also discussed. Finally, we bring up for discussion a direct and relatively simpler solution to the problem. We discuss this in detail after having proposed the use of the intranasal administration route as a way to circumvent the BBB. This route has not been extensively studied yet for metal nanoparticles, although it could be used as a research tool for mechanistic understanding and toxicity as well as an added value for medical practice. © 2016 Elsevier Inc. All rights reserved.

Gene expression profiling of immune-competent human cells exposed to engineered zinc oxide or titanium dioxide nanoparticles.

PubMed

Tuomela, Soile; Autio, Reija; Buerki-Thurnherr, Tina; Arslan, Osman; Kunzmann, Andrea; Andersson-Willman, Britta; Wick, Peter; Mathur, Sanjay; Scheynius, Annika; Krug, Harald F; Fadeel, Bengt; Lahesmaa, Riitta

2013-01-01

A comprehensive in vitro assessment of two commercial metal oxide nanoparticles, TiO2 and ZnO, was performed using human monocyte-derived macrophages (HMDM), monocyte-derived dendritic cells (MDDC), and Jurkat T cell leukemia-derived cell line. TiO2 nanoparticles were found to be non-toxic whereas ZnO nanoparticles caused dose-dependent cell death. Subsequently, global gene expression profiling was performed to identify transcriptional response underlying the cytotoxicity caused by ZnO nanoparticles. Analysis was done with doses 1 µg/ml and 10 µg/ml after 6 and 24 h of exposure. Interestingly, 2703 genes were significantly differentially expressed in HMDM upon exposure to 10 µg/ml ZnO nanoparticles, while in MDDCs only 12 genes were affected. In Jurkat cells, 980 genes were differentially expressed. It is noteworthy that only the gene expression of metallothioneins was upregulated in all the three cell types and a notable proportion of the genes were regulated in a cell type-specific manner. Gene ontology analysis revealed that the top biological processes disturbed in HMDM and Jurkat cells were regulating cell death and growth. In addition, genes controlling immune system development were affected. Using a panel of modified ZnO nanoparticles, we obtained an additional support that the cellular response to ZnO nanoparticles is largely dependent on particle dissolution and show that the ligand used to modify ZnO nanoparticles modulates Zn(2+) leaching. Overall, the study provides an extensive resource of transcriptional markers for mediating ZnO nanoparticle-induced toxicity for further mechanistic studies, and demonstrates the value of assessing nanoparticle responses through a combined transcriptomics and bioinformatics approach.

Gene Expression Profiling of Immune-Competent Human Cells Exposed to Engineered Zinc Oxide or Titanium Dioxide Nanoparticles

PubMed Central

Tuomela, Soile; Autio, Reija; Buerki-Thurnherr, Tina; Arslan, Osman; Kunzmann, Andrea; Andersson-Willman, Britta; Wick, Peter; Mathur, Sanjay; Scheynius, Annika; Krug, Harald F.; Fadeel, Bengt; Lahesmaa, Riitta

2013-01-01

A comprehensive in vitro assessment of two commercial metal oxide nanoparticles, TiO2 and ZnO, was performed using human monocyte-derived macrophages (HMDM), monocyte-derived dendritic cells (MDDC), and Jurkat T cell leukemia-derived cell line. TiO2 nanoparticles were found to be non-toxic whereas ZnO nanoparticles caused dose-dependent cell death. Subsequently, global gene expression profiling was performed to identify transcriptional response underlying the cytotoxicity caused by ZnO nanoparticles. Analysis was done with doses 1 µg/ml and 10 µg/ml after 6 and 24 h of exposure. Interestingly, 2703 genes were significantly differentially expressed in HMDM upon exposure to 10 µg/ml ZnO nanoparticles, while in MDDCs only 12 genes were affected. In Jurkat cells, 980 genes were differentially expressed. It is noteworthy that only the gene expression of metallothioneins was upregulated in all the three cell types and a notable proportion of the genes were regulated in a cell type-specific manner. Gene ontology analysis revealed that the top biological processes disturbed in HMDM and Jurkat cells were regulating cell death and growth. In addition, genes controlling immune system development were affected. Using a panel of modified ZnO nanoparticles, we obtained an additional support that the cellular response to ZnO nanoparticles is largely dependent on particle dissolution and show that the ligand used to modify ZnO nanoparticles modulates Zn2+ leaching. Overall, the study provides an extensive resource of transcriptional markers for mediating ZnO nanoparticle-induced toxicity for further mechanistic studies, and demonstrates the value of assessing nanoparticle responses through a combined transcriptomics and bioinformatics approach. PMID:23894303

Surface engineering of macrophages with nanoparticles to generate a cell-nanoparticle hybrid vehicle for hypoxia-targeted drug delivery.

PubMed

Holden, Christopher A; Yuan, Quan; Yeudall, W Andrew; Lebman, Deborah A; Yang, Hu

2010-02-02

Tumors frequently contain hypoxic regions that result from a shortage of oxygen due to poorly organized tumor vasculature. Cancer cells in these areas are resistant to radiation- and chemotherapy, limiting the treatment efficacy. Macrophages have inherent hypoxia-targeting ability and hold great advantages for targeted delivery of anticancer therapeutics to cancer cells in hypoxic areas. However, most anticancer drugs cannot be directly loaded into macrophages because of their toxicity. In this work, we designed a novel drug delivery vehicle by hybridizing macrophages with nanoparticles through cell surface modification. Nanoparticles immobilized on the cell surface provide numerous new sites for anticancer drug loading, hence potentially minimizing the toxic effect of anticancer drugs on the viability and hypoxia-targeting ability of the macrophage vehicles. In particular, quantum dots and 5-(aminoacetamido) fluorescein-labeled polyamidoamine dendrimer G4.5, both of which were coated with amine-derivatized polyethylene glycol, were immobilized to the sodium periodate-treated surface of RAW264.7 macrophages through a transient Schiff base linkage. Further, a reducing agent, sodium cyanoborohydride, was applied to reduce Schiff bases to stable secondary amine linkages. The distribution of nanoparticles on the cell surface was confirmed by fluorescence imaging, and it was found to be dependent on the stability of the linkages coupling nanoparticles to the cell surface.

Role of Physicochemical Properties in Nanoparticle Toxicity

PubMed Central

Shin, Seung Won; Song, In Hyun; Um, Soong Ho

2015-01-01

With the recent rapid growth of technological comprehension in nanoscience, researchers have aimed to adapt this knowledge to various research fields within engineering and applied science. Dramatic advances in nanomaterials marked a new epoch in biomedical engineering with the expectation that they would have huge contributions to healthcare. However, several questions regarding their safety and toxicity have arisen due to numerous novel properties. Here, recent studies of nanomaterial toxicology will be reviewed from several physiochemical perspectives. A variety of physiochemical properties such as size distribution, electrostatics, surface area, general morphology and aggregation may significantly affect physiological interactions between nanomaterials and target biological areas. Accordingly, it is very important to finely tune these properties in order to safely fulfill a bio-user’s purpose. PMID:28347068

Nano-Engineered Mesenchymal Stem Cells Increase Therapeutic Efficacy of Anticancer Drug Through True Active Tumor Targeting.

PubMed

Layek, Buddhadev; Sadhukha, Tanmoy; Panyam, Jayanth; Prabha, Swayam

2018-06-01

Tumor-targeted drug delivery has the potential to improve therapeutic efficacy and mitigate non-specific toxicity of anticancer drugs. However, current drug delivery approaches rely on inefficient passive accumulation of the drug carrier in the tumor. We have developed a unique, truly active tumor-targeting strategy that relies on engineering mesenchymal stem cells (MSC) with drug-loaded nanoparticles. Our studies using the A549 orthotopic lung tumor model show that nano-engineered MSCs carrying the anticancer drug paclitaxel (PTX) home to tumors and create cellular drug depots that release the drug payload over several days. Despite significantly lower doses of PTX, nano-engineered MSCs resulted in significant inhibition of tumor growth and superior survival. Anticancer efficacy of nano-engineered MSCs was confirmed in immunocompetent C57BL/6 albino female mice bearing orthotopic Lewis Lung Carcinoma (LL/2-luc) tumors. Furthermore, at doses that resulted in equivalent therapeutic efficacy, nano-engineered MSCs had no effect on white blood cell count, whereas PTX solution and PTX nanoparticle treatments caused leukopenia. Biodistribution studies showed that nano-engineered MSCs resulted in greater than 9-fold higher AUC lung of PTX (1.5 μg.day/g) than PTX solution and nanoparticles (0.2 and 0.1 μg.day/g tissue, respectively) in the target lung tumors. Furthermore, the lung-to-liver and the lung-to-spleen ratios of PTX were several folds higher for nano-engineered MSCs relative to those for PTX solution and nanoparticle groups, suggesting that nano-engineered MSCs demonstrate significantly less off-target deposition. In summary, our results demonstrate that nano-engineered MSCs can serve as an efficient carrier for tumor-specific drug delivery and significantly improved anti-cancer efficacy of conventional chemotherapeutic drugs. Mol Cancer Ther; 17(6); 1196-206. ©2018 AACR . ©2018 American Association for Cancer Research.

Prospects of nanoparticle-DNA binding and its implications in medical biotechnology.

PubMed

An, Hongjie; Jin, Bo

2012-01-01

Bio-nanotechnology is a new interdisciplinary R&D area that integrates engineering and physical science with biology through the development of multifunctional devices and systems, focusing biology inspired processes or their applications, in particular in medical biotechnology. DNA based nanotechnology, in many ways, has been one of the most intensively studied fields in recent years that involves the use and the creation of bio-inspired materials and their technologies for highly selective biosensing, nanoarchitecture engineering and nanoelectronics. Increasing researches have been offered to a fundamental understanding how the interactions between the nanoparticles and DNA molecules could alter DNA molecular structure and its biochemical activities. This minor review describes the mechanisms of the nanoparticle-DNA binding and molecular interactions. We present recent discoveries and research progresses how the nanoparticle-DNA binding could vary DNA molecular structure, DNA detection, and gene therapy. We report a few case studies associated with the application of the nanoparticle-DNA binding devices in medical detection and biotechnology. The potential impacts of the nanoparticles via DNA binding on toxicity of the microorganisms are briefly discussed. The nanoparticle-DNA interactions and their impact on molecular and microbial functionalities have only drown attention in recent a few years. The information presented in this review can provide useful references for further studies on biomedical science and technology. Copyright © 2012 Elsevier Inc. All rights reserved.

Toxicity of Engineered Nickel Oxide and Cobalt Oxide Nanoparticles to Artemia salina in seawater

PubMed Central

Ates, Mehmet; Demir, Veysel; Arslan, Zikri; Camas, Mustafa; Celik, Fatih

2016-01-01

In this study, the effects of exposure to engineered nickel oxide (NiO 40–60 nm) and cobalt oxide (CoO <100 nm) nanoparticles (NP) were investigated on Artemia salina. Aggregation and stability of the aqueous NP suspensions were characterized by DLS and TEM. Acute exposure was conducted on nauplii (larvae) in seawater in a concentration range from 0.2 to 50 mg/L NPs for 24 h (short term) and 96 h (long term). The hydrodynamic diameters of NiO and CoO NPs in exposure medium were larger than those estimated by TEM. Accumulation rate of NiO NPs were found to be four times higher than that of CoO NPs under the same experimental conditions. Examinations under phase contrast microscope showed that the nanoparticles accumulated in the intestine of artemia, which increased with increasing exposure concentration. Differences were observed in the extent of dissolution of the NPs in the seawater. The CoO NPs dissolved significantly while NiO NPs were relatively more stable. Oxidative stress induced by the NP suspensions was measured by malondialdehyde assay. Suspensions of NiO NPs caused higher oxidative stress on nauplii than those of CoO NPs. The results imply that CoO and NiO NPs exhibit toxicity on artemia (e.g., zooplankton) that are an important source of food in aquatic food chain. PMID:27152058

Mechanisms of carbon nanotube-induced toxicity: Focus on oxidative stress

PubMed Central

Shvedova, Anna A.; Pietroiusti, Antonio; Fadeel, Bengt; Kagan, Valerian E.

2015-01-01

Nanotechnologies are emerging as highly promising technologies in many sectors in the society. However, the increasing use of engineered nanomaterials also raises concerns about inadvertent exposure to these materials and the potential for adverse effects on human health and the environment. Despite several years of intensive investigations, a common paradigm for the understanding of nanoparticle-induced toxicity remains to be firmly established. Here, the so-called oxidative stress paradigm is scrutinized. Does oxidative stress represent a secondary event resulting inevitably from disruption of biochemical processes and the demise of the cell, or a specific, non-random event that plays a role in the induction of cellular damage e.g. apoptosis? The answer to this question will have important ramifications for the development of strategies for mitigation of adverse effects of nanoparticles. Recent examples of global lipidomics studies of nanoparticle-induced tissue damage are discussed along with proteomics and transcriptomics approaches to achieve a comprehensive understanding of the complex and interrelated molecular changes in cells and tissues exposed to nanoparticles. We also discuss instances of non-oxidative stress-mediated cellular damage resulting from direct physical interference of nanomaterials with cellular structures. PMID:22513272

Engineered Nanomaterials, Sexy New Technology and Potential Hazards

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beaulieu, R A

Engineered nanomaterials enhance exciting new applications that can greatly benefit society in areas of cancer treatments, solar energy, energy storage, and water purification. While nanotechnology shows incredible promise in these and other areas by exploiting nanomaterials unique properties, these same properties can potentially cause adverse health effects to workers who may be exposed during work. Dispersed nanoparticles in air can cause adverse health effects to animals not merely due to their chemical properties but due to their size, structure, shape, surface chemistry, solubility, carcinogenicity, reproductive toxicity, mutagenicity, dermal toxicity, and parent material toxicity. Nanoparticles have a greater likelihood of lungmore » deposition and blood absorption than larger particles due to their size. Nanomaterials can also pose physical hazards due to their unusually high reactivity, which makes them useful as catalysts, but has the potential to cause fires and explosions. Characterization of the hazards (and potential for exposures) associated with nanomaterial development and incorporation in other products is an essential step in the development of nanotechnologies. Developing controls for these hazards are equally important. Engineered controls should be integrated into nanomaterial manufacturing process design according to 10CFR851, DOE Policy 456.1, and DOE Notice 456.1 as safety-related hardware or administrative controls for worker safety. Nanomaterial hazards in a nuclear facility must also meet control requirements per DOE standards 3009, 1189, and 1186. Integration of safe designs into manufacturing processes for new applications concurrent with the developing technology is essential for worker safety. This paper presents a discussion of nanotechnology, nanomaterial properties/hazards and controls.« less

Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through the γ-H2AX and NF-κB signaling pathways.

PubMed

Liu, Jing; Zhao, Yong; Ge, Wei; Zhang, Pengfei; Liu, Xinqi; Zhang, Weidong; Hao, Yanan; Yu, Shuai; Li, Lan; Chu, Meiqiang; Min, Lingjiang; Zhang, Hongfu; Shen, Wei

2017-06-27

The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn2+. Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use.

Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through the γ-H2AX and NF-κB signaling pathways

PubMed Central

Liu, Jing; Zhao, Yong; Ge, Wei; Zhang, Pengfei; Liu, Xinqi; Zhang, Weidong; Hao, Yanan; Yu, Shuai; Li, Lan; Chu, Meiqiang; Min, Lingjiang; Zhang, Hongfu; Shen, Wei

2017-01-01

The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn2+. Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use. PMID:28487501

Silver nanoparticle modulates gene expressions, glyoxalase system and oxidative stress markers in fluoride stressed Cajanus cajan L.

PubMed

Yadu, Bhumika; Chandrakar, Vibhuti; Korram, Jyoti; Satnami, Manmohan L; Kumar, Meetul; S, Keshavkant

2018-07-05

Application of engineered nanomaterials has increased these days due to their beneficial impacts on several sectors of the economy, including agriculture. Silver nanoparticles (AgNP) are commonly used to improve rate of seed germination, and growth and development of plants. The present study was aimed to monitor the role of engineered AgNP (non-dialysed) in the amelioration of fluoride (F)-induced oxidative injuries in Cajanus cajan L. Experimental results revealed that F-exposure inhibited growth and membrane stability index, while were enhanced with the augmentation of AgNP. The results also demonstrated that F treatment enhanced the accumulations of reactive oxygen species, malondialdehyde and oxidized glutathione, gene expression of NADPH oxidase, and activity of lipoxygenase, but were decreased by the addition of AgNP. The results indicated that exogenous application of AgNP provided tolerance against F-toxicity via enhancing the levels of proline, total and reduced glutathione, glyoxalase I and II activities, and expression of pyrroline-5-carboxylate synthetase gene. Conducted study uniquely suggested potential role of AgNP in the remediation of F-toxicity, at least in the Cajanus cajan L. radicles. Further research would be intended to unravel the molecular mechanism(s) involved precisely in the AgNP mediated alleviation of F-toxicity. Copyright © 2018 Elsevier B.V. All rights reserved.

Immunogenicity and ecotoxicity of engineered nanoparticles

NASA Astrophysics Data System (ADS)

Maurer-Jones, Melissa Ann

The growing use of nanoscale materials in commercially available products and therapeutics has created an urgent need to determine the toxicity of these materials so that they may be designed and employed safely. As nanoparticles have unique physical and chemical properties, the challenges in determining their physiological and environmental impact have been numerous. It is, therefore, the goal of my thesis work to employ sensitive analytical tools to fundamentally understand the how nanoparticles interact with immunologically and ecologically relevant models. My project approaches nanotoxicity studies starting with a relevant model system exposed to well-characterized nanoparticles to (1) determine if cells/organisms survive exposure using traditional toxicological assays and, if the majority survives exposure, (2) use sensitive analytical tools to determine if there are changes to critical cell/organism function. If perturbation of function is detected, (3) the mechanism or cause of changes in cell function should be determined, including assessment of nanoparticle uptake and localization. Once a mechanism of interaction is determined, this process could begin again with a modified particle that may address the toxic response. Chapter Two describes the impact of metal oxide (TiO2 and SiO2) nanoparticles on mast cells, critical immune system cells, and utilizes the sensitive technique of carbon-fiber microelectrode amperometry (CFMA) to monitor changes in the important mast cell function of exocytosis. Chapter Three expands upon Chapter Two and examines in more detail the mechanism by which TiO2 nanoparticles impact exocytotic cell function, completing the process nanotoxicity described above. From these studies, it was determined that, while nanoparticles do not decrease the viability of mast cells, there are significant changes to exocytosis upon nanoparticle exposure, and in the case of TiO2, these changes in exocytosis are correlated to nanoparticle-induced oxidative stress. The generalizability of the mechanism of TiO2 toxicity, as detailed in Chapter Two and Three, is explored in Chapter Four in a bacteria model, Shewanella oneidensis, studying the functions of biofilm formation using a quartz crystal microbalance (QCM) and flavin secretion using high performance liquid chromatography (HPLC). This study revealed that the proximity of the TiO 2 nanoparticles to S. oneidensis caused changes in gene expression resulting in an observed delay in biofilm growth and increase in riboflavin secretion. Chapter Five works to develop an in situ Ag nanoparticle characterization tool using fluorous-phase ion selective electrodes to measure dissolved Ag+, with preliminary investigation into the toxicity of Ag nanoparticles and Ag+ ions to S. oneidensis, resulting in one of the first in situ characterization tools for nanoparticles during toxicity assessments. Moving beyond laboratory work, Chapter Six examines bench scientists' perspective on the regulation of nanotherapies moving from pre-clinical to first-in-human trials and the ethical considerations for the implementation of nanotechnology. Finally, Chapter Seven details the development of a 3-day nanotoxicity laboratory for introductory chemistry classes to introduce students to interdisciplinary science and the cutting edge research field of nanotoxicology. In total, my project has considered the scientific, ethical, and educational implications for nanotoxicology and has ultimately contributed to a better understanding of the nanoparticle-cell interaction.

DR5 mAb-conjugated, DTIC-loaded immuno-nanoparticles effectively and specifically kill malignant melanoma cells in vivo.

PubMed

Ding, Baoyue; Zhang, Wei; Wu, Xin; Wang, Jeffrey; Xie, Chen; Huang, Xuan; Zhan, Shuyu; Zheng, Yongxia; Huang, Yueyan; Xu, Ningyin; Ding, Xueying; Gao, Shen

2016-08-30

We combined chemo- and immunotherapies by constructing dual therapeutic function immuno-nanoparticles (NPs) consisting of death receptor 5 monoclonal antibody (DR5 mAb)-conjugated nanoparticles loaded with dacarbazine (DTIC) (DTIC-NPs-DR5 mAb). We determined the in vivo targeting specificity of DTIC-NPs-DR5 mAb by evaluating distribution in tumor-bearing nude mice using a real-time imaging system. Therapeutic efficacy was assessed in terms of its effect on tumor volume, survival time, histomorphology, microvessel density (MVD), and apoptotic index (AI). Systemic toxicity was evaluated by measuring white blood cells (WBC) counts, alanine aminotransferase (ALT) levels, and creatinine clearance (CR).In vivo and ex vivo imaging indicates that DR5 mAb modification enhanced the accumulation of NPs within the xenograft tumor. DTIC-NPs-DR5 mAb inhibited tumor growth more effectively than DTIC or DR5 mAb alone, indicating that combining DTIC and DR5 mAb through pharmaceutical engineering achieves a better therapeutic effect. Moreover, the toxicity of DTIC-NPs-DR5 mAb was much lower than that of DTIC, implying that DR5 mAb targeting reduces nonspecific uptake of DTIC into normal tissue and thus decreases toxic side effects. These results demonstrate that DTIC-NPs-DR5 mAb is a safe and effective nanoparticle formulation with the potential to improve the efficacy and specificity of melanoma treatment.

DR5 mAb-conjugated, DTIC-loaded immuno-nanoparticles effectively and specifically kill malignant melanoma cells in vivo

PubMed Central

Wang, Jeffrey; Xie, Chen; Huang, Xuan; Zhan, Shuyu; Zheng, Yongxia; Huang, Yueyan; Xu, Ningyin; Ding, Xueying; Gao, Shen

2016-01-01

We combined chemo- and immunotherapies by constructing dual therapeutic function immuno-nanoparticles (NPs) consisting of death receptor 5 monoclonal antibody (DR5 mAb)-conjugated nanoparticles loaded with dacarbazine (DTIC) (DTIC-NPs-DR5 mAb). We determined the in vivo targeting specificity of DTIC-NPs-DR5 mAb by evaluating distribution in tumor-bearing nude mice using a real-time imaging system. Therapeutic efficacy was assessed in terms of its effect on tumor volume, survival time, histomorphology, microvessel density (MVD), and apoptotic index (AI). Systemic toxicity was evaluated by measuring white blood cells (WBC) counts, alanine aminotransferase (ALT) levels, and creatinine clearance (CR).In vivo and ex vivo imaging indicates that DR5 mAb modification enhanced the accumulation of NPs within the xenograft tumor. DTIC-NPs-DR5 mAb inhibited tumor growth more effectively than DTIC or DR5 mAb alone, indicating that combining DTIC and DR5 mAb through pharmaceutical engineering achieves a better therapeutic effect. Moreover, the toxicity of DTIC-NPs-DR5 mAb was much lower than that of DTIC, implying that DR5 mAb targeting reduces nonspecific uptake of DTIC into normal tissue and thus decreases toxic side effects. These results demonstrate that DTIC-NPs-DR5 mAb is a safe and effective nanoparticle formulation with the potential to improve the efficacy and specificity of melanoma treatment. PMID:27494835

A biological method for in-situ synthesis of hydroxyapatite-coated magnetite nanoparticles using Enterobacter aerogenes: Characterization and acute toxicity assessments.

PubMed

Ahmadzadeh, Elham; Talebnia Rowshan, Farid; Hosseini, Morteza

2017-04-01

Hydroxyapatite (HA)-coated magnetite nanoparticles (MNPs) are being widely investigated for various applications in medical engineering and wastewater treatment. In this work, the MNPs were thoroughly coated by bacterial synthesized HA nanoparticles during biomineralization process using Enterobacter aerogenes. The resulting bacterial-induced precipitate was then calcined at 600°C and investigated with respect to structural characteristics, particle size and magnetic strength by XRD, FT-IR, SEM, EDS, TEM and VSM analyses. The effects of MNPs and HA-coated MNPs (HA-MNPs) on the viability of human MCF-7 cell lines were also investigated via mitochondrial activity test (MTT) and lactate dehydrogenase (LDH) assays. The powder characterization results showed appropriate structural properties for HA-MNPs samples. The particles diameter size of the MNPs and HA-MNPs were in the range of 3-25nm and 20-80nm, respectively. The biologically-synthesized HA-MNPs formed a stable suspension in water while keeping their magnetic property. The saturation magnetization (Ms) of HA-MNPs was measured at ~10emug -1 which was in good agreement with the structural composition of this sample. Finally, the results of the cell lines viability indicated that coating of toxic MNPs via biomineralization was a promising approach in order to synthesize bio-compatible magnetic nanoparticles with suitable physical and chemical structural characteristics. The toxicity level of MNPs was reduced by 10 fold when coated by bacterial-synthesized HA. Copyright © 2016 Elsevier B.V. All rights reserved.

Calpain activation and disturbance of autophagy are induced in cortical neurons in vitro by exposure to HA/β-Ga2O3:Cr3+ nanoparticles.

PubMed

Lei, Yu; Wang, Chengkun; Jiang, Quan; Sun, Xiaoyi; Du, Yongzhong; Zhu, Yaofeng; Lu, Yingmei

2018-01-01

The toxicity of engineered nanoparticles remains a concern. The knowledge of biohazards associated with particular nanoparticles is crucial to make this cutting-edge technology more beneficial and safe. Here, we evaluated the toxicity of Ga 2 O 3 nanoparticles (NPs), which are frequently used to enhance the performance of metal catalysts in a variety of catalytic reactions. The potential inflammatory signaling associated with the toxicity of HA/β-Ga 2 O 3 :Cr 3+ NPs in primary cortical neurons was examined. We observed a dose-dependent decrease in cell viability and an increase in apoptosis in neurons following various concentrations (0, 1, 5, 25, 50, 100 µg/ml) of HA/β-Ga 2 O 3 :Cr 3+ NPs treatment. Consistently, constitutively active forms of calcineurin (48 kDa) were significantly elevated in cultured primary cortical neurons, which was consistent with calpain activation indicated by the breakdown products of spectrin. Moreover, HA/β-Ga 2 O 3 :Cr 3+ NPs result in the elevation of LC3-II formation, SQSTM/p62, and Cathepsin B, whereas phosphorylation of CaMKII (Thr286) and Synapsin I (Ser603) were downregulated in the same context. Taken together, these results demonstrate for the first time that calpain activation and a disturbance of autophagy signaling are evoked by exposure to HA/β-Ga 2 O 3 :Cr 3+ NPs, which may contribute to neuronal injury in vitro .

Calpain activation and disturbance of autophagy are induced in cortical neurons in vitro by exposure to HA/β-Ga2O3:Cr3+ nanoparticles

PubMed Central

Jiang, Quan; Sun, Xiaoyi; Du, Yongzhong

2018-01-01

The toxicity of engineered nanoparticles remains a concern. The knowledge of biohazards associated with particular nanoparticles is crucial to make this cutting-edge technology more beneficial and safe. Here, we evaluated the toxicity of Ga2O3 nanoparticles (NPs), which are frequently used to enhance the performance of metal catalysts in a variety of catalytic reactions. The potential inflammatory signaling associated with the toxicity of HA/β-Ga2O3:Cr3+ NPs in primary cortical neurons was examined. We observed a dose-dependent decrease in cell viability and an increase in apoptosis in neurons following various concentrations (0, 1, 5, 25, 50, 100 µg/ml) of HA/β-Ga2O3:Cr3+ NPs treatment. Consistently, constitutively active forms of calcineurin (48 kDa) were significantly elevated in cultured primary cortical neurons, which was consistent with calpain activation indicated by the breakdown products of spectrin. Moreover, HA/β-Ga2O3:Cr3+ NPs result in the elevation of LC3-II formation, SQSTM/p62, and Cathepsin B, whereas phosphorylation of CaMKII (Thr286) and Synapsin I (Ser603) were downregulated in the same context. Taken together, these results demonstrate for the first time that calpain activation and a disturbance of autophagy signaling are evoked by exposure to HA/β-Ga2O3:Cr3+ NPs, which may contribute to neuronal injury in vitro. PMID:29441243

Applications of nanotechnology in dermatology.

PubMed

DeLouise, Lisa A

2012-03-01

What are nanoparticles and why are they important in dermatology? These questions are addressed by highlighting recent developments in the nanotechnology field that have increased the potential for intentional and unintentional nanoparticle skin exposure. The role of environmental factors in the interaction of nanoparticles with skin and the potential mechanisms by which nanoparticles may influence skin response to environmental factors are discussed. Trends emerging from recent literature suggest that the positive benefit of engineered nanoparticles for use in cosmetics and as tools for understanding skin biology and curing skin disease outweigh potential toxicity concerns. Discoveries reported in this journal are highlighted. This review begins with a general introduction to the field of nanotechnology and nanomedicine. This is followed by a discussion of the current state of understanding of nanoparticle skin penetration and their use in three therapeutic applications. Challenges that must be overcome to derive clinical benefit from the application of nanotechnology to skin are discussed last, providing perspective on the significant opportunity that exists for future studies in investigative dermatology.

Applications of Nanotechnology in Dermatology

PubMed Central

DeLouise, Lisa A.

2014-01-01

What are nanoparticles and why are they important in dermatology? These questions are addressed by highlighting recent developments in the nanotechnology field that have increased the potential for intentional and unintended nanoparticle skin exposure. The role of environmental factors in the interaction of nanoparticles with skin and the potential mechanisms by which nanoparticles may influence skin response to environmental factors are discussed. Trends emerging from recent literature suggest that the positive benefit of engineered nanoparticles for use in cosmetics and as tools for understanding skin biology and curing skin disease, out weigh potential toxicity concerns. Discoveries reported in this journal are highlighted. This review begins with a general introduction to the field of nanotechnology and nanomedicine. This is followed by a discussion of the current state of understanding of nanoparticle skin penetration and their use in three different therapeutic applications. Challenges that must be overcome to derive clinical benefit from the application of nanotechnology to skin are discussed last, providing perspective on the significant opportunity that exists for future studies in investigative dermatology. PMID:22217738

TOXICITY OF SILVER NANOPARTICLES TO DAPHNIA MAGNA

EPA Science Inventory

Relatively little is known regarding toxicity of nanoparticles in the environment. It is widely assumed that the toxicity of nanoparticles will be less than that of their metallic ions. Also the effect of organics on metal toxicity is well established. Presented here are the resu...

Toxic effect of silver and platinum nanoparticles toward the freshwater microalga Pseudokirchneriella subcapitata.

PubMed

Książyk, Małgorzata; Asztemborska, Monika; Stęborowski, Romuald; Bystrzejewska-Piotrowska, Grażyna

2015-05-01

The growing use of nanoparticles in a wide range of products has resulted in their release into the aquatic environment; therefore, an understanding of the toxic effects of nanoparticles on aquatic organisms is of permanent importance. The aim of this study was to evaluate the toxicity of silver and platinum nanoparticles toward the freshwater microalga, Pseudokirchneriella subcapitata. Algal growth and photosynthetic pigments were determined to quantitate the effects of varying concentrations of Ag and Pt nanoparticles. The silver nanoparticles were much more toxic than the platinum ones. The concentrations causing total inhibition of algal growth were 5.0 and 22.2 mg L(-1), respectively. Similar results were obtained by analyzing the concentration of photosynthetic pigments in P. subcapitata exposed to nanoparticles. Thus, simple spectrophotometric determination of chlorophyll is a convenient tool for the analysis of nanoparticle toxicity to algae.

Toxicity of food-relevant nanoparticles in intestinal epithelial models

NASA Astrophysics Data System (ADS)

McCracken, Christie

Nanoparticles are increasingly being incorporated into common consumer products, including in foods and food packaging, for their unique properties at the nanoscale. Food-grade silica and titania are used as anti-caking and whitening agents, respectively, and these particle size distributions are composed of approximately one-third nanoparticles. Zinc oxide and silver nanoparticles can be used for their antimicrobial properties. However, little is known about the interactions of nanoparticles in the body upon ingestion. This study was performed to investigate the role of nanoparticle characteristics including surface chemistry, dissolution, and material type on toxicity to the intestinal epithelium. Only mild acute toxicity of zinc oxide nanoparticles was observed after 24-hour treatment of intestinal epithelial C2BBe1 cells based on the results of toxicity assays measuring necrosis, apoptosis, membrane damage, and mitochondrial activity. Silica and titanium dioxide nanoparticles were not observed to be toxic although all nanoparticles were internalized by cells. In vitro digestion of nanoparticles in solutions representing the stomach and intestines prior to treatment of cells did not alter nanoparticle toxicity. Long-term repeated treatment of cells weekly for 24 hours with nanoparticles did not change nanoparticle cytotoxicity or the growth rate of the treated cell populations. Thus, silica, titanium dioxide, and zinc oxide nanoparticles were found to induce little toxicity in intestinal epithelial cells. Fluorescent silica nanoparticles were synthesized as a model for silica used in foods that could be tracked in vitro and in vivo. To maintain an exterior of pure silica, a silica shell was hydrolyzed around a core particle of quantum dots or a fluorescent dye electrostatically associated with a commercial silica particle. The quantum dots used were optimized from a previously reported microwave quantum dot synthesis to a quantum yield of 40%. Characterization of the silica particles showed that the surface properties resembled pure silica. These particles were able to be detected in vitro as well as in vivo after oral administration of nanoparticles to mice by gavage. After four daily administrations, nanoparticles were detected by fluorescence confocal microscopy in intestines as well as liver, kidney, spleen, lung, and brain. Thus, silica nanoparticles were able to traverse the intestinal epithelium. Further investigation is needed to determine nanoparticle accumulation and potential functional consequences throughout the body. Silver nanoparticles were particularly toxic to proliferating (subconfluent) C2BBe1 cells plated at low density, inducing 15% necrosis and a 76% decrease in mitochondrial activity. Silver nanoparticle treatment induced oxidative stress in cells based on increased GSH/GSSG ratios. In addition, silver nanoparticles induced G2/M phase cell cycle arrest and inhibited cell proliferation at doses forty times lower than those at which silica, titanium dioxide, and zinc oxide nanoparticles had inhibitory effects. Silver nanoparticles subjected to in vitro digestion before cell exposure required higher doses to induce toxicity, likely due to slower dissolution because of greater surface species adsorption. Silver nanoparticles did not cause toxicity or oxidative stress in confluent (stationary) cells. Thus, upon ingestion, silver nanoparticles may be especially toxic to proliferating stem cells in intestinal crypts, particularly in disease states with a compromised epithelium.

Vectorization by nanoparticles decreases the overall toxicity of airborne pollutants.

PubMed

Carpentier, Rodolphe; Platel, Anne; Maiz-Gregores, Helena; Nesslany, Fabrice; Betbeder, Didier

2017-01-01

Atmospheric pollution is mainly composed of volatile pollutants and particulate matter that strongly interact. However, their specific roles in the induction of cellular toxicity, in particular the impact of the vectorization of atmospheric pollutants by ultrafine particles, remains to be fully elucidated. For this purpose, non-toxic poly-lactic co-glycolic acid (PLGA) nanoparticles were synthesized and three pollutants (benzo(a)pyrene, naphthalene and di-ethyl-hexyl-phthalate) were adsorbed on the surface of the nanoparticles in order to evaluate the toxicity (cytotoxicity, genotoxicity and ROS induction) of these complexes to a human airway epithelial cell line. The adsorption of the pollutants onto the nanoparticles was confirmed by HPLC analysis. Interestingly, the cytotoxicity assays (MTT, LDH and CellTox Green) clearly demonstrated that the vectorization by nanoparticles decreases the toxicity of the adsorbed pollutants. Genotoxicity was assessed by the micronucleus test and the comet assay and showed no increase in primary DNA damage or in chromosomal aberrations of nanoparticle vectorized pollutants. Neither cytotoxicity nor genotoxicity was correlated with ROS induction. To conclude, our results indicate that the vectorization of pollutants by nanoparticles does not potentiate the toxicity of the pollutants studied and that, on the contrary, adsorption onto nanoparticles could protect cells against pollutants' toxicity.

Nanomaterials and Water Purification: Opportunities and Challenges

NASA Astrophysics Data System (ADS)

Savage, Nora; Diallo, Mamadou S.

2005-10-01

Advances in nanoscale science and engineering suggest that many of the current problems involving water quality could be resolved or greatly ameliorated using nanosorbents, nanocatalysts, bioactive nanoparticles, nanostructured catalytic membranes and nanoparticle enhanced filtration among other products and processes resulting from the development of nanotechnology. Innovations in the development of novel technologies to desalinate water are among the most exciting and promising. Additionally, nanotechnology-derived products that reduce the concentrations of toxic compounds to sub-ppb levels can assist in the attainment of water quality standards and health advisories. This article gives an overview of the use of nanomaterials in water purification. We highlight recent advances on the development of novel nanoscale materials and processes for treatment of surface water, groundwater and industrial wastewater contaminated by toxic metal ions, radionuclides, organic and inorganic solutes, bacteria and viruses. In addition, we discuss some challenges associated with the development of cost effective and environmentally acceptable functional nanomaterials for water purification.

Biogenic synthesized nanoparticles and their applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Abhijeet, E-mail: abhijeet.singh@jaipur.manipal.edu; Sharma, Madan Mohan

In the present scenario, there are growing concerns over the potential impacts of bioengineered nanoparticles in the health sector. However, our understanding of how bioengineered nanoparticles may affect organisms within natural ecosystems, lags far behind our rapidly increasing ability to engineer novel nanoparticles. To date, research on the biological impacts of bioengineered nanoparticles has primarily consisted of controlled lab studies of model organisms with single species in culture media. Here, we described a cost effective and environment friendly technique for green synthesis of silver nanoparticles. Silver nanoparticles were successfully synthesized from 1 mM AgNO{sub 3} via a green synthesis processmore » using leaf extract as reducing as well as capping agent. Nanoparticles were characterized with the help of UV–vis absorption spectroscopy, X-ray diffraction and TEM analysis which revealed the size of nanoparticles of 30-40 nm size. Further the nanoparticles synthesized by green route are found highly toxic against pathogenic bacteria and plant pathogenic fungi viz. Escherichia coli, Pseudomonas syringae and Sclerotiniasclerotiorum. The most important outcome of this work will be the development of value-added products and protection of human health from pathogens viz., bacteria, virus, fungi etc.« less

Toxicity of CeO2 nanoparticles - the effect of nanoparticle properties.

PubMed

Leung, Yu Hang; Yung, Mana M N; Ng, Alan M C; Ma, Angel P Y; Wong, Stella W Y; Chan, Charis M N; Ng, Yip Hang; Djurišić, Aleksandra B; Guo, Muyao; Wong, Mabel Ting; Leung, Frederick C C; Chan, Wai Kin; Leung, Kenneth M Y; Lee, Hung Kay

2015-04-01

Conflicting reports on the toxicity of CeO2 nanomaterials have been published in recent years, with some studies finding CeO2 nanoparticles to be toxic, while others found it to have protective effects against oxidative stress. To investigate the possible reasons for this, we have performed a comprehensive study on the physical and chemical properties of nanosized CeO2 from three different suppliers as well as CeO2 synthesized by us, and tested their toxicity. For toxicity tests, we have studied the effects of CeO2 nanoparticles on a Gram-negative bacterium Escherichia coli in the dark, under ambient and UV illuminations. We have also performed toxicity tests on the marine diatom Skeletonema costatum under ambient and UV illuminations. We found that the CeO2 nanoparticle samples exhibited significantly different toxicity, which could likely be attributed to the differences in interactions with cells, and possibly to differences in nanoparticle compositions. Our results also suggest that toxicity tests on bacteria may not be suitable for predicting the ecotoxicity of nanomaterials. The relationship between the toxicity and physicochemical properties of the nanoparticles is explicitly discussed in the light of the current results. Copyright © 2015 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kotula, Paul Gabriel; Brozik, Susan Marie; Achyuthan, Komandoor E.

Engineered nanomaterials (ENMs) are increasingly being used in commercial products, particularly in the biomedical, cosmetic, and clothing industries. For example, pants and shirts are routinely manufactured with silver nanoparticles to render them 'wrinkle-free.' Despite the growing applications, the associated environmental health and safety (EHS) impacts are completely unknown. The significance of this problem became pervasive within the general public when Prince Charles authored an article in 2004 warning of the potential social, ethical, health, and environmental issues connected to nanotechnology. The EHS concerns, however, continued to receive relatively little consideration from federal agencies as compared with large investments in basicmore » nanoscience R&D. The mounting literature regarding the toxicology of ENMs (e.g., the ability of inhaled nanoparticles to cross the blood-brain barrier; Kwon et al., 2008, J. Occup. Health 50, 1) has spurred a recent realization within the NNI and other federal agencies that the EHS impacts related to nanotechnology must be addressed now. In our study we proposed to address critical aspects of this problem by developing primary correlations between nanoparticle properties and their effects on cell health and toxicity. A critical challenge embodied within this problem arises from the ability to synthesize nanoparticles with a wide array of physical properties (e.g., size, shape, composition, surface chemistry, etc.), which in turn creates an immense, multidimensional problem in assessing toxicological effects. In this work we first investigated varying sizes of quantum dots (Qdots) and their ability to cross cell membranes based on their aspect ratio utilizing hyperspectral confocal fluorescence microscopy. We then studied toxicity of epithelial cell lines that were exposed to different sized gold and silver nanoparticles using advanced imaging techniques, biochemical analyses, and optical and mass spectrometry methods. Finally we evaluated a new assay to measure transglutaminase (TG) activity; a potential marker for cell toxicity.« less

Cytotoxicity and oxidative stress induced by different metallic nanoparticles on human kidney cells

PubMed Central

2011-01-01

Background Some manufactured nanoparticles are metal-based and have a wide variety of applications in electronic, engineering and medicine. Until now, many studies have described the potential toxicity of NPs on pulmonary target, while little attention has been paid to kidney which is considered to be a secondary target organ. The objective of this study, on human renal culture cells, was to assess the toxicity profile of metallic nanoparticles (TiO2, ZnO and CdS) usable in industrial production. Comparative studies were conducted, to identify whether particle properties impact cytotoxicity by altering the intracellular oxidative status. Results Nanoparticles were first characterized by size, surface charge, dispersion and solubility. Cytotoxicity of NPs was then evaluated in IP15 (glomerular mesangial) and HK-2 (epithelial proximal) cell lines. ZnO and CdS NPs significantly increased the cell mortality, in a dose-dependent manner. Cytotoxic effects were correlated with the physicochemical properties of NPs tested and the cell type used. Analysis of reactive oxygen species and intracellular levels of reduced and oxidized glutathione revealed that particles induced stress according to their composition, size and solubility. Protein involved in oxidative stress such as NF-κb was activated with ZnO and CdS nanoparticles. Such effects were not observed with TiO2 nanoparticles. Conclusion On glomerular and tubular human renal cells, ZnO and CdS nanoparticles exerted cytotoxic effects that were correlated with metal composition, particle scale and metal solubility. ROS production and oxidative stress induction clearly indicated their nephrotoxic potential. PMID:21371295

Toxic behavior of silver and zinc oxide nanoparticles on environmental microorganisms.

PubMed

Dhas, Sindhu Priya; Shiny, Punalur John; Khan, Sudheer; Mukherjee, Amitava; Chandrasekaran, Natrajan

2014-09-01

Silver and zinc oxide nanoparticles (Ag and ZnO NPs) are widely used as antimicrobial agents. However, their potential toxicological impact on environmental microorganisms is largely unexplored. The aim of this work was to investigate the sensitivity and adaptability of five bacterial species isolated from sewage towards Ag and ZnO NPs. The bacterial species were exposed to increasing concentration of nanoparticles and the growth inhibitory effect, exopolysaccharides (EPSs) and extracellular proteins (ECPs) productions were determined. The involvement of surface charge in nanoparticles toxicity was also determined. The bacterial species were constantly exposed to nanoparticles to determine the adaptation behavior toward nanoparticles. The nanoparticles exhibited remarkable growth inhibitory effect on tested bacterial species. The toxicity of nanoparticles was found to be strongly dependent on surface charge effects. Though, these organisms are highly sensitive to Ag and ZnO NPs, the continuous exposure to these nanoparticles leads to moderate adaptation of bacterial species and the adapted bacterial species convert the highly toxic nano form to less toxic microform. Finally we predict that the continuing applications of nanoparticles in consumer products may lead to the development of nanoparticles resistant bacterial strains in future. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Non-toxic engineered carbon nanodiamond concentrations induce oxidative/nitrosative stress, imbalance of energy metabolism, and mitochondrial dysfunction in microglial and alveolar basal epithelial cells.

PubMed

Fresta, Claudia G; Chakraborty, Aishik; Wijesinghe, Manjula B; Amorini, Angela M; Lazzarino, Giacomo; Lazzarino, Giuseppe; Tavazzi, Barbara; Lunte, Susan M; Caraci, Filippo; Dhar, Prajnaparamita; Caruso, Giuseppe

2018-02-14

Engineered nanoparticles are finding a wide spectrum of biomedical applications, including drug delivery and capacity to trigger cytotoxic phenomena, potentially useful against tumor cells. The full understanding of their biosafety and interactions with cell processes is mandatory. Using microglial (BV-2) and alveolar basal epithelial (A549) cells, in this study we determined the effects of engineered carbon nanodiamonds (ECNs) on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) production, as well as on energy metabolism. Particularly, we initially measured decrease in cell viability as a function of increasing ECNs doses, finding similar cytotoxic ECN effects in the two cell lines. Subsequently, using apparently non-cytotoxic ECN concentrations (2 µg/mL causing decrease in cell number < 5%) we determined NO and ROS production, and measured the concentrations of compounds related to energy metabolism, mitochondrial functions, oxido-reductive reactions, and antioxidant defences. We found that in both cell lines non-cytotoxic ECN concentrations increased NO and ROS production with sustained oxidative/nitrosative stress, and caused energy metabolism imbalance (decrease in high energy phosphates and nicotinic coenzymes) and mitochondrial malfunctioning (decrease in ATP/ADP ratio).These results underline the importance to deeply investigate the molecular and biochemical changes occurring upon the interaction of ECNs (and nanoparticles in general) with living cells, even at apparently non-toxic concentration. Since the use of ECNs in biomedical field is attracting increasing attention the complete evaluation of their biosafety, toxicity and/or possible side effects both in vitro and in vivo is mandatory before these highly promising tools might find the correct application.

Protein Corona Modulates Uptake and Toxicity of Nanoceria via Clathrin-Mediated Endocytosis.

PubMed

Mazzolini, Julie; Weber, Ralf J M; Chen, Hsueh-Shih; Khan, Abdullah; Guggenheim, Emily; Shaw, Robert K; Chipman, James K; Viant, Mark R; Rappoport, Joshua Z

2016-08-01

Particles present in diesel exhaust have been proposed as a significant contributor to the development of acute and chronic lung diseases, including respiratory infection and allergic asthma. Nanoceria (CeO2 nanoparticles) are used to increase fuel efficiency in internal combustion engines, are present in exhaust fumes, and could affect cells of the airway. Components from the environment such as biologically derived proteins, carbohydrates, and lipids can form a dynamic layer, commonly referred to as the "protein corona" which alters cellular nanoparticle interactions and internalization. Using confocal reflectance microscopy, we quantified nanoceria uptake by lung-derived cells in the presence and absence of a serum-derived protein corona. Employing mass spectrometry, we identified components of the protein corona, and demonstrated that the interaction between transferrin in the protein corona and the transferrin receptor is involved in mediating the cellular entry of nanoceria via clathrin-mediated endocytosis. Furthermore, under these conditions nanoceria does not affect cell growth, viability, or metabolism, even at high concentration. Alternatively, despite the antioxidant capacity of nanoceria, in serum-free conditions these nanoparticles induce plasma membrane disruption and cause changes in cellular metabolism. Thus, our results identify a specific receptor-mediated mechanism for nanoceria entry, and provide significant insight into the potential for nanoparticle-dependent toxicity. © 2016 Marine Biological Laboratory.

Artefactual nanoparticle activation of the inflammasome platform: in vitro evidence with a nano-formed calcium phosphate

PubMed Central

Pele, Laetitia; Haas, Carolin T; Hewitt, Rachel; Faria, Nuno; Brown, Andy; Powell, Jonathan

2015-01-01

Aim To determine whether in vitro experimental conditions dictate cellular activation of the inflammasome by apatitic calcium phosphate nanoparticles. Material & methods The responses of blood-derived primary human cells to in situ-formed apatite were investigated under different experimental conditions to assess the effect of aseptic culture, cell rest and duration of particle exposure. Cell death and particle uptake were assessed, while IL-1β and caspase 1 responses, with and without lipopolysaccharide prestimulation, were evaluated as markers of inflammasome activation. Results Under carefully addressed experimental conditions, apatitic nanoparticles did not induce cell death or engage the inflammasome platform, although both could be triggered through artefacts of experimentation. Conclusion In vitro studies often predict that engineered nanoparticles, such as synthetic apatite, are candidates for inflammasome activation and, hence, are toxic. However, the experimental setting must be very carefully considered as it may promote false-positive outcomes. PMID:24991724

Vectorization by nanoparticles decreases the overall toxicity of airborne pollutants

PubMed Central

Maiz-Gregores, Helena; Nesslany, Fabrice; Betbeder, Didier

2017-01-01

Atmospheric pollution is mainly composed of volatile pollutants and particulate matter that strongly interact. However, their specific roles in the induction of cellular toxicity, in particular the impact of the vectorization of atmospheric pollutants by ultrafine particles, remains to be fully elucidated. For this purpose, non-toxic poly-lactic co-glycolic acid (PLGA) nanoparticles were synthesized and three pollutants (benzo(a)pyrene, naphthalene and di-ethyl-hexyl-phthalate) were adsorbed on the surface of the nanoparticles in order to evaluate the toxicity (cytotoxicity, genotoxicity and ROS induction) of these complexes to a human airway epithelial cell line. The adsorption of the pollutants onto the nanoparticles was confirmed by HPLC analysis. Interestingly, the cytotoxicity assays (MTT, LDH and CellTox Green) clearly demonstrated that the vectorization by nanoparticles decreases the toxicity of the adsorbed pollutants. Genotoxicity was assessed by the micronucleus test and the comet assay and showed no increase in primary DNA damage or in chromosomal aberrations of nanoparticle vectorized pollutants. Neither cytotoxicity nor genotoxicity was correlated with ROS induction. To conclude, our results indicate that the vectorization of pollutants by nanoparticles does not potentiate the toxicity of the pollutants studied and that, on the contrary, adsorption onto nanoparticles could protect cells against pollutants’ toxicity. PMID:28813539

Toxicity of Silver Nanoparticles at the Air-Liquid Interface

PubMed Central

Holder, Amara L.; Marr, Linsey C.

2013-01-01

Silver nanoparticles are one of the most prevalent nanomaterials in consumer products. Some of these products are likely to be aerosolized, making silver nanoparticles a high priority for inhalation toxicity assessment. To study the inhalation toxicity of silver nanoparticles, we have exposed cultured lung cells to them at the air-liquid interface. Cells were exposed to suspensions of silver or nickel oxide (positive control) nanoparticles at concentrations of 2.6, 6.6, and 13.2 μg cm−2 (volume concentrations of 10, 25, and 50 μg ml−1) and to 0.7 μg cm−2 silver or 2.1 μg cm−2 nickel oxide aerosol at the air-liquid interface. Unlike a number of in vitro studies employing suspensions of silver nanoparticles, which have shown strong toxic effects, both suspensions and aerosolized nanoparticles caused negligible cytotoxicity and only a mild inflammatory response, in agreement with animal exposures. Additionally, we have developed a novel method using a differential mobility analyzer to select aerosolized nanoparticles of a single diameter to assess the size-dependent toxicity of silver nanoparticles. PMID:23484109

Polymeric nanoparticles for targeted drug delivery system for cancer therapy.

PubMed

Masood, Farha

2016-03-01

A targeted delivery system based on the polymeric nanoparticles as a drug carrier represents a marvelous avenue for cancer therapy. The pivotal characteristics of this system include biodegradability, biocompatibility, non-toxicity, prolonged circulation and a wide payload spectrum of a therapeutic agent. Other outstanding features are their distinctive size and shape properties for tissue penetration via an active and passive targeting, specific cellular/subcellular trafficking pathways and facile control of cargo release by sophisticated material engineering. In this review, the current implications of encapsulation of anticancer agents within polyhydroxyalkanoates, poly-(lactic-co-glycolic acid) and cyclodextrin based nanoparticles to precisely target the tumor site, i.e., cell, tissue and organ are highlighted. Furthermore, the promising perspectives in this emerging field are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Biomimicry 3D gastrointestinal spheroid platform for the assessment of toxicity and inflammatory effects of zinc oxide nanoparticles.

PubMed

Chia, Sing Ling; Tay, Chor Yong; Setyawati, Magdiel I; Leong, David T

2015-02-11

Our current mechanistic understanding on the effects of engineered nanoparticles (NPs) on cellular physiology is derived mainly from 2D cell culture studies. However, conventional monolayer cell culture may not accurately model the mass transfer gradient that is expected in 3D tissue physiology and thus may lead to artifactual experimental conclusions. Herein, using a micropatterned agarose hydrogel platform, the effects of ZnO NPs (25 nm) on 3D colon cell spheroids of well-defined sizes are examined. The findings show that cell dimensionality plays a critical role in governing the spatiotemporal cellular outcomes like inflammatory response and cytotoxicity in response to ZnO NPs treatment. More importantly, ZnO NPs can induce different modes of cell death in 2D and 3D cell culture systems. Interestingly, the outer few layers of cells in 3D model could only protect the inner core of cells for a limited time and periodically slough off from the spheroids surface. These findings suggest that toxicological conclusions made from 2D cell models might overestimate the toxicity of ZnO NPs. This 3D cell spheroid model can serve as a reproducible platform to better reflect the actual cell response to NPs and to study a more realistic mechanism of nanoparticle-induced toxicity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An Investigative Study on the Effect of Silver Nanoparticles on E.Coli K12 in Various Sodium Chloride Concentrations

NASA Astrophysics Data System (ADS)

Levard, C.; Mitra, S.; Badireddy, A.; Jew, A. D.; Brown, G. E.

2011-12-01

Engineered nanomaterials have had an increasing presence in consumer products. Consequently, their release in wastewater systems is believed to pose a viable threat to the environment. NPs are used for drug delivery devices, imaging agents, and consumer products like sunscreens, paints, and cosmetics. Among the major types of manufactured nanoparticles, silver nanoparticles (Ag-NPs) are currently the most widely used in the nanotechnology industry. These particles have unique antibacterial, antiviral, and antifungal properties and as a result, there is a growing concern about the environmental impact of released Ag nanoparticles, particularly their unintended impact on organisms and ecosystems. Even though the toxicity of Ag-NPs has been extensively studied, the environmental transformations that the Ag-NPs may experience once released in the environment have not been considered. These transformations can readily impact their properties and therefore their behavior in terms of reactivity and toxicity. For example, it is known that silver strongly react with Chloride (Cl), which is ubiquitous in natural waters. At a low Cl/Ag ratio, Cl may precipitate on the surface and partly inhibit dissolution. On the contrary, for a high Cl/Ag ratio, chloride may enhance dissolution and therefore toxicity since soluble Ag species are a main source of toxicity. In this context, the focus of this study is on understanding the toxicity of coated Ag-NPs at various concentrations (1ppb-100ppm) on E.Coli (K12) in deionized water and various sodium chloride concentrations that mimic natural conditions (.5, .1 and .01 M NaCl). Ag+ ions (100 ppm-1ppb) were also tested in these salt concentrations as a control. Samples were inoculated in bacteria and incubated for 24 hours. Based on this test, we inferred that increasing concentrations of Ag+ ions/ AgNps played a role in the inhibition of growth of E.Coli K12. A live-dead staining test has shown the correlation between inhibition of growth and toxicity. No significant toxicity was noted until concentrations of 1-10 ppm for Ag+ and 10-100 ppm for AgNPs. In all NaCl concentrations, Ag+ is more toxic than for AgNPs. In addition, we noted that AgNPs in the .5 M of NaCl had the largest toxicity compared to the other salt concentrations and can be explained by the high Cl/Ag ratio. The concentrations for which toxicity has been observed are fewer orders of magnitude higher than the predicted Ag-NPs concentration released in natural waters in the next years.

Impact of solar UV radiation on toxicity of ZnO nanoparticles through photocatalytic reactive oxygen species (ROS) generation and photo-induced dissolution.

PubMed

Ma, Hongbo; Wallis, Lindsay K; Diamond, Steve; Li, Shibin; Canas-Carrell, Jaclyn; Parra, Amanda

2014-10-01

The present study investigated the impact of solar UV radiation on ZnO nanoparticle toxicity through photocatalytic ROS generation and photo-induced dissolution. Toxicity of ZnO nanoparticles to Daphnia magna was examined under laboratory light versus simulated solar UV radiation (SSR). Photocatalytic ROS generation and particle dissolution were measured on a time-course basis. Two toxicity mitigation assays using CaCl2 and N-acetylcysteine were performed to differentiate the relative importance of these two modes of action. Enhanced ZnO nanoparticle toxicity under SSR was in parallel with photocatalytic ROS generation and enhanced particle dissolution. Toxicity mitigation by CaCl2 to a less extent under SSR than under lab light demonstrates the role of ROS generation in ZnO toxicity. Toxicity mitigation by N-acetylcysteine under both irradiation conditions confirms the role of particle dissolution and ROS generation. These findings demonstrate the importance of considering environmental solar UV radiation when assessing ZnO nanoparticle toxicity and risk in aquatic systems. Copyright © 2014 Elsevier Ltd. All rights reserved.

Release, transport and toxicity of engineered nanoparticles.

PubMed

Soni, Deepika; Naoghare, Pravin K; Saravanadevi, Sivanesan; Pandey, Ram Avatar

2015-01-01

Recent developments in nanotechnology have facilitated the synthesis of novel engineered nanoparticles (ENPs) that possess new and different physicochemical properties. These ENPs have been ex tensive ly used in various commercial sectors to achieve both social and economic benefits. However. the increasing production and consumption of ENPs by many different industries has raised concerns about their possible release and accumulation in the environment. Released EN Ps may either remain suspended in the atmosphere for several years or may accumulate and eventually be modified int o other substances. Settled nanoparticles can he easily washed away during ra in s. and therefore may easily enter the food chain via water and so il. Thus. EN Ps can contaminate air. water and soil and can subsequently pose adverse risks to the health of different organisms. Studies to date indicate that ENP transport to and within the ecosystem depend on their chemical and physical properties (viz .. size. shape and solubility) . Therefore. the EN Ps display variable behavior in the environment because of their individual properties th at affect their tendency for adsorption, absorption, diffusional and colloidal interaction. The transport of EN Ps also influences their fate and chemical transformation in ecosystems. The adsorption, absorption and colloidal interaction of ENPs affect their capacity to be degraded or transformed, whereas the tendency of ENPs to agglomerate fosters their sedimentation. How widely ENPs are transported and their environmental fate influence how tox ic they may become to environmental organisms. One barrier to fully understanding how EN Ps are transformed in the environment and how best to characterize their toxicity, is related to the nature of their ultrafine structure. Experiments with different animals, pl ants, and cell lines have revealed that ENPs induce toxicity via several cellular pathways that is linked to the size. shape. surface area, agglomeration state. and sur face charge of the ENP involved. Future research is needed to elucidate the mechanisms by which nanoparticles act to induce their tox ic effects aft er they reach various ecosystems. Moreover. work is needed to develop a holistic approach for better understanding the effects that ENPs produce at the cellular and genetic level.

Photocatalytic effects of titanium dioxide nanoparticles on aquatic organisms-Current knowledge and suggestions for future research.

PubMed

Haynes, Vena N; Ward, J Evan; Russell, Brandon J; Agrios, Alexander G

2017-04-01

Nanoparticles are entering natural systems through product usage, industrial waste and post-consumer material degradation. As the production of nanoparticles is expected to increase in the next decade, so too are predicted environmental loads. Engineered metal-oxide nanomaterials, such as titanium dioxide, are known for their photocatalytic capabilities. When these nanoparticles are exposed to ultraviolet radiation in the environment, however, they can produce radicals that are harmful to aquatic organisms. There have been a number of studies that have reported the toxicity of titanium dioxide nanoparticles in the absence of light. An increasing number of studies are assessing the interactive effects of nanoparticles and ultraviolet light. However, most of these studies neglect environmentally-relevant experimental conditions. For example, researchers are using nanoparticle concentrations and light intensities that are too high for natural systems, and are ignoring water constituents that can alter the light field. The purpose of this review is to summarize the current knowledge of the photocatalytic effects of TiO 2 nanoparticles on aquatic organisms, discuss the limitations of these studies, and outline environmentally-relevant factors that need to be considered in future experiments. Copyright © 2017 Elsevier B.V. All rights reserved.

Surface and interfacial engineering of iron oxide nanoplates for highly efficient magnetic resonance angiography.

PubMed

Zhou, Zijian; Wu, Changqiang; Liu, Hanyu; Zhu, Xianglong; Zhao, Zhenghuan; Wang, Lirong; Xu, Ye; Ai, Hua; Gao, Jinhao

2015-03-24

Magnetic resonance angiography using gadolinium-based molecular contrast agents suffers from short diagnostic window, relatively low resolution and risk of toxicity. Taking into account the chemical exchange between metal centers and surrounding protons, magnetic nanoparticles with suitable surface and interfacial features may serve as alternative T1 contrast agents. Herein, we report the engineering on surface structure of iron oxide nanoplates to boost T1 contrast ability through synergistic effects between exposed metal-rich Fe3O4(100) facets and embedded Gd2O3 clusters. The nanoplates show prominent T1 contrast in a wide range of magnetic fields with an ultrahigh r1 value up to 61.5 mM(-1) s(-1). Moreover, engineering on nanobio interface through zwitterionic molecules adjusts the in vivo behaviors of nanoplates for highly efficient magnetic resonance angiography with steady-state acquisition window, superhigh resolution in vascular details, and low toxicity. This study provides a powerful tool for sophisticated design of MRI contrast agents for diverse use in bioimaging applications.

Toxicity of PEG-Coated CoFe2O4 Nanoparticles with Treatment Effect of Curcumin

NASA Astrophysics Data System (ADS)

Akhtar, Shahnaz; An, Wenzhen; Niu, Xiaoying; Li, Kang; Anwar, Shahzad; Maaz, Khan; Maqbool, Muhammad; Gao, Lan

2018-02-01

In this work, CoFe2O4 nanoparticles coated with polyethylene glycol (PEG) were successfully synthesized via a hydrothermal technique. Morphological studies of the samples confirmed the formation of polycrystalline pure-phase PEG-CoFe2O4 nanoparticles with sizes of about 24 nm. Toxicity induced by CoFe2O4 nanoparticles was investigated, and biological assays were performed to check the toxicity effects of CoFe2O4 nanoparticles. Moreover, the healing effect of toxicity induced in living organisms was studied using curcumin and it was found that biochemical indexes detoxified and improved to reach its normal level after curcumin administration. Thus, PEG-coated CoFe2O4 synthesized through a hydrothermal method can be utilized in biomedical applications and curcumin, which is a natural chemical with no side effects, can be used for the treatment of toxicity induced by the nanoparticles in living organisms.

Acute toxicity of nickel nanoparticles in rats after intravenous injection

PubMed Central

Magaye, Ruth R; Yue, Xia; Zou, Baobo; Shi, Hongbo; Yu, Hongsheng; Liu, Kui; Lin, Xialu; Xu, Jin; Yang, Cui; Wu, Aiguo; Zhao, Jinshun

2014-01-01

This study was carried out to add scientific data in regard to the use of metallic nanoparticles in nanomedicine. The acute toxicity of nickel (Ni) nanoparticles (50 nm), intravenously injected through the dorsal penile vein of Sprague Dawley rats was evaluated in this study. Fourteen days after injection, Ni nanoparticles induced liver and spleen injury, lung inflammation, and caused cardiac toxicity. These results indicate that precautionary measures should be taken with regard to the use of Ni nanoparticles or Ni compounds in nanomedicine. PMID:24648736

Carbon Nanotubes and Other Engineered Nanoparticles Induced Pathophysiology on Mesothelial Cells and Mesothelial Membranes

PubMed Central

Sinis, Sotirios I.; Hatzoglou, Chrissi; Gourgoulianis, Konstantinos I.; Zarogiannis, Sotirios G.

2018-01-01

Nanoparticles have great potential for numerous applications due to their unique physicochemical properties. However, concerns have been raised that they may induce deleterious effects on biological systems. There is accumulating evidence that, like asbestos, inhaled nanomaterials of >5 μm and high aspect ratio (3:1), particularly rod-like carbon nanotubes, may inflict pleural disease including mesothelioma. Additionally, a recent set of case reports suggests that inhalation of polyacrylate/nanosilica could in part be associated with inflammation and fibrosis of the pleura of factory workers. However, the adverse outcomes of nanoparticle exposure to mesothelial tissues are still largely unexplored. In that context, the present review aims to provide an overview of the relevant pathophysiological implications involving toxicological studies describing effects of engineered nanoparticles on mesothelial cells and membranes. In vitro studies primarily emphasize on simulating cellular uptake and toxicity of nanotubes on benign or malignant cell lines. On the other hand, in vivo studies focus on illustrating endpoints of serosal pathology in rodent animal models. From a molecular aspect, some nanoparticle categories are shown to be cytotoxic and genotoxic after acute treatment, whereas chronic incubation may lead to malignant-like transformation. At an organism level, a number of fibrous shaped nanotubes are related with features of chronic inflammation and MWCNT-7 is the only type to consistently inflict mesothelioma. PMID:29651248

Toxicity of polymeric nanoparticles in vivo and in vitro

NASA Astrophysics Data System (ADS)

Voigt, Nadine; Henrich-Noack, Petra; Kockentiedt, Sarah; Hintz, Werner; Tomas, Jürgen; Sabel, Bernhard A.

2014-06-01

Polybutylcyanoacrylate nanoparticles (PBCA NPs) are candidates for a drug delivery system, which can cross the blood-brain barrier (BBB). Because little is known about their toxicity, we exposed cells to PBCA NPs in vitro and in vivo and monitored their life and death assays. PBCA NPs were fabricated with different surfactants according to the mini-emulsion technique. Viabilities of HeLa and HEK293 cells after NP incubation were quantified by analysing cellular metabolic activity (MTT-test). We then repetitively injected i.v. rhodamine-labelled PBCA NP variations into rats and monitored the survival and morphology of retrogradely labelled neurons by in vivo confocal neuroimaging (ICON) for five weeks. To test for carrier-efficacy and safety, PBCA NPs loaded with Kyotorphin were injected in rats, and a hot plate test was used to quantify analgesic effects. In vitro, we found dose-dependent cell death which was, however, only detectable at very high doses and mainly seen in the cultures incubated with NPs fabricated with the tensids SDS and Tween. However, the in vivo experiments did not show any NP-induced neuronal death, even with particles which were toxic at high dose in vitro, i.e. NPs with Tween and SDS. The increased pain threshold at the hot plate test demonstrated that PBCA NPs are able to cross the BBB and thus comprise a useful tool for drug delivery into the central nervous system (CNS). Our findings showing that different nanoparticle formulations are non-toxic have important implications for the value of NP engineering approaches in medicine.

Toxicity of fungal-generated silver nanoparticles to soil-inhabiting Pseudomonas putida KT2440, a rhizospheric bacterium responsible for plant protection and bioremediation.

PubMed

Gupta, Indarchand R; Anderson, Anne J; Rai, Mahendra

2015-04-09

Silver nanoparticles have attracted considerable attention due to their beneficial properties. But toxicity issues associated with them are also rising. The reports in the past suggested health hazards of silver nanoparticles at the cellular, molecular, or whole organismal level in eukaryotes. Whereas, there is also need to examine the exposure effects of silver nanoparticle to the microbes, which are beneficial to humans as well as environment. The available literature suggests the harmful effects of physically and chemically synthesised silver nanoparticles. The toxicity of biogenically synthesized nanoparticles has been less studied than physically and chemically synthesised nanoparticles. Hence, there is a greater need to study the toxic effects of biologically synthesised silver nanoparticles in general and mycosynthesized nanoparticles in particular. In the present study, attempts have been made to assess the risk associated with the exposure of mycosynthesized silver nanoparticles on a beneficial soil microbe Pseudomonas putida. KT2440. The study demonstrates mycosynthesis of silver nanoparticles and their characterisation by UV-vis spectrophotometry, FTIR, X-ray diffraction, nanosight LM20--a particle size distribution analyzer and TEM. Silver nanoparticles obtained herein were found to exert the hazardous effect at the concentration of 0.4 μg/ml, which warrants further detailed investigations concerning toxicity. Copyright © 2014 Elsevier B.V. All rights reserved.

Toxicity testing of four silver nanoparticle-coated dental castings in 3-D LO2 cell cultures.

PubMed

Zhao, Yi-Ying; Chu, Qiang; Shi, Xu-Er; Zheng, Xiao-Dong; Shen, Xiao-Ting; Zhang, Yan-Zhen

To address the controversial issue of the toxicity of dental alloys and silver nanoparticles in medical applications, an in vivo-like LO2 3-D model was constructed within polyvinylidene fluoride hollow fiber materials to mimic the microenvironment of liver tissue. The use of microscopy methods and the measurement of liver-specific functions optimized the model for best cell performances and also proved the superiority of the 3-D LO2 model when compared with the traditional monolayer model. Toxicity tests were conducted using the newly constructed model, finding that four dental castings coated with silver nanoparticles were toxic to human hepatocytes after cell viability assays. In general, the toxicity of both the castings and the coated silver nanoparticles aggravated as time increased, yet the nanoparticles attenuated the general toxicity by preventing metal ion release, especially at high concentrations.

Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, Wan-Seob; Cho, Minjung; Jeong, Jinyoung

2009-04-01

In general, gold nanoparticles are recognized as being as nontoxic. Still, there have been some reports on their toxicity, which has been shown to depend on the physical dimension, surface chemistry, and shape of the nanoparticles. In this study, we carry out an in vivo toxicity study using 13 nm-sized gold nanoparticles coated with PEG (MW 5000). In our findings the 13 nm sized PEG-coated gold nanoparticles were seen to induce acute inflammation and apoptosis in the liver. These nanoparticles were found to accumulate in the liver and spleen for up to 7 days after injection and to have longmore » blood circulation times. In addition, transmission electron microscopy showed that numerous cytoplasmic vesicles and lysosomes of liver Kupffer cells and spleen macrophages contained the PEG-coated gold nanoparticles. These findings of toxicity and kinetics of PEG-coated gold nanoparticles may have important clinical implications regarding the safety issue as PEG-coated gold nanoparticles are widely used in biomedical applications.« less

Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine.

PubMed

das Neves, José; Michiels, Johan; Ariën, Kevin K; Vanham, Guido; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

2012-06-01

To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(ε-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine. Dapivirine-loaded nanoparticles with different surface properties were produced using three surface modifiers: poloxamer 338 NF (PEO), sodium lauryl sulfate (SLS) and cetyl trimethylammonium bromide (CTAB). The ability of nanoparticles to promote intracellular drug delivery was assessed in different cell types relevant for vaginal HIV transmission/microbicide development. Also, antiretroviral activity of nanoparticles was determined in different cell models, as well as their cytotoxicity. Dapivirine-loaded nanoparticles were readily taken up by different cells, with particular kinetics depending on the cell type and nanoparticles, resulting in enhanced intracellular drug delivery in phagocytic cells. Different nanoparticles showed similar or improved antiviral activity compared to free drug. There was a correlation between increased antiviral activity and increased intracellular drug delivery, particularly when cell models were submitted to a single initial short-course treatment. PEO-PCL and SLS-PCL nanoparticles consistently showed higher selectivity index values than free drug, contrasting with high cytotoxicity of CTAB-PCL. These results provide evidence on the potential of PCL nanoparticles to affect in vitro toxicity and activity of dapivirine, depending on surface engineering. Thus, this formulation approach may be a promising strategy for the development of next generation microbicides.

Dependence of Nanoparticle Toxicity on Their Physical and Chemical Properties

NASA Astrophysics Data System (ADS)

Sukhanova, Alyona; Bozrova, Svetlana; Sokolov, Pavel; Berestovoy, Mikhail; Karaulov, Alexander; Nabiev, Igor

2018-02-01

Studies on the methods of nanoparticle (NP) synthesis, analysis of their characteristics, and exploration of new fields of their applications are at the forefront of modern nanotechnology. The possibility of engineering water-soluble NPs has paved the way to their use in various basic and applied biomedical researches. At present, NPs are used in diagnosis for imaging of numerous molecular markers of genetic and autoimmune diseases, malignant tumors, and many other disorders. NPs are also used for targeted delivery of drugs to tissues and organs, with controllable parameters of drug release and accumulation. In addition, there are examples of the use of NPs as active components, e.g., photosensitizers in photodynamic therapy and in hyperthermic tumor destruction through NP incorporation and heating. However, a high toxicity of NPs for living organisms is a strong limiting factor that hinders their use in vivo. Current studies on toxic effects of NPs aimed at identifying the targets and mechanisms of their harmful effects are carried out in cell culture models; studies on the patterns of NP transport, accumulation, degradation, and elimination, in animal models. This review systematizes and summarizes available data on how the mechanisms of NP toxicity for living systems are related to their physical and chemical properties.

Zinc oxide and silver nanoparticles toxicity in the baker's yeast, Saccharomyces cerevisiae.

PubMed

Galván Márquez, Imelda; Ghiyasvand, Mergan; Massarsky, Andrey; Babu, Mohan; Samanfar, Bahram; Omidi, Katayoun; Moon, Thomas W; Smith, Myron L; Golshani, Ashkan

2018-01-01

Engineered nanomaterials (ENMs) are increasingly incorporated into a variety of commercial applications and consumer products; however, ENMs may possess cytotoxic properties due to their small size. This study assessed the effects of two commonly used ENMs, zinc oxide nanoparticles (ZnONPs) and silver nanoparticles (AgNPs), in the model eukaryote Saccharomyces cerevisiae. A collection of ≈4600 S. cerevisiae deletion mutant strains was used to deduce the genes, whose absence makes S. cerevisiae more prone to the cytotoxic effects of ZnONPs or AgNPs. We demonstrate that S. cerevisiae strains that lack genes involved in transmembrane and membrane transport, cellular ion homeostasis, and cell wall organization or biogenesis exhibited the highest sensitivity to ZnONPs. In contrast, strains that lack genes involved in transcription and RNA processing, cellular respiration, and endocytosis and vesicular transport exhibited the highest sensitivity to AgNPs. Secondary assays confirmed that ZnONPs affected cell wall function and integrity, whereas AgNPs exposure decreased transcription, reduced endocytosis, and led to a dysfunctional electron transport system. This study supports the use of S. cerevisiae Gene Deletion Array as an effective high-throughput technique to determine cellular targets of ENM toxicity.

Nanoparticles Made From Xyloglucan-Block-Polycaprolactone Copolymers: Safety Assessment for Drug Delivery.

PubMed

Mazzarino, Letícia; Loch-Neckel, Gecioni; Dos Santos Bubniak, Lorena; Ourique, Fabiana; Otsuka, Issei; Halila, Sami; Curi Pedrosa, Rozangela; Santos-Silva, Maria Cláudia; Lemos-Senna, Elenara; Curti Muniz, Edvani; Borsali, Redouane

2015-09-01

Xyloglucan-block-polycaprolactone (XGO-PCL) copolymer nanoparticles have been proposed as nanocarriers for drug delivery. However, the possible harmful effects of exposure to nanoparticles still remain a concern. Therefore, the aim of this study is to evaluate the potential toxicity of XGO-PCL nanoparticles using in vitro and in vivo assays. Cytotoxicity and genotoxicity studies were conducted on MRC-5 human fetal lung fibroblast cells upon exposure to XGO-PCL nanoparticles. No significant reduction in the cell viability and no DNA damage were observed at the different concentrations tested. Erythrocyte toxicity was assessed by the incubation of nanoparticles with human blood. XGO-PCL nanoparticles induced a hemolytic ratio of less than 1%, indicating good blood compatibility. Finally, the subacute toxicity of XGO-PCL nanoparticles (10 mg/kg/day) was evaluated in BALB/c mice when administered orally or intraperitoneally for 14 days. Results of the in vivo toxicity study showed no clinical signs of toxicity, mortality, weight loss, or hematological and biochemical alterations after treatment with nanoparticles. Also, microscopic analysis of the major organs revealed no histopathological abnormalities, corroborating the previous results. Thus, it can be concluded that XGO-PCL nanoparticles induced no effect indicative of toxicity, indicating their potential use as drug delivery systems. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thrall, Brian D.; Minard, Kevin R.; Teeguarden, Justin G.

A Cooperative Research and Development Agreement (CRADA) was sponsored by Battelle Memorial Institute (Battelle, Columbus), to initiate a collaborative research program across multiple Department of Energy (DOE) National Laboratories aimed at developing a suite of new capabilities for predictive toxicology. Predicting the potential toxicity of emerging classes of engineered nanomaterials was chosen as one of two focusing problems for this program. PNNL’s focus toward this broader goal was to refine and apply experimental and computational tools needed to provide quantitative understanding of nanoparticle dosimetry for in vitro cell culture systems, which is necessary for comparative risk estimates for different nanomaterialsmore » or biological systems. Research conducted using lung epithelial and macrophage cell models successfully adapted magnetic particle detection and fluorescent microscopy technologies to quantify uptake of various forms of engineered nanoparticles, and provided experimental constraints and test datasets for benchmark comparison against results obtained using an in vitro computational dosimetry model, termed the ISSD model. The experimental and computational approaches developed were used to demonstrate how cell dosimetry is applied to aid in interpretation of genomic studies of nanoparticle-mediated biological responses in model cell culture systems. The combined experimental and theoretical approach provides a highly quantitative framework for evaluating relationships between biocompatibility of nanoparticles and their physical form in a controlled manner.« less

Engineering biofunctional magnetic nanoparticles for biotechnological applications

NASA Astrophysics Data System (ADS)

Moros, Maria; Pelaz, Beatriz; López-Larrubia, Pilar; García-Martin, Maria L.; Grazú, Valeria; de La Fuente, Jesus M.

2010-09-01

Synthesis and characterization of magnetic nanoparticles with excellent size control are showed here. Their functionalization using an amphiphilic polymer is also described. This strategy allows the stabilization of magnetic nanoparticles in aqueous solvents and in addition, the polymer shell serves as a platform to incorporate relevant biomolecules, such as poly(ethylene glycol) and a number of carbohydrates. Nanoparticles functionalized with carbohydrates show the ability to avoid unspecific interactions between proteins present in the working medium and the nanoparticles, so can be used as an alternative to poly(ethylene glycol) molecules. Results confirm these nanoparticles as excellent contrast agents for magnetic resonance imaging. Changes in the spin-spin transversal relaxation times of the surrounding water protons due to nanoparticle aggregation demonstrates the bioactivity of these nanoparticles functionalized with carbohydrates. To finish with, nanoparticle toxicity is evaluated by means of MTT assay. The obtained results clearly indicate that these nanoparticles are excellent candidates for their further application in nanomedicine or nanobiotechnology.Synthesis and characterization of magnetic nanoparticles with excellent size control are showed here. Their functionalization using an amphiphilic polymer is also described. This strategy allows the stabilization of magnetic nanoparticles in aqueous solvents and in addition, the polymer shell serves as a platform to incorporate relevant biomolecules, such as poly(ethylene glycol) and a number of carbohydrates. Nanoparticles functionalized with carbohydrates show the ability to avoid unspecific interactions between proteins present in the working medium and the nanoparticles, so can be used as an alternative to poly(ethylene glycol) molecules. Results confirm these nanoparticles as excellent contrast agents for magnetic resonance imaging. Changes in the spin-spin transversal relaxation times of the surrounding water protons due to nanoparticle aggregation demonstrates the bioactivity of these nanoparticles functionalized with carbohydrates. To finish with, nanoparticle toxicity is evaluated by means of MTT assay. The obtained results clearly indicate that these nanoparticles are excellent candidates for their further application in nanomedicine or nanobiotechnology. Electronic supplementary information (ESI) available: Chemical, physical and magnetic characterization; R2 maps; stability of NPs at different conditions; size of glucose NPs in the presence of Concanavalin A; MTT assays of the samples are shown in figures S1-S10. Table S1 represents the hydrodynamic size of PMAO NPs after being washed with different solvents. See DOI: 10.1039/c0nr00104j

Impact of solar UV radiation on toxicity of ZnO nanoparticles through photocatalytic reactive oxygen species (ROS) generation and photo-induced dissolution

EPA Science Inventory

The present study investigated the impact of solar UV radiation on ZnO nanoparticle toxicity through photocatalytic ROS generation and photo-induced dissolution. Toxicity of ZnO nanoparticles to Daphnia magna was examined under laboratory light versus simulated solar UV radiatio...

Effects from Filtration, Capping Agents, and Presence/Absence of Food on the Toxicity of Silver Nanoparticles to Daphnia Magna

EPA Science Inventory

Relatively little is known regarding the behavior and toxicity of nanoparticles in the environment. The objectives of the work presented here include establishing the toxicity of a variety of silver nanoparticles (AgNPs) to Daphnia magna neonates, assessing the applicability of ...

A general mechanism for intracellular toxicity of metal-containing nanoparticles

NASA Astrophysics Data System (ADS)

Sabella, Stefania; Carney, Randy P.; Brunetti, Virgilio; Malvindi, Maria Ada; Al-Juffali, Noura; Vecchio, Giuseppe; Janes, Sam M.; Bakr, Osman M.; Cingolani, Roberto; Stellacci, Francesco; Pompa, Pier Paolo

2014-05-01

The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment - where particles are abundantly internalized - is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a ``lysosome-enhanced Trojan horse effect'' since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments.The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment - where particles are abundantly internalized - is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a ``lysosome-enhanced Trojan horse effect'' since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01234h

A review on plants extract mediated synthesis of silver nanoparticles for antimicrobial applications: A green expertise

PubMed Central

Ahmed, Shakeel; Ahmad, Mudasir; Swami, Babu Lal; Ikram, Saiqa

2015-01-01

Metallic nanoparticles are being utilized in every phase of science along with engineering including medical fields and are still charming the scientists to explore new dimensions for their respective worth which is generally attributed to their corresponding small sizes. The up-and-coming researches have proven their antimicrobial significance. Among several noble metal nanoparticles, silver nanoparticles have attained a special focus. Conventionally silver nanoparticles are synthesized by chemical method using chemicals as reducing agents which later on become accountable for various biological risks due to their general toxicity; engendering the serious concern to develop environment friendly processes. Thus, to solve the objective; biological approaches are coming up to fill the void; for instance green syntheses using biological molecules derived from plant sources in the form of extracts exhibiting superiority over chemical and/or biological methods. These plant based biological molecules undergo highly controlled assembly for making them suitable for the metal nanoparticle syntheses. The present review explores the huge plant diversity to be utilized towards rapid and single step protocol preparatory method with green principles over the conventional ones and describes the antimicrobial activities of silver nanoparticles. PMID:26843966

Review of health safety aspects of nanotechnologies in food production.

PubMed

Bouwmeester, Hans; Dekkers, Susan; Noordam, Maryvon Y; Hagens, Werner I; Bulder, Astrid S; de Heer, Cees; ten Voorde, Sandra E C G; Wijnhoven, Susan W P; Marvin, Hans J P; Sips, Adriënne J A M

2009-02-01

Due to new, previously unknown, properties attributed to engineered nanoparticles many new products are introduced in the agro-food area. Nanotechnologies cover many aspects, such as disease treatment, food security, new materials for pathogen detection, packaging materials and delivery systems. As with most new and evolving technologies, potential benefits are emphasized, while little is known on safety of the application of nanotechnologies in the agro-food sector. This review gives an overview of scientific issues that need to be addressed with priority in order to improve the risk assessment for nanoparticles in food. The following research topics are considered to contribute pivotally to risk assessment of nanotechnologies and nanoparticles in food products. Set a definition for NPs to facilitate regulatory discussions, prioritization of research and exchange of study results. Develop analytical tools for the characterization of nanoparticles in complex biological matrices like food. Establish relevant dose metrics for nanoparticles used for both interpretation of scientific studies as well as regulatory frameworks. Search for deviant behavior (kinetics) and novel effects (toxicity) of nanoparticles and assess the validity of currently used test systems following oral exposure. Estimate the consumer exposure to nanoparticles.

An improved methodology of asymmetric flow field flow fractionation hyphenated with inductively coupled mass spectrometry for the determination of size distribution of gold nanoparticles in dietary supplements.

PubMed

Mudalige, Thilak K; Qu, Haiou; Linder, Sean W

2015-11-13

Engineered nanoparticles are available in large numbers of commercial products claiming various health benefits. Nanoparticle absorption, distribution, metabolism, excretion, and toxicity in a biological system are dependent on particle size, thus the determination of size and size distribution is essential for full characterization. Number based average size and size distribution is a major parameter for full characterization of the nanoparticle. In the case of polydispersed samples, large numbers of particles are needed to obtain accurate size distribution data. Herein, we report a rapid methodology, demonstrating improved nanoparticle recovery and excellent size resolution, for the characterization of gold nanoparticles in dietary supplements using asymmetric flow field flow fractionation coupled with visible absorption spectrometry and inductively coupled plasma mass spectrometry. A linear relationship between gold nanoparticle size and retention times was observed, and used for characterization of unknown samples. The particle size results from unknown samples were compared to results from traditional size analysis by transmission electron microscopy, and found to have less than a 5% deviation in size for unknown product over the size range from 7 to 30 nm. Published by Elsevier B.V.

Development of a biopolymer nanoparticle-based method of oral toxicity testing in aquatic invertebrates.

PubMed

Gott, Ryan C; Luo, Yangchao; Wang, Qin; Lamp, William O

2014-06-01

Aquatic toxicity testing generally focuses on the water absorption/dermal route of exposure to potential toxic chemicals, while much less work has been done on the oral route of exposure. This is due in part to the difficulties of applying traditional oral toxicity testing to aquatic environments, including the tendency for test chemicals to dissolve into water. The use of biopolymer nanoparticles to encapsulate test chemicals onto food to prevent dissolution is one solution presented herein. The biopolymers zein and chitosan were explored for their previously known nanoparticle-forming abilities. Nanoparticles containing the test chemical rhodamine B were formed, applied as films to coat food, and then fed to the test organism, the freshwater amphipod Hyalella azteca. In feeding trials both zein and chitosan nanoparticles showed a significantly lower release rate of rhodamine B into water than food dyed with rhodamine B without biopolymer nanoparticles. Zein nanoparticles also showed better retention ability than chitosan nanoparticles. Both kinds of nanoparticles showed no significant effect on the survival, growth, or feeding behavior of H. azteca. Thus these biopolymers may be an effective system to encapsulate and deliver chemicals to aquatic invertebrates without interfering with common toxicity assessment endpoints like survival and growth. Copyright © 2014 Elsevier Inc. All rights reserved.

Guidelines for safe handling, use and disposal of nanoparticles

NASA Astrophysics Data System (ADS)

Amoabediny, G. H.; Naderi, A.; Malakootikhah, J.; Koohi, M. K.; Mortazavi, S. A.; Naderi, M.; Rashedi, H.

2009-05-01

Health, safety and environmental (HSE) risks of a technology is an inseparable part of it which threatens all exposed employees. It has been proved for many years that exposure to particles, in an occupational setting, could be linked with the onset of lung diseases, such as pneumoconiosis, chronic obstructive pulmonary disease (COPD), and mesotelioma and lung cancer. Nanoparticles, due to their unique characteristics including; small size, shape, high surface area, charge, chemical properties, solubility, and degree of agglomeration can cross cell boundaries or pass directly from the lungs into the blood stream and ultimately reach to all of the organs in the body. This is the reason why they may pose higher risk than the same mass and material of larger particles. Moreover, biodegradation of nanoparticles by some kinds of fungi (like wood decay fungi) may result in metabolites which may be toxic to microorganisms under aerobic and anaerobic conditions. Bacteria and living cells can take up nanoparticles, providing the basis for potential bioaccumulation in the food chain. Considering Iran's prominent position in nanotechnologies and fast-growing in research and industrial activities, controlling nanoparticles related HSE risks should be highly considered. In general, there are three main approaches to risk and exposure control: engineering techniques, administrative means and personal protective equipments. These complementary approaches especially engineering techniques should be considered starting with the design stage of an industrial process. Administrative means of control constitute an additional approach when the other methods have not achieved the expected control levels. Administrative means of control must never substitute for engineering techniques, which always be performed according to standard practices. In some situations, due to insufficiently advanced technology and prohibitive costs, engineering measerus can not be implemended. In these situations, performing administrative means of control constitute other ways of limiaiting the occupational exposure risks. Accordingly, to minimize the risks from know and unknown health, safety and invironment hazards in research and occupational setting of the country, guideline for safe handling, use and disposal of manopractical has provided.

From basic physics to mechanisms of toxicity: the "liquid drop" approach applied to develop predictive classification models for toxicity of metal oxide nanoparticles.

PubMed

Sizochenko, Natalia; Rasulev, Bakhtiyor; Gajewicz, Agnieszka; Kuz'min, Victor; Puzyn, Tomasz; Leszczynski, Jerzy

2014-11-21

Many metal oxide nanoparticles are able to cause persistent stress to live organisms, including humans, when discharged to the environment. To understand the mechanism of metal oxide nanoparticles' toxicity and reduce the number of experiments, the development of predictive toxicity models is important. In this study, performed on a series of nanoparticles, the comparative quantitative-structure activity relationship (nano-QSAR) analyses of their toxicity towards E. coli and HaCaT cells were established. A new approach for representation of nanoparticles' structure is presented. For description of the supramolecular structure of nanoparticles the "liquid drop" model was applied. It is expected that a novel, proposed approach could be of general use for predictions related to nanomaterials. In addition, in our study fragmental simplex descriptors and several ligand-metal binding characteristics were calculated. The developed nano-QSAR models were validated and reliably predict the toxicity of all studied metal oxide nanoparticles. Based on the comparative analysis of contributed properties in both models the LDM-based descriptors were revealed to have an almost similar level of contribution to toxicity in both cases, while other parameters (van der Waals interactions, electronegativity and metal-ligand binding characteristics) have unequal contribution levels. In addition, the models developed here suggest different mechanisms of nanotoxicity for these two types of cells.

Ocean acidification increases the toxic effects of TiO2 nanoparticles on the marine microalga Chlorella vulgaris.

PubMed

Xia, Bin; Sui, Qi; Sun, Xuemei; Han, Qian; Chen, Bijuan; Zhu, Lin; Qu, Keming

2018-03-15

Concerns about the environmental effects of engineered nanoparticles (NPs) on marine ecosystems are increasing. Meanwhile, ocean acidification (OA) has become a global environmental problem. However, the combined effects of NPs and OA on marine organisms are still not well understood. In this study, we investigated the effects of OA (pH values of 7.77 and 7.47) on the bioavailability and toxicity of TiO 2 NPs to the marine microalga Chlorella vulgaris. The results showed that OA enhanced the growth inhibition of algal cells caused by TiO 2 NPs. We observed synergistic interactive effects of pH and TiO 2 NPs on oxidative stress, indicating that OA significantly increased the oxidative damage of TiO 2 NPs on the algal cells. Importantly, the elevated toxicity of TiO 2 NPs associated with OA could be explained by the enhanced internalization of NPs in algal cells, which was attributed to the slighter aggregation and more suspended particles in acidified seawater. Overall, these findings provide useful information on marine environmental risk assessments of NPs under near future OA conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessing protein oxidation by inorganic nanoparticles with enzyme-linked immunosorbent assay (ELISA).

PubMed

Sun, Wenjie; Luna-Velasco, Antonia; Sierra-Alvarez, Reyes; Field, Jim A

2013-03-01

Growth in the nanotechnology industry is leading to increased production of engineered nanoparticles (NPs). This has given rise to concerns about the potential adverse and toxic effects to biological system and the environment. An important mechanism of NP toxicity is oxidative stress caused by the formation of reactive oxygen species (ROS) or via direct oxidation of biomolecules. In this study, a protein oxidation assay was developed as an indicator of biomolecule oxidation by NPs. The oxidation of the protein, bovine serum albumin (BSA) was evaluated with an enzyme-linked immunosorbent assay (ELISA) to measure the protein carbonyl derivatives formed from protein oxidation. The results showed that some NPs such as Cu(0), CuO, Mn(2)O(3), and Fe(0) caused oxidation of BSA; whereas, many of the other NPs tested were not reactive or very slowly reactive with BSA. The mechanisms involved in the oxidation of BSA protein by the reactive NPs could be attributed to the combined effects of ROS-dependent and direct protein oxidation mechanisms. The ELISA assay is a promising method for the assessment of protein oxidation by NPs, which can provide insights on NP toxicity mechanisms. Copyright © 2012 Wiley Periodicals, Inc.

Toward toxicity testing of nanomaterials in the 21st century: a paradigm for moving forward.

PubMed

Lai, David Y

2012-01-01

A challenge-facing hazard identification and safety evaluation of engineered nanomaterials being introduced to market is the diversity and complexity of the types of materials with varying physicochemical properties, many of which can affect their toxicity by different mechanisms. In general, in vitro test systems have limited usefulness for hazard identification of nanoparticles due to various issues. Meanwhile, conducting chronic toxicity/carcinogenicity studies in rodents for every new nanomaterial introduced into the commerce is impractical if not impossible. New toxicity testing systems which rely on predictive, high-throughput technologies may be the ultimate goal of evaluating the potential hazard of nanomaterials. However, at present, this approach alone is unlikely to succeed in evaluating the toxicity of the wide array of nanomaterials and requires validation from in vivo studies. This article proposes a paradigm for toxicity testing and elucidation of the molecular mechanisms of reference materials for specific nanomaterial classes/subclasses using short-term in vivo animal studies in conjunction with high-throughput screenings and mechanism-based short-term in vitro assays. The hazard potential of a particular nanomaterial can be evaluated by conducting only in vitro high-throughput assays and mechanistic studies and comparing the data with those of the reference materials in the specific class/subclass-an approach in line with the vision for 'Toxicity Testing in the 21st Century' of chemicals. With well-designed experiments, testing nanomaterials of varying/selected physicochemical parameters may be able to identify the physicochemical parameters contributing to toxicity. The data so derived could be used for the development of computer model systems to predict the hazard potential of specific nanoparticles based on property-activity relationships. Copyright © 2011 John Wiley & Sons, Inc.

Functional surface engineering of C-dots for fluorescent biosensing and in vivo bioimaging.

PubMed

Ding, Changqin; Zhu, Anwei; Tian, Yang

2014-01-21

Nanoparticles are promising scaffolds for applications such as imaging, chemical sensors and biosensors, diagnostics, drug delivery, catalysis, energy, photonics, medicine, and more. Surface functionalization of nanoparticles introduces an additional dimension in controlling nanoparticle interfacial properties and provides an effective bridge to connect nanoparticles to biological systems. With fascinating photoluminescence properties, carbon dots (C-dots), carbon-containing nanoparticles that are attracting considerable attention as a new type of quantum dot, are becoming both an important class of imaging probes and a versatile platform for engineering multifunctional nanosensors. In order to transfer C-dots from proof-of-concept studies toward real world applications such as in vivo bioimaging and biosensing, careful design and engineering of C-dot probes is becoming increasingly important. A comprehensive knowledge of how C-dot surfaces with various properties behave is essential for engineering C-dots with useful imaging properties such as high quantum yield, stability, and low toxicity, and with desirable biosensing properties such as high selectivity, sensitivity, and accuracy. Several reviews in recent years have reported preparation methods and properties of C-dots and described their application in biosensors, catalysis, photovoltatic cells, and more. However, no one has yet systematically summarized the surface engineering of C-dots, nor the use of C-dots as fluorescent nanosensors or probes for in vivo imaging in cells, tissues, and living organisms. In this Account, we discuss the major design principles and criteria for engineering the surface functionality of C-dots for biological applications. These criteria include brightness, long-term stability, and good biocompatibility. We review recent developments in designing C-dot surfaces with various functionalities for use as nanosensors or as fluorescent probes with fascinating analytical performance, and we emphasize applications in bioimaging and biosensing in live cells, tissues, and animals. In addition, we highlight our work on the design and synthesis of a C-dot ratiometric biosensor for intracellular Cu(2+) detection, and a twophoton fluorescent probe for pH measurement in live cells and tissues. We conclude this Account by outlining future directions in engineering the functional surface of C-dots for a variety of in vivo imaging applications, including dots with combined targeting, imaging and therapeutic-delivery capabilities, or high-resolution multiplexed vascular imaging. With each application C-dots should open new horizons of multiplexed quantitative detection, high-resolution fluorescence imaging, and long-term, real-time monitoring of their target.

Toxicity of zero-valent iron nanoparticles to a trichloroethylene-degrading groundwater microbial community.

PubMed

Zabetakis, Kara M; Niño de Guzmán, Gabriela T; Torrents, Alba; Yarwood, Stephanie

2015-01-01

The microbiological impact of zero-valent iron used in the remediation of groundwater was investigated by exposing a trichloroethylene-degrading anaerobic microbial community to two types of iron nanoparticles. Changes in total bacterial and archaeal population numbers were analyzed using qPCR and were compared to results from a blank and negative control to assess for microbial toxicity. Additionally, the results were compared to those of samples exposed to silver nanoparticles and iron filings in an attempt to discern the source of toxicity. Statistical analysis revealed that the three different iron treatments were equally toxic to the total bacteria and archaea populations, as compared with the controls. Conversely, the silver nanoparticles had a limited statistical impact when compared to the controls and increased the microbial populations in some instances. Therefore, the findings suggest that zero-valent iron toxicity does not result from a unique nanoparticle-based effect.

In vitro and in vivo toxicity assessment of nanoparticles

NASA Astrophysics Data System (ADS)

Kumar, Vinay; Sharma, Neha; Maitra, S. S.

2017-11-01

Nanotechnology has revolutionized gene therapy, diagnostics and environmental remediation. Their bulk production, uses and disposal have posed threat to the environment. With the appearance of these nanoparticles in the environment, their toxicity assessment is an immediate concern. This review is an attempt to summarize the major techniques used in cytotoxity determination. The review also presents a detailed and elaborative discussion on the toxicity imposed by different types of nanoparticles including carbon nanotubes, gold nanoparticles, silver nanoparticles, quantum dots, fullerenes, aluminium nanoparticles, zinc nanoparticles, iron nanoparticles, titanium nanoparticles and silica nanoparticles. It discusses the in vitro and in vivo toxological effects of nanoparticles on bacteria, microalgae, zebrafish, crustacean, fish, rat, mouse, pig, guinea pig, human cell lines and human. It also discusses toxological effects on organs such as liver, kidney, spleen, sperm, neural tissues, liver lysosomes, spleen macrophages, glioblastoma cells, hematoma cells and various mammalian cell lines. It provides information about the effects of nanoparticles on the gene-expression, growth and reproduction of the organisms.

Influence of soil properties on the toxicity of TiO₂ nanoparticles on carbon mineralization and bacterial abundance.

PubMed

Simonin, Marie; Guyonnet, Julien P; Martins, Jean M F; Ginot, Morgane; Richaume, Agnès

2015-01-01

Information regarding the impact of low concentration of engineered nanoparticles on soil microbial communities is currently limited and the importance of soil characteristics is often neglected in ecological risk assessment. To evaluate the impact of TiO2 nanoparticles (NPs) on soil microbial communities (measured on bacterial abundance and carbon mineralization activity), 6 agricultural soils exhibiting contrasted textures and organic matter contents were exposed for 90 days to a low environmentally relevant concentration or to an accidental spiking of TiO2-NPs (1 and 500mgkg(-1) dry soil, respectively) in microcosms. In most soils, TiO2-NPs did not impact the activity and abundance of microbial communities, except in the silty-clay soil (high OM) where C-mineralization was significantly lowered, even with the low NPs concentration. Our results suggest that TiO2-NPs toxicity does not depend on soil texture but likely on pH and OM content. We characterized TiO2-NPs aggregation and zeta potential in soil solutions, in order to explain the difference of TiO2-NPs effects on soil C-mineralization. Zeta potential and aggregation of TiO2-NPs in the silty-clay (high OM) soil solution lead to a lower stability of TiO2-NP-aggregates than in the other soils. Further experiments would be necessary to evaluate the relationship between TiO2-NPs stability and toxicity in the soil. Copyright © 2014 Elsevier B.V. All rights reserved.

Metal Oxide Nanoparticles: The Importance of Size, Shape, Chemical Composition, and Valence State in Determining Toxicity

NASA Astrophysics Data System (ADS)

Dunnick, Katherine

Nanoparticles, which are defined as a structure with at least one dimension between 1 and 100 nm, have the potential to be used in a variety of consumer products due to their improved functionality compared to similar particles of larger size. Their small size is associated with increased strength, improved catalytic properties, and increased reactivity; however, their size is also associated with increased toxicity in vitro and in vivo. Numerous toxicological studies have been conducted to determine the properties of nanomaterials that increase their toxicity in order to manufacture new nanomaterials with decreased toxicity. Data indicates that size, shape, chemical composition, and valence state of nanomaterials can dramatically alter their toxicity profile. Therefore, the purpose of this dissertation was to determine how altering the shape, size, and chemical composition of various metal oxide nanoparticles would affect their toxicity. Metal oxides are used in variety of consumer products, from spray-sun screens, to food coloring agents; thus, understanding the toxicity of metal oxides and determining which aspects affect their toxicity may provide safe alternatives nanomaterials for continued use in manufacturing. Tungstate nanoparticles toxicity was assessed in an in vitro model using RAW 264.7 cells. The size, shape, and chemical composition of these nanomaterials were altered and the effect on reactive oxygen species and general cytotoxicity was determined using a variety of techniques. Results demonstrate that shape was important in reactive oxygen species production as wires were able to induce significant reactive oxygen species compared to spheres. Shape, size, and chemical composition did not have much effect on the overall toxicity of these nanoparticles in RAW 264.7 cells over a 72 hour time course, implicating that the base material of the nanoparticles was not toxic in these cells. To further assess how chemical composition can affect toxicity, cerium oxide nanoparticles were chemically modified using a process known as doping, to alter their valence state. The size and shape of the cerium oxide nanoparticles remained constant. Overall, results indicated that cerium oxide was not toxic in both RLE-6TN and NR8383 pulmonary rat cells, however, chemically modifying the valence state of the nanomaterial did affect the antioxidant potential. To determine if this trend was measureable in vivo, rats were exposed to various cerium oxide nanoparticles via intratracheal instillation and damage, changes in pulmonary cell differentials, and phagocytic cell activity were assessed. Results implicate that chemically modifying the nanoparticles had an effect on the overall damage induced by the material but did not dramatically affect inflammatory potential or phagocytic cell activity. Overall the data from these studies imply that size, shape, chemical composition, and valence state of nanomaterials can be manipulated to alter their toxicity.

Formation of organobromine and organoiodine compounds by engineered TiO2 nanoparticle-induced photohalogenation of dissolved organic matter in environmental waters.

PubMed

Hao, Zhineng; Yin, Yongguang; Wang, Juan; Cao, Dong; Liu, Jingfu

2018-08-01

There are increasing concerns about the adverse effects of released engineered nanoparticles and photochemically formed organohalogen compounds (OHCs) on human health and the environment. Herein, we report that titanium dioxide nanoparticles (TiO 2 NPs) can photocatalytically halogenate dissolved organic matter (DOM) to form a large number of organobromine compounds (OBCs) and organoiodine compounds (OICs), as characterized by negative ion electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry. Compared with no OHCs produced in control samples in darkness and/or without TiO 2 NPs under sunlight irradiation, various OBCs and OICs were detected in freshwater and seawater under sunlight irradiation for 12h and 24h even in the presence of 1mgL -1 TiO 2 NPs, indicating the photocatalytic roles TiO 2 NPs played in DOM halogenation. Furthermore, TiO 2 NPs could result in the photodegradation of newly formed OHCs, as evidenced by the intensity and the number of some OHCs decreased with reaction time. In addition, many TiO 2 NP-induced OBCs contained two or three bromine atoms, and/or nitrogen and sulfur elements, belonging to lignin-like, tannin-like, unsaturated hydrocarbon and aliphatic compounds. While the OICs were primarily contained one iodine, and very few consisted of nitrogen and sulfur elements, most were lignin-like and tannin-like compounds. Finally, the OBCs in freshwater were found to be formed mainly via a substitution reaction or addition reaction and were accompanied by other reactions such as photooxidation, while the OBCs in seawater and OICs were formed primarily via substitution reactions. Given the abundance of produced OHCs and their toxicity, our findings call for further studies on the exact structure and toxicity of the formed OHCs, taking account the TiO 2 NP-induced DOM photohalogenation in aquatic environments during the evaluation of the environmental effects of engineered TiO 2 NPs. Copyright © 2018 Elsevier B.V. All rights reserved.

Current Demands for Food-Approved Liposome Nanoparticles in Food and Safety Sector

PubMed Central

Shukla, Shruti; Haldorai, Yuvaraj; Hwang, Seung Kyu; Bajpai, Vivek K.; Huh, Yun Suk; Han, Young-Kyu

2017-01-01

Safety of food is a noteworthy issue for consumers and the food industry. A number of complex challenges associated with food engineering and food industries, including quality food production and safety of the food through effective and feasible means can be explained by nanotechnology. However, nanoparticles have unique physicochemical properties compared to normal macroparticles of the same composition and thus could interact with living system in surprising ways to induce toxicity. Further, few toxicological/safety assessments have been performed on nanoparticles, thereby necessitating further research on oral exposure risk prior to their application to food. Liposome nanoparticles are viewed as attractive novel materials by the food and medical industries. For example, nanoencapsulation of bioactive food compounds is an emerging application of nanotechnology. In several food industrial practices, liposome nanoparticles have been utilized to improve flavoring and nutritional properties of food, and they have been examined for their capacity to encapsulate natural metabolites that may help to protect the food from spoilage and degradation. This review focuses on ongoing advancements in the application of liposomes for food and pharma sector. PMID:29259595

Assessment of the Toxicity of CuO Nanoparticles by Using Saccharomyces cerevisiae Mutants with Multiple Genes Deleted

PubMed Central

Bao, Shaopan; Lu, Qicong; Dai, Heping; Zhang, Chao

2015-01-01

To develop applicable and susceptible models to evaluate the toxicity of nanoparticles, the antimicrobial effects of CuO nanoparticles (CuO-NPs) on various Saccharomyces cerevisiae (S. cerevisiae) strains (wild type, single-gene-deleted mutants, and multiple-gene-deleted mutants) were determined and compared. Further experiments were also conducted to analyze the mechanisms associated with toxicity using copper salt, bulk CuO (bCuO), carbon-shelled copper nanoparticles (C/Cu-NPs), and carbon nanoparticles (C-NPs) for comparisons. The results indicated that the growth inhibition rates of CuO-NPs for the wild-type and the single-gene-deleted strains were comparable, while for the multiple-gene deletion mutant, significantly higher toxicity was observed (P < 0.05). When the toxicity of the CuO-NPs to yeast cells was compared with the toxicities of copper salt and bCuO, we concluded that the toxicity of CuO-NPs should be attributed to soluble copper rather than to the nanoparticles. The striking difference in adverse effects of C-NPs and C/Cu-NPs with equivalent surface areas also proved this. A toxicity assay revealed that the multiple-gene-deleted mutant was significantly more sensitive to CuO-NPs than the wild type. Specifically, compared with the wild-type strain, copper was readily taken up by mutant strains when cell permeability genes were knocked out, and the mutants with deletions of genes regulated under oxidative stress (OS) were likely producing more reactive oxygen species (ROS). Hence, as mechanism-based gene inactivation could increase the susceptibility of yeast, the multiple-gene-deleted mutants should be improved model organisms to investigate the toxicity of nanoparticles. PMID:26386067

Toxicity and developmental defects of different sizes and shape nickel nanoparticles in zebrafish

PubMed Central

Ispas, Cristina; Andreescu, Daniel; Patel, Avni; Goia, Dan V.; Andreescu, Silvana; Wallace, Kenneth N.

2009-01-01

Metallic nanoparticles such as nickel are used in catalytic, sensing and electronic applications, but health and environmental affects have not been fully investigated. While some metal nanoparticles result in toxicity, it is also important to determine whether nanoparticles of the same metal but of different size and shape changes toxicity. Three different size nickel nanoparticle (Ni NPs) of 30, 60, and 100 nm and larger particle clusters of aggregated 60 nm entities with a dendritic structure were synthesized and exposed to zebrafish embryos assessing mortality and developmental defects. Ni NPs exposure was compared to soluble nickel salts. All three 30, 60, and 100 nm Ni NPs are equal to or less toxic than soluble nickel while dendritic clusters were more toxic. With each Ni NP exposure, thinning of the intestinal epithelium first occurs around the LD10 continuing into the LD50. LD50 exposure also results in skeletal muscle fiber separation. Exposure to soluble nickel does not cause intestinal defects while skeletal muscle separation occurs at concentrations well over LD50. These results suggest that configuration of nanoparticles may affect toxicity more than size and defects from Ni NPs exposure occur by different biological mechanisms than soluble nickel. PMID:19746736

Dynamic protein coronas revealed as a modulator of silver nanoparticle sulphidation in vitro

NASA Astrophysics Data System (ADS)

Miclăuş, Teodora; Beer, Christiane; Chevallier, Jacques; Scavenius, Carsten; Bochenkov, Vladimir E.; Enghild, Jan J.; Sutherland, Duncan S.

2016-06-01

Proteins adsorbing at nanoparticles have been proposed as critical toxicity mediators and are included in ongoing efforts to develop predictive tools for safety assessment. Strongly attached proteins can be isolated, identified and correlated to changes in nanoparticle state, cellular association or toxicity. Weakly attached, rapidly exchanging proteins are also present at nanoparticles, but are difficult to isolate and have hardly been examined. Here we study rapidly exchanging proteins and show for the first time that they have a strong modulatory effect on the biotransformation of silver nanoparticles. Released silver ions, known for their role in particle toxicity, are found to be trapped as silver sulphide nanocrystals within the protein corona at silver nanoparticles in serum-containing cell culture media. The strongly attached corona acts as a site for sulphidation, while the weakly attached proteins reduce nanocrystal formation in a serum-concentration-dependent manner. Sulphidation results in decreased toxicity of Ag NPs.

Inhibition effect of engineered silver nanoparticles to bloom forming cyanobacteria

NASA Astrophysics Data System (ADS)

Thuy Duong, Thi; Son Le, Thanh; Thu Huong Tran, Thi; Kien Nguyen, Trung; Ho, Cuong Tu; Hien Dao, Trong; Phuong Quynh Le, Thi; Chau Nguyen, Hoai; Dang, Dinh Kim; Thu Huong Le, Thi; Thu Ha, Phuong

2016-09-01

Silver nanoparticle (AgNP) has a wide range antibacterial effect and is extensively used in different aspects of medicine, food storage, household products, disinfectants, biomonitoring and environmental remediation etc. In the present study, we examined the growth inhibition effect of engineered silver nanoparticles against bloom forming cyanobacterial M. aeruginosa strain. AgNPs were synthesized by a chemical reduction method at room temperature and UV-Vis spectroscopy, scanning electron microscopy (SEM), transmission electron microscope (TEM) showed that they presented a maximum absorption at 410 nm and size range between 10 and 18 nm. M. aeruginosa cells exposed during 10 d to AgNPs to a range of concentrations from 0 to 1 mg l-1. The changes in cell density and morphology were used to measure the responses of the M. aeruginosa to AgNPs. The control and treatment units had a significant difference in terms of cell density and growth inhibition (p < 0.05). Increasing the concentration of AgNPs, a reduction of the cell growths in all treatment was observed. The inhibition efficiency was reached 98.7% at higher concentration of AgNPs nanoparticles. The term half maximal effective concentration (EC50) based on the cell growth measured by absorbance at 680 nm (A680) was 0.0075 mg l-1. The inhibition efficiency was 98.7% at high concentration of AgNPs (1 mg l-1). Image of SEM and TEM reflected a shrunk and damaged cell wall indicating toxicity of silver nanoparticles toward M. aeruginosa.

Toxicity of silver nanoparticles towards tumoral human cell lines U-937 and HL-60.

PubMed

Barbasz, Anna; Oćwieja, Magdalena; Roman, Maciej

2017-08-01

The toxicity of three types of silver nanoparticles towards histiocytic lymphoma (U-937) and human promyelocytic cells (HL-60) was studied. The nanoparticles were synthesized in a chemical reduction method using sodium borohydride. Trisodium citrate and cysteamine hydrochloride were used to generate a negative and positive nanoparticle surface charge. The evaluation of cell viability, membrane integrity, antioxidant activity and the induction of inflammation were used to evaluate the difference in cellular response to the nanoparticle treatment. The results revealed that the cysteamine-stabilized (positively charged) nanoparticles (SBATE) were the least toxic although they exhibited a similar ion release profile as the unmodified (negatively charged) nanoparticles obtained using sodium borohydride (SBNM). Citrate-stabilized nanoparticles (SBTC) induced superoxide dismutase (SOD) activity in the HL-60 cells and total antioxidant activity in the U-937 cells despite their resistance to oxidative dissolution. The toxicity of SBNM nanoparticles was manifested in the disruption of membrane integrity, decrease in the mitochondrial functions of cells and the induction of inflammation. These findings allowed to conclude that mechanism of silver nanoparticle cytotoxicity is the combination of effects coming from the surface charge of nanoparticles, released silver ions and biological activity of stabilizing agent molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

Nanoparticles for Imaging: Top or Flop?

PubMed Central

Mertens, Marianne E.; Grimm, Jan; Lammers, Twan

2014-01-01

Nanoparticles are frequently suggested as diagnostic agents. However, except for iron oxide nanoparticles, diagnostic nanoparticles have been barely incorporated into clinical use so far. This is predominantly due to difficulties in achieving acceptable pharmacokinetic properties and reproducible particle uniformity as well as to concerns about toxicity, biodegradation, and elimination. Reasonable indications for the clinical utilization of nanoparticles should consider their biologic behavior. For example, many nanoparticles are taken up by macrophages and accumulate in macrophage-rich tissues. Thus, they can be used to provide contrast in liver, spleen, lymph nodes, and inflammatory lesions (eg, atherosclerotic plaques). Furthermore, cells can be efficiently labeled with nanoparticles, enabling the localization of implanted (stem) cells and tissue-engineered grafts as well as in vivo migration studies of cells. The potential of using nanoparticles for molecular imaging is compromised because their pharmacokinetic properties are difficult to control. Ideal targets for nanoparticles are localized on the endothelial luminal surface, whereas targeted nanoparticle delivery to extravascular structures is often limited and difficult to separate from an underlying enhanced permeability and retention (EPR) effect. The majority of clinically used nanoparticle-based drug delivery systems are based on the EPR effect, and, for their more personalized use, imaging markers can be incorporated to monitor biodistribution, target site accumulation, drug release, and treatment efficacy. In conclusion, although nanoparticles are not always the right choice for molecular imaging (because smaller or larger molecules might provide more specific information), there are other diagnostic and theranostic applications for which nanoparticles hold substantial clinical potential. PMID:25247562

Sex differences in the toxicity of polyethylene glycol-coated gold nanoparticles in mice

PubMed Central

Chen, Jie; Wang, Hao; Long, Wei; Shen, Xiu; Wu, Di; Song, Sha-Sha; Sun, Yuan-Ming; Liu, Pei-Xun; Fan, Saijun; Fan, Feiyue; Zhang, Xiao-Dong

2013-01-01

Gold nanoparticles have received wide interest in disease diagnosis and therapy, but one of the important issues is their toxicological effects in vivo. Sex differences in the toxicity of gold nanoparticles are not clear. In this work, body weight, organ weight, hematology, and biochemistry were used to evaluate sex differences in immune response and liver and kidney damage. Pathology was used to observe the general toxicity of reproductive organs. The immune response was influenced significantly in female mice, with obvious changes in spleen and thymus index. Hematology results showed that male mice treated with 22.5 nm gold nanoparticles received more significant infection and inflammation than female mice. Meanwhile, the biochemistry results showed that 4.4 and 22.5 nm gold nanoparticles caused more significant liver damage in male mice than female mice, while 22.5, 29.3, and 36.1 nm gold nanoparticles caused more significant kidney damage in female mice than male mice. No significant toxicological response was found in the reproductive system for female or male mice. It was found that gold nanoparticles caused more serious liver toxicity and infection in male mice than female mice. These findings indicated that sex differences may be one of the important elements for in vivo toxicity of gold nanoparticles. PMID:23861586

Probing the toxicity of nanoparticles: a unified in silico machine learning model based on perturbation theory.

PubMed

Concu, Riccardo; Kleandrova, Valeria V; Speck-Planche, Alejandro; Cordeiro, M Natália D S

2017-09-01

Nanoparticles (NPs) are part of our daily life, having a wide range of applications in engineering, physics, chemistry, and biomedicine. However, there are serious concerns regarding the harmful effects that NPs can cause to the different biological systems and their ecosystems. Toxicity testing is an essential step for assessing the potential risks of the NPs, but the experimental assays are often very expensive and usually too slow to flag the number of NPs that may cause adverse effects. In silico models centered on quantitative structure-activity/toxicity relationships (QSAR/QSTR) are alternative tools that have become valuable supports to risk assessment, rationalizing the search for safer NPs. In this work, we develop a unified QSTR-perturbation model based on artificial neural networks, aimed at simultaneously predicting general toxicity profiles of NPs under diverse experimental conditions. The model is derived from 54,371 NP-NP pair cases generated by applying the perturbation theory to a set of 260 unique NPs, and showed an accuracy higher than 97% in both training and validation sets. Physicochemical interpretation of the different descriptors in the model are additionally provided. The QSTR-perturbation model is then employed to predict the toxic effects of several NPs not included in the original dataset. The theoretical results obtained for this independent set are strongly consistent with the experimental evidence found in the literature, suggesting that the present QSTR-perturbation model can be viewed as a promising and reliable computational tool for probing the toxicity of NPs.

Synthesis of β-cyclodextrin hydrogel nanoparticles for improving the solubility of dexibuprofen: characterization and toxicity evaluation.

PubMed

Khalid, Qandeel; Ahmad, Mahmood; Minhas, Muhammad Usman

2017-11-01

This study was aimed to enhance aqueous solubility of dexibuprofen through designing β-cyclodextrin (βCD) hydrogel nanoparticles and to evaluate toxicological potential through acute toxicity studies in rats. Dexibuprofen is a non-steroidal analgesic and anti-inflammatory drug that is one of safest over the counter medications. However, its clinical effectiveness is hampered due to poor aqueous solubility. βCD hydrogel nanoparticles were prepared and characterized by percent yield, drug loading, solubilization efficiency, FTIR, XRD, DSC, FESEM and in-vitro dissolution studies. Acute oral toxicity study was conducted to assess safety of oral administration of prepared βCD hydrogel nanoparticles. βCD hydrogel nanoparticles dramatically enhanced the drug loading and solubilization efficiency of dexibuprofen in aqueous media. FTIR, TGA and DSC studies confirmed the formation of new and a stable nano-polymeric network and interactions of dexibuprofen with these nanoparticles. Resulting nanoparticles were highly porous with 287 nm in size. XRD analysis revealed pronounced reduction in crystalline nature of dexibuprofen within nanoparticles. Release of dexibuprofen in βCD hydrogel nanoparticles was significantly higher compared with dexibuprofen tablet at pH 1.2 and 6.8. In acute toxicity studies, no significant changes in behavioral, physiological, biochemical or histopathologic parameters of animals were observed. The efficient preparation, high solubility, excellent physicochemical characteristics, improved dissolution and non-toxic βCD hydrogel nanoparticles may be a promising approach for oral delivery of lipophilic drugs.

Development and characterization of hyaluronic acid decorated PLGA nanoparticles for delivery of 5-fluorouracil.

PubMed

Yadav, Awesh K; Agarwal, Abhinav; Rai, Gopal; Mishra, Pradeep; Jain, Sanyog; Mishra, Anil K; Agrawal, Himanshu; Agrawal, Govind P

2010-11-01

The present investigation was aimed to develop and explore the prospective of engineered PLGA nanoparticles as vehicles for targeted delivery of 5-fluorouracil (5-FU). Nanoparticles of 5-FU-loaded hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide) (HA-PEG-PLGA-FU) copolymer were prepared and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, DSC, and X-ray diffractometer measurement studies. The nanoparticulate formulation was evaluated for in vitro release, hemolytic toxicity, and hematological toxicity. Cytotoxicity studies were performed on Ehrlich ascites tumor (EAT) cell lines using MTT cell proliferation assay. Biodistribution studies of 99m Tc labeled formulation were conducted on EAT-bearing mice. The in vivo tumor inhibition study was also performed after i.v. administration of HA-PEG-PLGA-FU nanoparticles. The HA conjugated formulation was found to be less hemolytic but more cytotoxic as compared to free drug. The hematological data suggested that HA-PEG-PLGA-FU formulation was less immunogenic compared to plain drug. The tissue distribution studies displayed that HA-PEG-PLGA-FU were able to deliver a higher concentration of 5-FU in the tumor mass. In addition, the HA-PEG-PLGA-FU nanoparticles reduced tumor volume significantly in comparison with 5-FU. Thus, it was concluded that the conjugation of HA imparts targetability to the formulation, and enhanced permeation and retention effect ruled out its access to the non-tumor tissues, at the same time favored selective entry in tumors, thereby reducing the side-effects both in vitro and in vivo.

Imaging interactions of metal oxide nanoparticles with macrophage cells by ultra-high resolution scanning electron microscopy techniques.

PubMed

Plascencia-Villa, Germán; Starr, Clarise R; Armstrong, Linda S; Ponce, Arturo; José-Yacamán, Miguel

2012-11-01

Use of engineered metal oxide nanoparticles in a plethora of biological applications and custom products has warned about some possible dose-dependent cytotoxic effects. Macrophages are key components of the innate immune system used to study possible toxic effects and internalization of different nanoparticulate materials. In this work, ultra-high resolution field emission scanning electron microscopy (FE-SEM) was used to offer new insights into the dynamical processes of interaction of nanomaterials with macrophage cells dosed with different concentrations of metal oxide nanoparticles (CeO(2), TiO(2) and ZnO). The versatility of FE-SEM has allowed obtaining a detailed characterization of processes of adsorption and endocytosis of nanoparticles, by using advanced analytical and imaging techniques on complete unstained uncoated cells, including secondary electron imaging, high-sensitive backscattered electron imaging, X-ray microanalysis and stereoimaging. Low voltage BF/DF-STEM confirmed nanoparticle adsorption and internalization into endosomes of CeO(2) and TiO(2), whereas ZnO develop apoptosis after 24 h of interaction caused by dissolution and invasion of cell nucleus. Ultra-high resolution scanning electron microscopy techniques provided new insights into interactions of inorganic nanoparticles with macrophage cells with high spatial resolution.

Developmental toxicity and DNA damaging properties of silver nanoparticles in the catfish (Clarias gariepinus).

PubMed

Sayed, Alaa El-Din H; Soliman, Hamdy A M

2017-10-01

Although, silver nanoparticles (AgNPs) are used in many different products, little information is known about their toxicity in tropical fish embryos. Therefore, this study evaluated the developmental toxicity of waterborne silver nanoparticles in embryos of Clarias gariepinus. Embryos were treated with (0, 25, 50, 75ng/L silver nanoparticles) in water up to 144h postfertilization stage (PFS). Results revealed various morphological malformations including notochord curvature and edema. The mortality rate, malformations, and DNA fragmentation in embryos exposed to silver nanoparticles increased in a dose- and embryonic stage-dependent manner. The total antioxidant capacity and the activity of catalase in embryos exposed to 25ng/L silver nanoparticles were decreased significantly while the total antioxidant capacity and the activity of catalase were insignificantly increased with increasing concentrations in the embryos from 24 to 144 h-PFS exposed to 50 and 75ng/L silver nanoparticles. Lipid peroxidation values showed fluctuations with doses of silver nanoparticles. Histopathological lesions including severely distorted and wrinkled notochord were observed. The current data propose that the toxicity of silver nanoparticles in C. gariepinus embryos is caused by oxidative stress and genotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Beneficial role of carbon nanotubes on mustard plant growth: an agricultural prospect

NASA Astrophysics Data System (ADS)

Mondal, Anindita; Basu, Ruma; Das, Sukhen; Nandy, Papiya

2011-10-01

Nowadays an increasing application of nanotechnology in different fields has arisen an extensive debate about the effect of the engineered nanoparticles on environment . Phytotoxicity of nanoparticles has come into limelight in the last few years. However, very few studies have been done so far on the beneficial aspects of nanoparticles on plants. In this article, we report the beneficial effect of multi-walled carbon nanotubes (MWCNTs) having diameter of 30 nm on Brassica juncea (mustard) seeds. Measurements of germination rate, T 50 (time taken for 50% germination), shoot and root growth have shown encouraging results using low concentration of oxidized MWCNT (OMWCNT) treated seeds as compared to non-oxidized as well as high concentration OMWCNT treated seeds. For toxicity study we measured the germination index and relative root elongation, while conductivity test and infra-red spectra were also performed to study the overall effect of oxidized and non-oxidized nanotubes on mustard seeds and seedlings.

Biokinetics of different-shaped copper oxide nanoparticles in the freshwater gastropod, Potamopyrgus antipodarum

USGS Publications Warehouse

Ramskov, Tina; Croteau, Marie-Noele; Forbes, Valery E.; Selck, Henriette

2015-01-01

Sediment is recognized as a major environmental sink for contaminants, including engineered nanoparticles (NPs). Consequently, sediment-living organisms are likely to be exposed to NPs. There is evidence that both accumulation and toxicity of metal NPs to sediment-dwellers increase with decreasing particle size, although NP size does not always predict effects. In contrast, not much is known about the influence of particle shape on bioaccumulation and toxicity. Here, we examined the influence of copper oxide (CuO) NP shape (rods, spheres, and platelets) on their bioaccumulation kinetics and toxicity to the sediment-dwelling gastropod, Potamopyrgus antipodarum. The influence of Cu added as CuCl2 (i.e., aqueous Cu treatment) was also examined. Exposure to sediment mixed with aqueous Cu or with different-shaped CuO NPs at an average measured exposure concentration of 207 μg Cu per g dry weight sediment for 14 days did not significantly affect snail mortality. However, growth decreased for snails exposed to sediment amended with CuO NP spheres and platelets. P. antipodarum accumulated Cu from all Cu forms/shapes in significant amounts compared to control snails. In addition, once accumulated, Cu was efficiently retained (i.e., elimination rate constants were generally not significantly different from zero). Consequently, snails are likely to concentrate Cu over time, from both aqueous and NP sources, resulting in a high potential for toxicity.

Lipid Layers on Polyelectrolyte Multilayers: Understanding Lipid-Polyelectrolyte Interactions and Applications on the Surface Engineering of Nanomaterials.

PubMed

Diamanti, Eleftheria; Gregurec, Danijela; Gabriela, Romero; Cuellar, J L; Donath, E; Moya, S E

2016-06-01

In this manuscript we review work of our group on the assembly of lipid layers on top of polyelectrolyte multilayers (PEMs). The assembly of lipid layers with zwitterionic and charged lipids on PEMs is studied as a function of lipid and polyelectrolyte composition by the Quartz Crystal Microbalance. Polyelectrolyte lipid interactions are studied by means of Atomic Force Spectroscopy. We also show the coating of lipid layers for engineering different nanomaterials, i.e., carbon nanotubes and poly(lactic-co-glycolic) nanoparticles and how these can be used to decrease in vitro toxicity and to direct the intracellular localization of nanomaterials.

Genetic toxicity assessment of engineered nanoparticles using a 3D in vitro skin model (EpiDerm™).

PubMed

Wills, John W; Hondow, Nicole; Thomas, Adam D; Chapman, Katherine E; Fish, David; Maffeis, Thierry G; Penny, Mark W; Brown, Richard A; Jenkins, Gareth J S; Brown, Andy P; White, Paul A; Doak, Shareen H

2016-09-09

The rapid production and incorporation of engineered nanomaterials into consumer products alongside research suggesting nanomaterials can cause cell death and DNA damage (genotoxicity) makes in vitro assays desirable for nanosafety screening. However, conflicting outcomes are often observed when in vitro and in vivo study results are compared, suggesting more physiologically representative in vitro models are required to minimise reliance on animal testing. BASF Levasil® silica nanoparticles (16 and 85 nm) were used to adapt the 3D reconstructed skin micronucleus (RSMN) assay for nanomaterials administered topically or into the growth medium. 3D dose-responses were compared to a 2D micronucleus assay using monocultured human B cells (TK6) after standardising dose between 2D / 3D assays by total nanoparticle mass to cell number. Cryogenic vitrification, scanning electron microscopy and dynamic light scattering techniques were applied to characterise in-medium and air-liquid interface exposures. Advanced transmission electron microscopy imaging modes (high angle annular dark field) and X-ray spectrometry were used to define nanoparticle penetration / cellular uptake in the intact 3D models and 2D monocultured cells. For all 2D exposures, significant (p < 0.002) increases in genotoxicity were observed (≥100 μg/mL) alongside cell viability decreases (p < 0.015) at doses ≥200 μg/mL (16 nm-SiO2) and ≥100 μg/mL (85 nm-SiO2). In contrast, 2D-equivalent exposures to the 3D models (≤300 μg/mL) caused no significant DNA damage or impact on cell viability. Further increasing dose to the 3D models led to probable air-liquid interface suffocation. Nanoparticle penetration / cell uptake analysis revealed no exposure to the live cells of the 3D model occurred due to the protective nature of the skin model's 3D cellular microarchitecture (topical exposures) and confounding barrier effects of the collagen cell attachment layer (in-medium exposures). 2D monocultured cells meanwhile showed extensive internalisation of both silica particles causing (geno)toxicity. The results establish the importance of tissue microarchitecture in defining nanomaterial exposure, and suggest 3D in vitro models could play a role in bridging the gap between in vitro and in vivo outcomes in nanotoxicology. Robust exposure characterisation and uptake assessment methods (as demonstrated) are essential to interpret nano(geno)toxicity studies successfully.

Encapsulation of Aconitine in Self-Assembled Licorice Protein Nanoparticles Reduces the Toxicity In Vivo

NASA Astrophysics Data System (ADS)

Ke, Li-jing; Gao, Guan-zhen; Shen, Yong; Zhou, Jian-wu; Rao, Ping-fan

2015-11-01

Many herbal medicines and compositions are clinically effective but challenged by its safety risks, i.e., aconitine (AC) from aconite species. The combined use of Radix glycyrrhizae (licorice) with Radix aconite L. effectively eliminates toxicity of the later while increasing efficacy. In this study, a boiling-stable 31-kDa protein (namely GP) was purified from licorice and self-assembled into nanoparticles (206.2 ± 2.0 nm) at pH 5.0, 25 °C. The aconitine-encapsulated GP nanoparticles (238.2 ± 1.2 nm) were prepared following the same procedure and tested for its toxicity by intraperitoneal injection on ICR mouse ( n = 8). Injection of GP-AC nanoparticles and the mixed licorice-aconite decoction, respectively, caused mild recoverable toxic effects and no death, while the aconitine, particle-free GP-AC mixture and aconite decoction induced sever toxic effects and 100 % death. Encapsulation of poisonous alkaloids into self-assembled herbal protein nanoparticles contributes to toxicity attenuation of combined use of herbs, implying a prototype nanostructure and a universal principle for the safer clinical applications of herbal medicines.

Reducing Environmental Toxicity of Silver Nanoparticles through Shape Control.

PubMed

Gorka, Danielle E; Osterberg, Joshua S; Gwin, Carley A; Colman, Benjamin P; Meyer, Joel N; Bernhardt, Emily S; Gunsch, Claudia K; DiGulio, Richard T; Liu, Jie

2015-08-18

The use of antibacterial silver nanomaterials in consumer products ranging from textiles to toys has given rise to concerns over their environmental toxicity. These materials, primarily nanoparticles, have been shown to be toxic to a wide range of organisms; thus methods and materials that reduce their environmental toxicity while retaining their useful antibacterial properties can potentially solve this problem. Here we demonstrate that silver nanocubes display a lower toxicity toward the model plant species Lolium multiflorum while showing similar toxicity toward other environmentally relevant and model organisms (Danio rerio and Caenorhabditis elegans) and bacterial species (Esherichia coli, Bacillus cereus, and Pseudomonas aeruginosa) compared to quasi-spherical silver nanoparticles and silver nanowires. More specifically, in the L. multiflorum experiments, the roots of silver nanocube treated plants were 5.3% shorter than the control, while silver nanoparticle treated plant roots were 39.6% shorter than the control. The findings here could assist in the future development of new antibacterial products that cause less environmental toxicity after their intended use.

Toxicity of tungsten carbide and cobalt-doped tungsten carbide nanoparticles in mammalian cells in vitro.

PubMed

Bastian, Susanne; Busch, Wibke; Kühnel, Dana; Springer, Armin; Meissner, Tobias; Holke, Roland; Scholz, Stefan; Iwe, Maria; Pompe, Wolfgang; Gelinsky, Michael; Potthoff, Annegret; Richter, Volkmar; Ikonomidou, Chrysanthy; Schirmer, Kristin

2009-04-01

Tungsten carbide nanoparticles are being explored for their use in the manufacture of hard metals. To develop nanoparticles for broad applications, potential risks to human health and the environment should be evaluated and taken into consideration. We aimed to assess the toxicity of well-characterized tungsten carbide (WC) and cobalt-doped tungsten carbide (WC-Co) nanoparticle suspensions in an array of mammalian cells. We examined acute toxicity of WC and of WC-Co (10% weight content Co) nanoparticles in different human cell lines (lung, skin, and colon) as well as in rat neuronal and glial cells (i.e., primary neuronal and astroglial cultures and the oligodendrocyte precursor cell line OLN-93). Furthermore, using electron microscopy, we assessed whether nanoparticles can be taken up by living cells. We chose these in vitro systems in order to evaluate for potential toxicity of the nanoparticles in different mammalian organs (i.e., lung, skin, intestine, and brain). Chemical-physical characterization confirmed that WC as well as WC-Co nanoparticles with a mean particle size of 145 nm form stable suspensions in serum-containing cell culture media. WC nanoparticles were not acutely toxic to the studied cell lines. However, cytotoxicity became apparent when particles were doped with Co. The most sensitive were astrocytes and colon epithelial cells. Cytotoxicity of WC-Co nanoparticles was higher than expected based on the ionic Co content of the particles. Analysis by electron microscopy demonstrated presence of WC nanoparticles within mammalian cells. Our findings demonstrate that doping of WC nanoparticles with Co markedly increases their cytotoxic effect and that the presence of WC-Co in particulate form is essential to elicit this combinatorial effect.

Toxicity of Tungsten Carbide and Cobalt-Doped Tungsten Carbide Nanoparticles in Mammalian Cells in Vitro

PubMed Central

Bastian, Susanne; Busch, Wibke; Kühnel, Dana; Springer, Armin; Meißner, Tobias; Holke, Roland; Scholz, Stefan; Iwe, Maria; Pompe, Wolfgang; Gelinsky, Michael; Potthoff, Annegret; Richter, Volkmar; Ikonomidou, Chrysanthy; Schirmer, Kristin

2009-01-01

Background Tungsten carbide nanoparticles are being explored for their use in the manufacture of hard metals. To develop nanoparticles for broad applications, potential risks to human health and the environment should be evaluated and taken into consideration. Objective We aimed to assess the toxicity of well-characterized tungsten carbide (WC) and cobaltdoped tungsten carbide (WC-Co) nanoparticle suspensions in an array of mammalian cells. Methods We examined acute toxicity of WC and of WC-Co (10% weight content Co) nanoparticles in different human cell lines (lung, skin, and colon) as well as in rat neuronal and glial cells (i.e., primary neuronal and astroglial cultures and the oligodendro cyte precursor cell line OLN-93). Furthermore, using electron microscopy, we assessed whether nanoparticles can be taken up by living cells. We chose these in vitro systems in order to evaluate for potential toxicity of the nanoparticles in different mammalian organs (i.e., lung, skin, intestine, and brain). Results Chemical–physical characterization confirmed that WC as well as WC-Co nanoparticles with a mean particle size of 145 nm form stable suspensions in serum-containing cell culture media. WC nanoparticles were not acutely toxic to the studied cell lines. However, cytotoxicity became apparent when particles were doped with Co. The most sensitive were astrocytes and colon epithelial cells. Cytotoxicity of WC-Co nanoparticles was higher than expected based on the ionic Co content of the particles. Analysis by electron microscopy demonstrated presence of WC nanoparticles within mammalian cells. Conclusions Our findings demonstrate that doping of WC nanoparticles with Co markedly increases their cytotoxic effect and that the presence of WC-Co in particulate form is essential to elicit this combinatorial effect. PMID:19440490

A polymer nanoparticle with engineered affinity for a vascular endothelial growth factor (VEGF165)

NASA Astrophysics Data System (ADS)

Koide, Hiroyuki; Yoshimatsu, Keiichi; Hoshino, Yu; Lee, Shih-Hui; Okajima, Ai; Ariizumi, Saki; Narita, Yudai; Yonamine, Yusuke; Weisman, Adam C.; Nishimura, Yuri; Oku, Naoto; Miura, Yoshiko; Shea, Kenneth J.

2017-07-01

Protein affinity reagents are widely used in basic research, diagnostics and separations and for clinical applications, the most common of which are antibodies. However, they often suffer from high cost, and difficulties in their development, production and storage. Here we show that a synthetic polymer nanoparticle (NP) can be engineered to have many of the functions of a protein affinity reagent. Polymer NPs with nM affinity to a key vascular endothelial growth factor (VEGF165) inhibit binding of the signalling protein to its receptor VEGFR-2, preventing receptor phosphorylation and downstream VEGF165-dependent endothelial cell migration and invasion into the extracellular matrix. In addition, the NPs inhibit VEGF-mediated new blood vessel formation in Matrigel plugs in vivo. Importantly, the non-toxic NPs were not found to exhibit off-target activity. These results support the assertion that synthetic polymers offer a new paradigm in the search for abiotic protein affinity reagents by providing many of the functions of their protein counterparts.

Ecotoxic effect of photocatalytic active nanoparticles (TiO2) on algae and daphnids.

PubMed

Hund-Rinke, Kerstin; Simon, Markus

2006-07-01

Due to their large potential for manifold applications, the use of nanoparticles is of increasing importance. As large amounts of nanoparticles may reach the environment voluntarily or by accident, attention should be paid on the potential impacts on the environment. First studies on potential environmental effects of photocatalytic TiO2 nanoparticles have been performed on the basis of widely accepted, standardized test systems which originally had been developed for the characterization of chemicals. The methods were adapted to the special requirements of testing photocatalytic nanoparticles. Suspensions of two different nanoparticles were illuminated to induce their photocatalytic activity. For testing, the growth inhibition test with the green alga Desmodesmus subspicatus and the immobilization test with the daphnid Daphnia magna were selected and performed following the relevant guidelines (algae: ISO 8692, OECD 201, DIN 38412-33; daphnids: ISO 6341, OECD 202, DIN 38412-30). The guidelines were adapted to meet the special requirements for testing photocatalytic nanoparticles. The results indicate that it is principally possible to determine the ecotoxicity of nanoparticles. It was shown that nanoparticles may have ecotoxicological effects which depend on the nature of the particles. Both products tested differ in their toxicity. Product 1 shows a clear concentration-effect curve in the test with algae (EC50: 44 mg/L). It could be proven that the observed toxicity was not caused by accompanying contaminants, since the toxic effect was comparable for the cleaned and the commercially available product. For product 2, no toxic effects were determined (maximum concentration: 50 mg/L). In the tests with daphnids, toxicity was observed for both products, although the concentration effect-curves were less pronounced. The two products differed in their toxicity; moreover, there was a difference in the toxicity of illuminated and non-illuminated products. Both products differ in size and crystalline form, so that these parameters are assumed to contribute to the different toxicities. The concentration-effect curves for daphnids, which are less-pronounced than the curves obtained for algae, may be due to the different test organisms and/or the differing test designs. The increased toxicity of pre-illuminated particles in the tests with daphnids demonstrates that the photocatalytic activity of nanoparticles lasts for a period of time. The following conclusions can be drawn from the test results: (I) It is principally possible to determine the ecotoxicity of (photocatalytic) nanoparticles. Therefore, they can be assessed using methods comparable to the procedures applied for assessing soluble chemicals. (II) Nanoparticles may exert ecotoxicological effects, which depend on the specific nanoparticle. (III) Comparable to traditional chemicals, the ecotoxicity depends on the test organisms and their physiology. (IV) The photocatalytic activity of nanoparticles lasts for a relevant period of time. Therefore, pre-illumination may be sufficient to detect a photocatalytic activity even by using test organisms which are not suitable for application in the pre-illumination-phase. First results are presented which indicate that the topic 'ecotoxicity and environmental effects of nanoparticles' should not be neglected. In testing photocatalytic nanoparticles, there are still many topics that need clarification or improvement, such as the cause for an observed toxicity, the improvement of the test design, the elaboration of a test battery and an assessment strategy. On the basis of optimized test systems, it will be possible to test nanoparticles systematically. If a potential risk by specific photocatalytic particles is known, a risk-benefit analysis can be performed and, if required, risk reducing measures can be taken.

Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery.

PubMed

Tian, Xi; Lara, Haydee; Wagner, Kyle T; Saripalli, Srinivas; Hyder, Syed Nabeel; Foote, Michael; Sethi, Manish; Wang, Edina; Caster, Joseph M; Zhang, Longzhen; Wang, Andrew Z

2015-12-21

Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment.

Copper Nanoparticle Induced Cytotoxicity to Nitrifying Bacteria ...

EPA Pesticide Factsheets

With the inclusion of engineered nanomaterials in industrial processes and consumer products, wastewater treatments plants (WWTPs) will serve as a major sink for these emerging contaminants. Previous research has demonstrated that nanomaterials are potentially toxic to microbial communities utilized in biological wastewater treatment (BWT). Copper-based nanoparticles (CuNPs) are of particular interest based on their increasing use in wood treatment, paints, household products, coatings, and byproducts of semiconductor manufacturing. A critical step in BWT is nutrient removal via denitrification. This study examined the potential toxicity of bare and polyvinylpyrrolidone (PVP) coated CuO, and Cu2O nanoparticles, as well as Cu ions to microbial communities responsible for nitrogen removal in BWT. Inhibition was inferred from changes to the specific oxygen uptake rate (sOUR) in the absence and presence of Cu ions and CuNPs. X-ray absorption fine structure spectroscopy, with Linear Combination Fitting (LCF), was utilized to track changes to Cu speciation throughout exposure. Results indicate that the dissolution of Cu ions from CuNPs drive microbial inhibition. The presence of a PVP coating on CuNPs has little effect on inhibition. LCF fitting of the biomass combined with metal partitioning analysis supports the current hypothesis that Cu-induced cytotoxicity is primarily caused by reactive oxygen species formed from ionic Cu in solution via catalytic reaction inter

Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

NASA Astrophysics Data System (ADS)

Tian, Xi; Lara, Haydee; Wagner, Kyle T.; Saripalli, Srinivas; Hyder, Syed Nabeel; Foote, Michael; Sethi, Manish; Wang, Edina; Caster, Joseph M.; Zhang, Longzhen; Wang, Andrew Z.

2015-11-01

Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment.

IMEC-9: The 9th Israel Materials Engineering Conference. Program & Abstracts

DTIC Science & Technology

1999-12-07

non- toxic , magnetite (FesC^) nanoparticles of very narrow size distribution in sizes ranging from approximately 20 nm up to 0.1 urn. The process for...Israel 17 Composites I Hall G Chair: R. Albalak 13:30 -13:50 Synthesis of Dense Oxide -Based In Situ Composites via Thermal Explosion/SHS...Tsionsky, Israel 16:00 -16:20 The Effect of Composition and Microstructure on the Corrosion Behavior of Magnesium- Aluminium Alloys P. Uzan, D. Eliezer

TiO2 nanoparticles alleviate toxicity by reducing free Zn2+ ion in human primary epidermal keratinocytes exposed to ZnO nanoparticles

NASA Astrophysics Data System (ADS)

Kathawala, Mustafa Hussain; Ng, Kee Woei; Loo, Say Chye Joachim

2015-06-01

Nanoparticles have been a subject of intense safety screenings due to their influx in various applications. Although recent studies have reported on the plausible cytotoxicity of nanoparticles, many of these focused only on single-material nanoparticles, while the cytotoxicity of dual-nanoparticle systems (e.g., ZnO with TiO2) has remained unexplored. For example, commercial products like sunscreens and cosmetics contain both nano-sized ZnO and TiO2, but cytotoxicity studies of such systems are meager. In this paper, the cytotoxicity of this dual-nanoparticle system comprising both ZnO and TiO2 was evaluated in vitro on skin-mimicking human primary epidermal keratinocytes (HPEKs). Inductively coupled plasma mass spectrometry, flow cytometry, and confocal microscopy were used to investigate the uptake of nanoparticles and free ions. Results revealed that ZnO nanoparticles were partially soluble (up to 20 μg ml-1 after 1 day) and could induce strong cytotoxicity as compared to the insoluble TiO2 nanoparticles which remained non-toxic until very high concentrations. It was found that TiO2 nanoparticles could play "vigilante" by protecting keratinocytes from acute toxicity of ZnO nanoparticles. This is in agreement with the observation that TiO2 nanoparticles caused an attenuation of free intracellular Zn2+ ions concentration, by adsorbing and immobilizing free Zn2+ ions. This study reveals a unique dual-nanoparticle observation in vitro on HPEKs, and highlights the importance of dual-nanoparticulate toxicity studies, especially in applications where more than one nanoparticle material-type is present.

Identifying a size-specific hazard of silica nanoparticles after intravenous administration and its relationship to the other hazards that have negative correlations with the particle size in mice

NASA Astrophysics Data System (ADS)

Handa, Takayuki; Hirai, Toshiro; Izumi, Natsumi; Eto, Shun-ichi; Tsunoda, Shin-ichi; Nagano, Kazuya; Higashisaka, Kazuma; Yoshioka, Yasuo; Tsutsumi, Yasuo

2017-03-01

Many of the beneficial and toxic biological effects of nanoparticles have been shown to have a negative correlation with particle size. However, few studies have demonstrated biological effects that only occur at specific nanoparticle sizes. Further elucidation of the size-specific biological effects of nanoparticles may reveal not only unknown toxicities, but also novel benefits of nanoparticles. We used surface-unmodified silica particles with a wide range of diameters and narrow size intervals between the diameters (10, 30, 50, 70, 100, 300, and 1000 nm) to investigate the relationship between particle size and acute toxicity after intravenous administration in mice. Negative correlations between particle size and thrombocytopenia, liver damage, and lethal toxicity were observed. However, a specific size-effect was observed for the severity of hypothermia, where silica nanoparticles with a diameter of 50 nm induced the most severe hypothermia. Further investigation revealed that this hypothermia was mediated not by histamine, but by platelet-activating factor, and it was independent of the thrombocytopenia and the liver damage. In addition, macrophages/Kupffer cells and platelets, but not neutrophils, play a critical role in the hypothermia. The present results reveal that silica nanoparticles have particle size-specific toxicity in mice, suggesting that other types of nanoparticles may also have biological effects that only manifest at specific particle sizes. Further study of the size-specific effects of nanoparticles is essential for safer and more effective nanomedicines.

The species origin of the serum in the culture medium influences the in vitro toxicity of silica nanoparticles to HepG2 cells.

PubMed

Pisani, Cédric; Rascol, Estelle; Dorandeu, Christophe; Gaillard, Jean-Charles; Charnay, Clarence; Guari, Yannick; Chopineau, Joël; Armengaud, Jean; Devoisselle, Jean-Marie; Prat, Odette

2017-01-01

The formation of a protein corona around nanoparticles can influence their toxicity, triggering cellular responses that may be totally different from those elicited by pristine nanoparticles. The main objective of this study was to investigate whether the species origin of the serum proteins forming the corona influences the in vitro toxicity assessment of silica nanoparticles. Coronas were preformed around nanoparticles before cell exposures by incubation in fetal bovine (FBS) or human (HS) serum. The compositions of these protein coronas were assessed by nano-LC MS/MS. The effects of these protein-coated nanoparticles on HepG2 cells were monitored using real-time cell impedance technology. The nanoparticle coronas formed in human or fetal bovine serum comprised many homologous proteins. Using human compared with fetal bovine serum, nanoparticle toxicity in HepG2 cells decreased by 4-fold and 1.5-fold, when used at 50 and 10μg/mL, respectively. It is likely that "markers of self" are present in the serum and are recognized by human cell receptors. Preforming a corona with human serum seems to be more appropriate for in vitro toxicity testing of potential nanocarriers using human cells. In vitro cytotoxicity assays must reflect in vivo conditions as closely as possible to provide solid and useful results.

A comparative ecotoxicity analysis of α- and γ-phase aluminium oxide nanoparticles towards a freshwater bacterial isolate Bacillus licheniformis.

PubMed

Pakrashi, Sunandan; Kumar, Deepak; Iswarya, V; Bhuvaneshwari, M; Chandrasekaran, N; Mukherjee, Amitava

2014-12-01

Crystalline structure of nanoparticles may influence their physicochemical behaviour as well as their toxicological impact on biota. The differences in orientation of the atoms result in the variations in chemical stability. Thus, toxicological impacts of different crystalline phases of aluminium oxide nanoparticles are expected to vary. The present study brings out a comparative toxicity analysis of γ-phase and α-phase aluminium oxide nanoparticles of comparable hydrodynamic size range towards a freshwater bacterial isolate Bacillus licheniformis at low exposure concentrations (5, 1, 0.5 and 0.05 µg/mL). Upon 2-h exposure, the α-aluminium oxide particles showed lower toxicity than the γ-phase aluminium oxide. The lower level of oxidative stress generation and cell membrane damage in case of the α-phase aluminium oxide nanoparticles substantiated the toxicity results. The involvement of protein, lipopolysaccharides in nanoparticle-cell surface interaction, was noted in both the cases. To conclude, the crystallinity of aluminium oxide nanoparticles played an important role in the interaction and the toxicity response.

Comparison of the toxicity of silver, gold and platinum nanoparticles in developing zebrafish embryos.

PubMed

Asharani, P V; Lianwu, Yi; Gong, Zhiyuan; Valiyaveettil, Suresh

2011-03-01

Nanoparticles have diverse applications in electronics, medical devices, therapeutic agents and cosmetics. While the commercialization of nanoparticles is rapidly expanding, their health and environmental impact is not well understood. Toxicity assays of silver, gold, and platinum nanoparticles, using zebrafish embryos to study their developmental effects were carried out. Gold (Au-NP, 15-35 nm), silver (Ag-NP, 5-35 nm) and platinum nanoparticles (Pt-NP, 3-10 nm) were synthesized using polyvinyl alcohol (PVA) as a capping agent. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. The addition of Ag-NP resulted in a concentration-dependant increase in mortality rate. Both Ag-NP and Pt-NP induced hatching delays, as well as a concentration dependant drop in heart rate, touch response and axis curvatures. Ag-NP also induced other significant phenotypic changes including pericardial effusion, abnormal cardiac morphology, circulatory defects and absence or malformation of the eyes. In contrast, Au-NP did not show any indication of toxicity. Uptake and accumulation of nanoparticles in embryos was confirmed by inductively coupled plasma optical emission spectroscopy (ICP-OES), which revealed detectable levels in embryos within 72 hpf. Ag-NP and Au-NP were taken up by the embryos in relatively equal amounts whereas lower Pt concentrations were observed in embryos exposed to Pt-NP. This was probably due to the small size of the Pt nanoparticles compared to Ag-NP and Au-NP, thus resulting in fewer metal atoms being retained in the embryos. Among the nanoparticles studied, Ag-NPs were found to be the most toxic and Au-NPs the non-toxic. The toxic effects exhibited by the zebrafish embryos as a consequence of nanoparticle exposure, accompanied by the accumulation of metals inside the body calls for urgent further investigations in this field.

Toxicity, Bioaccumulation and Biotransformation of Silver Nanoparticles in Marine Organisms.

EPA Science Inventory

The toxicity, bioaccumulation and biotransformation of citrate and polyvinylpyrrolidone (PVP) coated silver nanoparticles (NPs) (AgNP-citrate and AgNP-PVP) in marine organisms via marine sediment exposure was investigated. Results from 7-d sediment toxicity tests indicate that Ag...

Active targeting of cancer cells using folic acid-conjugated platinum nanoparticles.

PubMed

Teow, Yiwei; Valiyaveettil, Suresh

2010-12-01

Interaction of nanoparticles with human cells is an interesting topic for understanding toxicity and developing potential drug candidates. Water soluble platinum nanoparticles were synthesized via reduction of hexachloroplatinic acid using sodium borohydride in the presence of capping agents. The bioactivity of folic acid and poly(vinyl pyrrolidone) capped platinum nanoparticles (Pt-nps) has been investigated using commercially available cell lines. In the cell viability experiments, PVP-capped nanoparticles were found to be less toxic (>80% viability), whereas, folic acid-capped platinum nanoparticles showed a reduced viability down to 24% after 72 h of exposure at a concentration of 100 μg ml(-1) for MCF7 breast cancer cells. Such toxicity, combined with the possibility to incorporate functional organic molecules as capping agents, can be used for developing new drug candidates.

Bioaccumulation and toxicity of CuO nanoparticles by a freshwater invertebrate after waterborne and dietborne exposures

USGS Publications Warehouse

Croteau, Marie-Noele; Misra, Superb K.; Luoma, Samuel N.; Valsami-Jones, Eugenia

2014-01-01

The incidental ingestion of engineered nanoparticles (NPs) can be an important route of uptake for aquatic organisms. Yet, knowledge of dietary bioavailability and toxicity of NPs is scarce. Here we used isotopically modified copper oxide (65CuO) NPs to characterize the processes governing their bioaccumulation in a freshwater snail after waterborne and dietborne exposures. Lymnaea stagnalis efficiently accumulated 65Cu after aqueous and dietary exposures to 65CuO NPs. Cu assimilation efficiency and feeding rates averaged 83% and 0.61 g g–1 d–1 at low exposure concentrations (–1), and declined by nearly 50% above this concentration. We estimated that 80–90% of the bioaccumulated 65Cu concentration in L. stagnalis originated from the 65CuO NPs, suggesting that dissolution had a negligible influence on Cu uptake from the NPs under our experimental conditions. The physiological loss of 65Cu incorporated into tissues after exposures to 65CuO NPs was rapid over the first days of depuration and not detectable thereafter. As a result, large Cu body concentrations are expected in L. stagnalis after exposure to CuO NPs. To the degree that there is a link between bioaccumulation and toxicity, dietborne exposures to CuO NPs are likely to elicit adverse effects more readily than waterborne exposures.

Human health no-effect levels of TiO2 nanoparticles as a function of their primary size

NASA Astrophysics Data System (ADS)

Laurent, Alexis; Harkema, Jack R.; Andersen, Elisabeth W.; Owsianiak, Mikołaj; Vea, Eldbjørg B.; Jolliet, Olivier

2017-04-01

As engineered nanomaterials are increasingly introduced on the market into a broad range of commodities or nanoproducts, there is a need for operational, reliable tool, enabling to consistently assess the risks and impacts associated with the releases of nanoparticles. The lack of a developed metric that accurately represents their toxic effects while capturing the influence of the most relevant physicochemical properties is one of the major impediments. Here, we investigate the relationships between the toxic responses of nano-sized and micro-sized particles in in vivo toxicological studies and their physicochemical properties. Our results for TiO2 particles indicate statistically significant associations between the primary particle size and their toxicity responses for combined inhalation and ingestion exposure routes, although the numerical values should be considered with care due to the inability to encompass influences from other relevant physicochemical properties like surface coatings. These findings allow for expressing mass-based adverse effect levels as a continuous function of the primary size of particles. This meaningful, exploratory metric can thus be used for screening purposes and pave the way for reaching adaptive, robust risk assessments of nanomaterials, e.g. for setting up consistent threshold levels, as well as consistent life cycle assessments of nanoproducts. We provide examples of such applications.

In vitro and ex vivo evaluation of polymeric nanoparticles for vaginal and rectal delivery of the anti-HIV drug dapivirine.

PubMed

das Neves, José; Araújo, Francisca; Andrade, Fernanda; Michiels, Johan; Ariën, Kevin K; Vanham, Guido; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

2013-07-01

Prevention strategies such as the development of microbicides are thought to be valuable in the fight against HIV/AIDS. Despite recent achievements, there is still a long road ahead in the field, particularly at the level of drug formulation. Drug nanocarriers based on polymers may be useful in enhancing local drug delivery while limiting systemic exposure. We prepared differently surface-engineered poly(ε-caprolactone) (PCL) nanoparticles (NPs) and tested their ability to modulate the permeability and retention of dapivirine in cell monolayers and pig vaginal and rectal mucosa. NPs coated with poly(ethylene oxide) (PEO) were shown able to reduce permeability across monolayers/tissues, while modification of nanosystems with cetyl trimethylammonium bromide (CTAB) enhanced transport. In the case of coating NPs with sodium lauryl sulfate (SLS), dapivirine permeability was unchanged. All NPs increased monolayer/tissue drug retention as compared to unformulated dapivirine. This fact was associated, at least partially, to the ability of NPs to be taken up by cells or penetrate mucosal tissue. Cell and tissue toxicity was also affected differently by NPs: PEO modification decreased the in vitro (but not ex vivo) toxicity of dapivirine, while higher toxicity was generally observed for NPs coated with SLS or CTAB. Overall, presented results support that PCL nanoparticles are capable of modulating drug permeability and retention in cell monolayers and mucosal tissues relevant for vaginal and rectal delivery of microbicides. In particular, PEO-modified dapivirine-loaded PCL NPs may be advantageous in increasing drug residence at epithelial cell lines/mucosal tissues, which may potentially increase the efficacy of microbicide drugs.

The Developmental Toxicity of Complex Silica-Embedded Nickel Nanoparticles Is Determined by Their Physicochemical Properties

PubMed Central

Mahoney, Sharlee; Najera, Michelle; Bai, Qing; Burton, Edward A.; Veser, Götz

2016-01-01

Complex engineered nanomaterials (CENs) are a rapidly developing class of structurally and compositionally complex materials that are expected to dominate the next generation of functional nanomaterials. The development of methods enabling rapid assessment of the toxicity risk associated with this type of nanomaterial is therefore critically important. We evaluated the toxicity of three differently structured nickel-silica nanomaterials as prototypical CENs: simple, surface-deposited Ni-SiO2 and hollow and non-hollow core-shell Ni@SiO2 materials (i.e., ~1–2 nm Ni nanoparticles embedded into porous silica shells with and without a central cavity, respectively). Zebrafish embryos were exposed to these CENs, and morphological (survival and malformations) and physiological (larval motility) endpoints were coupled with thorough characterization of physiochemical characteristics (including agglomeration, settling and nickel ion dissolution) to determine how toxicity differed between these CENs and equivalent quantities of Ni2+ salt (based on total Ni). Exposure to Ni2+ ions strongly compromised zebrafish larva viability, and surviving larvae showed severe malformations. In contrast, exposure to the equivalent amount of Ni CEN did not result in these abnormalities. Interestingly, exposure to Ni-SiO2 and hollow Ni@SiO2 provoked abnormalities of zebrafish larval motor function, indicating developmental toxicity, while non-hollow Ni@SiO2 showed no toxicity. Correlating these observations with physicochemical characterization of the CENs suggests that the toxicity of the Ni-SiO2 and hollow Ni@SiO2 material may result partly from an increased effective exposure at the bottom of the well due to rapid settling. Overall, our data suggest that embedding nickel NPs in a porous silica matrix may be a straightforward way to mitigate their toxicity without compromising their functional properties. At the same time, our results also indicate that it is critical to consider modification of the effective exposure when comparing different nanomaterial configurations, because effective exposure might influence NP toxicity more than specific “nano-chemistry” effects. PMID:27031643

Acute toxicity of 31 different nanoparticles to zebrafish (Danio rerio) tested in adulthood and in early life stages – comparative study

PubMed Central

Kovrižnych, Jevgenij A.; Zeljenková, Dagmar; Rollerová, Eva; Szabová, Elena; Wimmerová, Soňa

2013-01-01

At present, nanoparticles are beginning to influence our lives in many ways and understanding the environmental health and safety aspect of nanomaterials has become a crucial issue. The aim of the work was to assess and compare the acute toxicity of 31 different nanomaterials to fish mature individuals Danio rerio with that to fish early life stages on using evaluation of the 48- and 96- hour LC50 values. A further aim was to evaluate teratogenicity of the nanoparticles tested to fish eggs. The nanoparticles tested were: 8 pure metals, 10 metal oxides, 5 other metal compounds and their mixtures, 2 silicon compounds, 3 calcium compounds, and 3 carbon compounds. Using 48-h and 96-h tests of acute toxicity (according to OECD 203), we evaluated mortality data, LC50 values, occurrence of malformations, as well as hatching time. In our study, 6 kinds of nanoparticles – calcium oxide, copper, copper in the form of oxide and CuZnFe4O4, magnesium oxide, and nickel – caused cumulative mortality. Two kinds of nanoparticles – copper and silver – were toxic for fish with LC50 values of approximately 3 mg/L. We did not observe marked differences between the 48-hour and 96-hour acute toxicity LC50 values, yet the possibility to evaluate hatching time in the 96-h acute fish toxicity test seems to be an advantage against that of the 48-hour toxicity. PMID:24179431

Toxicity Assessment of Six Titanium Dioxide Nanoparticles in Human Epidermal Keratinocytes

EPA Science Inventory

Toxicity Assessment of Six Titanium Dioxide Nanoparticles in Human Epidermal Keratinocytes Nanoparticle uptake in cells may be an important determinant of their potential cytotoxic and inflammatory effects. Six commercial TiO2 NP (A=Alfa Aesar,10nm, A*=Alfa Aesar 32nm, B=P25 27...

Ingestion of gallium phosphide nanowires has no adverse effect on Drosophila tissue function.

PubMed

Adolfsson, Karl; Schneider, Martina; Hammarin, Greger; Häcker, Udo; Prinz, Christelle N

2013-07-19

Engineered nanoparticles have been under increasing scrutiny in recent years. High aspect ratio nanoparticles such as carbon nanotubes and nanowires have raised safety concerns due to their geometrical similarity to asbestos fibers. III-V epitaxial semiconductor nanowires are expected to be utilized in devices such as LEDs and solar cells and will thus be available to the public. In addition, clean-room staff fabricating and characterizing the nanowires are at risk of exposure, emphasizing the importance of investigating their possible toxicity. Here we investigated the effects of gallium phosphide nanowires on the fruit fly Drosophila melanogaster. Drosophila larvae and/or adults were exposed to gallium phosphide nanowires by ingestion with food. The toxicity and tissue interaction of the nanowires was evaluated by investigating tissue distribution, activation of immune response, genome-wide gene expression, life span, fecundity and somatic mutation rates. Our results show that gallium phosphide nanowires applied through the diet are not taken up into Drosophila tissues, do not elicit a measurable immune response or changes in genome-wide gene expression and do not significantly affect life span or somatic mutation rate.

Ingestion of gallium phosphide nanowires has no adverse effect on Drosophila tissue function

NASA Astrophysics Data System (ADS)

Adolfsson, Karl; Schneider, Martina; Hammarin, Greger; Häcker, Udo; Prinz, Christelle N.

2013-07-01

Engineered nanoparticles have been under increasing scrutiny in recent years. High aspect ratio nanoparticles such as carbon nanotubes and nanowires have raised safety concerns due to their geometrical similarity to asbestos fibers. III-V epitaxial semiconductor nanowires are expected to be utilized in devices such as LEDs and solar cells and will thus be available to the public. In addition, clean-room staff fabricating and characterizing the nanowires are at risk of exposure, emphasizing the importance of investigating their possible toxicity. Here we investigated the effects of gallium phosphide nanowires on the fruit fly Drosophila melanogaster. Drosophila larvae and/or adults were exposed to gallium phosphide nanowires by ingestion with food. The toxicity and tissue interaction of the nanowires was evaluated by investigating tissue distribution, activation of immune response, genome-wide gene expression, life span, fecundity and somatic mutation rates. Our results show that gallium phosphide nanowires applied through the diet are not taken up into Drosophila tissues, do not elicit a measurable immune response or changes in genome-wide gene expression and do not significantly affect life span or somatic mutation rate.

Aerosolized ZnO nanoparticles induce toxicity in alveolar type II epithelial cells at the air-liquid interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Yumei; Williams, Nolann G.; Tolic, Ana

The majority of in vitro studies characterizing the impact of engineered nanoparticles (NPs) on cells that line the respiratory tract were conducted in cells exposed to NPs in suspension. This approach introduces processes that are unlikely to occur during inhaled NP exposures in vivo, such as the shedding of toxic doses of dissolved ions. ZnO NPs are used extensively and pose significant sources for human exposure. Exposures to airborne ZnO NPs can induce adverse effects, but the relevance of the dissolved Zn2+ to the observed effects in vivo is still unclear. Our goal was to mimic in vivo exposures tomore » airborne NPs and decipher the contribution of the intact NP from the contribution of the dissolved ions to airborne ZnO NP toxicity. We established the exposure of alveolar type II epithelial cells to aerosolized NPs at the air-liquid interface (ALI), and compared the impact of aerosolized ZnO NPs and NPs in suspension at the same cellular doses, measured as the number of particles per cell. By evaluating membrane integrity and cell viability 6 and 24 hours post exposure we found that aerosolized NPs induced toxicity at the ALI at doses that were in the same order of magnitude as doses required to induce toxicity in submersed cultures. In addition, distinct patterns of oxidative stress were observed in the two exposure systems. These observations unravel the ability of airborne ZnO NPs to induce toxicity without the contribution of dissolved Zn2+ and suggest distinct mechanisms at the ALI and in submersed cultures.« less

Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review.

PubMed

Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F; Huo, Li-Jun

2017-01-01

In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations.

Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review

PubMed Central

Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F.; Huo, Li-Jun

2017-01-01

In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations. PMID:28928662

Comparative Proteomic Analysis of the Molecular Responses of Mouse Macrophages to Titanium Dioxide and Copper Oxide Nanoparticles Unravels Some Toxic Mechanisms for Copper Oxide Nanoparticles in Macrophages

PubMed Central

Triboulet, Sarah; Aude-Garcia, Catherine; Armand, Lucie; Collin-Faure, Véronique; Chevallet, Mireille; Diemer, Hélène; Gerdil, Adèle; Proamer, Fabienne; Strub, Jean-Marc; Habert, Aurélie; Herlin, Nathalie; Van Dorsselaer, Alain; Carrière, Marie; Rabilloud, Thierry

2015-01-01

Titanium dioxide and copper oxide nanoparticles are more and more widely used because of their catalytic properties, of their light absorbing properties (titanium dioxide) or of their biocidal properties (copper oxide), increasing the risk of adverse health effects. In this frame, the responses of mouse macrophages were studied. Both proteomic and targeted analyses were performed to investigate several parameters, such as phagocytic capacity, cytokine release, copper release, and response at sub toxic doses. Besides titanium dioxide and copper oxide nanoparticles, copper ions were used as controls. We also showed that the overall copper release in the cell does not explain per se the toxicity observed with copper oxide nanoparticles. In addition, both copper ion and copper oxide nanoparticles, but not titanium oxide, induced DNA strands breaks in macrophages. As to functional responses, the phagocytic capacity was not hampered by any of the treatments at non-toxic doses, while copper ion decreased the lipopolysaccharide-induced cytokine and nitric oxide productions. The proteomic analyses highlighted very few changes induced by titanium dioxide nanoparticles, but an induction of heme oxygenase, an increase of glutathione synthesis and a decrease of tetrahydrobiopterin in response to copper oxide nanoparticles. Subsequent targeted analyses demonstrated that the increase in glutathione biosynthesis and the induction of heme oxygenase (e.g. by lovastatin/monacolin K) are critical for macrophages to survive a copper challenge, and that the intermediates of the catecholamine pathway induce a strong cross toxicity with copper oxide nanoparticles and copper ions. PMID:25902355

Ceriodaphnia dubia as a Potential Bio-Indicator for Assessing Acute Aluminum Oxide Nanoparticle Toxicity in Fresh Water Environment

PubMed Central

Pakrashi, Sunandan; Dalai, Swayamprava; Humayun, Ahmed; Chakravarty, Sujay; Chandrasekaran, Natarajan; Mukherjee, Amitava

2013-01-01

Growing nanomaterials based consumer applications have raised concerns about their potential release into the aquatic ecosystems and the consequent toxicological impacts. So environmental monitoring of the nanomaterials in aqueous systems becomes imperative. The current study reveals the potential of Ceriodaphnia dubia (C. dubia) as a bio-indicator for aluminum oxide nanoparticles in a fresh water aquatic ecosystem where it occupies an important ecological niche as a primary consumer. This study aims to investigate the aluminium oxide nanoparticle induced acute toxicity on Ceriodaphnia dubia in a freshwater system. The bioavailability of the aluminum oxide nanoparticles has been studied with respect to their aggregation behavior in the system and correlated with the toxicity endpoints. The oxidative stress generated by the particles contributed greatly toward their toxicity. The crucial role of leached aluminium ion mediated toxicity in the later phases (48 h and 72 h) in conjunction with the effects from the nano-sized particles in the initial phases (24 h) puts forth the dynamics of nanotoxicity in the test system. The internalization of nanoparticles (both gross and systemic uptake) as substantiated through the transmission electron microscopy (TEM) and inductively coupled plasma optical emission spectral (ICP-OES) analysis was another major contributor toward acute toxicity. Concluding the present study, Ceriodaphnia dubia can be a promising candidate for bio-monitoring the aluminium oxide nanoparticles in a fresh water system. PMID:24040143

Ceriodaphnia dubia as a potential bio-indicator for assessing acute aluminum oxide nanoparticle toxicity in fresh water environment.

PubMed

Pakrashi, Sunandan; Dalai, Swayamprava; Humayun, Ahmed; Chakravarty, Sujay; Chandrasekaran, Natarajan; Mukherjee, Amitava

2013-01-01

Growing nanomaterials based consumer applications have raised concerns about their potential release into the aquatic ecosystems and the consequent toxicological impacts. So environmental monitoring of the nanomaterials in aqueous systems becomes imperative. The current study reveals the potential of Ceriodaphnia dubia (C. dubia) as a bio-indicator for aluminum oxide nanoparticles in a fresh water aquatic ecosystem where it occupies an important ecological niche as a primary consumer. This study aims to investigate the aluminium oxide nanoparticle induced acute toxicity on Ceriodaphnia dubia in a freshwater system. The bioavailability of the aluminum oxide nanoparticles has been studied with respect to their aggregation behavior in the system and correlated with the toxicity endpoints. The oxidative stress generated by the particles contributed greatly toward their toxicity. The crucial role of leached aluminium ion mediated toxicity in the later phases (48 h and 72 h) in conjunction with the effects from the nano-sized particles in the initial phases (24 h) puts forth the dynamics of nanotoxicity in the test system. The internalization of nanoparticles (both gross and systemic uptake) as substantiated through the transmission electron microscopy (TEM) and inductively coupled plasma optical emission spectral (ICP-OES) analysis was another major contributor toward acute toxicity. Concluding the present study, Ceriodaphnia dubia can be a promising candidate for bio-monitoring the aluminium oxide nanoparticles in a fresh water system.

Zinc Oxide Nanoparticle Induces Microglial Death by NADPH-Oxidase-Independent Reactive Oxygen Species as well as Energy Depletion.

PubMed

Sharma, Anuj Kumar; Singh, Vikas; Gera, Ruchi; Purohit, Mahaveer Prasad; Ghosh, Debabrata

2017-10-01

Zinc oxide nanoparticle (ZnO-NP) is one of the most widely used engineered nanoparticles. Upon exposure, nanoparticle can eventually reach the brain through various routes, interact with different brain cells, and alter their activity. Microglia is the fastest glial cell to respond to any toxic insult. Nanoparticle exposure can activate microglia and induce neuroinflammation. Simultaneous to activation, microglial death can exacerbate the scenario. Therefore, we focused on studying the effect of ZnO-NP on microglia and finding out the pathway involved in the microglial death. The present study showed that the 24 h inhibitory concentration 50 (IC 50 ) of ZnO-NP for microglia is 6.6 μg/ml. Early events following ZnO-NP exposure involved increase in intracellular calcium level as well as reactive oxygen species (ROS). Neither of NADPH oxidase inhibitors, apocynin, (APO) and diphenyleneiodonium chloride (DPIC) were able to reduce the ROS level and rescue microglia from ZnO-NP toxicity. In contrary, N-acetyl cysteine (NAC) showed opposite effect. Exogenous supplementation of superoxide dismutase (SOD) reduced ROS significantly even beyond control level but partially rescued microglial viability. Interestingly, pyruvate supplementation rescued microglia near to control level. Following 10 h of ZnO-NP exposure, intracellular ATP level was measured to be almost 50 % to the control. ZnO-NP-induced ROS as well as ATP depletion both disturbed mitochondrial membrane potential and subsequently triggered the apoptotic pathway. The level of apoptosis-inducing proteins was measured by western blot analysis and found to be upregulated. Taken together, we have deciphered that ZnO-NP induced microglial apoptosis by NADPH oxidase-independent ROS as well as ATP depletion.

Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and protein interaction

PubMed Central

Choi, Soo-Jin; Choy, Jin-Ho

2014-01-01

Biokinetic studies of zinc oxide (ZnO) nanoparticles involve systematic and quantitative analyses of absorption, distribution, metabolism, and excretion in plasma and tissues of whole animals after exposure. A full understanding of the biokinetics provides basic information about nanoparticle entry into systemic circulation, target organs of accumulation and toxicity, and elimination time, which is important for predicting the long-term toxic potential of nanoparticles. Biokinetic behaviors can be dependent on physicochemical properties, dissolution property in biological fluids, and nanoparticle–protein interaction. Moreover, the determination of biological fates of ZnO nanoparticles in the systemic circulation and tissues is critical in interpreting biokinetic behaviors and predicting toxicity potential as well as mechanism. This review focuses on physicochemical factors affecting the biokinetics of ZnO nanoparticles, in concert with understanding bioavailable fates and their interaction with proteins. PMID:25565844

Effect of flexing and massage on in vivo human skin penetration and toxicity of zinc oxide nanoparticles.

PubMed

Leite-Silva, Vânia R; Liu, David C; Sanchez, Washington Y; Studier, Hauke; Mohammed, Yousuf H; Holmes, Amy; Becker, Wolfgang; Grice, Jeffrey E; Benson, Heather Ae; Roberts, Michael S

2016-05-01

We assessed the effects of flexing and massage on human skin penetration and toxicity of topically applied coated and uncoated zinc oxide nanoparticles (˜75 nm) in vivo. Noninvasive multiphoton tomography with fluorescence lifetime imaging was used to evaluate the penetration of nanoparticles through the skin barrier and cellular apoptosis in the viable epidermis. All nanoparticles applied to skin with flexing and massage were retained in the stratum corneum or skin furrows. No significant penetration into the viable epidermis was seen and no cellular toxicity was detected. Exposure of normal in vivo human skin to these nanoparticles under common in-use conditions of flexing or massage is not associated with significant adverse events.

Chitosan-Acrylic Polymeric Nanoparticles with Dynamic Covalent Bonds. Synthesis and Stimuli Behavior.

PubMed

Palacio, Herman; Otálvaro, Felipe; Giraldo, Luis Fernando; Ponchel, Gilles; Segura-Sánchez, Freimar

2017-12-01

Drug delivery represents one of the most important research fields within the pharmaceutical industry. Different strategies are reported every day in a dynamic search for carriers with the ability to transport drugs across the body, avoiding or decreasing toxic issues and improving therapeutic activity. One of the most interesting strategies currently under research is the development of drug delivery systems sensitive to different stimuli, due to the high potential attributed to the selective delivery of the payload. In this work, a stimuli-sensitive nanocarrier was built with a bifunctional acrylic polymer, linked by imine and disulfide bonds to thiolate chitosan, the latter being a biopolymer widely known in the field of tissue engineering and drug delivery by its biodegradability and biocompatibility. These polymer nanoparticles were exposed to different changes in pH and redox potential, which are environments commonly found inside cancer cells. The results proof the ability of the nanoparticles to keep the original structure when either changes in pH or redox potential were applied individually. However, when both stimuli were applied simultaneously, a disassembly of the nanoparticles was evident. These special characteristics make these nanoparticles suitable nanocarriers with potential for the selective delivery of anticancer drugs.

Simplified TiO2 force fields for studies of its interaction with biomolecules

NASA Astrophysics Data System (ADS)

Luan, Binquan; Huynh, Tien; Zhou, Ruhong

2015-06-01

Engineered TiO2 nanoparticles have been routinely applied in nanotechnology, as well as in cosmetics and food industries. Despite active experimental studies intended to clarify TiO2's biological effects, including potential toxicity, the relation between experimentally inferred nanotoxicity and industry standards for safely applying nanoparticles remains somewhat ambiguous with justified concerns. Supplemental to experiments, molecular dynamics simulations have proven to be efficacious in investigating the molecular mechanism of a biological process occurring at nanoscale. In this article, to facilitate the nanotoxicity and nanomedicine research related to this important metal oxide, we provide a simplified force field, based on the original Matsui-Akaogi force field but compatible to the Lennard-Jones potentials normally used in modeling biomolecules, for simulating TiO2 nanoparticles interacting with biomolecules. The force field parameters were tested in simulating the bulk structure of TiO2, TiO2 nanoparticle-water interaction, as well as the adsorption of proteins on the TiO2 nanoparticle. We demonstrate that these simulation results are consistent with experimental data/observations. We expect that simulations will help to better understand the interaction between TiO2 and molecules.

In vitro toxicity of nanoparticles in BRL 3A rat liver cells.

PubMed

Hussain, S M; Hess, K L; Gearhart, J M; Geiss, K T; Schlager, J J

2005-10-01

This study was undertaken to address the current deficient knowledge of cellular response to nanosized particle exposure. The study evaluated the acute toxic effects of metal/metal oxide nanoparticles proposed for future use in industrial production methods using the in vitro rat liver derived cell line (BRL 3A). Different sizes of nanoparticles such as silver (Ag; 15, 100 nm), molybdenum (MoO(3); 30, 150 nm), aluminum (Al; 30, 103 nm), iron oxide (Fe(3)O(4); 30, 47 nm), and titanium dioxide (TiO(2); 40 nm) were evaluated for their potential toxicity. We also assessed the toxicity of relatively larger particles of cadmium oxide (CdO; 1 microm), manganese oxide (MnO(2); 1-2 microm), and tungsten (W; 27 microm), to compare the cellular toxic responses with respect to the different sizes of nanoparticles with different core chemical compositions. For toxicity evaluations, cellular morphology, mitochondrial function (MTT assay), membrane leakage of lactate dehydrogenase (LDH assay), reduced glutathione (GSH) levels, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were assessed under control and exposed conditions (24h of exposure). Results showed that mitochondrial function decreased significantly in cells exposed to Ag nanoparticles at 5-50 microg/ml. However, Fe(3)O(4), Al, MoO(3) and TiO(2) had no measurable effect at lower doses (10-50 microg/ml), while there was a significant effect at higher levels (100-250 microg/ml). LDH leakage significantly increased in cells exposed to Ag nanoparticles (10-50 microg/ml), while the other nanoparticles tested displayed LDH leakage only at higher doses (100-250 microg/ml). In summary the Ag was highly toxic whereas, MoO(3) moderately toxic and Fe(3)O(4), Al, MnO(2) and W displayed less or no toxicity at the doses tested. The microscopic studies demonstrated that nanoparticle-exposed cells at higher doses became abnormal in size, displaying cellular shrinkage, and an acquisition of an irregular shape. Due to toxicity of silver, further study conducted with reference to its oxidative stress. The results exhibited significant depletion of GSH level, reduced mitochondrial membrane potential and increase in ROS levels, which suggested that cytotoxicity of Ag (15, 100 nm) in liver cells is likely to be mediated through oxidative stress.

Developmental phytotoxicity of metal oxide nanoparticles to Arabidopsis thaliana.

PubMed

Lee, Chang Woo; Mahendra, Shaily; Zodrow, Katherine; Li, Dong; Tsai, Yu-Chang; Braam, Janet; Alvarez, Pedro J J

2010-03-01

Phytotoxicity is an important consideration to understand the potential environmental impacts of manufactured nanomaterials. Here, we report on the effects of four metal oxide nanoparticles, aluminum oxide (nAl(2)O(3)), silicon dioxide (nSiO(2)), magnetite (nFe(3)O(4)), and zinc oxide (nZnO), on the development of Arabidopsis thaliana (Mouse-ear cress). Three toxicity indicators (seed germination, root elongation, and number of leaves) were quantified following exposure to each nanoparticle at three concentrations: 400, 2,000, and 4,000 mg/L. Among these particles, nZnO was most phytotoxic, followed by nFe(3)O(4), nSiO(2), and nAl(2)O(3), which was not toxic. Consequently, nZnO was further studied to discern the importance of particle size and zinc dissolution as toxicity determinants. Soluble zinc concentrations in nanoparticle suspensions were 33-fold lower than the minimum inhibitory concentration of dissolved zinc salt (ZnCl(2)), indicating that zinc dissolution could not solely account for the observed toxicity. Inhibition of seed germination by ZnO depended on particle size, with nanoparticles exerting higher toxicity than larger (micron-sized) particles at equivalent concentrations. Overall, this study shows that direct exposure to nanoparticles significantly contributed to phytotoxicity and underscores the need for eco-responsible disposal of wastes and sludge containing metal oxide nanoparticles.

Recent trends in drug delivery system using protein nanoparticles.

PubMed

Sripriyalakshmi, S; Jose, Pinkybel; Ravindran, Aswathy; Anjali, C H

2014-09-01

Engineered nanoparticles that can facilitate drug formulation and passively target tumours have been under extensive research in recent years. These successes have driven a new wave of significant innovation in the generation of advanced particles. The fate and transport of diagnostic nanoparticles would significantly depend on nonselective drug delivery, and hence the use of high drug dosage is implemented. In this perspective, nanocarrier-based drug targeting strategies can be used which improve the selective delivery of drugs to the site of action, i.e. drug targeting. Pharmaceutical industries majorly focus on reducing the toxicity and side effects of drugs but only recently it has been realised that carrier systems themselves may pose risks to the patient. Proteins are compatible with biological systems and they are biodegradable. They offer a multitude of moieties for modifications to tailor drug binding, imaging or targeting entities. Thus, protein nanoparticles provide outstanding contributions as a carrier for drug delivery systems. This review summarises recent progress in particle-based therapeutic delivery and discusses important concepts in particle design and biological barriers for developing the next generation of particles drug delivery systems.

In vitro toxicity of zinc oxide nanoparticles: a review

NASA Astrophysics Data System (ADS)

Pandurangan, Muthuraman; Kim, Doo Hwan

2015-03-01

The toxic effect of ZnO nanoparticles is due to their solubility. ZnO nanoparticles dissolve in the extracellular region, which in turn increases the intracellular [Zn2+] level. The mechanism for increased intracellular [Zn2+] level and ZnO nanoparticles dissolution in the medium is still unclear. Cytotoxicity, increased oxidative stress, increased intracellular [Ca2+] level, decreased mitochondrial membrane potential, and interleukin-8 productions occur in the BEAS-2B bronchial epithelial cells and A549 alveolar adenocarcinoma cells following the exposure of ZnO nanoparticles. Confluent C2C12 cells are more resistant to ZnO nanoparticles compared to the sparse monolayer. Loss of 3T3-L1 cell viability, membrane leakage, and morphological changes occurs due to exposure of ZnO nanoparticles. ZnO nanoparticle induces cytotoxicity and mitochondrial dysfunction in RKO colon carcinoma cells. The occurrence of apoptosis, increased ROS level, reduced mitochondrial activity and formation of tubular intracellular structures are reported following exposure of ZnO nanoparticles in skin cells. Macrophages, monocytes, and dendritic cells are affected by ZnO nanoparticles. In addition, genotoxicity is also induced. The present review summarizes the literature on in vitro toxicity of ZnO nanoparticles (10-100 nm) on various cell lines.

The toxic effects of l-Cysteine-capped cadmium sulfide nanoparticles on the aquatic plant Spirodela polyrrhiza

NASA Astrophysics Data System (ADS)

Khataee, Alireza; Movafeghi, Ali; Nazari, Fatemeh; Vafaei, Fatemeh; Dadpour, Mohammad Reza; Hanifehpour, Younes; Joo, Sang Woo

2014-12-01

Plants play an important role in the fate of nanoparticles in the environment through their uptake, bioaccumulation, and transfer to trophic chains. However, the impacts of nanoparticles on plants as essential components of all ecosystems are not well documented. In the present study, the toxic effects of l-Cysteine-capped CdS nanoparticles on Spirodela polyrrhiza as an aquatic higher plant species were studied. l-Cysteine-capped CdS nanoparticles were synthesized using hydrothermal method and their characteristics were determined by XRD, SEM, HR-TEM, and FT-IR techniques. The diameter of majority of synthesized nanoparticles was about 15-20 nm. Subsequently, the uptake of l-Cysteine-capped CdS nanoparticles by the plant species was confirmed using epifluorescence microscopy. The activity of peroxidase and superoxide dismutase as antioxidant enzymes was assayed and the relative frond number was calculated in the presence of different concentrations of l-Cysteine-capped CdS nanoparticles. The obtained results revealed the toxic effects of the synthesized nanoparticles on S. polyrrhiza, leading to growth reduction and significant changes in antioxidant enzymes' activity.

Development and evaluation of co-formulated docetaxel and curcumin biodegradable nanoparticles for parenteral administration.

PubMed

Pawar, Harish; Wankhade, Shrikant Rameshrao; Yadav, Dharmendra K; Suresh, Sarasija

2016-09-01

Technology for development of biodegradable nanoparticles encapsulating combinations for enhanced efficacy. To develop docetaxel (DTX) and curcumin (CRM) co-encapsulated biodegradable nanoparticles for parenteral administration with potential for prolonged release and decreased toxicity. Modified emulsion solvent-evaporation technique was employed in the preparation of the nanoparticles optimized by the face centered-central composite design (FC-CCD). The uptake potential was studied in MCF-7 cells, while the toxicity was evaluated by in vitro hemolysis test. In vivo pharmacokinetic was evaluated in male Wistar rats. Co-encapsulated nanoparticles were developed of 219 nm size, 0.154 PDI, -13.74 mV zeta potential and 67.02% entrapment efficiency. Efficient uptake was observed by the nanoparticles in MCF-7 cells with decreased toxicity in comparison with the commercial DTX intravenous injection, Taxotere®. The nanoparticles exhibited biphasic release with initial burst release followed by sustained release for 5 days. The nanoparticles displayed a 4.3-fold increase in AUC (391.10 ± 32.94 versus 89.77 ± 10.58 μg/ml min) in comparison to Taxotere® with a 6.2-fold increase in MRT (24.78 ± 2.36 versus 3.58 ± 0.21 h). The nanoparticles exhibited increased uptake, prolonged in vitro and in vivo release, with decreased toxicity thus exhibiting potential for enhanced efficacy.

Imaging interactions of metal oxide nanoparticles with macrophage cells by ultra-high resolution scanning electron microscopy techniques†

PubMed Central

Plascencia-Villa, Germán; Starr, Clarise R.; Armstrong, Linda S.; Ponce, Arturo

2016-01-01

Use of engineered metal oxide nanoparticles in a plethora of biological applications and custom products has warned about some possible dose-dependent cytotoxic effects. Macrophages are key components of the innate immune system used to study possible toxic effects and internalization of different nanoparticulate materials. In this work, ultra-high resolution field emission scanning electron microscopy (FE-SEM) was used to offer new insights into the dynamical processes of interaction of nanomaterials with macrophage cells dosed with different concentrations of metal oxide nanoparticles (CeO2, TiO2 and ZnO). The versatility of FE-SEM has allowed obtaining a detailed characterization of processes of adsorption and endocytosis of nanoparticles, by using advanced analytical and imaging techniques on complete unstained uncoated cells, including secondary electron imaging, high-sensitive backscattered electron imaging, X-ray microanalysis and stereoimaging. Low voltage BF/DF-STEM confirmed nanoparticle adsorption and internalization into endosomes of CeO2 and TiO2, whereas ZnO develop apoptosis after 24 h of interaction caused by dissolution and invasion of cell nucleus. Ultra-high resolution scanning electron microscopy techniques provided new insights into interactions of inorganic nanoparticles with macrophage cells with high spatial resolution. PMID:23023106

Particles in the oceans: Implication for a safe marine environment.

PubMed

Blasco, Julian; Corsi, Ilaria; Matranga, Valeria

2015-10-01

Strategies and technologies for the ecosafety assessment and design of engineered particles entering the marine environment are urgently needed. As the application of nanoparticles in science and technology grows, the need to understand their impact on the marine environment becomes increasingly important. This Editorial introduces a Special Issue on the topic of a sustainable and safety use of nanoparticles for protecting, recovering and supporting the oceans' environment and consequently human health. The issue focus on the impact of micro/nano-plastics and metallic nanoparticles on marine organisms, as well as some methodological aspects associated to the eco/toxicity and analytical approaches for in deep physico-chemical characterization of nanoparticles in marine waters and sediment media. Important and urgent topics are addressed in the field of nano-ecosafety in order to assess more precisely both exposure routes and environmental hazards of nanoparticles in the ocean. Ecotoxicological and toxicological data, obtained using a wide variety of organisms representative of different trophic levels and biological organization, from whole animals to macromolecules, will be useful for a better definition of cleaner and safer nanoparticles. Efforts in developing a broad understanding of target species, expected results, benchmarks and timelines, will be of primary importance. Copyright © 2015. Published by Elsevier Ltd.

High-sensitivity, real-time, ratiometric imaging of surface-enhanced Raman scattering nanoparticles with a clinically translatable Raman endoscope device.

PubMed

Garai, Ellis; Sensarn, Steven; Zavaleta, Cristina L; Van de Sompel, Dominique; Loewke, Nathan O; Mandella, Michael J; Gambhir, Sanjiv S; Contag, Christopher H

2013-09-01

Topical application and quantification of targeted, surface-enhanced Raman scattering (SERS) nanoparticles offer a new technique that has the potential for early detection of epithelial cancers of hollow organs. Although less toxic than intravenous delivery, the additional washing required to remove unbound nanoparticles cannot necessarily eliminate nonspecific pooling. Therefore, we developed a real-time, ratiometric imaging technique to determine the relative concentrations of at least two spectrally unique nanoparticle types, where one serves as a nontargeted control. This approach improves the specific detection of bound, targeted nanoparticles by adjusting for working distance and for any nonspecific accumulation following washing. We engineered hardware and software to acquire SERS signals and ratios in real time and display them via a graphical user interface. We report quantitative, ratiometric imaging with nanoparticles at pM and sub-pM concentrations and at varying working distances, up to 50 mm. Additionally, we discuss optimization of a Raman endoscope by evaluating the effects of lens material and fiber coating on background noise, and theoretically modeling and simulating collection efficiency at various working distances. This work will enable the development of a clinically translatable, noncontact Raman endoscope capable of rapidly scanning large, topographically complex tissue surfaces for small and otherwise hard to detect lesions.

Smart blood cell and microvesicle-based Trojan horse drug delivery: Merging expertise in blood transfusion and biomedical engineering in the field of nanomedicine.

PubMed

Wu, Yu-Wen; Goubran, Hadi; Seghatchian, Jerard; Burnouf, Thierry

2016-04-01

Therapeutic and diagnostic applications of nanomedicine are playing increasingly important roles in human health. Various types of synthetic nanoparticles, including liposomes, micelles, and other nanotherapeutic platforms and conjugates, are being engineered to encapsulate or carry drugs for treating diseases such as cancer, cardiovascular disorders, neurodegeneration, and inflammations. Nanocarriers are designed to increase the half-life of drugs, decrease their toxicity and, ideally, target pathological sites. Developing smart carriers with the capacity to deliver drugs specifically to the microenvironment of diseased cells with minimum systemic toxicity is the goal. Blood cells, and potentially also the liposome-like micro- and nano-vesicles they generate, may be regarded as ideally suited to perform such specific targeting with minimum immunogenic risks. Blood cell membranes are "decorated" with complex physiological receptors capable of targeting and communicating with other cells and tissues and delivering their content to the surrounding pathological microenvironment. Blood cells, such as erythrocytes, have been developed as permeable carriers to release drugs to diseased tissues or act as biofactory allowing enzymatic degradation of a pathological substrate. Interestingly, attempts are also being made to improve the targeting capacity of synthetic nanoparticles by "decorating" their surface with blood cell membrane receptor-like biochemical structures. Research is needed to further explore the benefits that blood cell-derived microvesicles, as a Trojan horse delivery systems, can bring to the arsenal of therapeutic micro- and nanotechnologies. This short review focuses on the therapeutic roles that red blood cells and platelets can play as smart drug-delivery systems, and highlights the benefits that blood transfusion expertise can bring to this exciting and novel biomedical engineering field. Copyright © 2016 Elsevier Ltd. All rights reserved.

ZnO, TiO(2), SiO(2,) and Al(2)O(3) nanoparticles-induced toxic effects on human fetal lung fibroblasts.

PubMed

Zhang, Xiao Qiang; Yin, Li Hong; Tang, Meng; Pu, Yue Pu

2011-12-01

This study aims to investigate and compare the toxic effects of four types of metal oxide (ZnO, TiO(2), SiO(2,) and Al(2)O(3)) nanoparticles with similar primary size (∼20 nm) on human fetal lung fibroblasts (HFL1) in vitro. The HFL1 cells were exposed to the nanoparticles, and toxic effects were analyzed by using MTT assay, cellular morphology observation and Hoechst 33 258 staining. The results show that the four types of metal oxide nanoparticles lead to cellular mitochondrial dysfunction, morphological modifications and apoptosis at the concentration range of 0.25-1.50 mg/mL and the toxic effects are obviously displayed in dose-dependent manner. ZnO is the most toxic nanomaterials followed by TiO(2), SiO(2), and Al(2)O(3) nanoparticles in a descending order. The results highlight the differential cytotoxicity associated with exposure to ZnO, TiO(2), SiO(2), and Al(2)O(3) nanoparticles, and suggest an extreme attention to safety utilization of these nanomaterials. Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

Oxidative Stress and Nano-Toxicity Induced by TiO2 and ZnO on WAG Cell Line

PubMed Central

Dubey, Akhilesh; Goswami, Mukunda; Yadav, Kamalendra; Chaudhary, Dharmendra

2015-01-01

Metallic nanoparticles are widely used in cosmetics, food products and textile industry. These particles are known to cause respiratory toxicity and epithelial inflammation. They are eventually released to aquatic environment necessitating toxicity studies in cells from respiratory organs of aquatic organisms. Hence, we have developed and characterized a new cell line, WAG, from gill tissue of Wallago attu for toxicity assessment of TiO2 and ZnO nanoparticles. The efficacy of the cell line as an in vitro system for nanoparticles toxicity studies was established using electron microscopy, cytotoxicity assays, genotoxicity assays and oxidative stress biomarkers. Results obtained with MTT assay, neutral red uptake assay and lactate dehydrogenase assay showed acute toxicity to WAG cells with IC50 values of 25.29±0.12, 34.99±0.09 and 35.06±0.09 mg/l for TiO2 and 5.716±0.1, 3.160±0.1 and 5.57±0.12 mg/l for ZnO treatment respectively. The physicochemical properties and size distribution of nanoparticles were characterized using electron microscopy with integrated energy dispersive X-ray spectroscopy and Zetasizer. Dose dependent increase in DNA damage, lipid peroxidation and protein carbonylation along with a significant decrease in activity of Superoxide Dismutase, Catalase, total Glutathione levels and total antioxidant capacity with increasing concentration of exposed nanoparticles indicated that the cells were under oxidative stress. The study established WAG cell line as an in vitro system to study toxicity mechanisms of nanoparticles on aquatic organisms. PMID:26011447

Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups

PubMed Central

Ekkapongpisit, Maneerat; Giovia, Antonino; Follo, Carlo; Caputo, Giuseppe; Isidoro, Ciro

2012-01-01

Background and methods Nanoparticles engineered to carry both a chemotherapeutic drug and a sensitive imaging probe are valid tools for early detection of cancer cells and to monitor the cytotoxic effects of anticancer treatment simultaneously. Here we report on the effect of size (10–30 nm versus 50 nm), type of material (mesoporous silica versus polystyrene), and surface charge functionalization (none, amine groups, or carboxyl groups) on biocompatibility, uptake, compartmentalization, and intracellular retention of fluorescently labeled nanoparticles in cultured human ovarian cancer cells. We also investigated the involvement of caveolae in the mechanism of uptake of nanoparticles. Results We found that mesoporous silica nanoparticles entered via caveolae-mediated endocytosis and reached the lysosomes; however, while the 50 nm nanoparticles permanently resided within these organelles, the 10 nm nanoparticles soon relocated in the cytoplasm. Naked 10 nm mesoporous silica nanoparticles showed the highest and 50 nm carboxyl-modified mesoporous silica nanoparticles the lowest uptake rates, respectively. Polystyrene nanoparticle uptake also occurred via a caveolae-independent pathway, and was negatively affected by serum. The 30 nm carboxyl-modified polystyrene nanoparticles did not localize in lysosomes and were not toxic, while the 50 nm amine-modified polystyrene nanoparticles accumulated within lysosomes and eventually caused cell death. Ovarian cancer cells expressing caveolin-1 were more likely to endocytose these nanoparticles. Conclusion These data highlight the importance of considering both the physicochemical characteristics (ie, material, size and surface charge on chemical groups) of nanoparticles and the biochemical composition of the cell membrane when choosing the most suitable nanotheranostics for targeting cancer cells. PMID:22904626

Plasmonic engineering of spontaneous emission from silicon nanocrystals.

PubMed

Goffard, Julie; Gérard, Davy; Miska, Patrice; Baudrion, Anne-Laure; Deturche, Régis; Plain, Jérôme

2013-01-01

Silicon nanocrystals offer huge advantages compared to other semi-conductor quantum dots as they are made from an abundant, non-toxic material and are compatible with silicon devices. Besides, among a wealth of extraordinary properties ranging from catalysis to nanomedicine, metal nanoparticles are known to increase the radiative emission rate of semiconductor quantum dots. Here, we use gold nanoparticles to accelerate the emission of silicon nanocrystals. The resulting integrated hybrid emitter is 5-fold brighter than bare silicon nanocrystals. We also propose an in-depth analysis highlighting the role of the different physical parameters in the photoluminescence enhancement phenomenon. This result has important implications for the practical use of silicon nanocrystals in optoelectronic devices, for instance for the design of efficient down-shifting devices that could be integrated within future silicon solar cells.

Cancer Theranostic Nanoparticles Self-Assembled from Amphiphilic Small Molecules with Equilibrium Shift-Induced Renal Clearance

PubMed Central

Ma, Yuan; Mou, Quanbing; Sun, Mo; Yu, Chunyang; Li, Jianqi; Huang, Xiaohua; Zhu, Xinyuan; Yan, Deyue; Shen, Jian

2016-01-01

Nano drug delivery systems have emerged as promising candidates for cancer therapy, whereas their uncertainly complete elimination from the body within specific timescales restricts their clinical translation. Compared with hepatic clearance of nanoparticles, renal excretion of small molecules is preferred to minimize the agent-induced toxicity. Herein, we construct in vivo renal-clearable nanoparticles, which are self-assembled from amphiphilic small molecules holding the capabilities of magnetic resonance imaging (MRI) and chemotherapy. The assembled nanoparticles can accumulate in tumor tissues for their nano-characteristics, while the small molecules dismantled from the nanoparticles can be efficiently cleared by kidneys. The renal-clearable nanoparticles exhibit excellent tumor-inhibition performance as well as low side effects and negligible chronic toxicity. These results demonstrate a potential strategy for small molecular nano drug delivery systems with obvious anticancer effect and low-toxic metabolism pathway for clinical applications. PMID:27446502

Toxicity evaluation of cordycepin and its delivery system for sustained in vitro anti-lung cancer activity

NASA Astrophysics Data System (ADS)

Aramwit, Pornanong; Porasuphatana, Supatra; Srichana, Teerapol; Nakpheng, Titpawan

2015-03-01

In the previous study, we have found that the cordycepin which was extracted from Cordyceps mycelia produced by growing Cordyceps militaris on the dead larva of Bombyx mori silkworms showed the anti-proliferative effect toward lung cancer cells without toxicity to non-cancer cells. In this work, the cordycepin was tested for its in vitro mutagenicity and in vivo toxicity. From the Ames test and subacute toxicity test using oral administration in a rat model, the cordycepin was proved to be a non-mutagenic and non-toxic compound. The hematology and blood chemistry as well as the microanatomical characteristic of the tissues of rats fed with cordycepin every day for consecutive 30 days were comparable to those of the normal ones. Then, the cordycepin was incorporated in gelatin type A (GA) and gelatin type B (GB) nanoparticles aimed to sustain its release and activity. The cordycepin incorporated in both GA and GB nanoparticles showed the sustained release profiles. GA nanoparticles could encapsulate cordycepin at higher encapsulation efficiency due to the attractive electrostatic interaction between the positive-charged GA and the negative-charged cordycepin. However, GA nanoparticles released cordycepin at the higher amount possibly because of the large surface area of small size nanoparticles. Comparing to GB nanoparticles, the higher amount of cordycepin released from GA nanoparticles showed the higher anti-proliferative and anti-migratory effects on A549 lung cancer cells. In conclusion, GA nanoparticles were suggested as a suitable carrier for the sustained release of cordycepin. The GA nanoparticles releasing cordycepin could be an effective and non-invasive material for the treatment of lung cancer cells.

In vitro investigation of oxide nanoparticle and carbon nanotube toxicity and intracellular accumulation in A549 human pneumocytes.

PubMed

Simon-Deckers, A; Gouget, B; Mayne-L'hermite, M; Herlin-Boime, N; Reynaud, C; Carrière, M

2008-11-20

If released in the environment, nanomaterials might be inhaled by populations and cause damage to the deepest regions of the respiratory tract, i.e., the alveolar compartment. To model this situation, we studied the response of A549 human pneumocytes after exposure to aluminium oxide or titanium oxide nanoparticles, and to multi-walled carbon nanotubes. The influence of size, crystalline structure and chemical composition was investigated. After a detailed identification of nanomaterial physico-chemical characteristics, cells were exposed in vitro and viability and intracellular accumulation were assessed. In our conditions, carbon nanotubes were more toxic than metal oxide nanoparticles. Our results confirmed that both nanotubes and nanoparticles are able to rapidly enter into cells, and distribute in the cytoplasm and intracellular vesicles. Among nanoparticles, we demonstrate significant difference in biological response as a function of size, crystalline phase and chemical composition. Their toxicity was globally lower than nanotubes toxicity. Among nanotubes, the length did not influence cytotoxicity, neither the presence of metal catalyst impurities.

Albumin nanoparticle encapsulation of potent cytotoxic therapeutics shows sustained drug release and alleviates cancer drug toxicity.

PubMed

Wang, Hangxiang; Wu, Jiaping; Xu, Li; Xie, Ke; Chen, Chao; Dong, Yuehan

2017-02-23

We here provide the first report on the construction of nanoparticles formulating highly potent cytotoxic therapeutics using albumin. Maytansinoid DM1 can be efficiently integrated into albumin nanoparticles, resulting in remarkable alleviation of in vivo drug toxicity and expanding the repertoire of albumin technology available for cancer therapy.

Study of ecotoxicity of silver nanoparticles using algae

NASA Astrophysics Data System (ADS)

Kustov, L. M.; Abramenko, N. B.

2016-11-01

Silver nanoparticles have been prepared and tested for their ecotoxicity using Chlorella vulgaris Beijer. algae as a hydrobiotic test organism and a photometric method of control. The toxicity was supposed to originate from Ag+ ions released into the aqueous solution. Also, the toxicity of the stabilizing agent was found to be comparable to that of silver nanoparticles.

Gene transcription patterns and energy reserves in Daphnia magna show no nanoparticle specific toxicity when exposed to ZnO and CuO nanoparticles.

PubMed

Adam, Nathalie; Vergauwen, Lucia; Blust, Ronny; Knapen, Dries

2015-04-01

There is still a lot of contradiction on whether metal ions are solely responsible for the observed toxicity of ZnO and CuO nanoparticles to aquatic species. While most experiments have studied nanoparticle effects at organismal levels (e.g. mortality, reproduction), effects at lower levels of biological organization may clarify the role of metal ions, nanoparticles and nanoparticle aggregates. In this study, the effect of ZnO and CuO nanoparticles was tested at two lower levels: energy reserves and gene transcription and compared with zinc and copper salts. Daphnia magna was exposed during 96h to 10% immobilization concentrations of all chemicals, after which daphnids were sampled for determination of glycogen, lipid and protein concentration and for a differential gene transcription analysis using microarray. The dissolved, nanoparticle and aggregated fraction in the medium was characterized. The results showed that ZnO nanoparticles had largely dissolved directly after addition to the test medium. The CuO nanoparticles mostly formed aggregates, while only a small fraction dissolved. The exposure to zinc (both nano and metal salt) had no effect on the available energy reserves. However, in the copper exposure, the glycogen, lipid and protein concentration in the exposed daphnids was lower than in the unexposed ones. When comparing the nanoparticle (ZnO or CuO) exposed daphnids to the metal salt (zinc or copper salt) exposed daphnids, the microarray results showed no significantly differentially transcribed gene fragments. The results indicate that under the current exposure conditions the toxicity of ZnO and CuO nanoparticles to D. magna is solely caused by toxic metal ions. Copyright © 2015 Elsevier Inc. All rights reserved.

Nanometrology and its perspectives in environmental research.

PubMed

Kim, Hyun-A; Seo, Jung-Kwan; Kim, Taksoo; Lee, Byung-Tae

2014-01-01

Rapid increase in engineered nanoparticles (ENPs) in many goods has raised significant concern about their environmental safety. Proper methodologies are therefore needed to conduct toxicity and exposure assessment of nanoparticles in the environment. This study reviews several analytical techniques for nanoparticles and summarizes their principles, advantages and disadvantages, reviews the state of the art, and offers the perspectives of nanometrology in relation to ENP studies. Nanometrology is divided into five techniques with regard to the instrumental principle: microscopy, light scattering, spectroscopy, separation, and single particle inductively coupled plasma-mass spectrometry. Each analytical method has its own drawbacks, such as detection limit, ability to quantify or qualify ENPs, and matrix effects. More than two different analytical methods should be used to better characterize ENPs. In characterizing ENPs, the researchers should understand the nanometrology and its demerits, as well as its merits, to properly interpret their experimental results. Challenges lie in the nanometrology and pretreatment of ENPs from various matrices; in the extraction without dissolution or aggregation, and concentration of ENPs to satisfy the instrumental detection limit.

Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy.

PubMed

McLaughlin, Mark F; Woodward, Jonathan; Boll, Rose A; Wall, Jonathan S; Rondinone, Adam J; Kennel, Stephen J; Mirzadeh, Saed; Robertson, J David

2013-01-01

Targeted radiotherapies maximize cytotoxicty to cancer cells. In vivo α-generator targeted radiotherapies can deliver multiple α particles to a receptor site dramatically amplifying the radiation dose delivered to the target. The major challenge with α-generator radiotherapies is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate which is critical to minimize toxicity to healthy, non-target tissue. The recoil energy of the (225)Ac daughters following α decay will sever any metal-ligand bond used to form the bioconjugate. This work demonstrates that an engineered multilayered nanoparticle-antibody conjugate can deliver multiple α radiations and contain the decay daughters of (225)Ac while targeting biologically relevant receptors in a female BALB/c mouse model. These multi-shell nanoparticles combine the radiation resistance of lanthanide phosphate to contain (225)Ac and its radioactive decay daughters, the magnetic properties of gadolinium phosphate for easy separation, and established gold chemistry for attachment of targeting moieties.

Evaluating the potential of gold, silver, and silica nanoparticles to saturate mononuclear phagocytic system tissues under repeat dosing conditions.

PubMed

Weaver, James L; Tobin, Grainne A; Ingle, Taylor; Bancos, Simona; Stevens, David; Rouse, Rodney; Howard, Kristina E; Goodwin, David; Knapton, Alan; Li, Xiaohong; Shea, Katherine; Stewart, Sharron; Xu, Lin; Goering, Peter L; Zhang, Qin; Howard, Paul C; Collins, Jessie; Khan, Saeed; Sung, Kidon; Tyner, Katherine M

2017-07-17

As nanoparticles (NPs) become more prevalent in the pharmaceutical industry, questions have arisen from both industry and regulatory stakeholders about the long term effects of these materials. This study was designed to evaluate whether gold (10 nm), silver (50 nm), or silica (10 nm) nanoparticles administered intravenously to mice for up to 8 weeks at doses known to be sub-toxic (non-toxic at single acute or repeat dosing levels) and clinically relevant could produce significant bioaccumulation in liver and spleen macrophages. Repeated dosing with gold, silver, and silica nanoparticles did not saturate bioaccumulation in liver or spleen macrophages. While no toxicity was observed with gold and silver nanoparticles throughout the 8 week experiment, some effects including histopathological and serum chemistry changes were observed with silica nanoparticles starting at week 3. No major changes in the splenocyte population were observed during the study for any of the nanoparticles tested. The clinical impact of these changes is unclear but suggests that the mononuclear phagocytic system is able to handle repeated doses of nanoparticles.

Antitubercular activity of ZnO nanoparticles prepared by solution combustion synthesis using lemon juice as bio-fuel.

PubMed

Gopala Krishna, Prashanth; Paduvarahalli Ananthaswamy, Prashanth; Trivedi, Priyanka; Chaturvedi, Vinita; Bhangi Mutta, Nagabhushana; Sannaiah, Ananda; Erra, Amani; Yadavalli, Tejabhiram

2017-06-01

In this study, we report the synthesis, structural and morphological characteristics of zinc oxide (ZnO) nanoparticles using solution combustion synthesis method where lemon juice was used as the fuel. In vitro anti-tubercular activity of the synthesized ZnO nanoparticles and their biocompatibility studies, both in vitro and in vivo were carried out. The synthesized nanoparticles showed inhibition of Mycobacterium tuberculosis H37Ra strain at concentrations as low as 12.5μg/mL. In vitro cytotoxicity study performed with normal mammalian cells (L929, 3T3-L1) showed that ZnO nanoparticles are non-toxic with a Selectivity Index (SI) >10. Cytotoxicity performed on two human cancer cell lines DU-145 and Calu-6 indicated the anti-cancer activity of ZnO nanoparticles at varied concentrations. Results of blood hemolysis indicated the biocompatibility of ZnO nanoparticles. Furthermore, in vivo toxicity studies of ZnO nanoparticles conducted on Swiss albino mice (for 14days as per the OECD 423 guidelines) showed no evident toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effects of Toxic Particles in Human Lung Cells - Research Area 8. Life Sciences

DTIC Science & Technology

2016-01-05

Characterization of Metal Nanoparticles 2.1. Synthesis and Characterization of Nanoparticles We generated and tested a silver colloid solution with a mean... silver and gold nanoparticle -induced effects; and 6) Assess metal levels in whale skin biopsies in the Gulf of Mexico. The first five aims focused...We found that silver , gold and titanium dioxide nanoparticles were relatively non-toxic. Only silver 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND

Effects of sub-acute exposure to TiO2, ZnO and Al2O3 nanoparticles on oxidative stress and histological changes in mouse liver and brain.

PubMed

Shrivastava, Rupal; Raza, Saimah; Yadav, Abhishek; Kushwaha, Pramod; Flora, Swaran J S

2014-07-01

Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. However the information regarding toxicity of these nanoparticles on humans and environment is still deficient. The present study investigated the toxic effects of three metal oxide nanoparticles, TiO2, ZnO and Al2O3 on mouse erythrocytes, brain and liver. Male mice were administered a single oral dose of 500 mg/kg of each nanoparticles for 21 consecutive days. The results suggest that exposure to these nano metallic particles produced a significant oxidative stress in erythrocyte, liver and brain as evident from enhanced levels of Reactive Oxygen Species (ROS) and altered antioxidant enzymes activities. A significant increase in dopamine and norepinephrine levels in brain cerebral cortex and increased brain oxidative stress suggest neurotoxic potential of these nanoparticles. Transmission electron microscopic (TEM) analysis indicated the presence of these nanoparticles inside the cytoplasm and nucleus. These changes were also supported by the inhibition of CuZnSOD and MnSOD, considered as important biomarkers of oxidative stress. The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide and titanium dioxide, respectively. The present results further suggest the involvement of oxidative stress as one of the main mechanisms involved in nanoparticles induced toxic manifestations.

Predictive tests to evaluate oxidative potential of engineered nanomaterials

NASA Astrophysics Data System (ADS)

Ghiazza, Mara; Carella, Emanuele; Oliaro-Bosso, Simonetta; Corazzari, Ingrid; Viola, Franca; Fenoglio, Ivana

2013-04-01

Oxidative stress constitutes one of the principal injury mechanisms through which particulate toxicants (asbestos, crystalline silica, hard metals) and engineered nanomaterials can induce adverse health effects. ROS may be generated indirectly by activated cells and/or directly at the surface of the material. The occurrence of these processes depends upon the type of material. Many authors have recently demonstrated that metal oxides and carbon-based nanoparticles may influence (increasing or decreasing) the generation of oxygen radicals in a cell environment. Metal oxide, such as iron oxides, crystalline silica, and titanium dioxide are able to generate free radicals via different mechanisms causing an imbalance within oxidant species. The increase of ROS species may lead to inflammatory responses and in some cases to the development of cancer. On the other hand carbon-based nanomaterials, such as fullerene, carbon nanotubes, carbon black as well as cerium dioxide are able to scavenge the free radicals generated acting as antioxidant. The high numbers of new-engineered nanomaterials, which are introduced in the market, are exponentially increasing. Therefore the definition of toxicological strategies is urgently needed. The development of acellular screening tests will make possible the reduction of the number of in vitro and in vivo tests to be performed. An integrated protocol that may be used to predict the oxidant/antioxidant potential of engineered nanoparticles will be here presented.

Gold-magnetite nanoparticle-biomolecule conjugates: Synthesis, properties and toxicity studies

NASA Astrophysics Data System (ADS)

Pariti, Akshay

This thesis study focuses on synthesizing and characterizing gold-magnetite optically active magnetic nanoparticle and its conjugation with biomolecules for biomedical applications, especially magnetic fluid hyperthermia treatment for cancerous tissue. Gold nanoparticles have already displayed their potential in the biomedical field. They exhibit excellent optical properties and possess strong surface chemistry which renders them suitable for various biomolecule attachments. Studies have showed gold nanoparticles to be a perfect biocompatible vector. However, clinical trials for gold mediated drug delivery and treatment studied in rat models identified some problems. Of these problems, the low retention time in bloodstream and inability to maneuver externally has been the consequential. To further enhance their potential applications and overcome the problems faced in using gold nanoparticles alone, many researchers have synthesized multifunctional magnetic materials with gold at one terminal. Magnetite, among the investigated magnetic materials is a promising and reliable candidate because of its high magnetic saturation moment and low toxicity. This thesis showcases a simple and facile one pot synthesis of gold-magnetite nanoparticles with an average particle size of 80 nm through hot injection method. The as-synthesized nanoparticles were characterized by XRD, TEM, Mossbauer spectroscopy, SQUID and MTS toxicity studies. The superparamagnetism of the as-synthesized nanoparticles has an interestingly high saturation magnetization moment and low toxicity than the literature values reported earlier. L-cysteine and (-)-EGCG (epigallacatechin-3-gallate) were attached to this multifunctional nanoparticles through the gold terminal and characterized to show the particles applicability through Raman, FTIR and UV-Vis spectroscopy.

Nuclear microscopy as a tool in TiO2 nanoparticles bioaccumulation studies in aquatic species

NASA Astrophysics Data System (ADS)

Pinheiro, Teresa; Moita, Liliana; Silva, Luís; Mendonça, Elsa; Picado, Ana

2013-07-01

Engineered Titanium nanoparticles are used for a wide range of applications from coatings, sunscreen cosmetic additives to solar cells or water treatment agents. Inevitably environmental exposure can be expected and data on the ecotoxicological evaluation of nanoparticles are still scarce. The potential effects of nanoparticles of titanium dioxide (TiO2) on two model organisms, the water flea, Daphnia magna and the duckweed Lemna minor, were examined in semichronic toxicity tests. Daphnia and Lemna were exposed to TiO2 nanoparticles (average particle size value of 28 ± 11 nm (n = 42); concentration range, 1.4-25 mg/L) by dietary route and growth in medium containing the nanoparticles of TiO2, respectively. Both morphology and microdistribution of Ti in the individuals were examined by nuclear microscopy techniques. A significant amount of TiO2 was found accumulated in Daphnia exposed to nanoparticles. Nuclear microscopy imaging revealed that Ti was localized only in the digestive tract of the Daphnia, which displayed difficulty in eliminating the nanoparticles from their body. Daphnia showed higher mortality when exposed to higher concentrations of TiO2 (>10 mg/L). The exposure to TiO2 nanoparticles above 25 mg/L caused morphological alterations in Lemna. The roots became stiff and fronds colorless. The Ti mapping of cross-sections of roots and fronds showed that Ti was mainly deposited in the epidermis of the fronds and roots, with minor internalization. In summary, exposure of aquatic organisms to TiO2 nanoparticles may alter the physiology of these organisms at individual and population levels, posing risks to aquatic ecosystems.

Sharpening the focus on occupational safety and health in nanotechnology.

PubMed

Schulte, Paul; Geraci, Charles; Zumwalde, Ralph; Hoover, Mark; Castranova, Vincent; Kuempel, Eileen; Murashov, Vladimir; Vainio, Harri; Savolainen, Kai

2008-12-01

Increasing numbers of workers are involved with the production, use, distribution, and disposal of nanomaterials. At the same time, there is a growing number of reports of adverse biological effects of engineered nanoparticles in test systems. It is useful, at this juncture, to identify critical questions that will help address knowledge gaps concerning the potential occupational hazards of these materials. The questions address (i) hazard classification of engineered nanoparticles, (ii) exposure metrics, (iii) the actual exposures to the different engineered nanoparticles in the workplace, (iv) the limits of engineering controls and personal protective equipment with respect to engineered nanoparticles, (v) the kinds of surveillance programs that may be required at workplaces to protect potentially exposed workers, (vi) whether exposure registers should be established for workers potentially exposed to engineered nanoparticles, and, (vii) whether engineered nanoparticles should be treated as "new" substances and evaluated for safety and hazards?

Interaction of silver nanoparticles with biological objects: antimicrobial properties and toxicity for the other living organisms

NASA Astrophysics Data System (ADS)

Egorova, E. M.

2011-04-01

This paper presents several examples of the biological effects of small-sized silver nanoparticles (10.5±3.5nm) observed in experiments on bacteria, slim mold, unicellular alga and plant seeds. The nanoparticles were prepared by the biochemical synthesis, based on the reduction of metal ions in reverse vicelles by biological reductants - natural plant pigments (flavonoids). It is found that, except for the plant seeds, silver nanoparticles (SNP) act as a strong toxic agent, both in water solution and as part of liquid-phase material. It is shown also that the biological action of silver nanoparticles can not be reduced to the toxic action of silver ions in equivalent concentrations or to that of the surfactant (the SNP stabilizer) present in the SNP water solution. Possible SNP applications are suggested.

Surface functionalization of titanium dioxide nanoparticles: Photo-stability and reactive oxygen species (ROS) generation

NASA Astrophysics Data System (ADS)

Louis, Kacie M.

Metal oxide nanoparticles are becoming increasingly prevalent in society for applications of sunscreens, cosmetics, paints, biomedical imaging, and photovoltaics. Due to the increased surface area to volume ratio of nanoparticles compared to bulk materials, it is important to know the health and safety impacts of these materials. One mechanism of toxicity of nominally "safe" materials such as TiO 2 is through the photocatalytic generation of reactive oxygen species (ROS). ROS production and ligand degradation can affect the bioavailability of these particles in aqueous organisms. We have investigated ROS generation by functionalized TiO2 nanoparticles and its influence on aggregation and bioavailability and toxicity to zebrafish embryos/larvae. For these studies we investigated anatase TiO2 nanoparticles. For application purposes and solution stability, the TiO2 nanoparticles were functionalized with a variety of ligands such as citrate, 3,4-dihydroxybenzaldehyde, and ascorbate. We quantitatively examined the amount of ROS produced in aqueous solution using fluorescent probes and see that more ROS is produced under UV light than in the dark control. Our measurements show that TiO2 toxicity reaches a maximum for nanoparticles with smaller diameters, and is correlated with surface area dependent changes in ROS generation. In an effort to reduce toxicity through control of the surface and surface ligands, we synthesized anatase nanoparticles of different sizes, functionalized them with different ligands, and examined the resulting ROS generation and ligand stability. Using a modular ligand containing a hydrophobic inner region and a hydrophilic outer region, we synthesized water-stable nanoparticles, via two different chemical reactions, having much-reduced ROS generation and thus reduced toxicity. These results suggest new strategies for making safer nanoparticles while still retaining their desired properties. We also examine the degradation of the different ligands on the surface of the particles using XPS and FTIR. The combination of ROS production and ligand degradation can affect the bioavailability of these particles in aqueous species.

Toxicological Assessment of CoO and La2O3 Metal Oxide Nanoparticles in Human Small Airway Epithelial Cells

PubMed Central

Pirela, Sandra V.; Shaffer, Justine; Mihalchik, Amy L.; Chisholm, William P.; Andrew, Michael E.; Schwegler-Berry, Diane; Castranova, Vincent; Demokritou, Philip; Qian, Yong

2016-01-01

Cobalt monoxide (CoO) and lanthanum oxide (La2O3) nanoparticles are 2 metal oxide nanoparticles with different redox potentials according to their semiconductor properties. By utilizing these two nanoparticles, this study sought to determine how metal oxide nanoparticle’s mode of toxicological action is related to their physio-chemical properties in human small airway epithelial cells (SAEC). We investigated cellular toxicity, production of superoxide radicals and alterations in gene expression related to oxidative stress, and cellular death at 6 and 24 h following exposure to CoO and La2O3 (administered doses: 0, 5, 25, and 50 µg/ml) nanoparticles. CoO nanoparticles induced gene expression related to oxidative stress at 6 h. After characterizing the nanoparticles, transmission electron microscope analysis showed SAEC engulfed CoO and La2O3 nanoparticles. CoO nanoparticles were toxic after 6 and 24 h of exposure to 25.0 and 50.0 µg/ml administered doses, whereas, La2O3 nanoparticles were toxic only after 24 h using the same administered doses. Based upon the Volumetric Centrifugation Method in vivo Sedimentation, Diffusion, and Dosimetry, the dose of CoO and La2O3 nanoparticles delivered at 6 and 24 h were determined to be: CoO: 1.25, 6.25, and 12.5 µg/ml; La2O3: 5, 25, and 50 µg/ml and CoO: 4, 20, and 40 µg/ml; and La2O3: 5, 25, 50 µg/ml, respectively. CoO nanoparticles produced more superoxide radicals and caused greater stimulation of total tyrosine and threonine phosphorylation at both 6 and 24 h when compared with La2O3 nanoparticles. Taken together, these data provide evidence that different toxicological modes of action were involved in CoO and La2O3 metal oxide nanoparticle-induced cellular toxicity. PMID:26769336

Influence of pH and media composition on suspension stability of silver, zinc oxide, and titanium dioxide nanoparticles and immobilization of Daphnia magna under guideline testing conditions.

PubMed

Cupi, Denisa; Hartmann, Nanna B; Baun, Anders

2016-05-01

In aquatic toxicity testing of engineered nanoparticles (ENPs) the process of agglomeration is very important as it may alter bioavailability and toxicity. In the present study, we aimed to identify test conditions that are favorable for maintaining stable ENP suspensions. We evaluated the influence of key environmental parameters: pH (2-12) and ionic strength using M7, Soft EPA (S EPA) medium, and Very Soft EPA (VS EPA) medium; and observed the influence of these parameters on zeta potential, zeta average, and acute immobilization of Daphnia magna for three different ENPs. Despite being sterically stabilized, test suspensions of silver (Ag) ENPs formed large agglomerates in both VS EPA and M7 media; and toxicity was found to be higher in VS EPA medium due to increased dissolution. Low-agglomerate suspensions for zinc oxide (ZnO) could be obtained at pH 7 in VS EPA medium, but the increase in dissolution caused higher toxicity than in M7 medium. Titanium dioxide (TiO2) ENPs had a point of zero charge in the range of pH 7-8. At pH 7 in VS EPA, agglomerates with smaller hydrodynamic diameters (~200nm) were present compared to the high ionic strength M7 medium where hydrodynamic diameters reached micrometer range. The stable suspensions of TiO2 ENPs caused immobilization of D. magna, 48-h EC50 value of 13.7mgL(-1) (95% CI, 2.4mg-79.1mgL(-1)); whereas no toxicity was seen in the unstable, highly agglomerated M7 medium suspensions, 48-h EC50 >100mgL(-1). The current study provides a preliminary approach for methodology in testing and assessing stability and toxicity of ENPs in aquatic toxicity tests of regulatory relevance. Copyright © 2016 Elsevier Inc. All rights reserved.

Individual and binary toxicity of anatase and rutile nanoparticles towards Ceriodaphnia dubia.

PubMed

Iswarya, V; Bhuvaneshwari, M; Chandrasekaran, N; Mukherjee, Amitava

2016-09-01

Increasing usage of engineered nanoparticles, especially Titanium dioxide (TiO2) in various commercial products has necessitated their toxicity evaluation and risk assessment, especially in the aquatic ecosystem. In the present study, a comprehensive toxicity assessment of anatase and rutile NPs (individual as well as a binary mixture) has been carried out in a freshwater matrix on Ceriodaphnia dubia under different irradiation conditions viz., visible and UV-A. Anatase and rutile NPs produced an LC50 of about 37.04 and 48mg/L, respectively, under visible irradiation. However, lesser LC50 values of about 22.56 (anatase) and 23.76 (rutile) mg/L were noted under UV-A irradiation. A toxic unit (TU) approach was followed to determine the concentrations of binary mixtures of anatase and rutile. The binary mixture resulted in an antagonistic and additive effect under visible and UV-A irradiation, respectively. Among the two different modeling approaches used in the study, Marking-Dawson model was noted to be a more appropriate model than Abbott model for the toxicity evaluation of binary mixtures. The agglomeration of NPs played a significant role in the induction of antagonistic and additive effects by the mixture based on the irradiation applied. TEM and zeta potential analysis confirmed the surface interactions between anatase and rutile NPs in the mixture. Maximum uptake was noticed at 0.25 total TU of the binary mixture under visible irradiation and 1 TU of anatase NPs for UV-A irradiation. Individual NPs showed highest uptake under UV-A than visible irradiation. In contrast, binary mixture showed a difference in the uptake pattern based on the type of irradiation exposed. Copyright © 2016 Elsevier B.V. All rights reserved.

The toxicity of silver to soil organisms exposed to silver nanoparticles and silver nitrate in biosolids-amended field soil.

PubMed

Jesmer, Alexander H; Velicogna, Jessica R; Schwertfeger, Dina M; Scroggins, Richard P; Princz, Juliska I

2017-10-01

The use of engineered silver nanoparticles (AgNPs) is widespread, with expected release to the terrestrial environment through the application of biosolids onto agricultural lands. The toxicity of AgNPs and silver nitrate (AgNO 3 ; as ionic Ag + ) to plant (Elymus lanceolatus and Trifolium pratense) and soil invertebrate (Eisenia andrei and Folsomia candida) species was assessed using Ag-amended biosolids applied to a natural sandy loam soil. Bioavailable Ag + in soil samples was estimated using an ion-exchange technique applied to KNO 3 soil extracts, whereas exposure to dispersible AgNPs was verified by single-particle inductively coupled plasma-mass spectrometry and transmission electron microscopy-energy dispersive X-ray spectroscopy analysis. Greater toxicity to plant growth and earthworm reproduction was observed in AgNP exposures relative to those of AgNO 3 , whereas no difference in toxicity was observed for F. candida reproduction. Transformation products in the AgNP-biosolids exposures resulted in larger pools of extractable Ag + than those from AgNO 3 -biosolids exposures, at similar total Ag soil concentrations. The results of the present study reveal intrinsic differences in the behavior and bioavailability of the 2 different forms of Ag within the biosolids-soils pathway. The present study demonstrates how analytical methods that target biologically relevant fractions can be used to advance the understanding of AgNP behavior and toxicity in terrestrial environments. Environ Toxicol Chem 2017;36:2756-2765. © 2017 Crown in the Right of Canada. Published Wiley Periodicals Inc., on behalf of SETAC. © 2017 Crown in the Right of Canada. Published Wiley Periodicals Inc., on behalf of SETAC.

Solubility of nano-zinc oxide in environmentally and biologically important matrices

PubMed Central

Reed, Robert B.; Ladner, David A.; Higgins, Christopher P.; Westerhoff, Paul; Ranville, James F.

2011-01-01

Increasing manufacture and use of engineered nanoparticles (NPs) is leading to a greater probability for release of ENPs into the environment and exposure to organisms. In particular, zinc oxide (ZnO) is toxic, although it is unclear whether this toxicity is due to the zinc oxide nanoparticles (ZnO), dissolution to Zn2+, or some combination thereof. The goal of this study was to determine the relative solubilites of both commercially available and in-house synthesized ZnO in matrices used for environmental fate and transport or biological toxicity studies. Dissolution of ZnO was observed in nanopure water (7.18– 7.40 mg/L dissolved Zn, as measured by filtration) and Roswell Park Memorial Institute medium (RPMI-1640) (~5 mg/L), but much more dissolution was observed in Dulbecco’s Modified Eagle’s Medium (DMEM), where the dissolved Zn concentration exceeded 34 mg/L. Moderately hard water exhibited low zinc solubility, likely due to precipitation of a zinc carbonate solid phase. Precipitation of a zinc-containing solid phase in RPMI also appeared to limit zinc solubility. Equilibrium conditions with respect to ZnO solubility were not apparent in these matrices, even after more than 1,000 h of dissolution. These results suggest that solution chemistry exerts a strong influence on ZnO dissolution and can result in limits on zinc solubility due to precipitation of less soluble solid phases. PMID:21994124

Toxicity profiling of water contextual zinc oxide, silver, and titanium dioxide nanoparticles in human oral and gastrointestinal cell systems.

PubMed

Giovanni, Marcella; Tay, Chor Yong; Setyawati, Magdiel Inggrid; Xie, Jianping; Ong, Choon Nam; Fan, Rongli; Yue, Junqi; Zhang, Lifeng; Leong, David Tai

2015-12-01

Engineered nanoparticles (ENPs) are increasingly detected in water supply due to environmental release of ENPs as the by-products contained within the effluent of domestic and industrial run-off. The partial recycling of water laden with ENPs, albeit at ultra-low concentrations, may pose an uncharacterized threat to human health. In this study, we investigated the toxicity of three prevalent ENPs: zinc oxide, silver, and titanium dioxide over a wide range of concentrations that encompasses drinking water-relevant concentrations, to cellular systems representing oral and gastrointestinal tissues. Based on published in silico-predicted water-relevant ENPs concentration range from 100 pg/L to 100 µg/L, we detected no cytotoxicity to all the cellular systems. Significant cytotoxicity due to the NPs set in around 100 mg/L with decreasing extent of toxicity from zinc oxide to silver to titanium dioxide NPs. We also found that noncytotoxic zinc oxide NPs level of 10 mg/L could elevate the intracellular oxidative stress. The threshold concentrations of NPs that induced cytotoxic effect are at least two to five orders of magnitude higher than the permissible concentrations of the respective metals and metal oxides in drinking water. Based on these findings, the current estimated levels of NPs in potable water pose little cytotoxic threat to the human oral and gastrointestinal systems within our experimental boundaries. © 2014 Wiley Periodicals, Inc.

Integrin-mediated targeting of protein polymer nanoparticles carrying a cytostatic macrolide

NASA Astrophysics Data System (ADS)

Shi, Pu

Cytotoxicity, low water solubility, rapid clearance from circulation, and offtarget side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or nonpolymeric. This chapter summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins. This chapter explores an alternative encapsulation strategy based on high-specificity avidity between a small molecule drug and its cognate protein target fused to the corona of protein polymer nanoparticles. With the new strategy, the drug associates tightly to the carrier and releases slowly, which may decrease toxicity and promote tumor accumulation via the enhanced permeability and retention effect. To test this hypothesis, the drug Rapamycin (Rapa) was selected for its potent anti-proliferative properties, which give it immunosuppressant and anti-tumor activity. Despite its potency, Rapa has low solubility, low oral bioavailability, and rapid systemic clearance, which make it an excellent candidate for nanoparticulate drug delivery. To explore this approach, genetically engineered diblock copolymers were constructed from elastin-like polypeptides (ELPs) that assemble small nanoparticles. ELPs are protein polymers of the sequence (Val-Pro-Gly-Xaa-Gly)n, where the identity of Xaa and n determine their assembly properties. Initially, a screening assay for model drug encapsulation in ELP nanoparticles was developed, which showed that Rose Bengal and Rapa have high non-specific encapsulation in the core of ELP nanoparticles with a sequence where Xaa = Ile or Phe. While excellent at entrapping these drugs, their release was relatively fast compared to their intended mean residence time in the human body. Having determined that Rapa can be non-specifically entrapped in the core of ELP nanoparticles, FK506 binding protein 12 (FKBP), which is the cognate protein target of Rapa, was genetically fused to the surface of these nanoparticles (FSI) to enhance their avidity towards Rapa. The fusion of FKBP to these nanoparticles slowed the terminal half-life of drug release to 57.8 h. To determine if this class of drug carriers has potential applications in vivo, FSI/Rapa was administered to mice carrying a human breast cancer model (MDA-MB-468). Compared to free drug, FSI encapsulation significantly decreased gross toxicity and enhanced the anti-cancer activity. In conclusion, protein polymer nanoparticles decorated with the cognate receptor of a high potency, low solubility drug (Rapa) efficiently improved drug loading capacity and its release. This approach has applications to the delivery of Rapa and its analogs; furthermore, this strategy has broader applications in the encapsulation, targeting, and release of other potent small molecules. Elastin-like polypeptides (ELPs) are genetically encoded protein polymers that reversibly phase separate in response to stimuli. They respond sharply to small shifts in temperature and form dense microdomains in the living eukaryotic cytosol. This chapter illustrates how to tune the ELP sequence and architecture for either coassembly or sorting of distinct proteins into microdomains within a living cell. Passive tumor targeting utilizing enhanced permeability and retention (EPR) effect has limited efficiency in targeting non-leaky tumors such as MDA-MB-468 breast tumor; however, an RGD tri-peptide decorated micelle nanoparticle can effectively accumulate in tumor site via integrin-mediated active tumor targeting. Different from inefficient and cytotoxic chemical linkage reactions, an elastin-based multi-functional nanocarrier can be assembled by genetic protein fusion and micelle co-assembly technology. The novel drug carrier contains the cognate Rapamycin (Rapa) receptor -- FK506 binding protein (FKBP) as the high-avidity drug binding domain and an RGD peptide as the active tumor targeting domain. Here we show that by co-assembling FKBP and RGD contained protein polymers into mixed micelle nanoparticles, they not only competently targeted endothelial and tumor cells in cell assays, but specifically delivered the drug with a slow release half-life of 38h. It was demonstrated that the active tumor targeting formulation of Rapa more effectively suppressed tumor growth compared to the passive tumor targeting formulation and free drug in tumor regression studies of mouse MDA-MB-468 xenografts. We believe that the exciting results will provide a new tool for the development of next-generation "smart" multi-functional drug carriers. (Abstract shortened by UMI.).

The delivery of poly(lactic acid)-poly(ethylene glycol) nanoparticles loaded with non-toxic drug to overcome drug resistance for the treatment of neuroblastoma

NASA Astrophysics Data System (ADS)

Dhulekar, Jhilmil

Neuroblastoma is a rare cancer of the sympathetic nervous system. A neuroblastoma tumor develops in the nerve tissue and is diagnosed in infants and children. Approximately 10.2 per million children under the age of 15 are affected in the United States and is slightly more common in boys. Neuroblastoma constitutes 6% of all childhood cancers and has a long-term survival rate of only 15%. There are approximately 700 new cases of neuroblastoma each year in the United States. With such a low rate of survival, the development of more effective treatment methods is necessary. A number of therapies are available for the treatment of these tumors; however, clinicians and their patients face the challenges of systemic side effects and drug resistance of the tumor cells. The application of nanoparticles has the potential to provide a safer and more effective method of delivery drugs to tumors. The advantage of using nanoparticles for drug delivery is the ability to specifically or passively target tumors while reducing the harmful side effects of chemotherapeutics. Drug delivery via nanoparticles can also allow for lower dosage requirements with controlled release of the drugs, which can further reduce systemic toxicity. The aim of this research was to develop a polymeric nanoparticle drug delivery system for the treatment of high-risk neuroblastoma. Nanoparticles composed of a poly(lactic acid)-poly(ethylene glycol) block copolymer were formulated to deliver a non-toxic drug in combination with Temozolomide, a commonly used chemotherapeutic drug for the treatment of neuroblastoma. The non-toxic drug acts as an inhibitor to the DNA-repair protein present in neuroblastoma cells that is responsible for inducing drug resistance in the cells, which would potentially allow for enhanced temozolomide activity. A variety of studies were completed to prove the nanoparticles' low toxicity, loading abilities, and uptake into cells. Additionally, studies were performed to determine the individual effect on cell toxicity of each drug and in combination. Finally, nanoparticles were loaded with the non-toxic drug and delivered with free temozolomide to determine the overall efficacy of the drugs in reducing neuroblastoma cell viability.

Tissue deposition and toxicological effects of commercially significant rare earth oxide nanomaterials: Material and physical properties.

PubMed

Das, Soumen; Reed McDonagh, Philip; Selvan Sakthivel, Tamil; Barkam, Swetha; Killion, Kelsey; Ortiz, Julian; Saraf, Shashank; Kumar, Amit; Gupta, Ankur; Zweit, Jamal; Seal, Sudipta

2017-03-01

Rare earth oxide (REO) materials are found naturally in earth's crust and at the nanoscale these REO nanoparticles exhibit unique thermal, electrical, and physicochemical properties. REO nanoparticles are widely used in different industrial sectors for ceramics, glass polishing, metallurgy, lasers, and magnets. Recently, some of these REO nanoparticles have been identified for their potential application in medicine, including therapy, imaging, and diagnostics. Concurrent research into the REO nanomaterials' toxicities has also raised concern for their environmental impacts. The correlation of REO nanoparticles mediated toxicity with their physiochemical properties can help to design nanoparticles with minimal effect on the environment and living organisms. In vitro assay revealed toxicity toward Human squamous epithelial cell line (CCL30) and Human umbilical vascular endothelial cells (HUVEC) at a concentration of 100 µM and higher. In vivo results showed, with the exception of CeO 2 and Gd 2 O 3 , most of the naoparticles did not clear or had minimum clearance (10-20%) from the system. Elevated levels of alanine transferase were seen for animals given each different nanoparticle, however the increases were not significant for CeO 2 and Dy 2 O 3 . Nephrotoxicity was only seen in case of Dy 2 O 3 and Gd 2 O 3 . Lastly, histological examination revealed presence of swollen hepatocytes which further confirms toxicity of the commercial REO nanomaterials. The in vivo toxicity is mainly due to excessive tissue deposition (70-90%) due to the commercial REO nanoparticles' poor physical properties (shape, stability, and extent of agglomeration). Therefore, optimization of nanoparticles physical properties is very important. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 904-917, 2017. © 2016 Wiley Periodicals, Inc.

Paracrine signalling of inflammatory cytokines from an in vitro blood brain barrier model upon exposure to polymeric nanoparticles.

PubMed

Raghnaill, Michelle Nic; Bramini, Mattia; Ye, Dong; Couraud, Pierre-Olivier; Romero, Ignacio A; Weksler, Babette; Åberg, Christoffer; Salvati, Anna; Lynch, Iseult; Dawson, Kenneth A

2014-03-07

Nanoparticle properties, such as small size relative to large highly modifiable surface area, offer great promise for neuro-therapeutics and nanodiagnostics. A fundamental understanding and control of how nanoparticles interact with the blood-brain barrier (BBB) could enable major developments in nanomedical treatment of previously intractable neurological disorders, and help ensure that nanoparticles not intended to reach the brain do not cause adverse effects. Nanosafety is of utmost importance to this field. However, a distinct lack of knowledge exists regarding nanoparticle accumulation within the BBB and the biological effects this may induce on neighbouring cells of the Central Nervous System (CNS), particularly in the long-term. This study focussed on the exposure of an in vitro BBB model to model carboxylated polystyrene nanoparticles (PS COOH NPs), as these nanoparticles are well characterised for in vitro experimentation and have been reported as non-toxic in many biological settings. TEM imaging showed accumulation but not degradation of 100 nm PS COOH NPs within the lysosomes of the in vitro BBB over time. Cytokine secretion analysis from the in vitro BBB post 24 h 100 nm PS COOH NP exposure showed a low level of pro-inflammatory RANTES protein secretion compared to control. In contrast, 24 h exposure of the in vitro BBB endothelium to 100 nm PS COOH NPs in the presence of underlying astrocytes caused a significant increase in pro-survival signalling. In conclusion, the tantalising possibilities of nanomedicine must be balanced by cautious studies into the possible long-term toxicity caused by accumulation of known 'toxic' and 'non-toxic' nanoparticles, as general toxicity assays may be disguising significant signalling regulation during long-term accumulation.

Preparation and characterization of the Adriamycin-loaded amphiphilic chitosan nanoparticles and their application in the treatment of liver cancer

PubMed Central

Kou, Chang-Hua; Han, Jin; Han, Xi-Lin; Zhuang, Hui-Jie; Zhao, Zi-Ming

2017-01-01

In the present study, two nanoparticles including lactose myristoyl carboxymethyl chitosan (LMCC) and algal polysaccharide myristoyl carboxymethyl chitosan (AMCC), were obtained for hepatic-targeted Adriamycin (ADM) drug delivery systems. ADM was successfully loaded into the LMCC or AMCC nanoparticle by dialysis. The release function and liver targeting of the nanoparticles was explored, and it was revealed that ADM release from the nanoparticles was greatest at acidic pH 5.5. ADM-conjugated nanoparticles were readily taken up by HU7 human hepatocellular carcinoma cells, relative to HT22 mouse hippocampal neuron cells in vitro. In vivo, ADM-loaded nanoparticles had significant antitumor efficacy with a 62.7% inhibition rate, followed by ADM and ADM-AMCC (51.2 and 42.5%, respectively). The tissue distribution study confirmed that ADM-LMCC had an improved liver delivery efficacy, by comparison with ADM. Furthermore, a series of safety studies, including hemolysis, acute toxicity and organ toxicity, revealed that the ADM-loaded LMCC and AMCC nanoparticles had advantages over the commercially available injectable preparation of Adriamycin hydrochloride, in terms of low toxicity levels and increased tolerated dose. These results indicated that LMCC is a promising carrier for injectable ADM nanoparticle and ADM-conjugated nanoparticles may improve the efficacy of ADM by hepatic targeting. PMID:29344229

Size-dependent in vivo toxicity of PEG-coated gold nanoparticles

PubMed Central

Zhang, Xiao-Dong; Wu, Di; Shen, Xiu; Liu, Pei-Xun; Yang, Na; Zhao, Bin; Zhang, Hao; Sun, Yuan-Ming; Zhang, Liang-An; Fan, Fei-Yue

2011-01-01

Background Gold nanoparticle toxicity research is currently leading towards the in vivo experiment. Most toxicology data show that the surface chemistry and physical dimensions of gold nanoparticles play an important role in toxicity. Here, we present the in vivo toxicity of 5, 10, 30, and 60 nm PEG-coated gold nanoparticles in mice. Methods Animal survival, weight, hematology, morphology, organ index, and biochemistry were characterized at a concentration of 4000 μg/kg over 28 days. Results The PEG-coated gold particles did not cause an obvious decrease in body weight or appreciable toxicity even after their breakdown in vivo. Biodistribution results show that 5 nm and 10 nm particles accumulated in the liver and that 30 nm particles accumulated in the spleen, while the 60 nm particles did not accumulate to an appreciable extent in either organ. Transmission electron microscopic observations showed that the 5, 10, 30, and 60 nm particles located in the blood and bone marrow cells, and that the 5 and 60 nm particles aggregated preferentially in the blood cells. The increase in spleen index and thymus index shows that the immune system can be affected by these small nanoparticles. The 10 nm gold particles induced an increase in white blood cells, while the 5 nm and 30 nm particles induced a decrease in white blood cells and red blood cells. The biochemistry results show that the 10 nm and 60 nm PEG-coated gold nanoparticles caused a significant increase in alanine transaminase and aspartate transaminase levels, indicating slight damage to the liver. Conclusion The toxicity of PEG-coated gold particles is complex, and it cannot be concluded that the smaller particles have greater toxicity. The toxicity of the 10 nm and 60 nm particles was obviously higher than that of the 5 nm and 30 nm particles. The metabolism of these particles and protection of the liver will be more important issues for medical applications of gold-based nanomaterials in future. PMID:21976982

Toxicity of silver nanoparticles in zebrafish models

NASA Astrophysics Data System (ADS)

Asharani, P. V.; Lian Wu, Yi; Gong, Zhiyuan; Valiyaveettil, Suresh

2008-06-01

This study was initiated to enhance our insight on the health and environmental impact of silver nanoparticles (Ag-np). Using starch and bovine serum albumin (BSA) as capping agents, silver nanoparticles were synthesized to study their deleterious effects and distribution pattern in zebrafish embryos (Danio rerio). Toxicological endpoints like mortality, hatching, pericardial edema and heart rate were recorded. A concentration-dependent increase in mortality and hatching delay was observed in Ag-np treated embryos. Additionally, nanoparticle treatments resulted in concentration-dependent toxicity, typified by phenotypes that had abnormal body axes, twisted notochord, slow blood flow, pericardial edema and cardiac arrhythmia. Ag+ ions and stabilizing agents showed no significant defects in developing embryos. Transmission electron microscopy (TEM) of the embryos demonstrated that nanoparticles were distributed in the brain, heart, yolk and blood of embryos as evident from the electron-dispersive x-ray analysis (EDS). Furthermore, the acridine orange staining showed an increased apoptosis in Ag-np treated embryos. These results suggest that silver nanoparticles induce a dose-dependent toxicity in embryos, which hinders normal development.

Systemic toxicity induced by aggregated layered double hydroxide nanoparticles

PubMed Central

Yan, Mina; Yang, Chanzhen; Huang, Binyao; Huang, Zeqian; Huang, Liangfeng; Zhang, Xuefei; Zhao, Chunshun

2017-01-01

Layered double hydroxide (LDH) nanoparticles are emerging as one of the promising nanomaterials for biomedical applications, but their systemic toxicity in vivo has received little attention. In the present study, the effects of inorganic nanoparticle aggregation on their systemic toxicity were examined. Remarkably, aggregation was observed after the mixing of naked LDH nanoparticles with saline or erythrocytes. Significant accumulation of the naked LDH nanoparticles in the lungs of mice was detected 1 h after intravenous administration, and the survival rate of mice was 0% after 6 repeated injections. Furthermore, flocculent precipitates in the alveoli and congestion in the lung interstitium were observed in the dead mice. However, lipid membrane-coated LDH nanoparticles would not form aggregates and could be injected intravenously >6 times without causing death. These findings suggested that repeated injections of LDH were lethal even at low dose (30 mg/kg), and lipid membrane coating can be considered as an approach for reducing this risk. PMID:29042768

Efficient intracellular delivery and improved biocompatibility of colloidal silver nanoparticles towards intracellular SERS immuno-sensing.

PubMed

Bhardwaj, Vinay; Srinivasan, Supriya; McGoron, Anthony J

2015-06-21

High throughput intracellular delivery strategies, electroporation, passive and TATHA2 facilitated diffusion of colloidal silver nanoparticles (AgNPs) are investigated for cellular toxicity and uptake using state-of-art analytical techniques. The TATHA2 facilitated approach efficiently delivered high payload with no toxicity, pre-requisites for intracellular applications of plasmonic metal nanoparticles (PMNPs) in sensing and therapeutics.

Rationally designed oxaliplatin-nanoparticle for enhanced antitumor efficacy

PubMed Central

Paraskar, Abhimanyu; Soni, Shivani; Roy, Bhaskar; Papa, Anne-Laure; Sengupta, Shiladitya

2012-01-01

Nanoscale drug delivery vehicles have been extensively studied as carriers for cancer chemotherapeutics. However the formulation of platinum chemotherapeutics in nanoparticles has been a challenge arising from their physicochemical properties. There are only few reports describing oxaliplatin nanoparticles. In this study, we derivatized the monomeric units of a polyisobutylene maleic acid copolymer with glucosamine, which chelates trans-1,2-diaminocyclohexane (DACH) platinum (II) through a novel monocarboxylato and O→Pt coordination linkage. At a specific polymer to platinum ratio, the complex self assembled into a nanoparticle, where the polymeric units act as the leaving group, releasing DACH-platinum in sustained pH-dependent manner. Sizing was done using dynamic light scatter and electron microscopy. The nanoparticles were evaluated for efficacy in vitro and in vivo. Biodistribution was quantified using inductive-coupled plasma-atomic absorption spectroscopy (ICP-AAS). The PIMA-GA-DACH-platinum nanoparticle was found to be more active than free oxaliplatin in vitro. In vivo, the nanoparticles resulted in greater tumor inhibition than oxaliplatin (equivalent to 5mg/kg platinum dose) with minimal nephrotoxicity or body weight loss. ICP-AAS revealed significant preferential tumor accumulation of platinum with reduced biodistribution to the kidney or liver following PIMA-GA-DACH-platinum nanoparticle administration as compared with free oxaliplatin. These results indicate that the rational engineering of a novel polymeric nanoparticle inspired by the bioactivation of oxaliplatin results in increased antitumor potency with reduced systemic toxicity compared with the parent cytotoxic. Rational design can emerge as an exciting strategy in the synthesis of nanomedicines for cancer chemotherapy. PMID:22275055

Computational ecotoxicology: simultaneous prediction of ecotoxic effects of nanoparticles under different experimental conditions.

PubMed

Kleandrova, Valeria V; Luan, Feng; González-Díaz, Humberto; Ruso, Juan M; Melo, André; Speck-Planche, Alejandro; Cordeiro, M Natália D S

2014-12-01

Nanotechnology has brought great advances to many fields of modern science. A manifold of applications of nanoparticles have been found due to their interesting optical, electrical, and biological/chemical properties. However, the potential toxic effects of nanoparticles to different ecosystems are of special concern nowadays. Despite the efforts of the scientific community, the mechanisms of toxicity of nanoparticles are still poorly understood. Quantitative-structure activity/toxicity relationships (QSAR/QSTR) models have just started being useful computational tools for the assessment of toxic effects of nanomaterials. But most QSAR/QSTR models have been applied so far to predict ecotoxicity against only one organism/bio-indicator such as Daphnia magna. This prevents having a deeper knowledge about the real ecotoxic effects of nanoparticles, and consequently, there is no possibility to establish an efficient risk assessment of nanomaterials in the environment. In this work, a perturbation model for nano-QSAR problems is introduced with the aim of simultaneously predicting the ecotoxicity of different nanoparticles against several assay organisms (bio-indicators), by considering also multiple measures of ecotoxicity, as well as the chemical compositions, sizes, conditions under which the sizes were measured, shapes, and the time during which the diverse assay organisms were exposed to nanoparticles. The QSAR-perturbation model was derived from a database containing 5520 cases (nanoparticle-nanoparticle pairs), and it was shown to exhibit accuracies of ca. 99% in both training and prediction sets. In order to demonstrate the practical applicability of our model, three different nickel-based nanoparticles (Ni) with experimental values reported in the literature were predicted. The predictions were found to be in very good agreement with the experimental evidences, confirming that Ni-nanoparticles are not ecotoxic when compared with other nanoparticles. The results of this study thus provide a single valuable tool toward an efficient prediction of the ecotoxicity of nanoparticles under multiple experimental conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

AMP-Conjugated Quantum Dots: Low Immunotoxicity Both In Vitro and In Vivo

NASA Astrophysics Data System (ADS)

Dai, Tongcheng; Li, Na; Liu, Lu; Liu, Qin; Zhang, Yuanxing

2015-11-01

Quantum dots (QDs) are engineered nanoparticles that possess special optical and electronic properties and have shown great promise for future biomedical applications. In this work, adenosine 5'-monophosphate (AMP), a small biocompatible molecular, was conjugated to organic QDs to produce hydrophilic AMP-QDs. Using macrophage J774A.1 as the cell model, AMP-QDs exhibited both prior imaging property and low toxicity, and more importantly, triggered limited innate immune responses in macrophage, indicating low immunotoxicity in vitro. Using BALB/c mice as the animal model, AMP-QDs were found to be detained in immune organs but did not evoke robust inflammation responses or obvious histopathological abnormalities, which reveals low immunotoxicity in vivo. This work suggests that AMP is an excellent surface ligand with low immunotoxicity, and potentially used in surface modification for more extensive nanoparticles.

PubMed Central

DOBRETSOV, K.; STOLYAR, S.

2015-01-01

SUMMARY Herein we examined the toxicity, penetration properties and ability of Fe2O3·nH2O magnetic nanoparticles extracted from silt of the Borovoye Lake (Krasnoyarsk, Russia) to bind an antibiotic. Experimental studies were carried out using magnetic nanoparticles alone and after antibiotic exposure in tissue samples from nasal mucosa, cartilage and bone (in vitro). Toxicity of particles was studied in laboratory animals (in vivo). Tissues removed at endonasal surgery (nasal mucosa, cartilage and bone of the nasal septum) were placed in solution containing nanoparticles and exposed to a magnetic field. Distribution of nanoparticles was determined by Perls' reaction. After intravenous injection, possible toxic effects of injected nanoparticles on the organs and tissues of rats were evaluated by histological examination. Binding between the nanoparticles and antibiotic (amoxicillin clavulanate) was studied using infrared spectroscopy. In 30 in vitro experiments, magnetisation of Fe2O3·nH2O nanoparticles resulted in their diffuse infiltration into the mucosa, cartilage and bone tissue of the nose and paranasal sinuses. Intravenous injection of 0.2 ml of magnetic nanoparticles into the rat's tail vein did not result in any changes in parenchymatous organs, and the nanoparticles were completely eliminated from the body within 24 hours. The interaction of nanoparticles with amoxicillin clavulanate was demonstrated by infrared spectroscopy. Positive results of experimental studies provide a basis for further clinical investigations of these magnetic nanoparticles and their use in otorhinolaryngology. PMID:26019393

Effect of different spiking procedures on the distribution and toxicity of ZnO nanoparticles in soil.

PubMed

Waalewijn-Kool, Pauline L; Diez Ortiz, Maria; van Gestel, Cornelis A M

2012-10-01

Due to the difficulty in dispersing some engineered nanomaterials in exposure media, realizing homogeneous distributions of nanoparticles (NP) in soil may pose major challenges. The present study investigated the distribution of zinc oxide (ZnO) NP (30 nm) and non-nano ZnO (200 nm) in natural soil using two different spiking procedures, i.e. as dry powder and as suspension in soil extract. Both spiking procedures showed a good recovery (>85 %) of zinc and based on total zinc concentrations no difference was found between the two spiking methods. Both spiking procedures resulted in a fairly homogeneous distribution of the ZnO particles in soil, as evidenced by the low variation in total zinc concentration between replicate samples (<12 % in most cases). Survival of Folsomia candida in soil spiked at concentrations up to 6,400 mg Zn kg(-1) d.w. was not affected for both compounds. Reproduction was reduced in a concentration-dependent manner with EC50 values of 3,159 and 2,914 mg Zn kg(-1) d.w. for 30 and 200 nm ZnO spiked as dry powder and 3,593 and 5,633 mg Zn kg(-1) d.w. introduced as suspension. Toxicity of ZnO at 30 and 200 nm did not differ. We conclude that the ZnO particle toxicity is not size related and that the spiking of the soil with ZnO as dry powder or as a suspension in soil extract does not affect its toxicity to F. candida.

Natural marine bacteria as model organisms for the hazard-assessment of consumer products containing silver nanoparticles.

PubMed

Echavarri-Bravo, Virginia; Paterson, Lynn; Aspray, Thomas J; Porter, Joanne S; Winson, Michael K; Hartl, Mark G J

2017-09-01

Scarce information is available regarding the fate and toxicology of engineered silver nanoparticles (AgNPs) in the marine environment, especially when compared to other environmental compartments. Hence, the antibacterial activity of the NM-300 AgNPs (OECD programme) and a household product containing colloidal AgNPs (Mesosilver) was investigated using marine bacteria, pure cultures and natural mixed populations (microcosm approach). Bacterial susceptibility to AgNPs was species-specific, with Gram negative bacteria being more resistant than the Gram positive species (NM-300 concentration used ranged between 0.062 and 1.5 mg L -1 ), and the Mesosilver product was more toxic than the NM-300. Bacterial viability and the physiological status (O 2 uptake measured by respirometry) of the microbial community in the microcosm was negatively affected at an initial concentration of 1 mg L -1 NM-300. The high chloride concentrations in the media/seawater led to the formation of silver-chloro complexes thus enhancing AgNP toxicity. We recommend the use of natural marine bacteria as models when assessing the environmental relevant antibacterial properties of products containing nanosilver. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Nanocolloids in Natural Water: Isolation, Characterization, and Toxicity.

PubMed

Ouyang, Shaohu; Hu, Xiangang; Zhou, Qixing; Li, Xiaokang; Miao, Xinyu; Zhou, Ruiren

2018-04-17

Nanocolloids are widespread in natural water systems, but their characterization and ecological risks are largely unknown. Herein, tangential flow ultrafiltration (TFU) was used to separate and concentrate nanocolloids from surface waters. Unexpectedly, nanocolloids were present in high concentrations ranging from 3.7 to 7.2 mg/L in the surface waters of the Harihe River in Tianjin City, China. Most of the nanocolloids were 10-40 nm in size, contained various trace metals and polycyclic aromatic hydrocarbons, and exhibited fluorescence properties. Envelopment effects and aggregation of Chlorella vulgaris in the presence of nanocolloids were observed. Nanocolloids entered cells and nanocolloid-exposed cells exhibited stronger plasmolysis, chloroplast damage and more starch grains than the control cells. Moreover, nanocolloids inhibited the cell growth, promoted reactive oxygen species (ROS), reduce the chlorophyll a content and increased the cell permeability. The genotoxicity of nanocolloids was also observed. The metabolomics analysis revealed a significant ( p < 0.05) downregulation of amino acids and upregulation of fatty acids contributing to ROS increase, chlorophyll a decrease and plasmolysis. The present work reveals that nanocolloids, which are different from specific, engineered nanoparticles (e.g., Ag nanoparticles), are present at high concentrations, exhibit an obvious toxicity in environments, and deserve more attention in the future.

Enhanced Colloidal Stability of CeO2 Nanoparticles by Ferrous Ions: Adsorption, Redox Reaction, and Surface Precipitation.

PubMed

Liu, Xuyang; Ray, Jessica R; Neil, Chelsea W; Li, Qingyun; Jun, Young-Shin

2015-05-05

Due to the toxicity of cerium oxide (CeO2) nanoparticles (NPs), a better understanding of the redox reaction-induced surface property changes of CeO2 NPs and their transport in natural and engineered aqueous systems is needed. This study investigates the impact of redox reactions with ferrous ions (Fe2+) on the colloidal stability of CeO2 NPs. We demonstrated that under anaerobic conditions, suspended CeO2 NPs in a 3 mM FeCl2 solution at pH 4.8 were much more stable against sedimentation than those in the absence of Fe2+. Redox reactions between CeO2 NPs and Fe2+ lead to the formation of 6-line ferrihydrite on the CeO2 surfaces, which enhanced the colloidal stability by increasing the zeta potential and hydrophilicity of CeO2 NPs. These redox reactions can affect the toxicity of CeO2 NPs by increasing cerium dissolution, and by creating new Fe(III) (hydr)oxide reactive surface layers. Thus, these findings have significant implications for elucidating the phase transformation and transport of redox reactive NPs in the environment.

Effects of zinc oxide and titanium dioxide nanoparticles on green algae under visible, UVA, and UVB irradiations: no evidence of enhanced algal toxicity under UV pre-irradiation.

PubMed

Lee, Woo-Mi; An, Youn-Joo

2013-04-01

Some metal oxide nanoparticles are photoreactive, thus raising concerns regarding phototoxicity. This study evaluated ecotoxic effects of zinc oxide nanoparticles and titanium dioxide nanoparticles to the green algae Pseudokirchneriella subcapitata under visible, UVA, and UVB irradiation conditions. The nanoparticles were prepared in algal test medium, and the test units were pre-irradiated by UV light in a photoreactor. Algal assays were also conducted with visible, UVA or UVB lights only without nanoparticles. Algal growth was found to be inhibited as the nanoparticle concentration increased, and ZnO NPs caused destabilization of the cell membranes. We also noted that the inhibitory effects on the growth of algae were not enhanced under UV pre-irradiation conditions. This phenomenon was attributed to the photocatalytic activities of ZnO NPs and TiO2 NPs in both the visible and UV regions. The toxicity of ZnO NPs was almost entirely the consequence of the dissolved free zinc ions. This study provides us with an improved understanding of toxicity of photoreactive nanoparticles as related to the effects of visible and UV lights. Copyright © 2012 Elsevier Ltd. All rights reserved.

Anaerobic Toxicity of Cationic Silver Nanoparticles

EPA Science Inventory

The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag⁺ under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged p...

Nickel nanoparticles exposure and reproductive toxicity in healthy adult rats.

PubMed

Kong, Lu; Tang, Meng; Zhang, Ting; Wang, Dayong; Hu, Ke; Lu, Weiqi; Wei, Chao; Liang, Geyu; Pu, Yuepu

2014-11-17

Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions.

Effects of particle size and coating on nanoscale Ag and TiO₂ exposure in zebrafish (Danio rerio) embryos.

PubMed

Osborne, Olivia J; Johnston, Blair D; Moger, Julian; Balousha, Mohammed; Lead, Jamie R; Kudoh, Tetsuhiro; Tyler, Charles R

2013-12-01

Manufactured metal (oxide) nanoparticles are entering the aquatic environment with little understanding on their potential health impacts for exposed organisms. Adopting an integrative approach, we investigated effects of particle size and coating on biological responses for two of the most commonly used metal (oxide) nanoscale particles, silver (Ag) and titanium dioxide (TiO₂) in zebrafish embryos. Titanium dioxide nanoparticles (nominally, 4 nm, 10 nm, 30 nm and 134 nm) had little or no toxicity on the endpoints measured. Ag both in nano form (10 nm and 35 nm) and its larger counterpart (600-1600 nm) induced dose-dependent lethality and morphological defects, occurring predominantly during gastrula stage. Of the silver material tested 10 nm nanoparticles appeared to be the most toxic. Coating Ag nanoparticles with citrate or fulvic acid decreased toxicity significantly. In situ hybridisation analysis identified the yolk syncytial layer (YSL) as a target tissue for Ag-nano toxicity where there was a significant induction of the heavy metal stress response gene, metallothionein 2 (Mt2) at sub-lethal exposures. Coherent Anti-stroke Raman Scattering (CARS) microscopy provided no evidence for silver particles crossing the chorionic membrane in exposed embryos. Collectively, our data suggest that silver ions play a major role in the toxicity of Ag nanoparticles.

Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

PubMed Central

Kong, Lu; Tang, Meng; Zhang, Ting; Wang, Dayong; Hu, Ke; Lu, Weiqi; Wei, Chao; Liang, Geyu; Pu, Yuepu

2014-01-01

Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions. PMID:25407529

Interaction of engineered nanoparticles with various components of the environment and possible strategies for their risk assessment.

PubMed

Bhatt, Indu; Tripathi, Bhumi Nath

2011-01-01

Nanoparticles are the materials with at least two dimensions between 1 and 100 nm. Mostly these nanoparticles are natural products but their tremendous commercial use has boosted the artificial synthesis of these particles (engineered nanoparticles). Accelerated production and use of these engineered nanoparticles may cause their release in the environment and facilitate the frequent interactions with biotic and abiotic components of the ecosystems. Despite remarkable commercial benefits, their presence in the nature may cause hazardous biological effects. Therefore, detail understanding of their sources, release interaction with environment, and possible risk assessment would provide a basis for safer use of engineered nanoparticles with minimal or no hazardous impact on environment. Keeping all these points in mind the present review provides updated information on various aspects, e.g. sources, different types, synthesis, interaction with environment, possible strategies for risk management of engineered nanoparticles. Copyright © 2010 Elsevier Ltd. All rights reserved.

Uptake route and resulting toxicity of silver nanoparticles in Eisenia fetida earthworm exposed through Standard OECD Tests.

PubMed

Garcia-Velasco, Nerea; Gandariasbeitia, Maite; Irizar, Amaia; Soto, Manuel

2016-10-01

Despite the increasing interest in silver nanoparticles toxicity still few works dealt with the hazards of nanosized Ag in soils (either dissolved in pore water or coupled to colloids) although disposal of biosolids in landfills has been reported as the major source of silver nanoparticles in terrestrial environments. Presently, Eisenia fetida was used to assess the toxicity of 5 nm sized PVP-PEI coated silver nanoparticles in soil through the implementation of different exposure media Standard Toxicity Tests (Paper Contact and Artificial Soil -OECD-207- and Reproduction -OECD-222- Tests) together with cellular biomarkers measured in extruded coelomocytes. In order to decipher the mode of action of silver nanoparticles in soil and the uptake routes in earthworms, special attention was given to the Ag accumulation and distribution in tissues. High Ag accumulation rates, weight loss, and mortality due to the disruption of the tegument could be the result of a dermal absorption of Ag ions released from silver nanoparticles (Paper Contact Test). However, autometallography showed metals mainly localized in the digestive tract after Artificial Soil Test, suggesting that Ag uptake occurred mostly through soil ingestion. That is, silver nanoparticles attached to soil colloids seemed to be internalized in earthworms after ingestion of soil and transferred to the digestive gut epithelium where at high doses they have triggered severe effects at different levels of biological complexity.

Comparative cytotoxicity of Al2O3, CeO2, TiO2 and ZnO nanoparticles to human lung cells.

PubMed

Kim, In-Sun; Baek, Miri; Choi, Soo-Jin

2010-05-01

The increased applications of nanoparticles in a wide range of industrial fields raise the concern about their potential toxicity to human. The aim of this study was to assess and compare the toxicity of four different oxide nanoparticles (Al2O3, CeO2, TiO2 and ZnO) to human lung epithelial cells, A549 carcinoma cells and L-132 normal cells, in vitro. We focused on the toxicological effects of the present nanoparticles on cell proliferation, cell viability, membrane integrity and oxidative stress. The long-term cytotoxicity of nanoparticles was also evaluated by employing the clonogenic assay. Among four nanoparticles tested, ZnO exhibited the highest cytotoxicity in terms of cell proliferation, cell viability, membrane integrity and colony formation in both cell lines. Al2O3, CeO2 and TiO2 showed little adverse effects on cell proliferation and cell viability. However, TiO2 induced oxidative stress in a concentration- and time-dependent manner. CeO2 caused membrane damage and inhibited colony formation in long-term, but with different degree depending on cell lines. Al2O3 seems to be less toxic than the other nanoparticles even after long time exposure. These results highlight the need for caution during manufacturing process of nanomaterials as well as further investigation on the toxicity mechanism.

Combined biocidal action of silver nanoparticles and ions against Chlorococcales (Scenedesmus quadricauda, Chlorella vulgaris) and filamentous algae (Klebsormidium sp.).

PubMed

Zouzelka, Radek; Cihakova, Pavlina; Rihova Ambrozova, Jana; Rathousky, Jiri

2016-05-01

Despite the extensive research, the mechanism of the antimicrobial and biocidal performance of silver nanoparticles has not been unequivocally elucidated yet. Our study was aimed at the investigation of the ability of silver nanoparticles to suppress the growth of three types of algae colonizing the wetted surfaces or submerged objects and the mechanism of their action. Silver nanoparticles exhibited a substantial toxicity towards Chlorococcales Scenedesmus quadricauda, Chlorella vulgaris, and filamentous algae Klebsormidium sp., which correlated with their particle size. The particles had very good stability against agglomeration even in the presence of multivalent cations. The concentration of silver ions in equilibrium with nanoparticles markedly depended on the particle size, achieving about 6 % and as low as about 0.1 % or even less for the particles 5 nm in size and for larger ones (40-70 nm), respectively. Even very limited proportion of small particles together with larger ones could substantially increase concentration of Ag ions in solution. The highest toxicity was found for the 5-nm-sized particles, being the smallest ones in this study. Their toxicity was even higher than that of silver ions at the same silver concentration. When compared as a function of the Ag(+) concentration in equilibrium with 5-nm particles, the toxicity of ions was at least 17 times higher than that obtained by dissolving silver nitrite (if not taking into account the effect of nanoparticles themselves). The mechanism of the toxicity of silver nanoparticles was found complex with an important role played by the adsorption of silver nanoparticles and the ions released from the particles on the cell surface. This mechanism could be described as some sort of synergy between nanoparticles and ions. While our study clearly showed the presence of this synergy, its detailed explanation is experimentally highly demanding, requiring a close cooperation between materials scientists, physical chemists, and biologists.

Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles

PubMed Central

Unzueta, Ugutz; Céspedes, María Virtudes; Ferrer-Miralles, Neus; Casanova, Isolda; Cedano, Juan; Corchero, José Luis; Domingo-Espín, Joan; Villaverde, Antonio; Mangues, Ramón; Vázquez, Esther

2012-01-01

Background Cell-targeting peptides or proteins are appealing tools in nanomedicine and innovative medicines because they increase the local drug concentration and reduce potential side effects. CXC chemokine receptor 4 (CXCR4) is a cell surface marker associated with several severe human pathologies, including colorectal cancer, for which intracellular targeting agents are currently missing. Results Four different peptides that bind CXCR4 were tested for their ability to internalize a green fluorescent protein-based reporter nanoparticle into CXCR4+ cells. Among them, only the 18 mer peptide T22, an engineered segment derivative of polyphemusin II from the horseshoe crab, efficiently penetrated target cells via a rapid, receptor-specific endosomal route. This resulted in accumulation of the reporter nanoparticle in a fully fluorescent and stable form in the perinuclear region of the target cells, without toxicity either in cell culture or in an in vivo model of metastatic colorectal cancer. Conclusion Given the urgent demand for targeting agents in the research, diagnosis, and treatment of CXCR4-linked diseases, including colorectal cancer and human immunodeficiency virus infection, T22 appears to be a promising tag for the intracellular delivery of protein drugs, nanoparticles, and imaging agents. PMID:22923991

Cellular uptake and intracellular fate of engineered nanoparticles: a review on the application of imaging techniques.

PubMed

Tantra, Ratna; Knight, Alex

2011-09-01

The use of imaging tools to probe nanoparticle-cell interactions will be crucial to elucidating the mechanisms of nanoparticle-induced toxicity. Of particular interest are mechanisms associated with cell penetration, translocation and subsequent accumulation inside the cell, or in cellular compartments. The objective of the present paper is to review imaging techniques that have been previously used in order to assess such interactions, and new techniques with the potential to be useful in this area. In order to identify the most suitable techniques, they were evaluated and matched against a list of evaluation criteria. We conclude that limitations exist with all of the techniques and the ultimate choice will thus depend on the needs of end users, and their particular application. The state-of-the-art techniques appear to have the least limitations, despite the fact that they are not so well established and still far from being routine. For example, super-resolution microscopy techniques appear to have many advantages for understanding the details of the interactions between nanoparticles and cells. Future research should concentrate on further developing or improving such novel techniques, to include the development of standardized methods and appropriate reference materials.

International Symposium on the Frontiers in Nanoscale Science, Technology and Education Held in Cochin, India, 16-19 August 2006

DTIC Science & Technology

2007-02-01

classify nanoparticles based on the nature of their toxicity . The main focus of this presentation will be to discuss basic research applied to...vitro reference studies on toxicity , serve to uncover critical mechanisms of toxic effects associated with nanoparticle interaction with the biological...advantage to reduce the toxic effects of the medicine. This work which Physics and Medicine Dept. of B.H.U. are jointly carrying out will also be

Targeted drug delivery using genetically engineered diatom biosilica.

PubMed

Delalat, Bahman; Sheppard, Vonda C; Rasi Ghaemi, Soraya; Rao, Shasha; Prestidge, Clive A; McPhee, Gordon; Rogers, Mary-Louise; Donoghue, Jacqueline F; Pillay, Vinochani; Johns, Terrance G; Kröger, Nils; Voelcker, Nicolas H

2015-11-10

The ability to selectively kill cancerous cell populations while leaving healthy cells unaffected is a key goal in anticancer therapeutics. The use of nanoporous silica-based materials as drug-delivery vehicles has recently proven successful, yet production of these materials requires costly and toxic chemicals. Here we use diatom microalgae-derived nanoporous biosilica to deliver chemotherapeutic drugs to cancer cells. The diatom Thalassiosira pseudonana is genetically engineered to display an IgG-binding domain of protein G on the biosilica surface, enabling attachment of cell-targeting antibodies. Neuroblastoma and B-lymphoma cells are selectively targeted and killed by biosilica displaying specific antibodies sorbed with drug-loaded nanoparticles. Treatment with the same biosilica leads to tumour growth regression in a subcutaneous mouse xenograft model of neuroblastoma. These data indicate that genetically engineered biosilica frustules may be used as versatile 'backpacks' for the targeted delivery of poorly water-soluble anticancer drugs to tumour sites.

Influence of surface charge on the potential toxicity of PLGA nanoparticles towards Calu-3 cells

PubMed Central

Mura, Simona; Hillaireau, Herve; Nicolas, Julien; Le Droumaguet, Benjamin; Gueutin, Claire; Zanna, Sandrine; Tsapis, Nicolas; Fattal, Elias

2011-01-01

Background Because of the described hazards related to inhalation of manufactured nanoparticles, we investigated the lung toxicity of biodegradable poly (lactide-co-glycolide) (PLGA) nanoparticles displaying various surface properties on human bronchial Calu-3 cells. Methods Positively and negatively charged as well as neutral nanoparticles were tailored by coating their surface with chitosan, Poloxamer, or poly (vinyl alcohol), respectively. Nanoparticles were characterized in terms of size, zeta potential, and surface chemical composition, confirming modifications provided by hydrophilic polymers. Results Although nanoparticle internalization by lung cells was clearly demonstrated, the cytotoxicity of the nanoparticles was very limited, with an absence of inflammatory response, regardless of the surface properties of the PLGA nanoparticles. Conclusion These in vitro results highlight the safety of biodegradable PLGA nanoparticles in the bronchial epithelium and provide initial data on their potential effects and the risks associated with their use as nanomedicines. PMID:22114491

Biosensors based on inorganic nanoparticles with biomimetic properties: Biomedical applications and in vivo cytotoxicity measurements

NASA Astrophysics Data System (ADS)

Ispas, Cristina R.

The rapid progress of nanotechnology and advanced nanomaterials production offer significant opportunities for designing powerful biosensing devices with enhanced performances. This thesis introduces ceria (CeO 2) nanoparticles and its congeners as a new class of materials with huge potential in bioanalytical and biosensing applications. Unique redox, catalytic and oxygen storage/release properties of ceria nanoparticles, originating from their dual oxidation state are used to design biomedical sensors with high sensitivity and low oxygen dependency. This thesis describes a new approach for fabrication of implantable microbiosensors designed for monitoring neurological activity in physiological conditions. Understanding the mechanisms involved in neurological signaling and functioning is of great physiological importance. In this respect, the development of effective methods that allow accurate detection and quantification of biological analytes (i.e. L-glutamate and glucose) associated with neurological processes is of paramount importance. The performance of most analytical techniques currently used to monitor L-glutamate and glucose is suboptimal and only a limited number of approaches address the problem of operation in oxygen-restricted conditions, such as ischemic brain injury. Over the past couple of years, enzyme based biosensors have been used to investigate processes related to L-glutamate release/uptake and the glucose cycle within the brain. However, most of these sensors, based on oxidoreductase enzymes, do not work in conditions of limited oxygen availability. This thesis presents the development of a novel sensing technology for the detection of L-glutamate and glucose in conditions of oxygen deprivation. This technology provides real-time assessment of the concentrations of these analytes with high sensitivity, wide linear range, and low oxygen dependence. The fabrication, characterization and optimization of enzyme microbiosensors are discussed. This work introduces a new generic approach of improving the sensitivity of oxidase-based enzymatic assays and indicates that ceria and its mixture with other metal oxide nanoparticles could be used to minimize the problems associated with variations of the oxygen. These materials have great potential in bioanalytical and biotechnological applications and offer great opportunities for development of implantable sensing devices for in vivo and in vitro monitoring of analytes of clinical relevance. Additionally, this thesis evaluates the toxicity of different metal and metal oxide nanoparticles by using zebrafish embryos as a toxicological target. Because of their similarities with other vertebrates, rapid development and low cost, zebrafish embryos are ideal animal models for probing toxicological effects of engineered nanomaterials. Among the nanomaterials tested, nickel nanoparticles were characterized by high toxicity and induced delayed development and morphological malformations, while metal oxides nanoparticles (i.e. ceria nanoparticles) had no toxic effects.

Nanoparticles Based on Chitosan as Carriers for the Combined Herbicides Imazapic and Imazapyr

PubMed Central

Maruyama, Cintia Rodrigues; Guilger, Mariana; Pascoli, Mônica; Bileshy-José, Natalia; Abhilash, P.C.; Fraceto, Leonardo Fernandes; de Lima, Renata

2016-01-01

The use of lower concentrations and fewer applications of herbicides is one of the prime objectives of the sustainable agriculture as it decreases the toxicity to non-targeted organisms and the risk of wider environmental contamination. In the present work, nanoparticles were developed for encapsulation of the herbicides imazapic and imazapyr. Alginate/chitosan and chitosan/tripolyphosphate nanoparticles were manufactured, and their physicochemical stability was evaluated. Determinations were made of the encapsulation efficiency and release kinetics, and the toxicity of the nanoparticles was evaluated using cytotoxicity and genotoxicity assays. The effects of herbicides and herbicide-loaded nanoparticles on soil microorganisms were studied in detail using real-time polymerase chain reactions. The nanoparticles showed an average size of 400 nm and remained stable during 30 days of storage at ambient temperature. Satisfactory encapsulation efficiencies of between 50 and 70% were achieved for both types of particles. Cytotoxicity assays showed that the encapsulated herbicides were less toxic, compared to the free compounds, and genotoxicity was decreased. Analyses of soil microbiota revealed changes in the bacteria of the soils exposed to the different treatments. Our study proves that encapsulation of the herbicides improved their mode of action and reduced their toxicity, indicating their suitability for use in future practical applications. PMID:26813942

Magnetic Nanoparticles: Material Engineering and Emerging Applications in Lithography and Biomedicine

PubMed Central

Bao, Yuping; Wen, Tianlong; Samia, Anna Cristina S.; Khandhar, Amit; Krishnan, Kannan M.

2015-01-01

We present an interdisciplinary overview of material engineering and emerging applications of iron oxide nanoparticles. We discuss material engineering of nanoparticles in the broadest sense, emphasizing size and shape control, large-area self-assembly, composite/hybrid structures, and surface engineering. This is followed by a discussion of several non-traditional, emerging applications of iron oxide nanoparticles, including nanoparticle lithography, magnetic particle imaging, magnetic guided drug delivery, and positive contrast agents for magnetic resonance imaging. We conclude with a succinct discussion of the pharmacokinetics pathways of iron oxide nanoparticles in the human body –– an important and required practical consideration for any in vivo biomedical application, followed by a brief outlook of the field. PMID:26586919

Magnetic Nanoparticles: Material Engineering and Emerging Applications in Lithography and Biomedicine.

PubMed

Bao, Yuping; Wen, Tianlong; Samia, Anna Cristina S; Khandhar, Amit; Krishnan, Kannan M

2016-01-01

We present an interdisciplinary overview of material engineering and emerging applications of iron oxide nanoparticles. We discuss material engineering of nanoparticles in the broadest sense, emphasizing size and shape control, large-area self-assembly, composite/hybrid structures, and surface engineering. This is followed by a discussion of several non-traditional, emerging applications of iron oxide nanoparticles, including nanoparticle lithography, magnetic particle imaging, magnetic guided drug delivery, and positive contrast agents for magnetic resonance imaging. We conclude with a succinct discussion of the pharmacokinetics pathways of iron oxide nanoparticles in the human body -- an important and required practical consideration for any in vivo biomedical application, followed by a brief outlook of the field.

Kupffer Cell Isolation for Nanoparticle Toxicity Testing

PubMed Central

Bourgognon, Maxime; Klippstein, Rebecca; Al-Jamal, Khuloud T.

2015-01-01

The large majority of in vitro nanotoxicological studies have used immortalized cell lines for their practicality. However, results from nanoparticle toxicity testing in immortalized cell lines or primary cells have shown discrepancies, highlighting the need to extend the use of primary cells for in vitro assays. This protocol describes the isolation of mouse liver macrophages, named Kupffer cells, and their use to study nanoparticle toxicity. Kupffer cells are the most abundant macrophage population in the body and constitute part of the reticulo-endothelial system (RES), responsible for the capture of circulating nanoparticles. The Kupffer cell isolation method reported here is based on a 2-step perfusion method followed by purification on density gradient. The method, based on collagenase digestion and density centrifugation, is adapted from the original protocol developed by Smedsrød et al. designed for rat liver cell isolation and provides high yield (up to 14 x 106 cells per mouse) and high purity (>95%) of Kupffer cells. This isolation method does not require sophisticated or expensive equipment and therefore represents an ideal compromise between complexity and cell yield. The use of heavier mice (35-45 g) improves the yield of the isolation method but also facilitates remarkably the procedure of portal vein cannulation. The toxicity of functionalized carbon nanotubes f-CNTs was measured in this model by the modified LDH assay. This method assesses cell viability by measuring the lack of structural integrity of Kupffer cell membrane after incubation with f-CNTs. Toxicity induced by f-CNTs can be measured consistently using this assay, highlighting that isolated Kupffer cells are useful for nanoparticle toxicity testing. The overall understanding of nanotoxicology could benefit from such models, making the nanoparticle selection for clinical translation more efficient. PMID:26327223

Effect of cysteine and humic acids on bioavailability of Ag from Ag nanoparticles to a freshwater snail

USGS Publications Warehouse

Luoma, Samuel N.; Tasha Stoiber,; Croteau, Marie-Noele; Isabelle Romer,; Ruth Merrifeild,; Lead, Jamie

2016-01-01

Metal-based engineered nanoparticles (NPs) will undergo transformations that will affect their bioavailability, toxicity and ecological risk when released to the environment, including interactions with dissolved organic material. The purpose of this paper is to determine how interactions with two different types of organic material affect the bioavailability of silver nanoparticles (AgNPs). Silver uptake rates by the pond snail Lymnaea stagnalis were determined after exposure to 25 nmol l-1 of Ag as PVP AgNPs, PEG AgNPs or AgNO3, in the presence of either Suwannee River humic acid or cysteine, a high-affinity thiol-rich organic ligand. Total uptake rate of Ag from the two NPs was either increased or not strongly affected in the presence of 1 – 10 mg 1-1 humic acid. Humic substances contain relatively few strong ligands for Ag explaining their limited effects on Ag uptake rate. In contrast, Ag uptake rate was substantially reduced by cysteine. Three components of uptake from the AgNPs were quantified in the presence of cysteine using a biodynamic modeling approach: uptake of dissolved Ag released by the AgNPs, uptake of a polymer or large (>3kD) Ag-cysteine complex and uptake of the nanoparticle itself. Addition of 1:1 Ag:cysteine reduced concentrations of dissolved Ag, which contributed to, but did not fully explain the reductions in uptake. A bioavailable Ag-cysteine complex (> 3kD) appeared to be the dominant avenue of uptake from both PVP AgNPs and PEG AgNPs in the presence of cysteine. Quantifying the different avenues of uptake sets the stage for studies to assess toxicity unique to NPs.

Occupational dermal exposure to nanoparticles and nano-enabled products: Part I-Factors affecting skin absorption.

PubMed

Larese Filon, Francesca; Bello, Dhimiter; Cherrie, John W; Sleeuwenhoek, Anne; Spaan, Suzanne; Brouwer, Derk H

2016-08-01

The paper reviews and critically assesses the evidence on the relevance of various skin uptake pathways for engineered nanoparticles, nano-objects, their agglomerates and aggregates (NOAA). It focuses especially in occupational settings, in the context of nanotoxicology, risk assessment, occupational medicine, medical/epidemiological surveillance efforts, and the development of relevant exposure assessment strategies. Skin uptake of nanoparticles is presented in the context of local and systemic health effects, especially contact dermatitis, skin barrier integrity, physico-chemical properties of NOAA, and predisposing risk factors, such as stratum corneum disruption due to occupational co-exposure to chemicals, and the presence of occupational skin diseases. Attention should be given to: (1) Metal NOAA, since the potential release of ions may induce local skin effects (e.g. irritation and contact dermatitis) and absorption of toxic or sensitizing metals; (2) NOAA with metal catalytic residue, since potential release of ions may also induce local skin effects and absorption of toxic metals; (3) rigid NOAA smaller than 45nm that can penetrate and permeate the skin; (4) non rigid or flexible NOAA, where due to their flexibility liposomes and micelles can penetrate and permeate the intact skin; (5) impaired skin condition of exposed workers. Furthermore, we outline possible situations where health surveillance could be appropriate where there is NOAA occupational skin exposures, e.g. when working with nanoparticles made of sensitizer metals, NOAA containing sensitizer impurities, and/or in occupations with a high prevalence of disrupted skin barrier integrity. The paper furthermore recommends a stepwise approach to evaluate risk related to NOAA to be applied in occupational exposure and risk assessment, and discusses implications related to health surveillance, labelling, and risk communication. Copyright © 2016 Elsevier GmbH. All rights reserved.

Quantifying engineered nanomaterial toxicity: comparison of common cytotoxicity and gene expression measurements.

PubMed

Atha, Donald H; Nagy, Amber; Steinbrück, Andrea; Dennis, Allison M; Hollingsworth, Jennifer A; Dua, Varsha; Iyer, Rashi; Nelson, Bryant C

2017-11-09

When evaluating the toxicity of engineered nanomaterials (ENMS) it is important to use multiple bioassays based on different mechanisms of action. In this regard we evaluated the use of gene expression and common cytotoxicity measurements using as test materials, two selected nanoparticles with known differences in toxicity, 5 nm mercaptoundecanoic acid (MUA)-capped InP and CdSe quantum dots (QDs). We tested the effects of these QDs at concentrations ranging from 0.5 to 160 µg/mL on cultured normal human bronchial epithelial (NHBE) cells using four common cytotoxicity assays: the dichlorofluorescein assay for reactive oxygen species (ROS), the lactate dehydrogenase assay for membrane viability (LDH), the mitochondrial dehydrogenase assay for mitochondrial function, and the Comet assay for DNA strand breaks. The cytotoxicity assays showed similar trends when exposed to nanoparticles for 24 h at 80 µg/mL with a threefold increase in ROS with exposure to CdSe QDs compared to an insignificant change in ROS levels after exposure to InP QDs, a twofold increase in the LDH necrosis assay in NHBE cells with exposure to CdSe QDs compared to a 50% decrease for InP QDs, a 60% decrease in the mitochondrial function assay upon exposure to CdSe QDs compared to a minimal increase in the case of InP and significant DNA strand breaks after exposure to CdSe QDs compared to no significant DNA strand breaks with InP. High-throughput quantitative real-time polymerase chain reaction (qRT-PCR) data for cells exposed for 6 h at a concentration of 80 µg/mL were consistent with the cytotoxicity assays showing major differences in DNA damage, DNA repair and mitochondrial function gene regulatory responses to the CdSe and InP QDs. The BRCA2, CYP1A1, CYP1B1, CDK1, SFN and VEGFA genes were observed to be upregulated specifically from increased CdSe exposure and suggests their possible utility as biomarkers for toxicity. This study can serve as a model for comparing traditional cytotoxicity assays and gene expression measurements and to determine candidate biomarkers for assessing the biocompatibility of ENMs.

Synthesis of Co3O4 nanoparticles with block and sphere morphology, and investigation into the influence of morphology on biological toxicity

PubMed Central

RAMAN, VENKATARAMANAN; SURESH, SHRUTHI; SAVARIMUTHU, PHILIP ANTHONY; RAMAN, THIAGARAJAN; TSATSAKIS, ARISTIDES MICHAEL; GOLOKHVAST, KIRIL SERGEEVICH; VADIVEL, VINOD KUMAR

2016-01-01

In the present study, cobalt oxide (Co3O4) magnetic nanoparticles with block and sphere morphologies were synthesized using various surfactants, and the toxicity of the particles was analyzed by monitoring biomarkers of nanoparticle toxicity in zebrafish. The use of tartarate as a surfactant produced highly crystalline blocks of Co3O4 nanoparticles with pores on the sides, whereas citrate lead to the formation of nanoparticles with a spherical morphology. Co3O4 structure, crystallinity, size and morphology were studied using X-ray diffractogram and field emission scanning electron microscopy. Following an increase in nanoparticle concentration from 1 to 200 ppm, there was a corresponding increase in nitric oxide (NO) generation, induced by both types of nanoparticles [Co3O4-NP-B (block), r=0.953; Co3O4-NP-S (sphere), r=1.140]. Comparative analyses indicated that both types of nanoparticle produced significant stimulation at ≥5 ppm (P<0.05) compared with a control. Upon analyzing the effect of nanoparticle morphology on NO generation, it was observed that Co3O4-NP-S was more effective compared with Co3O4-NP-B (5 and 100 ppm, P<0.05; 200 ppm, P<0.01). Exposure to both types of nanoparticles produced reduction in liver glutathione (GSH) activity with corresponding increase in dose (Co3O4-NP-B, r=−0.359; Co3O4-NP-S, r=−0.429). However, subsequent analyses indicated that Co3O4-NP-B was more potent in inhibiting liver GSH activity compared with Co3O4-NP-S. Co3O4-NP-B proved to be toxic at 5 ppm (P<0.05) and GSH activity was almost completely inhibited at 200 ppm. A similar toxicity was observed with both types of Co3O4-NPs against brain levels of acetylcholinesterase (AChE; Co3O4-NP-B, r=−0.180; Co3O4-NP-S, r=−0.230), indicating the ability of synthesized Co3O4-NPs to cross the blood-brain barrier and produce neuronal toxicity. Co3O4-NP-B showed increased inhibition of brain AChE activity compared with Co3O4-NP-S (1,5, and 10 ppm, P<0.05; 50, 100 and 200 ppm, P<0.01). These results suggested that the morphology of nanoparticle and surface area contribute to toxicity, which may have implications for their biological application. PMID:26893646

Engineering of near infrared fluorescent proteinoid-poly(L-lactic acid) particles for in vivo colon cancer detection.

PubMed

Kolitz-Domb, Michal; Grinberg, Igor; Corem-Salkmon, Enav; Margel, Shlomo

2014-08-12

The use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer owing to the negligible absorption and autofluorescence of water and other intrinsic biomolecules in this region. The main aim of the present study is to synthesize and characterize novel NIR fluorescent nanoparticles based on proteinoid and PLLA for early detection of colon tumors. The present study describes the synthesis of new proteinoid-PLLA copolymer and the preparation of NIR fluorescent nanoparticles for use in diagnostic detection of colon cancer. These fluorescent nanoparticles were prepared by a self-assembly process in the presence of the NIR dye indocyanine green (ICG), a FDA-approved NIR fluorescent dye. Anti-carcinoembryonic antigen antibody (anti-CEA), a specific tumor targeting ligand, was covalently conjugated to the P(EF-PLLA) nanoparticles through the surface carboxylate groups using the carbodiimide activation method. The P(EF-PLLA) nanoparticles are stable in different conditions, no leakage of the encapsulated dye into PBS containing 4% HSA was detected. The encapsulation of the NIR fluorescent dye within the P(EF-PLLA) nanoparticles improves significantly the photostability of the dye. The fluorescent nanoparticles are non-toxic, and the biodistribution study in a mouse model showed they evacuate from the body over 24 h. Specific colon tumor detection in a chicken embryo model and a mouse model was demonstrated for anti-CEA-conjugated NIR fluorescent P(EF-PLLA) nanoparticles. The results of this study suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent P(EF-PLLA) nanoparticles over colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs such as paclitaxel and/or doxorubicin, within these biodegradable NIR fluorescent P(EF-PLLA) nanoparticles, for both detection and therapy of colon cancer.

Impacts of chemical modification on the toxicity of diverse nanocellulose materials to developing zebrafish

PubMed Central

Harper, Bryan J.; Clendaniel, Alicea; Sinche, Federico; Way, Daniel; Hughes, Michael; Schardt, Jenna; Simonsen, John; Stefaniak, Aleksandr B.

2016-01-01

Cellulose is an abundant and renewable resource currently being investigated for utility in nanomaterial form for various promising applications ranging from medical and pharmaceutical uses to mechanical reinforcement and biofuels. The utility of nanocellulose and wide implementation ensures increasing exposure to humans and the environment as nanocellulose-based technologies advance. Here, we investigate how differences in aspect ratio and changes to surface chemistry, as well as synthesis methods, influence the biocompatibility of nanocellulose materials using the embryonic zebrafish. Investigations into the toxicity of neutral, cationic and anionic surface functionalities revealed that surface chemistry had a minimal influence on the overall toxicity of nanocellulose materials. Higher aspect ratio cellulose nanofibers produced by mechanical homogenization were, in some cases, more toxic than other cellulose-based nanofibers or nanocrystals produced by chemical synthesis methods. Using fluorescently labeled nanocellulose we were able to show that nanocellulose uptake did occur in embryonic zebrafish during development. We conclude that the benign nature of nanocellulose materials makes them an ideal platform to systematically investigate the inherent surface features driving nanomaterial toxicity in order to create safer design principles for engineered nanoparticles. PMID:27468180

A comparison of dispersing media for various engineered carbon nanoparticles.

PubMed

Buford, Mary C; Hamilton, Raymond F; Holian, Andrij

2007-07-27

With the increased manufacture and use of carbon nanoparticles (CNP) there has been increasing concern about the potential toxicity of fugitive CNP in the workplace and ambient environment. To address this matter a number of investigators have conducted in vitro and in vivo toxicity assessments. However, a variety of different approaches for suspension of these particles (culture media, Tween 80, dimethyl sulfoxide, phosphate-buffered saline, fetal calf serum, and others), and different sources of materials have generated potentially conflicting outcomes. The quality of the dispersion of nanoparticles is very dependent on the medium used to suspend them, and this then will most likely affect the biological outcomes. In this work, the distributions of different CNP (sources and types) have been characterized in various media. Furthermore, the outcome of instilling the different agglomerates, or size distributions, was examined in mouse lungs after one and seven days. Our results demonstrated that CNP suspended in serum produced particle suspensions with the fewest large agglomerates, and the most uniform distribution in mouse lungs. In addition, no apparent clearance of instilled CNP took place from lungs even after seven days. This work demonstrates that CNP agglomerates are present in all dispersing vehicles to some degree. The vehicle that contains some protein, lipid or protein/lipid component disperses the CNP best, producing fewer large CNP agglomerates. In contrast, vehicles absent of lipid and protein produce the largest CNP agglomerates. The source of the CNP is also a factor in the degree of particle agglomeration within the same vehicle.

Transport across the cell-membrane dictates nanoparticle fate and toxicity: a new paradigm in nanotoxicology

NASA Astrophysics Data System (ADS)

Guarnieri, Daniela; Sabella, Stefania; Muscetti, Ornella; Belli, Valentina; Malvindi, Maria Ada; Fusco, Sabato; de Luca, Elisa; Pompa, Pier Paolo; Netti, Paolo A.

2014-08-01

The toxicity of metallic nanoparticles (MNPs) has been fully ascertained, but the mechanisms underlying their cytotoxicity remain still largely unclear. Here we demonstrate that the cytotoxicity of MNPs is strictly reliant on the pathway of cellular internalization. In particular, if otherwise toxic gold, silver, and iron oxide NPs are forced through the cell membrane bypassing any form of active mechanism (e.g., endocytosis), no significant cytotoxic effect is registered. Pneumatically driven NPs across the cell membrane show a different distribution within the cytosol compared to NPs entering the cell by active endocytosis. Specifically, they exhibit free random Brownian motions within the cytosol and do not accumulate in lysosomes. Results suggest that intracellular accumulation of metallic nanoparticles into endo-lysosomal compartments is the leading cause of nanotoxicity, due to consequent nanoparticle degradation and in situ release of metal ions.The toxicity of metallic nanoparticles (MNPs) has been fully ascertained, but the mechanisms underlying their cytotoxicity remain still largely unclear. Here we demonstrate that the cytotoxicity of MNPs is strictly reliant on the pathway of cellular internalization. In particular, if otherwise toxic gold, silver, and iron oxide NPs are forced through the cell membrane bypassing any form of active mechanism (e.g., endocytosis), no significant cytotoxic effect is registered. Pneumatically driven NPs across the cell membrane show a different distribution within the cytosol compared to NPs entering the cell by active endocytosis. Specifically, they exhibit free random Brownian motions within the cytosol and do not accumulate in lysosomes. Results suggest that intracellular accumulation of metallic nanoparticles into endo-lysosomal compartments is the leading cause of nanotoxicity, due to consequent nanoparticle degradation and in situ release of metal ions. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr02008a

The biological effects and possible modes of action of nanosilver.

PubMed

Völker, Carolin; Oetken, Matthias; Oehlmann, Jörg

2013-01-01

Novel physicochemical and biological properties have led to a versatile spectrum of applications for nanosized silver particles. Silver nanoparticles are applied primarily for their antimicrobial effects, and may variety of commercially available products have emerged. To better predict and prevent possible environmental impacts from silver nanoparticles that are derived from increasing production volumes and environmental release, more data on the biological effects are needed on appropriate model organisms. We examined the literature that addressed the adverse effects of silver nanoparticles on different levels of biological integration, including in vitro and in vivo test systems. Results of in vitro studies indicate a dose-dependent programmed cell death included by oxidative stress as main possible pathway of toxicity. Furthermore, silver nanoparticles may affect cellular enzymes by interference with free thiol groups and mimicry of endogenous ions. Similar mechanisms may apply for antibacterial effects produced by nonasilver. These effects are primary from the interference nanosilver has with bacterial cell membranes. Few in vivo studies have been performed to evaluated the toxic mode of action of nanosilver or to provide evidence for oxidative stress as an important mechanism of nanosilver toxicity. Organisms that are most acutely sensitive to nanosilver toxicity are the freshwater filter-freeding organisms. Both in vitro and in vivo studies have demonstrated tha silver ions released from nanoparticle surface contribute to the toxicity, and, indeed, some findings indicated a unique nanoparticles effect. For an adequate evaluation of the environmental impact of nanosilver, greater emphasis should be placed on combining mechanistic investigations that are performed in vitro, with results obtained in in vivo test systems. Future in vivo test system studies should emphasize long-term exposure scenarios. Moreover, the dietary uptake of silver nanoparticles and the potential to bioaccumulate through the food web should be examined in detail.

Toxicity, Bioaccumulation and Biotransformation of Silver Nanoparticles in Marine Organisms

EPA Science Inventory

The toxicity, bioaccumulation and biotransformation of citrate and polyvinylpyrrolidone (PVP) capped silver nanoparticles (NPs) (AgNP-citrate and AgNP-PVP) and titanium dioxide (TiO2) NPs in marine organisms via marine sediment exposure were investigated. Results from 7-d sedimen...

A new medium for Caenorhabditis elegans toxicology and nanotoxicology studies designed to better reflect natural soil solution conditions.

PubMed

Tyne, William; Lofts, Stephen; Spurgeon, David J; Jurkschat, Kerstin; Svendsen, Claus

2013-08-01

A new toxicity test medium for Caenorhabditis elegans is presented. The test solution is designed to provide a better representation of natural soil pore water conditions than currently available test media. The medium has a composition that can readily be modified to allow for studies of the influences of a range of environmentally relevant parameters on nematode biology and toxicology. Tests conducted in the new medium confirmed that nematodes' reproduction was possible at a range of solution pH levels, offering the potential to conduct toxicity studies under a variety of conditions. A test to establish silver nanoparticle and dissolved silver nitrate toxicity, a study type not feasible in M9 or agar media due to precipitation and nanoparticle agglomeration, indicated lower silver nanoparticle (median effective concentration [EC50] of 6.5 mg Ag/L) than silver nitrate (EC50 0.28 mg Ag/L) toxicity. Characterization identified stable nanoparticle behavior in the new test medium. Copyright © 2013 SETAC.

Cerium dioxide (CeO2) nanoparticles decrease arsenite (As(III)) cytotoxicity to 16HBE14o- human bronchial epithelial cells.

PubMed

Zeng, Chao; Nguyen, Chi; Boitano, Scott; Field, Jim A; Shadman, Farhang; Sierra-Alvarez, Reyes

2018-07-01

The production and application of engineered nanoparticles (NPs) are increasing in demand with the rapid development of nanotechnology. However, there are concerns that some of these novel materials could lead to emerging environmental and health problems. Some NPs are able to facilitate the transport of contaminants into cells/organisms via a "Trojan Horse" effect which enhances the toxicity of the adsorbed materials. In this work, we evaluated the toxicity of arsenite (As(III)) adsorbed onto cerium dioxide (CeO 2 ) NPs to human bronchial epithelial cells (16HBE14o-) using the xCELLigence real time cell analyzing system (RTCA). Application of 0.5 mg/L As(III) resulted in 81.3% reduction of cell index (CI, an RTCA measure of cell toxicity) over 48 h when compared to control cells exposed to medium lacking As(III). However, when the cells were exposed to 0.5 mg/L As(III) in the presence of CeO 2 NPs (250 mg/L), the CI was only reduced by 12.9% compared to the control. The CeO 2 NPs had a high capacity for As(III) adsorption (20.2 mg/g CeO 2 ) in the bioassay medium, effectively reducing dissolved As(III) in the aqueous solution and resulting in reduced toxicity. Transmission electron microscopy was used to study the transport of CeO 2 NPs into 16HBE14o- cells. NP uptake via engulfment was observed and the internalized NPs accumulated in vesicles. The results demonstrate that dissolved As(III) in the aqueous solution was the decisive factor controlling As(III) toxicity of 16HBE14o- cells, and that CeO 2 NPs effectively reduced available As(III) through adsorption. These data emphasize the evaluation of mixtures when assaying toxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy

PubMed Central

Oberdörster, Günter; Maynard, Andrew; Donaldson, Ken; Castranova, Vincent; Fitzpatrick, Julie; Ausman, Kevin; Carter, Janet; Karn, Barbara; Kreyling, Wolfgang; Lai, David; Olin, Stephen; Monteiro-Riviere, Nancy; Warheit, David; Yang, Hong

2005-01-01

The rapid proliferation of many different engineered nanomaterials (defined as materials designed and produced to have structural features with at least one dimension of 100 nanometers or less) presents a dilemma to regulators regarding hazard identification. The International Life Sciences Institute Research Foundation/Risk Science Institute convened an expert working group to develop a screening strategy for the hazard identification of engineered nanomaterials. The working group report presents the elements of a screening strategy rather than a detailed testing protocol. Based on an evaluation of the limited data currently available, the report presents a broad data gathering strategy applicable to this early stage in the development of a risk assessment process for nanomaterials. Oral, dermal, inhalation, and injection routes of exposure are included recognizing that, depending on use patterns, exposure to nanomaterials may occur by any of these routes. The three key elements of the toxicity screening strategy are: Physicochemical Characteristics, In Vitro Assays (cellular and non-cellular), and In Vivo Assays. There is a strong likelihood that biological activity of nanoparticles will depend on physicochemical parameters not routinely considered in toxicity screening studies. Physicochemical properties that may be important in understanding the toxic effects of test materials include particle size and size distribution, agglomeration state, shape, crystal structure, chemical composition, surface area, surface chemistry, surface charge, and porosity. In vitro techniques allow specific biological and mechanistic pathways to be isolated and tested under controlled conditions, in ways that are not feasible in in vivo tests. Tests are suggested for portal-of-entry toxicity for lungs, skin, and the mucosal membranes, and target organ toxicity for endothelium, blood, spleen, liver, nervous system, heart, and kidney. Non-cellular assessment of nanoparticle durability, protein interactions, complement activation, and pro-oxidant activity is also considered. Tier 1 in vivo assays are proposed for pulmonary, oral, skin and injection exposures, and Tier 2 evaluations for pulmonary exposures are also proposed. Tier 1 evaluations include markers of inflammation, oxidant stress, and cell proliferation in portal-of-entry and selected remote organs and tissues. Tier 2 evaluations for pulmonary exposures could include deposition, translocation, and toxicokinetics and biopersistence studies; effects of multiple exposures; potential effects on the reproductive system, placenta, and fetus; alternative animal models; and mechanistic studies. PMID:16209704

Engineered nickel oxide nanoparticle causes substantial physicochemical perturbation in plants

NASA Astrophysics Data System (ADS)

Manna, Indrani; Bandyopadhyay, Maumita

2017-11-01

Concentration of engineered NiO-NP in nature is on the rise, owing to large scale industrial uses and human interventions, which have accreted the scope of exposure especially at the primary trophic levels of the ecosystem. Nickel content in air, drinking water and soil is already above permissible limits in most parts of the developed world. Though nickel oxide is an essential micronutrient in the animal system, it has already been graded as a human carcinogen by WHO, and numerous studies have established the toxic nature of nickel in higher dosage in the animal system. Though studies depicting toxicity and bioaccumulation of nickel in plants is documented, the interaction of nickel oxide nanoparticle with plants is not fully a well-studied, well elucidated topic. What is known is that, exposure to nickel oxide nanoparticle, arouses stress response and leads to cytotoxicity and growth retardation in a handful of plants, a defined work on the intricate physicochemical cellular responses and genotoxic challenges has been so far absent. We have tried to fill in such gaps with this study. We planned the work around pertinent hypotheses like: whether NiO-NP cause cytotoxicity in a model plant system (Allium cepa L.)?If so, does internalization of nickel ion (the potent toxic) take place in the tissue? Does internalized NiO-NP create furore in the antioxidant enzyme system of the plant leading to cytotoxicity? In that case, whether the ENP causes genotoxicity and leads to pycknosis of the cell. The study has been designed to assess the change in biochemical profile and genotoxicity potential of NiO-NP at a wide range of concentrations using root tips of Allium cepa L., the model system for study of cytotoxicity and genotoxicity, and four of its closest relatives, Allium sativum L., Allium schoenoprasum L., Allium porrum L., Allium fistulosum L., chosen for their immense economic importance. Growing root tips were treated with seven different concentrations of NiO-NP suspension (10 mg L‾1, 25 mg L‾1, 50 mg L‾1, 62.5 mg L‾1, 125 mg L‾1, 250 mg L‾1 and 500 mg L‾1) along with deionised distilled water as negative control and 0.4mM EMS solution as

Bioavailability, Intracellular Mobilization of Nickel, and HIF-1α Activation in Human Lung Epithelial Cells Exposed to Metallic Nickel and Nickel Oxide Nanoparticles

PubMed Central

Liu, Xinyuan; Smith, Ashley; McNeil, Kevin; Weston, Paula; Zhitkovich, Anatoly; Hurt, Robert; Kane, Agnes B.

2011-01-01

Micron-sized particles of poorly soluble nickel compounds, but not metallic nickel, are established human and rodent carcinogens. In contrast, little is known about the toxic effects of a growing number of Ni-containing materials in the nano-sized range. Here, we performed physicochemical characterization of NiO and metallic Ni nanoparticles and examined their metal ion bioavailability and toxicological properties in human lung epithelial cells. Cellular uptake of metallic Ni and NiO nanoparticles, but not metallic Ni microparticles, was associated with the release of Ni(II) ions after 24–48 h as determined by Newport Green fluorescence. Similar to soluble NiCl2, NiO nanoparticles induced stabilization and nuclear translocation of hypoxia-inducible factor 1α (HIF-1α) transcription factor followed by upregulation of its target NRDG1 (Cap43). In contrast to no response to metallic Ni microparticles, nickel nanoparticles caused a rapid and prolonged activation of the HIF-1α pathway that was stronger than that induced by soluble Ni (II). Soluble NiCl2 and NiO nanoparticles were equally toxic to H460 human lung epithelial cells and primary human bronchial epithelial cells; metallic Ni nanoparticles showed lower toxicity and Ni microparticles were nontoxic. Cytotoxicity induced by all forms of Ni occurred concomitant with activation of an apoptotic response, as determined by dose- and time-dependent cleavage of caspases and poly (ADP-ribose) polymerase. Our results show that metallic Ni nanoparticles, in contrast to micron-sized Ni particles, activate a toxicity pathway characteristic of carcinogenic Ni compounds. Moderate cytotoxicity and sustained activation of the HIF-1α pathway by metallic Ni nanoparticles could promote cell transformation and tumor progression. PMID:21828359

Assessment and prediction of joint algal toxicity of binary mixtures of graphene and ionic liquids.

PubMed

Wang, Zhuang; Zhang, Fan; Wang, Se; Peijnenburg, Willie J G M

2017-10-01

Graphene and ionic liquids (ILs) released into the environment will interact with each other. So far however, the risks associated with the concurrent exposure of biota to graphene and ILs in the environment have received little attention. The research reported here focused on observing and predicting the joint toxicity effects in the green alga Scenedesmus obliquus exposed to binary mixtures of intrinsic graphene (iG)/graphene oxide (GO) and five ILs of varying anionic and cationic types. The isolated ILs in the binary mixtures were the main contributors to toxicity. The binary GO-IL mixtures resulted in more severe joint toxicity than the binary iG-IL mixtures, irrespective of mixture ratios. The mechanism of the joint toxicity may be associated with the adsorption capability of the graphenes for the ILs, the dispersion stability of the graphenes in aquatic media, and modulation of the binary mixtures-induced oxidative stress. A toxic unit assessment showed that the graphene and IL toxicities were additive at low concentration of the mixtures but antagonistic at high concentration of the mixtures. Predictions made using the concentration addition and independent action models were close to the observed joint toxicities regardless of mixture types and mixture ratios. These findings provide new insights that are of use in the risk assessment of mixtures of engineered nanoparticles and other environmentally relevant contaminants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of ZnO and Ag Nanoparticles on Bacterial Growth and Viability

NASA Astrophysics Data System (ADS)

Olson, M. S.; Digiovanni, K. A.

2007-12-01

Hundreds of consumer products containing nanomaterials are currently available in the U.S., including computers, clothing, cosmetics, sports equipment, medical devices and product packaging. Metallic nanoparticles can be embedded in or coated on product surfaces to provide antimicrobial, deodorizing, and stain- resistant properties. Although these products have the potential to provide significant benefit to the user, the impact of these products on the environment remains largely unknown. The purpose of this project is to study the effect of metallic nanoparticles released to the environment on bacterial growth and viability. Inhibition of bacterial growth was tested by adding doses of suspended ZnO and Ag nanoparticles into luria broth prior to inoculation of Escherichia coli cells. ZnO particles (approximately 40 nm) were obtained commercially and Ag particles (12-14 nm) were fabricated by reduction of silver nitrate with sodium borohydride. Toxicity assays were performed to test the viability of E. coli cells exposed to both ZnO and Ag nanoparticles using the LIVE/DEAD BacLight bacterial viability kit (Invitrogen). Live cells stain green whereas cells with compromised membranes that are considered dead or dying stain red. Cells were first grown, stained, and exposed to varying doses of metallic nanoparticles, and then bacterial viability was measured hourly using fluorescence microscopy. Results indicate that both ZnO and Ag nanoparticles inhibit the growth of E. coli in liquid media. Preliminary results from toxicity assays confirm the toxic effect of ZnO and Ag nanoparticles on active cell cultures. Calculated death rates resulting from analyses of toxicity studies will be presented.

Effets antibacteriens des nanoparticules de cuivre, oxyde de cuivre et oxyde de fer

NASA Astrophysics Data System (ADS)

Talantikit, Myriam

Population longevity tends to increase in occidental countries inducing an increment in medical implants use. Resistant bacteria may contaminate those implants causing nosocomial infections. Common treatment for bacteria is antibiotic, used mainly for their speed and efficacy. An overuse of antibiotics induced bacteria to be resistant to them. Adding to this issue, when bacteria are in a certain environment, bacteria tend to communicate between themselves and create a biofilm (protective layer). Polysaccharides forming the biofilm don't allow antibiotics to penetrate inside the biofilm. Bacteria in a biofilm are extremely hard to kill. An alternative to resolve all those issues is to use nanoparticles as antimicrobial agents. They are known to have antibacterial effect. But the. The main objective is to study the effects develop "nano-biotics" that can prevent nosocomial infections due to surgical implants. In this project, we evaluated in vitro antibacterial effects of some nanoparticles (copper, copper oxide, superparamagnetic iron oxide, and superparamagnetic iron oxide coupled with nitric oxide (NO) on bacteria. Nanoparticles and microparticles characterizations have been done to determine their size, their composition and their surface chemistry using TEM and FTIR. Different parameters play a crucial role in antibacterial toxicity of particles. First, we adapted microbiological tests to elucidate nanoparticles biotoxicity. Then, pure copper and copper oxide nanoparticles have been studied to determine the importance of nanoparticles composition in toxicity. Size is another important parameter, explaining our interest to study both copper micro and nanoparticles on bacteria (S.aureus and E.coli). Bacterial toxicity of superparamagnetic iron oxide nanoparticles, used as a magnetic vehicle to deliver NO (antibacterial molecule), has been studied. Once NO is delivered, iron oxide nanoparticles still react with bacteria. Finally, copper and copper oxide nanoparticles were in contact with S.aureus biofilm to see their effect and the difference with planktonic bacteria. Our nanoparticles characterizations of copper shows that these nanoparticles are not completely pure but a thin oxide layer at their surface forms, which can lower their toxicity. Our results on the importance of particles size, confirm what was seen in the literature. Nanoparticles seems to be more toxic than microparticles. Superparamagnetic iron oxide nanoparticles results, alone, don't show a big antibacterial effect. Preliminary tests were done on NO coupled nanoparticles, and it seems there is an antibacterial effect. However, NO results are not conclusive because of some technical difficulties during NO attachment on nanoparticles. These studies allowed us to show that copper and copper oxide nanoparticles were a good antibacterial but the dose used might be too important for biomedical applications. Superparamagnetic iron oxide nanoparticles have a low antibacterial effect but are biocompatible. They are an excellent candidate as vehicle for NO delivery to a specific site. These studies are the first effort made to the development of new antimicrobial agents based on metallic nanoparticles. Key words: nanoparticles, copper, oxide copper, biofilm, antibacterial, iron oxide, nitric oxide.

Toxicity of silver nanoparticles in biological systems: Does the complexity of biological systems matter?

PubMed

Vazquez-Muñoz, Roberto; Borrego, Belen; Juárez-Moreno, Karla; García-García, Maritza; Mota Morales, Josué D; Bogdanchikova, Nina; Huerta-Saquero, Alejandro

2017-07-05

Currently, nanomaterials are more frequently in our daily life, specifically in biomedicine, electronics, food, textiles and catalysis just to name a few. Although nanomaterials provide many benefits, recently their toxicity profiles have begun to be explored. In this work, the toxic effects of silver nanoparticles (35nm-average diameter and Polyvinyl-Pyrrolidone-coated) on biological systems of different levels of complexity was assessed in a comprehensive and comparatively way, through a variety of viability and toxicological assays. The studied organisms included viruses, bacteria, microalgae, fungi, animal and human cells (including cancer cell lines). It was found that biological systems of different taxonomical groups are inhibited at concentrations of silver nanoparticles within the same order of magnitude. Thus, the toxicity of nanomaterials on biological/living systems, constrained by their complexity, e.g. taxonomic groups, resulted contrary to the expected. The fact that cells and virus are inhibited with a concentration of silver nanoparticles within the same order of magnitude could be explained considering that silver nanoparticles affects very primitive cellular mechanisms by interacting with fundamental structures for cells and virus alike. Copyright © 2017 Elsevier B.V. All rights reserved.

Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Eenograft Model

PubMed Central

Chen, Yan; Zheng, Xue-Lian; Fang, Dai-Long; Yang, Yang; Zhang, Jin-Kun; Li, Hui-Li; Xu, Bei; Lei, Yi; Ren, Ke; Song, Xiang-Rong

2014-01-01

Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic. PMID:24552875

Impact of nanoparticles on human and environment: review of toxicity factors, exposures, control strategies, and future prospects.

PubMed

Sajid, Muhammad; Ilyas, Muhammad; Basheer, Chanbasha; Tariq, Madiha; Daud, Muhammad; Baig, Nadeem; Shehzad, Farrukh

2015-03-01

Nanotechnology has revolutionized the world through introduction of a unique class of materials and consumer products in many arenas. It has led to production of innovative materials and devices. Despite of their unique advantages and applications in domestic and industrial sectors, use of materials with dimensions in nanometers has raised the issue of safety for workers, consumers, and human environment. Because of their small size and other unique characteristics, nanoparticles have ability to harm human and wildlife by interacting through various mechanisms. We have reviewed the characteristics of nanoparticles which form the basis of their toxicity. This paper also reviews possible routes of exposure of nanoparticles to human body. Dermal contact, inhalation, and ingestion have been discussed in detail. As very limited data is available for long-term human exposures, there is a pressing need to develop the methods which can determine short and long-term effects of nanoparticles on human and environment. We also discuss in brief the strategies which can help to control human exposures to toxic nanoparticles. We have outlined the current status of toxicological studies dealing with nanoparticles, accomplishments, weaknesses, and future challenges.

Development of a dose-controlled multiculture cell exposure chamber for efficient delivery of airborne and engineered nanoparticles

NASA Astrophysics Data System (ADS)

Asimakopoulou, Akrivi; Daskalos, Emmanouil; Lewinski, Nastassja; Riediker, Michael; Papaioannou, Eleni; Konstandopoulos, Athanasios G.

2013-04-01

In order to study the various health influencing parameters related to engineered nanoparticles as well as to soot emitted by Diesel engines, there is an urgent need for appropriate sampling devices and methods for cell exposure studies that simulate the respiratory system and facilitate associated biological and toxicological tests. The objective of the present work was the further advancement of a Multiculture Exposure Chamber (MEC) into a dose-controlled system for efficient delivery of nanoparticles to cells. It was validated with various types of nanoparticles (Diesel engine soot aggregates, engineered nanoparticles for various applications) and with state-of-the-art nanoparticle measurement instrumentation to assess the local deposition of nanoparticles on the cell cultures. The dose of nanoparticles to which cell cultures are being exposed was evaluated in the normal operation of the in vitro cell culture exposure chamber based on measurements of the size specific nanoparticle collection efficiency of a cell free device. The average efficiency in delivering nanoparticles in the MEC was approximately 82%. The nanoparticle deposition was demonstrated by Transmission Electron Microscopy (TEM). Analysis and design of the MEC employs Computational Fluid Dynamics (CFD) and true to geometry representations of nanoparticles with the aim to assess the uniformity of nanoparticle deposition among the culture wells. Final testing of the dose-controlled cell exposure system was performed by exposing A549 lung cell cultures to fluorescently labeled nanoparticles. Delivery of aerosolized nanoparticles was demonstrated by visualization of the nanoparticle fluorescence in the cell cultures following exposure. Also monitored was the potential of the aerosolized nanoparticles to generate reactive oxygen species (ROS) (e.g. free radicals and peroxides generation), thus expressing the oxidative stress of the cells which can cause extensive cellular damage or damage on DNA.

Toxicity assessment of Titanium Dioxide and Cerium Oxide nanoparticles in Arabidopsis thaliana L.

EPA Science Inventory

The production and applications of nanoparticles (NP) in diverse fields has steadily increased in recent decades; however, knowledge about risks of NP to human health and ecosystems is still scarce. In this study, we assessed potential toxicity of two commercially used engineere...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ema, Makoto, E-mail: ema-makoto@aist.go.jp; Gamo, Masashi; Honda, Kazumasa

We summarized significant effects reported in the literature on the developmental toxicity of engineered nanomaterials (ENMs) in rodents. The developmental toxicity of ENMs included not only structural abnormalities, but also death, growth retardation, and behavioral and functional abnormalities. Most studies were performed on mice using an injection route of exposure. Teratogenic effects were indicated when multi-walled carbon nanotubes (MWCNTs), single-walled carbon nanotubes (SWCNTs), and TiO{sub 2}-nanoparticles were administered to mice during early gestation. Reactive oxygen species levels were increased in placentas and malformed fetuses and their placentas after prenatal exposure to MWCNTs and SWCNTs, respectively. The pre- and postnatal mortalitiesmore » and growth retardation in offspring increased after prenatal exposure to ENMs. Histopathological and functional abnormalities were also induced in placentas after prenatal exposure to ENMs. Maternal exposure to ENMs induced behavioral alterations, histopathological and biochemical changes in the central nervous system, increased susceptibility to allergy, transplacental genotoxicity, and vascular, immunological, and reproductive effects in offspring. The size- and developmental stage-dependent placental transfer of ENMs was noted after maternal exposure. Silver accumulated in the visceral yolk sac after being injected with Ag-NPs during early gestation. Although currently available data has provided initial information on the potential developmental toxicity of ENMs, that on the developmental toxicity of ENMs is still very limited. Further studies using well-characterized ENMs, state-of the-art study protocols, and appropriate routes of exposure are required in order to clarify these developmental effects and provide information suitable for risk assessments of ENMs. - Highlights: • We review the developmental toxicity studies of engineered nanomaterials (ENMs). • Various developmental endpoints have been reported after exposure to ENMs. • Physico-chemical properties of ENMs are determinants of the developmental toxicity. • Oxidative stress/inflammation may be involved in the developmental toxicity of ENMs. • Further developmental toxicity studies of ENMs are needed to fill a data gap.« less

Biosynthesis of silver nanoparticles using dried fruit extract of Ficus carica - Screening for its anticancer activity and toxicity in animal models.

PubMed

Jacob, S Justin Packia; Prasad, V L Siva; Sivasankar, S; Muralidharan, P

2017-11-01

There is an increasing commercial demand for various nanoparticles due to their extensive applicability in various areas such as electronics, catalysis, chemistry, energy and medicine. Metallic nanoparticles are traditionally synthesized by wet chemical techniques, where the chemicals used are quite often toxic and flammable. Fig has been a typical fruit component of the health-promoting Mediterranean diet for a very long time. In the present study, we describe a cost effective and eco-friendly technique for green synthesis of silver nanoparticles from 1 mM AgNO3 solution through the extract of dried fig (Ficus carica L.) fruit as reducing as well as capping agent. Nanoparticles were characterized using UV absorption spectroscopy and SEM. The sizes of the spherical silver particles were found to be in the range of 54-89 nm. The biologically synthesized nanoparticles also exhibited a significant cytotoxic effect on MCF7cell lines and further animal acute toxicity results state that the above AgNPs are toxicologically safe by oral administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

The toxic effects of silver nanoparticles on blood mononuclear cells.

PubMed

Barkhordari, A; Barzegar, S; Hekmatimoghaddam, H; Jebali, A; Rahimi Moghadam, S; Khanjani, N

2014-07-01

Nanoparticles have become one of the leading technologies over the past two years. The extensive use of nanoparticles has raised great concern about their occupational fate and biological effects. With an increase in the production and use of nanomaterial, it is more likely to get exposed to them occupationally and environmentally. To assess the toxicity of silver nanoparticles on human mononuclear cells. In this in vitro experimental study, suspensions of blood mononuclear cells from 10 young healthy men were incubated with 10-nm silver nanoparticles in different concentrations (range: 1-500 μg/mL) for 6 and 24 hours by MTT assay. Positive and negative controls were used for comparison. After 6 hours of exposure, 10.9% to 48.4% of the cells died. After 24 hours of exposure, the rate ranged from 56.8% to 86.3%. Regardless of the exposure time, the maximum cytotoxicity was observed at the concentration of 500 μg/mL of silver nanoparticles. By increasing the exposure time to 24 hours, the cytotoxicity of nanoparticles substantially increased at all concentrations. Cell death was significantly higher when compared to the controls (p<0.01). Silver nanoparticles possess both time- and dose-dependent cytotoxicity and can thus be considered as very toxic for mononuclear cells.

The Fate of ZnO Nanoparticles Administered to Human Bronchial Epithelial Cells

PubMed Central

Gilbert, Benjamin; Fakra, Sirine C.; Xia, Tian; Pokhrel, Suman; Mädler, Lutz; Nel, André E.

2014-01-01

A particular challenge for nanotoxicology is the evaluation of the biological fate and toxicity of nanomaterials that dissolve in aqueous fluids. Zinc oxide nanomaterials are of particular concern because dissolution leads to release of the toxic divalent zinc ion. Although dissolved zinc ions have been implicated in ZnO cytotoxicity, direct identification of the chemical form of zinc taken up by cells exposed to ZnO nanoparticles, and its intracellular fate, has not yet been achieved. We combined high resolution X-ray spectromicroscopy and high elemental sensitivity X-ray microprobe analyses to determine the fate of ZnO and less soluble iron-doped ZnO nanoparticles following exposure to cultures of human bronchial epithelial cells, BEAS-2B. We complemented two-dimensional X-ray imaging methods with atomic force microscopy of cell surfaces to distinguish between nanoparticles that were transported inside the cells from those that adhered to the cell exterior. The data suggest cellular uptake of ZnO nanoparticles is a mechanism of zinc accumulation in cells. Following uptake, ZnO nanoparticles dissolved completely generating intracellular Zn2+ complexed by molecular ligands. These results corroborate a model for ZnO nanoparticle toxicity that is based on nanoparticle uptake followed by intracellular dissolution. PMID:22646753

Anaerobic Toxicity of Cationic Silver Nanoparticles | Science ...

EPA Pesticide Factsheets

The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag+ under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged polyvinylpyrrolidone coated AgNPs (PVP-AgNps) and (3) positively charged branched polyethyleneimine coated AgNPs (BPEI-AgNPs). The AgNPs investigated in this experiment were similar in size (10-15 nm), spherical in shape, but varied in surface charge which ranged from highly negative to highly positive. While, at AgNPs concentrations lower than 5 mg L-1, the anaerobic decomposition process was not influenced by the presence of the nanoparticles, there was an observed impact on the diversity of the microbial community. At elevated concentrations (100 mg L-1 as silver), only the cationic BPEI-AgNPs demonstrated toxicity similar in magnitude to that of Ag+. Both citrate and PVP-AgNPs did not exhibit toxicity at the 100 mg L-1 as measured by biogas evolution. These findings further indicate the varying modes of action for nanoparticle toxicity and represent one of the few studies that evaluate end-of-life management concerns with regards to the increasing use of nanomaterials in our everyday life. These findings also highlight some of the concerns with a one size fits all approach to the evaluation of environmental health and safety concerns associated with the use of nanoparticles. The current

Effects of Humic and Fulvic Acids on Silver Nanoparticle Stability, Dissolution, and Toxicity

PubMed Central

Gunsolus, Ian L.; Mousavi, Maral P. S.; Hussein, Kadir; Bühlmann, Philippe; Haynes, Christy L.

2015-01-01

The colloidal stability of silver nanoparticles (AgNPs) in natural aquatic environments influences their transport and environmental persistence, while their dissolution to Ag+ influences their toxicity to organisms. Here, we characterize the colloidal stability, dissolution behavior, and toxicity of two industrially relevant classes of AgNPs (i.e., AgNPs stabilized by citrate or polyvinylpyrrolidone) after exposure to natural organic matter (NOM, i.e., Suwannee River Humic and Fulvic Acid Standards and Pony Lake Fulvic Acid Reference). We show that NOM interaction with the nanoparticle surface depends on (i) the NOM’s chemical composition, where sulfur- and nitrogen-rich NOM more significantly increases colloidal stability, and (ii) the affinity of the capping agent for the AgNP surface, where nanoparticles with loosely bound capping agents are more effectively stabilized by NOM. Adsorption of NOM is shown to have little effect on AgNP dissolution under most experimental conditions, the exception being when the NOM is rich in sulfur and nitrogen. Similarly, the toxicity of AgNPs to a bacterial model (Shewanella oneidensis MR-1) decreases most significantly in the presence of sulfur- and nitrogen-rich NOM. Our data suggest that the rate of AgNP aggregation and dissolution in aquatic environments containing NOM will depend on the chemical composition of the NOM, and that the toxicity of AgNPs to aquatic microorganisms is controlled primarily by the extent of nanoparticle dissolution. PMID:26047330

Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harper, Bryan; Thomas, Dennis G.; Chikkagoudar, Satish

The integration of rapid assays, large data sets, informatics and modeling can overcome current barriers in understanding nanomaterial structure-toxicity relationships by providing a weight-of-the-evidence mechanism to generate hazard rankings for nanomaterials. Here we present the use of a rapid, low-cost assay to perform screening-level toxicity evaluations of nanomaterials in vivo. Calculated EZ Metric scores, a combined measure of morbidity and mortality, were established at realistic exposure levels and used to develop a predictive model of nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both core composition and outermost surface chemistrymore » of nanomaterials. The resulting clusters guided the development of a predictive model of gold nanoparticle toxicity to embryonic zebrafish. In addition, our findings suggest that risk assessments based on the size and core composition of nanomaterials alone may be wholly inappropriate, especially when considering complex engineered nanomaterials. These findings reveal the need to expeditiously increase the availability of quantitative measures of nanomaterial hazard and broaden the sharing of that data and knowledge to support predictive modeling. In addition, research should continue to focus on methodologies for developing predictive models of nanomaterial hazard based on sub-lethal responses to low dose exposures.« less

Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity

DOE PAGES

Harper, Bryan; Thomas, Dennis G.; Chikkagoudar, Satish; ...

2015-06-04

The integration of rapid assays, large data sets, informatics and modeling can overcome current barriers in understanding nanomaterial structure-toxicity relationships by providing a weight-of-the-evidence mechanism to generate hazard rankings for nanomaterials. Here we present the use of a rapid, low-cost assay to perform screening-level toxicity evaluations of nanomaterials in vivo. Calculated EZ Metric scores, a combined measure of morbidity and mortality, were established at realistic exposure levels and used to develop a predictive model of nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both core composition and outermost surface chemistrymore » of nanomaterials. The resulting clusters guided the development of a predictive model of gold nanoparticle toxicity to embryonic zebrafish. In addition, our findings suggest that risk assessments based on the size and core composition of nanomaterials alone may be wholly inappropriate, especially when considering complex engineered nanomaterials. These findings reveal the need to expeditiously increase the availability of quantitative measures of nanomaterial hazard and broaden the sharing of that data and knowledge to support predictive modeling. In addition, research should continue to focus on methodologies for developing predictive models of nanomaterial hazard based on sub-lethal responses to low dose exposures.« less

Cutaneous exposure scenarios for engineered nanoparticles used in semiconductor fabrication: a preliminary investigation of workplace surface contamination.

PubMed

Shepard, Michele; Brenner, Sara

2014-01-01

Numerous studies are ongoing in the fields of nanotoxicology and exposure science; however, gaps remain in identifying and evaluating potential exposures from skin contact with engineered nanoparticles in occupational settings. The aim of this study was to identify potential cutaneous exposure scenarios at a workplace using engineered nanoparticles (alumina, ceria, amorphous silica) and evaluate the presence of these materials on workplace surfaces. Process review, workplace observations, and preliminary surface sampling were conducted using microvacuum and wipe sample collection methods and transmission electron microscopy with elemental analysis. Exposure scenarios were identified with potential for incidental contact. Nanoparticles of silica or silica and/or alumina agglomerates (or aggregates) were identified in surface samples from work areas where engineered nanoparticles were used or handled. Additional data are needed to evaluate occupational exposures from skin contact with engineered nanoparticles; precautionary measures should be used to minimize potential cutaneous exposures in the workplace.

Distribution and Biological Effects of Nanoparticles in the Reproductive System.

PubMed

Liu, Ying; Li, Hongxia; Xiao, Kai

2016-01-01

Nanoparticles have shown great potential in biomedical applications such as imaging probes and drug delivery. However, the increasing use of nanoparticles has raised concerns about their adverse effects on human health and environment. Reproductive tissues and gametes represent highly delicate biological systems with the essential function of transmitting genetic information to the offspring, which is highly sensitive to environmental toxicants. This review aims to summarzie the penetration of physiological barriers (blood-testis barrier and placental barrier), distribution and biological effects of nanoparticles in the reproductive system, which is essential to control the beneficial effects of nanoparticles applications and to avoid their adverse effects on the reproductive system. We referred to a large number of relevant peer-reviewed research articles about the reproductive toxicity of nanoparticles. The comprehensive information was summarized into two parts: physiological barrier penetration and biological effects of nanoparticles in male or female reproductive system; distribution and metabolism of nanoparticles in the reproductive system. The representative examples were also presented in four tables. The in vitro and in vivo studies imply that some nanoparticles are able to cross the blood-testis barrier or placental barrier, and their penetration depends on the physicochemical characteristics of nanoparticles (e.g., composition, shape, particle size and surface coating). The toxicity assays indicate that nanoparticles might induce adverse physiological effects and impede fertility or embryogenesis. The barrier penetration, adverse physiological effects, distribution and metabolism are closely related to physicochemical characteristics of nanoparticles. Further systematic and mechanistic studies using well-characterized nanoparticles, relevant administration routes, and doses relevant to the expected exposure level are required to improve our understanding of biological effects of nanoparticles on the reproductive system.

Integrated Approach of Agri-nanotechnology: Challenges and Future Trends

PubMed Central

Mishra, Sandhya; Keswani, Chetan; Abhilash, P. C.; Fraceto, Leonardo F.; Singh, Harikesh Bahadur

2017-01-01

Nanotechnology representing a new frontier in modern agriculture is anticipated to become a major thrust in near future by offering potential applications. This integrating approach, i.e., agri-nanotechnology has great potential to cope with global challenges of food production/security, sustainability and climate change. However, despite the potential benefits of nanotechnology in agriculture so far, their relevance has not reached up to the field conditions. The elevating concerns about fate, transport, bioavailability, nanoparticles toxicity and inappropriateness of regulatory framework limit the complete acceptance and inclination to adopt nanotechnologies in agricultural sector. Moreover, the current research trends lack realistic approach that fail to attain comprehensive knowledge of risk assessment factors and further toxicity of nanoparticles toward agroecosystem components viz. plant, soil, soil microbiomes after their release into the environment. Hence in the present review we attempt to suggest certain key points to be addressed in the current and future agri-nanotechnology researches on the basis of recognized knowledge gaps with strong recommendation of incorporating biosynthesized nanoparticles to carry out analogous functions. In this perspective, the major points are as follows: (i) Mitigating risk assessment factors (responsible for fate, transport, behavior, bioavailability and toxicity) for alleviating the subsequent toxicity of nanoparticles. (ii) Optimizing permissible level of nanoparticles dose within the safety limits by performing dose dependent studies. (iii) Adopting realistic approach by designing the experiments in natural habitat and avoiding in vitro assays for accurate interpretation. (iv) Most importantly, translating environmental friendly and non-toxic biosynthesized nanoparticles from laboratory to field conditions for agricultural benefits. PMID:28421100

Effect of Nanoparticles on the Survival and Development of Vitrified Porcine GV Oocytes.

PubMed

Li, W J; Zhou, X L; Liu, B L; Dai, J J; Song, P; Teng, Y

BACKGROUND: Some mammalian oocytes have been successfully cryopreserved by vitrification. However, the survival and developmental rate of vitrified oocytes is still low. The incorporation of nanoparticles into cryoprotectant (CPA) may improve the efficiency of vitrification by changing the properties of solutions. The toxicity of different concentrations of hydroxy apatite (HA), silica dioxide (SO 2 ), aluminum oxide (Al 2 O 3 ) and titanium dioxide (TiO 2 ) nanoparticles (20 nm in diameter) to oocytes was tested and the toxicity threshold value of each nanoparticle was determined. Porcine GV oocytes were vitrified in optimized nano-CPA, and effects of diameter and concentration of nanoparticles on the survival rate and developmental rate of porcine GV oocytes were compared. HA nanoparticles have demonstrated the least toxicity among four nanoparticles and the developmental rate of GV-stage porcine oocytes was 100% when its concentration was lower than 0.5%. By adding 0.1% HA into VS, the developmental rate of GV-stage porcine oocytes (22%) was significantly higher than other groups. The effect of vitrification in nano-CPA on oocytes was related to the concentration of HA nanoparticles rather than their size. By adding 0.05% HA nanoparticles (60nm in diameter), the developmental rate increased dramatically from 14.7% to 30.4%. Nano-cryopreservation offers a new way to improve the effect of survival and development of oocytes, but the limitation of this technology shall not be ignored.

Versatile Methodology to Encapsulate Gold Nanoparticles in PLGA Nanoparticles Obtained by Nano-Emulsion Templating.

PubMed

Fornaguera, Cristina; Feiner-Gracia, Natàlia; Dols-Perez, Aurora; García-Celma, Maria José; Solans, Conxita

2017-05-01

Gold nanoparticles have been proved useful for many biomedical applications, specifically, for their use as advanced imaging systems. However, they usually present problems related with stability and toxicity. In the present work, gold-nanoparticles have been encapsulated in polymeric nanoparticles using a novel methodology based on nano-emulsion templating. Firstly, gold nanoparticles have been transferred from water to ethyl acetate, a solvent classified as class III by the NIH guidelines (low toxic potential). Next, the formation of nano-emulsions loaded with gold nanoparticles has been performed using a low-energy, the phase inversion composition (PIC) emulsification method, followed by solvent evaporation giving rise to polymeric nanoparticles. Using this methodology, high concentrations of gold nanoparticles (>100 pM) have been encapsulated. Increasing gold nanoparticle concentration, nano-emulsion and nanoparticle sizes increase, resulting in a decrease on the stability. It is noteworthy that the designed nanoparticles did not produce cytotoxicity neither hemolysis at the required concentration. Therefore, it can be concluded that a novel and very versatile methodology has been developed for the production of polymeric nanoparticles loaded with gold nanoparticles. Graphical Abstract Schematic representation of AuNP-loaded polymeric nanoparticles preparation from nano-emulsion templating.

EFFECT OF COPPER OXIDE NANOPARTICLES TO SHEEPSHEAD MINNOW (CYPRINODON VARIEGATUS) AT DIFFERENT SALINITIES

PubMed Central

ATES, M.; DUGO, M.A.; DEMIR, V.; ARSLAN, Z.; TCHOUNWOU, P.B.

2014-01-01

Nanotechnologies research has become a significant priority worldwide. Many engineered nano-sized materials have been increasingly used in consumer products. But the adverse effects of these nanoparticles on the environment and organisms have recently drawn much attention. The present study investigated the effects of different concentrations of copper oxide nanoparticles (CuO NPs) on the sheepshead minnow (Cyprinodon variegatus) at different salinity regimes, since it is able to withstand a wide range of salinities. The results indicated that CuO NPs could cause behavioral changes in the fish, such as increased mucus secretion, less general activity and loss of equilibrium. No mortality was observed at the presence of CuO NPs during the experiments. But higher oxidative stress was determined at half strength seawater than seawater exposure medium, which can be associated with the decreasing toxicity of CuO NPs as salinity increases. In addition, Cu contents in the tissues of the fish were significantly higher (p<0.05) in the low salinity. The order of Cu accumulation in the fish's organs was intestine > gills > liver. PMID:25411584

Toxicology of antimicrobial nanoparticles for prosthetic devices

PubMed Central

Nuñez-Anita, Rosa Elvira; Acosta-Torres, Laura Susana; Vilar-Pineda, Jorge; Martínez-Espinosa, Juan Carlos; de la Fuente-Hernández, Javier; Castaño, Víctor Manuel

2014-01-01

Advances in nanotechnology are producing an accelerated proliferation of new nanomaterial composites that are likely to become an important source of engineered health-related products. Nanoparticles with antifungal effects are of great interest in the formulation of microbicidal materials. Fungi are found as innocuous commensals and colonize various habitats in and on humans, especially the skin and mucosa. As growth on surfaces is a natural part of the Candida spp. lifestyle, one can expect that Candida organisms colonize prosthetic devices, such as dentures. Macromolecular systems, due to their properties, allow efficient use of these materials in various fields, including the creation of reinforced nanoparticle polymers with antimicrobial activity. This review briefly summarizes the results of studies conducted during the past decade and especially in the last few years focused on the toxicity of different antimicrobial polymers and factors influencing their activities, as well as the main applications of antimicrobial polymers in dentistry. The present study addresses aspects that are often overlooked in nanotoxicology studies, such as careful time-dependent characterization of agglomeration and ion release. PMID:25187703

Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles.

PubMed

Xie, Shuyu; Wang, Fenghua; Wang, Yan; Zhu, Luyan; Dong, Zhao; Wang, Xiaofang; Li, Xihe; Zhou, Wenzhong

2011-11-20

Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN) are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw) with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD(50)) was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw) was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the nanoparticles are considered low toxic according to the toxicity categories of chemicals. Moreover, HCO-SLN significantly decreased the toxicity of tilmicosin. Normal clinic dosage of Til-HCO-SLN is safe as evaluated by acute toxicity.

Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

PubMed Central

2011-01-01

Background Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN) are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Methods Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw) with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50) was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw) was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. Results After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. Conclusions The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the nanoparticles are considered low toxic according to the toxicity categories of chemicals. Moreover, HCO-SLN significantly decreased the toxicity of tilmicosin. Normal clinic dosage of Til-HCO-SLN is safe as evaluated by acute toxicity. PMID:22098626

Synthesis and Characterization of BSA Conjugated Silver Nanoparticles (Ag/BSA Nanoparticles) and Evaluation of Biological Properties of Ag/BSA Nanoparticles and Ag/BSA Nanoparticles Loaded Poly(hydroxy butyrate valerate) PHBV Films

NASA Astrophysics Data System (ADS)

Ambaye, Almaz

Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa are the etiological agents of several infectious diseases. Antibiotic resistance by these three microbes has emerged as a prevalent problem due in part to the misuse of existing antibiotics and the lack of novel antibiotics. Nanoparticles have emerged as an alternative antibacterial agents to conventional antibiotics owing to their high surface area to volume ratio and their unique chemical and physical properties. Among the nanoparticles, silver nanoparticles have gained increasing attention because silver nanoparticles exhibit antibacterial activity against a range of gram positive and gram negative bacteria. Nanoparticles of well-defined chemistry and morphology can be used in broad biomedical applications, especially in bone tissue engineering applications, where bone infection by bacteria can be acute and lethal. It is commonly noted in the literature that the activity of nanoparticles against microorganisms is dependent upon the size and concentration of the nanoparticles as well as the chemistry of stabilizing agent. To the best of our knowledge, a comprehensive study that evaluates the antibacterial activity of well characterized silver nanoparticles in particular Bovine Serum Albumin (BSA) stabilized against S. aureus and E. coli and cytotoxicity level of BSA stabilized silver nanoparticles towards osteoblast cells (MC3T3-E1) is currently lacking. Therefore, the primary objective of this study was to characterize protein conjugated silver nanoparticles prepared by chemical reduction of AgNO3 and BSA mixture. The formation of Ag/BSA nanoparticles was studied by UV-Vis spectroscopy. The molar ratio of silver to BSA in the Ag/BSA nanoparticles was established to be 27+/- 3: 1, based on Thermogravimetric Analysis and Atomic Absorption Spectroscopy. Based on atomic force microscopy, dynamic light scattering,and transmission electron microscopy(TEM) measurements, the particle size (diameter) of Ag/BSA nanoparticles was found to be in a range of 9-13 nm. X-ray photo electron spectroscopy measurements of argon sputtered Ag/BSA nanoparticles provided evidence that the outer and inner region of nanoparticles are mainly composed of BSA and silver, respectively. Having characterized the nanoparticles, the next phase of the study was to evaluate the antibacterial activity and cytotoxicity level of BSA stabilized silver nanoparticles. The antibacterial efficacy of Ag/BSA nanoparticles against E. coli and S. aureus was evaluated, and minimum lethal concentration was found to be 2ppm and 7ppm, respectively. E. coli showed a higher susceptibility to silver nanoparticles than S. aureus, which could be attributed to the difference in the cell wall structure. We have also investigated the cytotoxicity level of Ag/BSA nanoparticles towards MC3T3-E1 osteoblast cells. The minimum bactericidal concentration found for both strains is lower than the silver nanoparticles concentration that was toxic to the osteoblast cells. Preliminary studies of Ag/BSA nanoparticles loaded collagen immobilized PHBV film showed that the Ag/BSA nanoparticles loaded PHBV film inhibit bacterial growth. The findings of our study can be extremely useful in the design of novel scaffold to address the critical needs of bone tissue engineering community.

In vitro interactions between splenocytes and dansylamide dye-embedded nanoparticles detected by flow cytometry

PubMed Central

Nyland, Jennifer F.; Bai, Jennifer J. K.; Katz, Howard E.; Silbergeld, Ellen K.

2009-01-01

Engineered nanoparticles (NPs) possess a range of biological activity. In vitro methods for assessing toxicity and efficacy would be enhanced by simultaneous quantitative information on the behavior of NPs in culture systems and signals of cell response. We have developed a method for visualizing NPs within cells using standard flow cytometric techniques and uniquely designed spherical siloxane NPs with an embedded (covalently bound) dansylamide dye. This method allowed NP visualization without obscuring detection of relevant biomarkers of cell subtype, activation state, and other events relevant to assessing bioactivity. We determined that NPs penetrated cells and induced a range of biological signals consistent with activation and costimulation. These results indicate that NPs may affect cell function at concentrations below those inducing cytotoxicity or apoptosis and demonstrate a novel method to image both localization of NPs and cell-level effects. PMID:19523425

A biodistribution study of two differently shaped plant virus nanoparticles reveals new peculiar traits.

PubMed

Lico, Chiara; Giardullo, Paola; Mancuso, Mariateresa; Benvenuto, Eugenio; Santi, Luca; Baschieri, Selene

2016-12-01

Self-assembling plant virus nanoparticles (pVNPs) have started to be explored as nanometre-sized objects for biomedical applications, such as vaccine or drug delivery and imaging. Plant VNPs may be ideal tools in terms of biocompatibility and biodegradability endowed with a wide diversity of symmetries and dimensions, easy chemical/biological engineering, and rapid production in plants. Recently, we defined that icosahedral Tomato bushy stunt virus (TBSV) and filamentous Potato virus X (PVX) are neither toxic nor teratogenic. We report here the results of an interdisciplinary study aimed to define for the first time the biodistribution of unlabelled, unpegylated, underivatized TBSV and PVX by proved detecting antibodies. These data add new insights on the in vivo behaviour of these nano-objects and demonstrate that the pVNPs under scrutiny are each intrinsically endowed with peculiar properties foreshadowing different applications in molecular medicine. Copyright © 2016 Elsevier B.V. All rights reserved.

A study on the phytotoxicity of nano mullite and metal-amended nano mullite on mung bean plants.

PubMed

Dey, Anindita; Bagchi, Biswajoy; Das, Sukhen; Basu, Ruma; Nandy, Papiya

2011-06-01

The presence of engineered nanoparticles is continuously increasing in our environment and causing potential risks to the ecosystem. Researchers from various fields report many articles on the effects of different nanoparticles on plants, animals and microorganisms. Here we have studied for the first time the effect of nano mullite (NMu) and their metal- amended derivatives on the growth of mung bean plants. Results shows that the metal- amended NMu exerts adverse effects on the growth and biomass production of plants compared to NMu. For toxicity studies, we measured the germination index and relative root elongation, while leakage of electrolytes and root oxidizability were measured to study the effect of NMu on mung bean seeds and seedling tissues. Translocation and accumulation of NMu within different parts of the plant body were proved by elemental analysis of dried plant samples.

Potential impacts of silver nanoparticles on bacteria in the aquatic environment.

PubMed

Sheng, Zhiya; Liu, Yang

2017-04-15

It is inevitable that nano-silver will be released into the environment. Therefore, there is an urgent need to better understand the effects of silver nanoparticles (Ag-NPs) on microbes in natural and engineered environments. The most remarkable gap in our knowledge on this lies on the low Ag-NPs dose side. This review summarized studies on the effects of Ag-NPs on bacteria from simple to complicated aquatic systems. A hormetic model with a narrow stimulatory zone has been proposed based on both experimental phenomenon and the potential mechanisms of the observed effects. Spectrum of the stimulating zone depends on Ag-NP properties, bacterial types and environmental conditions tested. This may become a concern in terms of Ag-NP disposal, and further research is required to build a sophisticated toxicity model for Ag-NPs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ranking the in vivo toxicity of nanomaterials in Drosophila melanogaster

NASA Astrophysics Data System (ADS)

Vecchio, G.; Galeone, A.; Malvindi, M. A.; Cingolani, R.; Pompa, P. P.

2013-09-01

In this work, we propose a quantitative assessment of nanoparticles toxicity in vivo. We show a quantitative ranking of several types of nanoparticles (AuNPs, AgNPs, cadmium-based QDs, cadmium-free QDs, and iron oxide NPs, with different coating and/or surface chemistries), providing a categorization of their toxicity outcomes. This strategy may offer an innovative high-throughput screening tool of nanomaterials, of potential and broad interest to the nanoscience community.

Nanomaterials in the environment

NASA Astrophysics Data System (ADS)

Mrowiec, Bozena

2017-11-01

This paper considers engineered nanomaterials, deliberately engineered and manufactured to have certain properties and have at least one primary dimension of less than 100 nm. Materials produced with the aid of nanotechnologies are used in many areas of everyday life. Researches with nanomaterials have shown that the physiochemical characteristic of particles can influence their effects in biological systems. The field of nanotechnology has created risk for environment and human health. The toxicity of nanoparticles may be affected by different physicochemical properties, including size, shape, chemistry, surface properties, agglomeration, solubility, and charge, as well as effects from attached functional groups and crystalline structure. The greater surface-area-to-mass ratio of nanoparticles makes them generally more reactive than their macro-sized counterparts. Exposure to nanomaterials can occur at different life-cycle stages of the materials and/or products. The knowledge gaps limiting the understanding of the human and environment hazard and risk of nanotechnology should be explained by the scientific investigations for help to protect human and environmental health and to ensure the benefits of the nanotechnology products without excessive risk of this new technology. In this review are presented the proposal measurement methods for NMs characteristic.

Cell-based cytotoxicity assays for engineered nanomaterials safety screening: exposure of adipose derived stromal cells to titanium dioxide nanoparticles.

PubMed

Xu, Yan; Hadjiargyrou, M; Rafailovich, Miriam; Mironava, Tatsiana

2017-07-11

Increasing production of nanomaterials requires fast and proper assessment of its potential toxicity. Therefore, there is a need to develop new assays that can be performed in vitro, be cost effective, and allow faster screening of engineered nanomaterials (ENMs). Herein, we report that titanium dioxide (TiO 2 ) nanoparticles (NPs) can induce damage to adipose derived stromal cells (ADSCs) at concentrations which are rated as safe by standard assays such as measuring proliferation, reactive oxygen species (ROS), and lactate dehydrogenase (LDH) levels. Specifically, we demonstrated that low concentrations of TiO 2 NPs, at which cellular LDH, ROS, or proliferation profiles were not affected, induced changes in the ADSCs secretory function and differentiation capability. These two functions are essential for ADSCs in wound healing, energy expenditure, and metabolism with serious health implications in vivo. We demonstrated that cytotoxicity assays based on specialized cell functions exhibit greater sensitivity and reveal damage induced by ENMs that was not otherwise detected by traditional ROS, LDH, and proliferation assays. For proper toxicological assessment of ENMs standard ROS, LDH, and proliferation assays should be combined with assays that investigate cellular functions relevant to the specific cell type.

Silver nanoparticles: mechanism of antimicrobial action, synthesis, medical applications, and toxicity effects

NASA Astrophysics Data System (ADS)

Prabhu, Sukumaran; Poulose, Eldho K.

2012-10-01

Silver nanoparticles are nanoparticles of silver which are in the range of 1 and 100 nm in size. Silver nanoparticles have unique properties which help in molecular diagnostics, in therapies, as well as in devices that are used in several medical procedures. The major methods used for silver nanoparticle synthesis are the physical and chemical methods. The problem with the chemical and physical methods is that the synthesis is expensive and can also have toxic substances absorbed onto them. To overcome this, the biological method provides a feasible alternative. The major biological systems involved in this are bacteria, fungi, and plant extracts. The major applications of silver nanoparticles in the medical field include diagnostic applications and therapeutic applications. In most of the therapeutic applications, it is the antimicrobial property that is being majorly explored, though the anti-inflammatory property has its fair share of applications. Though silver nanoparticles are rampantly used in many medical procedures and devices as well as in various biological fields, they have their drawbacks due to nanotoxicity. This review provides a comprehensive view on the mechanism of action, production, applications in the medical field, and the health and environmental concerns that are allegedly caused due to these nanoparticles. The focus is on effective and efficient synthesis of silver nanoparticles while exploring their various prospective applications besides trying to understand the current scenario in the debates on the toxicity concerns these nanoparticles pose.

pH-Dependent Antimicrobial Properties of Copper Oxide Nanoparticles in Staphylococcus aureus

PubMed Central

Hsueh, Yi-Huang; Tsai, Ping-Han; Lin, Kuen-Song

2017-01-01

The antimicrobial properties of CuO nanoparticles have been investigated, but the underlying mechanisms of toxicity remain the subject of debate. Here, we show that CuO nanoparticles exhibit significant toxicity at pH 5 against four different Staphylococcus aureus (S. aureus) strains, including Newman, SA113, USA300, and ATCC6538. At this pH, but not at pH 6 and 7, 5 mM CuO nanoparticles effectively caused reduction of SA113 and Newman cells and caused at least 2 log reduction, whereas 20 mM killed most strains but not USA300. At 5 mM, the nanoparticles were also found to dramatically decrease reductase activity in SA113, Newman, and ATCC6538 cells, but not USA300 cells. In addition, analysis of X-ray absorption near-edge structure and extended X-ray absorption fine structure confirmed that S. aureus cells exposed to CuO nanoparticles contain CuO, indicating that Cu2+ ions released from nanoparticles penetrate bacterial cells and are subsequently oxidized intracellularly to CuO at mildly acidic pH. The CuO nanoparticles were more soluble at pH 5 than at pH 6 and 7. Taken together, the data conclusively show that the toxicity of CuO nanoparticles in mildly acidic pH is caused by Cu2+ release, and that USA300 is more resistant to CuO nanoparticles (NPs) than the other three strains. PMID:28397766

In vitro toxicity analysis of nanoscale aluminum: Particle size and shape effects

NASA Astrophysics Data System (ADS)

Palazuelos Jorganes, Maria

2007-12-01

Nanostructured materials promise to revolutionize many key areas of science and technology. As our ability to manipulate matter at the nanoscale increases, there is a need to assess the effects of these materials on human health and the environment. Materials at the nanoscale are interesting and useful because they possess properties that are different from the equivalent bulk or molecular scale. These same properties can make toxicological profiles very different from those of the same materials on a different scale. There is a rising consensus that toxicity analysis of nanomaterials should start from a thorough physicochemical characterization of the materials under investigation in order to be able to establish a proper correlation between the nanoparticles characteristics and their effects and behavior in physiological environments. This research is a clear example of the necessity of comprehensive studies when investigating the toxicity of nanomaterials. Aluminum nanoparticles are being extensively used for their very unique energetic properties. These materials offer a very promising market that is fostering many startup companies which are expected to consolidate on strong technological positions. Aluminum is generally recognized as a non-toxic material to humans and it is widely used for applications which imply direct human contact. The effect of aluminum nanoparticles in human health is still an unknown. My research consisted of an in vitro toxicity screening of aluminum materials from nano to micron size, including spherical irregularly shaped particles. Several issues relating to size, shape, detection and characterization of nanoparticles in the different environments relevant to in vitro toxicity analysis were addressed and suitable protocols were developed. Lung human epithelial cells were exposed to different concentrations of these materials and the effects were analyzed by means of various toxicity tests. Some of the materials investigated caused elevated in vitro toxicity. Cells endocytosed the particles and a clear correlation between the particle size, shape and the effects observed was established. The hypothesized toxicity mechanism was explored using different analytical techniques. The detected toxicity of aluminum nanoparticles was demonstrated to be a direct effect of their reactivity inside the cells.

Development of HSPA1A promoter-driven luciferase reporter gene assays in human cells for assessing the oxidative damage induced by silver nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xin, Lili, E-mail: llxin@suda.edu.cn

The exponential increase in the total number of engineered nanoparticles in consumer products requires novel tools for rapid and cost-effective toxicology screening. In order to assess the oxidative damage induced by nanoparticles, toxicity test systems based on a human HSPA1A promoter-driven luciferase reporter in HepG2, LO2, A549, and HBE cells were established. After treated with heat shock and a group of silver nanoparticles (AgNPs) with different primary particle sizes, the cell viability, oxidative damage, and luciferase activity were determined. The time-dependent Ag{sup +} ions release from AgNPs in cell medium was also evaluated. Our results showed that heat shock producedmore » a strong time-dependent induction of relative luciferase activity in the four luciferase reporter cells. Surprisingly, at 4 h of recovery, the relative luciferase activity was > 98 × the control level in HepG2-luciferase cells. Exposure to different sizes of AgNPs resulted in activation of the HSPA1A promoter in a dose-dependent manner, even at low cytotoxic or non-cytotoxic doses. The smaller (5 nm) AgNPs were more potent in luciferase induction than the larger (50 and 75 nm) AgNPs. These results were generally in accordance with the oxidative damage indicated by malondialdehyde concentration, reactive oxygen species induction and glutathione depletion, and Ag{sup +} ions release in cell medium. Compared with the other three luciferase reporter cells, the luciferase signal in HepG2-luciferase cells is obviously more sensitive and stable. We conclude that the luciferase reporter cells, especially the HepG2-luciferase cells, could provide a valuable tool for rapid screening of the oxidative damage induced by AgNPs. - Highlights: • We established the stable HSPA1A promoter-driven luciferase reporter cells. • Silver nanoparticles induced dose-dependent increases in luciferase activity. • HSPA1A promoter activity is a sensitive and responsive indicator of oxidative stress. • HepG2-luciferase cells can be used to assess the toxicity of silver nanoparticles.« less

Evaluation of the health impact of nanoparticles emitted from combustion sources: Comprehensive characterization of the physicochemical properties of nanoparticle emissions from wood combustion compliances, car- and ship diesel-engines as well as investigation of their toxicological effects on human lung cells and macrophages.

NASA Astrophysics Data System (ADS)

Zimmermann, R.; Dittmar, G.; Kanashova, T.; Buters, J.; Öder, S.; Paur, H. R.; Mülhopt, S.; Dilger, M.; Weiss, C.; Harndorf, H.; Stengel, B.; Hirvonen, M. R.; Jokiniemi, J.; Hiller, K.; Sapcariu, S.; Sippula, O.; Streibel, T.; Karg, E.; Weggler, B.; Schnelle-Kreis, J.; Lintelmann, J.; Sklorz, M.; Orasche, J.; Müller, L.; Passig, J.; Gröger, T.; BéruBé, K.; Krebs, T.

2016-12-01

Combustion emissions cause health effects. The HICE-Aerosol and Health project team studies the physicochemical properties as well as biological and toxicological effects on lung cells of combustion particle emissions. The chemical composition and physical parameters thoroughly characterized. Human lung cells are exposed to the diluted combustion exhaust fumes at the air-liquid interface (ALI), allowing a realistic lung-cell exposure by simulation of the lung situation. After exposure, cellular responses of the exposed lung cells are studied by multi-omics molecular biological analyses on transcriptomic, proteomic and metabolomic level. Emissions of wood combustion (log wood, pellet heater), ship diesel engines and car gasoline engines are addressed. Special field deployable ALI-exposition systems in a mobile S2-biological laboratory were set up and applied. Human alveolar epithelial cells (A549, BEAS2B and primary cells) as well as murine macrophages were ALI-exposed to diluted emissions. The cellular effects were then comprehensively characterized (viability, cyto-toxicology, multi-omics effects monitoring) and put in context with the chemical and physical aerosol data. The following order of overall cellular response-strength was observed: A relatively mild cellular effect is observed for the diluted wood combustion emissions. Interestingly the effects-strength for log-wood and pellet burner emissions are similar, although PM-concentrations are much higher for the log-wood heater. Similar mild biological effects are observed for the gasoline car emissions. The ship diesel engine emissions induced the most intense biological responses. A surprising result in this context is, that heavy fuel oil (HFO)-emissions showed lower biological effect strengths than the supposedly cleaner diesel fuel emissions (DF). The HFO-emission contain high concentrations of known toxicants (transition metals, polycyclic aromatics). This result was recently confirmed by experiments with murine RAW macrophages. Detailed analyses of the activated cellular response pathways, such as pro-inflammatory responses, xenobiotic metabolism, phagocytosis and oxidative stress were performed. The data is suggesting a large difference in relative toxicity for different combustion sources.

Casein-Coated Fe5C2 Nanoparticles with Superior r2 Relaxivity for Liver-Specific Magnetic Resonance Imaging.

PubMed

Cowger, Taku A; Tang, Wei; Zhen, Zipeng; Hu, Kai; Rink, David E; Todd, Trever J; Wang, Geoffrey D; Zhang, Weizhong; Chen, Hongmin; Xie, Jin

2015-01-01

Iron oxide nanoparticles have been extensively used as T2 contrast agents for liver-specific magnetic resonance imaging (MRI). The applications, however, have been limited by their mediocre magnetism and r2 relaxivity. Recent studies show that Fe5C2 nanoparticles can be prepared by high temperature thermal decomposition. The resulting nanoparticles possess strong and air stable magnetism, suggesting their potential as a novel type of T2 contrast agent. To this end, we improve the synthetic and surface modification methods of Fe5C2 nanoparticles, and investigated the impact of size and coating on their performances for liver MRI. Specifically, we prepared 5, 14, and 22 nm Fe5C2 nanoparticles and engineered their surface by: 1) ligand addition with phospholipids, 2) ligand exchange with zwitterion-dopamine-sulfonate (ZDS), and 3) protein adsorption with casein. It was found that the size and surface coating have varied levels of impact on the particles' hydrodynamic size, viability, uptake by macrophages, and r2 relaxivity. Interestingly, while phospholipid- and ZDS-coated Fe5C2 nanoparticles showed comparable r2, the casein coating led to an r2 enhancement by more than 2 fold. In particular, casein coated 22 nm Fe5C2 nanoparticle show a striking r2 of 973 mM(-1)s(-1), which is one of the highest among all of the T2 contrast agents reported to date. Small animal studies confirmed the advantage of Fe5C2 nanoparticles over iron oxide nanoparticles in inducing hypointensities on T2-weighted MR images, and the particles caused little toxicity to the host. The improvements are important for transforming Fe5C2 nanoparticles into a new class of MRI contrast agents. The observations also shed light on protein-based surface modification as a means to modulate contrast ability of magnetic nanoparticles.

Protein-only, antimicrobial peptide-containing recombinant nanoparticles with inherent built-in antibacterial activity.

PubMed

Serna, Naroa; Sánchez-García, Laura; Sánchez-Chardi, Alejandro; Unzueta, Ugutz; Roldán, Mónica; Mangues, Ramón; Vázquez, Esther; Villaverde, Antonio

2017-09-15

The emergence of bacterial antibiotic resistances is a serious concern in human and animal health. In this context, naturally occurring cationic antimicrobial peptides (AMPs) might play a main role in a next generation of drugs against bacterial infections. Taking an innovative approach to design self-organizing functional proteins, we have generated here protein-only nanoparticles with intrinsic AMP microbicide activity. Using a recombinant version of the GWH1 antimicrobial peptide as building block, these materials show a wide antibacterial activity spectrum in absence of detectable toxicity on mammalian cells. The GWH1-based nanoparticles combine clinically appealing properties of nanoscale materials with full biocompatibility, structural and functional plasticity and biological efficacy exhibited by proteins. Because of the largely implemented biological fabrication of recombinant protein drugs, the protein-based platform presented here represents a novel and scalable strategy in antimicrobial drug design, that by solving some of the limitations of AMPs offers a promising alternative to conventional antibiotics. The low molecular weight antimicrobial peptide GWH1 has been engineered to oligomerize as self-assembling protein-only nanoparticles of around 50nm. In this form, the peptide exhibits potent and broad antibacterial activities against both Gram-positive and Gram-negative bacteria, without any harmful effect over mammalian cells. As a solid proof-of-concept, this finding strongly supports the design and biofabrication of nanoscale antimicrobial materials with in-built functionalities. The protein-based homogeneous composition offer advantages over alternative materials explored as antimicrobial agents, regarding biocompatibility, biodegradability and environmental suitability. Beyond the described prototype, this transversal engineering concept has wide applicability in the design of novel nanomedicines for advanced treatments of bacterial infections. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Hotspots engineering by grafting Au@Ag core-shell nanoparticles on the Au film over slightly etched nanoparticles substrate for on-site paraquat sensing.

PubMed

Wang, Chaoguang; Wu, Xuezhong; Dong, Peitao; Chen, Jian; Xiao, Rui

2016-12-15

Paraquat (PQ) pollutions are ultra-toxic to human beings and hard to be decomposed in the environment, thus requiring an on-site detection strategy. Herein, we developed a robust and rapid PQ sensing strategy based on the surface-enhanced Raman scattering (SERS) technique. A hybrid SERS substrate was prepared by grafting the Au@Ag core-shell nanoparticles (NPs) on the Au film over slightly etched nanoparticles (Au FOSEN). Hotspots were engineered at the junctions as indicated by the finite difference time domain calculation. SERS performance of the hybrid substrate was explored using p-ATP as the Raman probe. The hybrid substrate gives higher enhancement factor comparing to either the Au FOSEN substrate or the Au@Ag core-shell NPs, and exhibits excellent reproducibility, homogeneity and stability. The proposed SERS substrates were prepared in batches for the practical PQ sensing. The total analysis time for a single sample, including the pre-treatment and measurement, was less than 5min with a PQ detection limit of 10nM. Peak intensities of the SERS signal were plotted as a function of the PQ concentrations to calibrate the sensitivity by fitting the Hill's equation. The plotted calibration curve showed a good log-log linearity with the coefficient of determination of 0.98. The selectivity of the sensing proposal was based on the "finger print" Raman spectra of the analyte. The proposed substrate exhibited good recovery when it applied to real water samples, including lab tap water, bottled water, and commercially obtained apple juice and grape juice. This SERS-based PQ detection method is simple, rapid, sensitive and selective, which shows great potential in pesticide residue and additives abuse monitoring. Copyright © 2016 Elsevier B.V. All rights reserved.

In Vitro Vascular Toxicity of Manufactured Metal Oxide Nanoparticles: Size Profile Predicts Cellular Specificity, Delivered Dose, and Toxicity

EPA Science Inventory

Metal oxide nanoparticles (NPs) are being used in an expanding range of products and applications due to their unique physicochemical properties. In vivo biokinetic studies have demonstrated the ability of metal oxide NPs to translocate to the distal organs, including the cardiov...

Unique Nanoparticle Optical Properties Confound Fluorescent Based Assays Widely Employed in Their In Vitro Toxicity Screening and Ranking

EPA Science Inventory

Nanoparticles (NPs) are novel materials having at least one dimension less than 100 nm and display unique physicochemical properties due to their nanoscale size. An emphasis has been placed on developing high throughput screening (HTS) assays to characterize and rank the toxiciti...

*Evaluating the toxicity of airborne particulate matter and nanoparticles by measuring oxidative strett potential - A workshop report and consensus statement

EPA Science Inventory

BACKGROUND: There is a strong need for laboratory in vitro test systems for the toxicity of airborne particulate matter and nanoparticles. The measurement of oxidative stress potential offers a promising way forward. OBJECTIVES: A workshop was convened involving leading workers f...

A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery.

PubMed

Yang, Conglian; Wu, Tingting; Qin, Yuting; Qi, Yan; Sun, Yu; Kong, Miao; Jiang, Xue; Qin, Xianya; Shen, Yaqi; Zhang, Zhiping

2018-01-01

Doxorubicin (DOX) is an effective chemotherapeutic agent but severe side effects limit its clinical application. Nanoformulations can reduce the toxicity while still have various limitations, such as complexity, low drug loading capability and excipient related concerns. An amphiphilic conjugate, doxorubicin-dichloroacetate, was synthesized and the corresponding nanoparticles were prepared. The in vitro cytotoxicity and intracellular uptake, in vivo imaging, antitumor effects and systemic toxicities of nanoparticles were carried out to evaluate the therapeutic efficiency of tumor. Doxorubicin-dichloroacetate conjugate can self-assemble into nanoparticles with small amount of DSPE-PEG 2000 , leading to high drug loading (71.8%, w/w) and diminished excipient associated concerns. The nanoparticles exhibited invisible systemic toxicity and high maximum tolerated dose of 75 mg DOX equiv./kg, which was 15-fold higher than that of free DOX. It also showed good tumor targeting capability and enhanced antitumor efficacy in murine melanoma model. This work provides a promising strategy to simplify the drug preparation process, increase drug loading content, reduce systemic toxicity as well as enhance antitumor efficiency.

Review on characterization of nano-particle emissions and PM morphology from internal combustion engines: Part 2 [Review on morphology and nanostructure characterization of nano-particle emission from internal combustion engines

DOE PAGES

Choi, Seungmok; Myung, C. L.; Park, S.

2014-03-05

This study presents a review of the characterization of physical properties, morphology, and nanostructure of particulate emissions from internal combustion engines. Because of their convenience and readiness of measurement, various on-line commercial instruments have been used to measure the mass, number, and size distribution of nano-particles from different engines. However, these on-line commercial instruments have inherent limitations in detailed analysis of chemical and physical properties, morphology, and nanostructure of engine soot agglomerates, information that is necessary to understand the soot formation process in engine combustion, soot particle behavior in after-treatment systems, and health impacts of the nano-particles. For these reasons,more » several measurement techniques used in the carbon research field, i.e., highresolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), and Raman spectroscopy, were used for analysis of engine particulate matter (PM). This review covers a brief introduction of several measurement techniques and previous results from engine nano-particle characterization studies using those techniques.« less

Assessment of in vivo systemic toxicity and biodistribution of iron-doped silica nanoshells.

PubMed

Mendez, Natalie; Liberman, Alexander; Corbeil, Jacqueline; Barback, Christopher; Viveros, Robert; Wang, James; Wang-Rodriguez, Jessica; Blair, Sarah L; Mattrey, Robert; Vera, David; Trogler, William; Kummel, Andrew C

2017-04-01

Silica nanoparticles are an emerging class of biomaterials which may be used as diagnostic and therapeutic tools for biomedical applications. In particular, hollow silica nanoshells are attractive due to their hollow core. Approximately 70% of a 500 nm nanoshell is hollow, therefore more particles can be administered on a mg/kg basis compared to solid nanoparticles. Additionally, their nanoporous shell permits influx/efflux of gases and small molecules. Since the size, shape, and composition of a nanoparticle can dramatically alter its toxicity and biodistribution, the toxicology of these nanomaterials was assessed. A single dose toxicity study was performed in vivo to assess the toxicity of 500 nm iron-doped silica nanoshells at clinically relevant doses of 10-20 mg/kg. This study showed that only a trace amount of silica was detected in the body 10 weeks post-administration. The hematology, biochemistry and pathological results show that the nanoshells exhibit no acute or chronic toxicity in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of toxicity of Ag nanoparticles on SERS spectral variance of bacteria

NASA Astrophysics Data System (ADS)

Cui, Li; Chen, Shaode; Zhang, Kaisong

2015-02-01

Ag nanoparticles (NPs) have been extensively utilized in surface-enhanced Raman scattering (SERS) spectroscopy for bacterial identification. However, Ag NPs are toxic to bacteria. Whether such toxicity can affect SERS features of bacteria and interfere with bacterial identification is still unknown and needed to explore. Here, by carrying out a comparative study on non-toxic Au NPs with that on toxic Ag NPs, we investigated the influence of nanoparticle concentration and incubation time on bacterial SERS spectral variance, both of which were demonstrated to be closely related to the toxicity of Ag NPs. Sensitive spectral alterations were observed on Ag NPs with increase of NPs concentration or incubation time, accompanied with an obvious decrease in number of viable bacteria. In contrast, SERS spectra and viable bacterial number on Au NPs were rather constant under the same conditions. A further analysis on spectral changes demonstrated that it was cell response (i.e. metabolic activity or death) to the toxicity of Ag NPs causing spectral variance. However, biochemical responses to the toxicity of Ag were very different in different bacteria, indicating the complex toxic mechanism of Ag NPs. Ag NPs are toxic to a great variety of organisms, including bacteria, fungi, algae, protozoa etc., therefore, this work will be helpful in guiding the future application of SERS technique in various complex biological systems.

In vitro and in vivo anti-tumor efficacy of 10-hydroxycamptothecin polymorphic nanoparticle dispersions: shape- and polymorph-dependent cytotoxicity and delivery of 10-hydroxycamptothecin to cancer cells.

PubMed

Wang, Hongdi; Feng, Jialing; Liu, Guijin; Chen, Baoqiong; Jiang, Yanbin; Xie, Qiuling

2016-05-01

Nanotechnology associated with a crystal engineering approach was proposed for improving the solubility and efficacy of hydrophobic drugs in this study. 10-hydroxycamptothecin polymorphic nanoparticle dispersions (HCPT-PNDs) were prepared using the supercritical anti-solvent technique coupled with the high-pressure homogenization method. Shape- and polymorph-dependent tumor suppression was observed in both in vitro and in vivo models, where needle-shaped HCPT-PND exhibited dramatic improvement of antitumor efficacy. A benefit of controllable size and a large surface-to-volume ratio of needle-shaped nanoparticles is the improvement of dissolution properties, which facilitates enhancing pharmacokinetic and pharmaco-dynamic properties. The needle-shaped HCPT-PND, which with longer blood retention time and more effective cellular uptake, makes it possible to accumulate drug in tumor tissues and exhibit higher cytotoxicity. No severe systemic toxicity was observed due to sustained-dissolution and the low dose of drug in normal tissues. The results suggest that the needle-shaped HCPT-PND is an interesting nano-formulation of HCPT. Nanotechnology has enabled the production of novel therapeutics drugs against cancer. Here, the authors investigated the use of a crystal engineering approach for the modification of camptothecin in order to improve its water solubility. Physicochemical and biological properties were studied. The results would suggest the applicability of this approach for nano-formulation. Copyright © 2016 Elsevier Inc. All rights reserved.

In Vitro Cytotoxicity Assessment of an Orthodontic Composite Containing Titanium-dioxide Nano-particles.

PubMed

Heravi, Farzin; Ramezani, Mohammad; Poosti, Maryam; Hosseini, Mohsen; Shajiei, Arezoo; Ahrari, Farzaneh

2013-01-01

Background and aims. Incorporation of nano-particles to orthodontic bonding systems has been considered to prevent enamel demineralization around appliances. This study investigated cytotoxicity of Transbond XT adhesive containing 1 wt% titanium dioxide (TiO2) nano-particles. Materials and methods. Ten composite disks were prepared from each of the conventional and TiO2-containg composites and aged for 1, 3, 5, 7 and 14 days in Dulbecco's Modified Eagle's Medium (DMEM). The extracts were obtained and exposed to culture media of human gingival fibroblasts (HGF) and mouse L929 fibroblasts. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results. Both adhesives were moderately toxic for HGF cells on the first day of the experiment, but the TiO2-containing adhesive produced significantly lower toxicity than the pure adhesive (P<0.05). No significant differences were found in cell viability percentages between the two groups on the other days (P>0.05). There was a significant reduction in cell toxicity with increasing pre-incubation time (P<0.001). L929 cells showed similar toxicity trends, but lower sensitivity to detect cytotoxicity of dental composites. Conclusion. The orthodontic adhesive containing TiO2 nano-particles indicated comparable or even lower toxicity than its nano-particle-free counterpart, indicating that incorporation of 1 wt% TiO2 nano-particles to the composite structure does not result in additional health hazards compared to that occurring with the pure adhesive.

Iron and iron oxide nanoparticles are highly toxic to Culex quinquefasciatus with little non-target effects on larvivorous fishes.

PubMed

Murugan, Kadarkarai; Dinesh, Devakumar; Nataraj, Devaraj; Subramaniam, Jayapal; Amuthavalli, Pandiyan; Madhavan, Jagannathan; Rajasekar, Aruliah; Rajan, Mariappan; Thiruppathi, Kulandhaivel Palani; Kumar, Suresh; Higuchi, Akon; Nicoletti, Marcello; Benelli, Giovanni

2018-04-01

The control of filariasis vectors has been enhanced in several areas, but there are main challenges, including increasing resistance to insecticides and lack of cheap and eco-friendly products. The toxicity of iron (Fe 0 ) and iron oxide (Fe 2 O 3 ) nanoparticles has been scarcely investigated yet. We studied the larvicidal and pupicidal activity of Fe 0 and Fe 2 O 3 nanoparticles against Culex quinquefasciatus. Fe 0 and Fe 2 O 3 nanoparticles produced by green (using a Ficus natalensis aqueous extract) and chemical nanosynthesis, respectively, were analyzed by UV-Vis spectrophotometry, FT-IR spectroscopy, XRD analysis, SEM, and EDX assays. In larvicidal and pupicidal experiments on Cx. quinquefasciatus, LC 50 of Fe 0 nanoparticles ranged from 20.9 (I instar larvae) to 43.7 ppm (pupae) and from 4.5 (I) to 22.1 ppm (pupae) for Fe 2 O 3 nanoparticles synthesized chemically. Furthermore, the predation efficiency of the guppy fish, Poecilia reticulata, after a single treatment with sub-lethal doses of Fe 0 and Fe 2 O 3 nanoparticles was magnified. Overall, this work provides new insights about the toxicity of Fe 0 and Fe 2 O 3 nanoparticles against mosquito vectors; we suggested that green and chemical fabricated nano-iron may be considered to develop novel and effective pesticides.

Comparative Toxicity of Nanoparticulate CuO and ZnO to Soil Bacterial Communities

PubMed Central

Rousk, Johannes; Ackermann, Kathrin; Curling, Simon F.; Jones, Davey L.

2012-01-01

The increasing industrial application of metal oxide Engineered Nano-Particles (ENPs) is likely to increase their environmental release to soils. While the potential of metal oxide ENPs as environmental toxicants has been shown, lack of suitable control treatments have compromised the power of many previous assessments. We evaluated the ecotoxicity of ENP (nano) forms of Zn and Cu oxides in two different soils by measuring their ability to inhibit bacterial growth. We could show a direct acute toxicity of nano-CuO acting on soil bacteria while the macroparticulate (bulk) form of CuO was not toxic. In comparison, CuSO4 was more toxic than either oxide form. Unlike Cu, all forms of Zn were toxic to soil bacteria, and the bulk-ZnO was more toxic than the nano-ZnO. The ZnSO4 addition was not consistently more toxic than the oxide forms. Consistently, we found a tight link between the dissolved concentration of metal in solution and the inhibition of bacterial growth. The inconsistent toxicological response between soils could be explained by different resulting concentrations of metals in soil solution. Our findings suggested that the principal mechanism of toxicity was dissolution of metal oxides and sulphates into a metal ion form known to be highly toxic to bacteria, and not a direct effect of nano-sized particles acting on bacteria. We propose that integrated efforts toward directly assessing bioavailable metal concentrations are more valuable than spending resources to reassess ecotoxicology of ENPs separately from general metal toxicity. PMID:22479561

Cutaneous exposure scenarios for engineered nanoparticles used in semiconductor fabrication: a preliminary investigation of workplace surface contamination

PubMed Central

Shepard, Michele; Brenner, Sara

2014-01-01

Background: Numerous studies are ongoing in the fields of nanotoxicology and exposure science; however, gaps remain in identifying and evaluating potential exposures from skin contact with engineered nanoparticles in occupational settings. Objectives: The aim of this study was to identify potential cutaneous exposure scenarios at a workplace using engineered nanoparticles (alumina, ceria, amorphous silica) and evaluate the presence of these materials on workplace surfaces. Methods: Process review, workplace observations, and preliminary surface sampling were conducted using microvacuum and wipe sample collection methods and transmission electron microscopy with elemental analysis. Results: Exposure scenarios were identified with potential for incidental contact. Nanoparticles of silica or silica and/or alumina agglomerates (or aggregates) were identified in surface samples from work areas where engineered nanoparticles were used or handled. Conclusions: Additional data are needed to evaluate occupational exposures from skin contact with engineered nanoparticles; precautionary measures should be used to minimize potential cutaneous exposures in the workplace. PMID:25000112

A hypothetical model for predicting the toxicity of high aspect ratio nanoparticles (HARN)

NASA Astrophysics Data System (ADS)

Tran, C. L.; Tantra, R.; Donaldson, K.; Stone, V.; Hankin, S. M.; Ross, B.; Aitken, R. J.; Jones, A. D.

2011-12-01

The ability to predict nanoparticle (dimensional structures which are less than 100 nm in size) toxicity through the use of a suitable model is an important goal if nanoparticles are to be regulated in terms of exposures and toxicological effects. Recently, a model to predict toxicity of nanoparticles with high aspect ratio has been put forward by a consortium of scientists. The High aspect ratio nanoparticles (HARN) model is a platform that relates the physical dimensions of HARN (specifically length and diameter ratio) and biopersistence to their toxicity in biological environments. Potentially, this model is of great public health and economic importance, as it can be used as a tool to not only predict toxicological activity but can be used to classify the toxicity of various fibrous nanoparticles, without the need to carry out time-consuming and expensive toxicology studies. However, this model of toxicity is currently hypothetical in nature and is based solely on drawing similarities in its dimensional geometry with that of asbestos and synthetic vitreous fibres. The aim of this review is two-fold: (a) to present findings from past literature, on the physicochemical property and pathogenicity bioassay testing of HARN (b) to identify some of the challenges and future research steps crucial before the HARN model can be accepted as a predictive model. By presenting what has been done, we are able to identify scientific challenges and research directions that are needed for the HARN model to gain public acceptance. Our recommendations for future research includes the need to: (a) accurately link physicochemical data with corresponding pathogenicity assay data, through the use of suitable reference standards and standardised protocols, (b) develop better tools/techniques for physicochemical characterisation, (c) to develop better ways of monitoring HARN in the workplace, (d) to reliably measure dose exposure levels, in order to support future epidemiological studies.

Synthesis of fluorapatite–hydroxyapatite nanoparticles and toxicity investigations

PubMed Central

Montazeri, N; Jahandideh, R; Biazar, Esmaeil

2011-01-01

In this study, calcium phosphate nanoparticles with two phases, fluorapatite (FA; Ca10(PO4)6F2) and hydroxyapatite (HA; Ca10(PO4)6(OH)2), were prepared using the solgel method. Ethyl phosphate, hydrated calcium nitrate, and ammonium fluoride were used, respectively, as P, Ca, and F precursors with a Ca:P ratio of 1:72. Powders obtained from the sol-gel process were studied after they were dried at 80°C and heat treated at 550°C. The degree of crystallinity, particle and crystallite size, powder morphology, chemical structure, and phase analysis were investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Zetasizer experiments. The results of XRD analysis and FTIR showed the presence of hydroxyapatite and fluorapatite phases. The sizes of the crystallites estimated from XRD patterns using the Scherrer equation and the crystallinity of the hydroxyapatite phase were about 20 nm and 70%, respectively. Transmission electron microscope and SEM images and Zetasizer experiments showed an average size of 100 nm. The in vitro behavior of powder was investigated with mouse fibroblast cells. The results of these experiments indicated that the powders were biocompatibile and would not cause toxic reactions. These compounds could be applied for hard-tissue engineering. PMID:21499417

Ceramic nanoparticles: Recompense, cellular uptake and toxicity concerns.

PubMed

Singh, Deependra; Singh, Satpal; Sahu, Jageshwari; Srivastava, Shikha; Singh, Manju Rawat

2016-01-01

Over the past few years, nanoparticles and their role in drug delivery have been the centre of attraction as new drug delivery systems. Various forms of nanosystems have been designed, such as nanoclays, scaffolds and nanotubes, having numerous applications in areas such as drug loading, target cell uptake, bioassay and imaging. The present study discusses various types of nanoparticles, with special emphasis on ceramic nanocarriers. Ceramic materials have high mechanical strength, good body response and low or non-existing biodegradability. In this article, the various aspects concerning ceramic nanoparticles, such as their advantages over other systems, their cellular uptake and toxicity concerns are discussed in detail.

Algae mediated synthesis of cadmium sulphide nanoparticles and their application in bioremediation

NASA Astrophysics Data System (ADS)

Prasad Mandal, Ranju; Sekh, Sanoyaz; Sarkar, Neera Sen; Chattopadhyay, Dipankar; De, Swati

2016-05-01

The present work is a study on the biological synthesis of cadmium sulphide (CdS) nanoparticles using blue-green algae that is popularly used as a food supplement. This synthesis is unique in the sense that no external sulphur precursor is required, the CdS nanoparticles are synthesized in situ in the algal medium. The CdS nanoparticles thus synthesized are photoluminescent and can act as highly efficient photocatalysts for degradation of the dye pollutant malachite green. Thus the CdS nanoparticles synthesized in situ in the algae conform to the desired criteria of waste water treatment i.e. biosorption of the pollutant and its subsequent degradation. The novelty of this work also lies in its potential for use in bioremediation by conversion of the toxic Cd(II) ion to less toxic CdS nanoparticles within the algal framework.

Probing cytotoxicity of nanoparticles and organic compounds using scanning proton microscopy, scanning electron microscopy and fluorescence microscopy

NASA Astrophysics Data System (ADS)

Tong, Yongpeng; Li, Changming; Liang, Feng; Chen, Jianmin; Zhang, Hong; Liu, Guoqing; Sun, Huibin; Luong, John H. T.

2008-12-01

Scanning proton microscopy, scanning electron microscopy (SEM) and fluorescence microscopy have been used to probe the cytotoxicity effect of benzo[a]pyrene (BaP), ethidium bromide (EB) and nanoparticles (ZnO, Al 2O 3 and TiO 2) on a T lymphoblastic leukemia Jurkat cell line. The increased calcium ion (from CaCl 2) in the culture medium stimulated the accumulation of BaP and EB inside the cell, leading to cell death. ZnO, Al 2O 3 and TiO 2 nanoparticles, however, showed a protective effect against these two organic compounds. Such inorganic nanoparticles complexed with BaP or EB which became less toxic to the cell. Fe 2O 3 nanoparticles as an insoluble particle model scavenged by macrophage were investigated in rats. They were scavenged out of the lung tissue about 48 h after infection. This result suggest that some insoluble inorganic nanoparticles of PM (particulate matters) showed protective effects on organic toxins induced acute toxic effects as they can be scavenged by macrophage cells. Whereas, some inorganic ions such as calcium ion in PM may help environmental organic toxins to penetrate cell membrane and induce higher toxic effect.

Zein Nanoparticles as Eco-Friendly Carrier Systems for Botanical Repellents Aiming Sustainable Agriculture.

PubMed

Oliveira, Jhones L de; Campos, Estefânia V R; Pereira, Anderson E S; Pasquoto, Tatiane; Lima, Renata; Grillo, Renato; Andrade, Daniel Junior de; Santos, Fabiano Aparecido Dos; Fraceto, Leonardo Fernandes

2018-02-14

Botanical repellents represent one of the main ways of reducing the use of synthetic pesticides and the contamination of soil and hydric resources. However, the poor stability and rapid degradation of these compounds in the environment hinder their effective application in the field. Zein nanoparticles can be used as eco-friendly carrier systems to protect these substances against premature degradation, provide desirable release characteristics, and reduce toxicity in the environment and to humans. In this study, we describe the preparation and characterization of zein nanoparticles loaded with the main constituents of the essential oil of citronella (geraniol and R-citronellal). The phytotoxicity, cytotoxicity, and insect activity of the nanoparticles toward target and nontarget organisms were also evaluated. The botanical formulations showed high encapsulation efficiency (>90%) in the nanoparticles, good physicochemical stability, and effective protection of the repellents against UV degradation. Cytotoxicity and phytotoxicity assays showed that encapsulation of the botanical repellents decreased their toxicity. Repellent activity tests showed that nanoparticles containing the botanical repellents were highly repellent against the Tetranychus urticae Koch mite. This nanotechnological formulation offers a new option for the effective use of botanical repellents in agriculture, reducing toxicity, protecting against premature degradation, and providing effective pest control.

Clearance Properties of Nano-sized Particles and Molecules as Imaging Agents: Considerations and Caveats

PubMed Central

Longmire, Michelle; Choyke, Peter L.; Kobayashi, Hisataka

2009-01-01

Summary Nanoparticles possess enormous potential as diagnostic imaging agents and hold promise for the development of multimodality agents with both imaging and therapeutic capabilities. Yet, some of the most promising nanoparticles demonstrate prolonged tissue retention and contain heavy metals. This presents serious concerns for toxicity. The creation of nanoparticles with optimal clearance characteristics will minimize toxicity risks by reducing the duration of exposure to these agents. Given that many nanoparticles possess easily modifiable surface and interior chemistry, if nanoparticle characteristics associated with optimal clearance from the body were well established, it would be feasible to design and create agents with more favorable clearance properties. This paper presents a thorough discussion of the physiologic aspects of nanoparticle clearance, focusing on renal mechanisms, as well as provides an overview of current research investigating clearance of specific types of nanoparticles and nano-sized macromolecules, including dendrimers, quantum dots, liposomes and carbon, gold, and silica-based nanoparticles. PMID:18817471

Nanoparticle-Delivered Chemotherapy: Old Drugs in New Packages.

PubMed

Lee, Michael S; Dees, E Claire; Wang, Andrew Z

2017-03-15

Cytotoxic chemotherapies have a narrow therapeutic window, with high peaks and troughs of plasma concentration. Novel nanoparticle formulations of cytotoxic chemotherapy drugs can enhance pharmacokinetic characteristics and facilitate passive targeting of drugs to tumors via the enhanced permeability and retention effect, thus mitigating toxicity. Nanoparticle vehicles currently in clinical use or undergoing clinical investigation for anticancer therapies include liposomes, polymeric micelles, protein-drug nanoparticles, and dendrimers. Multiple nanoparticle formulations of existing cytotoxic chemotherapies are approved for use in several indications, with clinical data indeed showing optimization of pharmacokinetics and different toxicity profiles compared with their parent drugs. There are also many new nanoparticle drug formulations in development and undergoing early- and late-phase clinical trials, including several that utilize active targeting or triggered release based on environmental stimuli. Here, we review the rationale for nanoparticle formulations of existing or previously investigated cytotoxic drugs, describe currently approved nanoparticle formulations of drugs, and discuss some of the most promising clinical trials currently underway.

Toxicity of ZnO nanoparticles to Escherichia coli: mechanism and the influence of medium components.

PubMed

Li, Mei; Zhu, Lizhong; Lin, Daohui

2011-03-01

Water chemistry can be a major factor regulating the toxicity mechanism of ZnO nanoparticles (nano-ZnO) in water. The effect of five commonly used aqueous media with various chemical properties on the toxicity of nano-ZnO to Escherichia coli O111 (E. coli) was investigated, including ultrapure water, 0.85% NaCl, phosphate-buffered saline (PBS), minimal Davis (MD), and Luria-Bertani (LB). Combined results of physicochemical characterization and antibacterial tests of nano-ZnO in the five media suggest that the toxicity of nano-ZnO is mainly due to the free zinc ions and labile zinc complexes. The toxicity of nano-ZnO in the five media deceased as follows: ultrapure water > NaCl > MD > LB > PBS. The generation of precipitates (Zn(3)(PO(4))(2) in PBS) and zinc complexes (of zinc with citrate and amino acids in MD and LB, respectively) dramatically decreased the concentration of Zn(2+) ions, resulting in the lower toxicity in these media. Additionally, the isotonic and rich nutrient conditions improved the tolerance of E. coli to toxicants. Considering the dramatic difference of the toxicity of nano-ZnO in various aqueous media, the effect of water chemistry on the physicochemical properties of nanoparticles should be paid more attention in future nanotoxicity evaluations.

Fate and risks of nanomaterials in aquatic and terrestrial environments.

PubMed

Batley, Graeme E; Kirby, Jason K; McLaughlin, Michael J

2013-03-19

Over the last decade, nanoparticles have been used more frequently in industrial applications and in consumer and medical products, and these applications of nanoparticles will likely continue to increase. Concerns about the environmental fate and effects of these materials have stimulated studies to predict environmental concentrations in air, water, and soils and to determine threshold concentrations for their ecotoxicological effects on aquatic or terrestrial biota. Nanoparticles can be added to soils directly in fertilizers orplant protection products or indirectly through application to land or wastewater treatment products such as sludges or biosolids. Nanoparticles may enter aquatic systems directly through industrial discharges or from disposal of wastewater treatment effluents or indirectly through surface runoff from soils. Researchers have used laboratory experiments to begin to understand the effects of nanoparticles on waters and soils, and this Account reviews that research and the translation of those results to natural conditions. In the environment, nanoparticles can undergo a number of potential transformations that depend on the properties both of the nanoparticle and of the receiving medium. These transformations largely involve chemical and physical processes, but they can involve biodegradation of surface coatings used to stabilize many nanomaterial formulations. The toxicity of nanomaterials to algae involves adsorption to cell surfaces and disruption to membrane transport. Higher organisms can directly ingest nanoparticles, and within the food web, both aquatic and terrestrial organisms can accumulate nanoparticles. The dissolution of nanoparticles may release potentially toxic components into the environment. Aggregation with other nanoparticles (homoaggregation) or with natural mineral and organic colloids (heteroaggregation) will dramatically change their fate and potential toxicity in the environment. Soluble natural organic matter may interact with nanoparticles to change surface charge and mobility and affect the interactions of those nanoparticles with biota. Ultimately, aquatic nanomaterials accumulate in bottom sediments, facilitated in natural systems by heteroaggregation. Homoaggregates of nanoparticles sediment more slowly. Nanomaterials from urban, medical, and industrial sources may undergo significant transformations during wastewater treatment processes. For example, sulfidation of silver nanoparticles in wastewater treatment systems converts most of the nanoparticles to silver sulfides (Ag₂S). Aggregation of the nanomaterials with other mineral and organic components of the wastewater often results in most of the nanomaterial being associated with other solids rather than remaining as dispersed nanosized suspensions. Risk assessments for nanomaterial releases to the environment are still in their infancy, and reliable measurements of nanomaterials at environmental concentrations remain challenging. Predicted environmental concentrations based on current usage are low but are expected to increase as use increases. At this early stage, comparisons of estimated exposure data with known toxicity data indicate that the predicted environmental concentrations are orders of magnitude below those known to have environmental effects on biota. As more toxicity data are generated under environmentally-relevant conditions, risk assessments for nanomaterials will improve to produce accurate assessments that assure environmental safety.

The potentiation effect makes the difference: non-toxic concentrations of ZnO nanoparticles enhance Cu nanoparticle toxicity in vitro.

PubMed

Li, Lingxiangyu; Fernández-Cruz, María Luisa; Connolly, Mona; Conde, Estefanía; Fernández, Marta; Schuster, Michael; Navas, José María

2015-02-01

Here we examined whether the addition of a non-toxic concentration (6.25 μg/mL) of zinc oxide nanoparticles (ZnONPs: 19, 35 and 57 nm, respectively) modulates the cytotoxicity of copper nanoparticles (CuNPs, 63 nm in size) in the human hepatoma cell line HepG2. The cytotoxic effect of CuNPs on HepG2 cells was markedly enhanced by the ZnONPs, the largest ZnONPs causing the highest increase in toxicity. However, CuNPs cytotoxicity was not affected by co-incubation with medium containing only zinc ions, indicating the increase in toxicity might be attributed to the particle form of ZnONPs. Transmission electron microscopy (TEM) revealed the presence of CuNPs and ZnONPs inside the cells co-exposed to both types of NP and outflow of cytoplasm through the damaged cell membrane. Inductively coupled plasma mass spectrometry (ICP-MS) determined an increase in the concentration of zinc and a decrease in that of copper in co-exposed cells. On the basis of these results, we propose that accumulation of large numbers of ZnONPs in the cells alters cellular membranes and the cytotoxicity of CuNPs is increased. Copyright © 2014 Elsevier B.V. All rights reserved.

Irradiation with visible light enhances the antibacterial toxicity of silver nanoparticles produced by laser ablation

NASA Astrophysics Data System (ADS)

Ratti, Matthew; Naddeo, J. J.; Tan, Yuying; Griepenburg, Julianne C.; Tomko, John; Trout, Cory; O'Malley, Sean M.; Bubb, Daniel M.; Klein, Eric A.

2016-04-01

The rise of antibiotic-resistant bacteria is a rapidly growing global health concern. According to the Center for Disease Control, approximately 2 million illnesses and 23,000 deaths per year occur in the USA due to antibiotic resistance. In recent years, there has been a surge in the use of metal nanoparticles as coatings for orthopedic implants, wound dressings, and food packaging, due to their antimicrobial properties. In this report, we demonstrate that the antibacterial efficacy of silver nanoparticles (AgNPs) is enhanced with exposure to light from the visible spectrum. We find that the increased toxicity is due to augmented silver ion release and bacterial uptake. Interestingly, silver ion toxicity does not appear to depend on the formation of reactive oxygen species. Our findings provide a novel paradigm for using light to regulate the toxicity of AgNPs which may have a significant impact in the development of new antimicrobial therapeutics.

Assessment of the In Vivo Toxicity of Gold Nanoparticles

NASA Astrophysics Data System (ADS)

Chen, Yu-Shiun; Hung, Yao-Ching; Liau, Ian; Huang, G. Steve

2009-08-01

The environmental impact of nanoparticles is evident; however, their toxicity due to their nanosize is rarely discussed. Gold nanoparticles (GNPs) may serve as a promising model to address the size-dependent biological response to nanoparticles because they show good biocompatibility and their size can be controlled with great precision during their chemical synthesis. Naked GNPs ranging from 3 to 100 nm were injected intraperitoneally into BALB/C mice at a dose of 8 mg/kg/week. GNPs of 3, 5, 50, and 100 nm did not show harmful effects; however, GNPs ranging from 8 to 37 nm induced severe sickness in mice. Mice injected with GNPs in this range showed fatigue, loss of appetite, change of fur color, and weight loss. Starting from day 14, mice in this group exhibited a camel-like back and crooked spine. The majority of mice in these groups died within 21 days. Injection of 5 and 3 nm GNPs, however, did not induce sickness or lethality in mice. Pathological examination of the major organs of the mice in the diseased groups indicated an increase of Kupffer cells in the liver, loss of structural integrity in the lungs, and diffusion of white pulp in the spleen. The pathological abnormality was associated with the presence of gold particles at the diseased sites, which were verified by ex vivo Coherent anti-Stoke Raman scattering microscopy. Modifying the surface of the GNPs by incorporating immunogenic peptides ameliorated their toxicity. This reduction in the toxicity is associated with an increase in the ability to induce antibody response. The toxicity of GNPs may be a fundamental determinant of the environmental toxicity of nanoparticles.

Comparative study on toxicity of ZnO and TiO2 nanoparticles on Artemia salina: effect of pre-UV-A and visible light irradiation.

PubMed

Bhuvaneshwari, M; Sagar, Bhawana; Doshi, Siddharth; Chandrasekaran, N; Mukherjee, Amitava

2017-02-01

This study evaluated the toxicity potential of ZnO and TiO 2 nanoparticles under pre-UV-A irradiation and visible light condition on Artemia salina. The nanoparticle suspension was prepared in seawater medium and exposed under pre-UV-A (0.23 mW/cm 2 ) and visible light (0.18 mW/cm 2 ) conditions. The aggregation profiles of both nanoparticles (NPs) and dissolution of ZnO NPs under both irradiation conditions at various kinetic intervals (1, 24, 48 h) were studied. The 48-h LC 50 values were found to be 27.62 and 71.63 mg/L for ZnO NPs and 117 and 120.9 mg/L for TiO 2 NPs under pre-UV-A and visible light conditions. ZnO NPs were found to be more toxic to A. salina as compared to TiO 2 NPs. The enhanced toxicity was observed under pre-UV-A-irradiated ZnO NPs, signifying its phototoxicity. Accumulation of ZnO and TiO 2 NPs into A. salina depends on the concentration of particles and type irradiations. Elimination of accumulated nanoparticles was also evident under both irradiation conditions. Other than ZnO NPs, the dissolved Zn 2+ also had a significant effect on toxicity and accumulation in A. salina. Increased catalase (CAT) activity in A. salina indicates the generation of oxidative stress due to NP interaction. Thus, this study provides an understanding of the toxicity of photoreactive ZnO and TiO 2 NPs as related to the effects of pre-UV-A and visible light irradiation.

Nano clay-enhanced calcium phosphate cements and hydrogels for biomedical applications

NASA Astrophysics Data System (ADS)

Jammalamadaka, Udayabhanu

Biomaterials are used as templates for drug delivery, scaffolds in tissue engineering, grafts in surgeries, and support for tissue regeneration. Novel biomaterial composites are needed to meet multifaceted requirements of compatibility, ease of fabrication and controlled drug delivery. Currently used biomaterials in orthopedics surgeries suffer limitations in toxicity and preventing infections. Polymethyl methacrylate (PMMA) used as bone cement suffers from limitations of thermal necrosis and monomer toxicity calls for development of better cementing biomaterials. A biodegradable/bioresorbable cement with good mechanical properties is needed to address this short coming. Metal implants used in fixing fractures or total joint replacement needs improvements in preventing biofilm formation and better tissue integration. This research addressed the above mentioned research gaps by formulating novel biomaterial composites. Calcium phosphate cements are the alternative bone cements that are bioresorbable and promote tissue integration. These cements lack sufficient mechanical strengths to be used in load bearing sites. The addition of nanoparticles is hypothesized to improve the mechanical properties without inducing toxicity to the tissue. This hypothesis was tested by evaluating compression and flexural strengths in addition to cytocompatibility tests. Results indicate that addition of nano-clay particles (halloysites nanotubes) improved the compressive strength and osteoinductive properties of calcium phosphate cements. To address the research need of preventing implant failure due to infection and aseptic loosening, novel coatings are needed. Hydrogels are well establish for their ability to mimic in vivo environment, promote cell viability and as drug delivery vehicles. Use of composites of hydrogels and drug-loaded nanoparticles to prevent infection was evaluated. Cytocompatibility results indicate good cell viability. Antibacterial results show sustained release of antibiotics from composite hydrogels and good zones of inhibition on agar plates inoculated with bacterial cultures. Fabricating a complex three-dimensional (3D) scaffold for tissue engineering was a huge challenge. With advancements in additive manufacturing, this research gap was addressed. Methods are needed to fabricate patient specific grafts made from biocompatible biomaterials. In this research, 3D printing was used as a platform to explore new biomaterials as grafts or scaffolds for tissue engineering. Computerized tomography scans were used to fabricate patient-specific grafts. The use of calcium cements to fabricate three-dimensionally complex scaffold or grafts reported in this research holds potential in personalized medicine.

Toxicity of nanoparticles of CuO, ZnO and TiO2 to microalgae Pseudokirchneriella subcapitata.

PubMed

Aruoja, Villem; Dubourguier, Henri-Charles; Kasemets, Kaja; Kahru, Anne

2009-02-01

Toxicities of ZnO, TiO2 and CuO nanoparticles to Pseudokirchneriella subcapitata were determined using OECD 201 algal growth inhibition test taking in account potential shading of light. The results showed that the shading effect by nanoparticles was negligible. ZnO nanoparticles were most toxic followed by nano CuO and nano TiO2. The toxicities of bulk and nano ZnO particles were both similar to that of ZnSO4 (72 h EC50 approximately 0.04 mg Zn/l). Thus, in this low concentration range the toxicity was attributed solely to solubilized Zn2+ ions. Bulk TiO2 (EC50=35.9 mg Ti/l) and bulk CuO (EC50=11.55 mg Cu/l) were less toxic than their nano formulations (EC50=5.83 mg Ti/l and 0.71 mg Cu/l). NOEC (no-observed-effect-concentrations) that may be used for risk assessment purposes for bulk and nano ZnO did not differ (approximately 0.02 mg Zn/l). NOEC for nano CuO was 0.42 mg Cu/l and for bulk CuO 8.03 mg Cu/l. For nano TiO2 the NOEC was 0.98 mg Ti/l and for bulk TiO2 10.1 mg Ti/l. Nano TiO2 formed characteristic aggregates entrapping algal cells that may contribute to the toxic effect of nano TiO2 to algae. At 72 h EC50 values of nano CuO and CuO, 25% of copper from nano CuO was bioavailable and only 0.18% of copper from bulk CuO. Thus, according to recombinant bacterial and yeast Cu-sensors, copper from nano CuO was 141-fold more bioavailable than from bulk CuO. Also, toxic effects of Cu oxides to algae were due to bioavailable copper ions. To our knowledge, this is one of the first systematic studies on effects of metal oxide nanoparticles on algal growth and the first describing toxic effects of nano CuO towards algae.

In Vitro Cytotoxicity of Nanoparticles in Mammalian Germline Stem Cells

PubMed Central

Braydich-Stolle, Laura; Hussain, Saber; Schlager, John J.; Hofmann, Marie-Claude

2010-01-01

Gametogenesis is a complex biological process that is particularly sensitive to environmental insults such as chemicals. Many chemicals have a negative impact on the germline, either by directly affecting the germ cells, or indirectly through their action on the somatic nursing cells. Ultimately, these effects can inhibit fertility, and they may have negative consequences for the development of the offspring. Recently, nanomaterials such as nanotubes, nanowires, fullerene derivatives (buckyballs), and quantum dots have received enormous national attention in the creation of new types of analytical tools for biotechnology and the life sciences. Despite the wide application of nanomaterials, there is a serious lack of information concerning their impact on human health and the environment. Thus, there are limited studies available on toxicity of nanoparticles for risk assessment of nanomaterials. The purpose of this study was to assess the suitability of a mouse spermatogonial stem cell line as a model to assess nanotoxicity in the male germline in vitro. The effects of different types of nanoparticles on these cells were evaluated by light microscopy, and by cell proliferation and standard cytotoxicity assays. Our results demonstrate a concentration-dependent toxicity for all types of particles tested, whereas the corresponding soluble salts had no significant effect. Silver nanoparticles were the most toxic while molybdenum trioxide (MoO3) nanoparticles were the least toxic. Our results suggest that this cell line provides a valuable model with which to assess the cytotoxicity of nanoparticles in the germ line in vitro. PMID:16014736

A comparison of dispersing media for various engineered carbon nanoparticles

PubMed Central

Buford, Mary C; Hamilton, Raymond F; Holian, Andrij

2007-01-01

Background With the increased manufacture and use of carbon nanoparticles (CNP) there has been increasing concern about the potential toxicity of fugitive CNP in the workplace and ambient environment. To address this matter a number of investigators have conducted in vitro and in vivo toxicity assessments. However, a variety of different approaches for suspension of these particles (culture media, Tween 80, dimethyl sulfoxide, phosphate-buffered saline, fetal calf serum, and others), and different sources of materials have generated potentially conflicting outcomes. The quality of the dispersion of nanoparticles is very dependent on the medium used to suspend them, and this then will most likely affect the biological outcomes. Results In this work, the distributions of different CNP (sources and types) have been characterized in various media. Furthermore, the outcome of instilling the different agglomerates, or size distributions, was examined in mouse lungs after one and seven days. Our results demonstrated that CNP suspended in serum produced particle suspensions with the fewest large agglomerates, and the most uniform distribution in mouse lungs. In addition, no apparent clearance of instilled CNP took place from lungs even after seven days. Conclusion This work demonstrates that CNP agglomerates are present in all dispersing vehicles to some degree. The vehicle that contains some protein, lipid or protein/lipid component disperses the CNP best, producing fewer large CNP agglomerates. In contrast, vehicles absent of lipid and protein produce the largest CNP agglomerates. The source of the CNP is also a factor in the degree of particle agglomeration within the same vehicle. PMID:17655771

Paradoxical Roles of Nanoparticles in Cancer Therapeutics and Carcinogenesis

NASA Astrophysics Data System (ADS)

Despeaux, Emily

Nanoparticles (NPs) are becoming increasingly common in consumer goods and are under investigation for a variety of industrial and biomedical applications. However, challenges in determining NP toxicity may prevent them from reaching their full potential. NPs cannot be treated as single class for toxicity evaluations. Even among particles made from the same material, particle-specific physical properties, including size, shape, surface charge, agglomeration state, and surface modifications have a strong effect on the toxicity. Even so, the obstacles to conclusively and reproducibly evaluating toxicity span all NP classes. NP literature is riddled with confusing and often contradictory reports regarding the biocompatibility of both engineered NPs, designed with biocompatibility as a priority, and NPs from occupational or environmental exposures. Incomplete NP characterization and sample inhomogeneity represent major confounding factors in disparate results from seemingly comparable study setups. Additionally, NPs can interfere with many conventional toxicity screening methods. Inappropriate doses, exposure routes, and toxicity endpoints further diminish the utility of many published studies. Given the burgeoning interest in NP-based therapeutic agents, consistent, reliable standards are needed to ensure the biocompatibility of new formulations. To those ends, the synthesis, characterization, and in vitro toxicity of a multi-functional NP therapeutic were investigated (Chapter 2). Specifically, superparamagnetic iron oxide nanoparticles (SPIONs) were coated with amphiphilic polymer and functionalized with antisense oligonucleotides targeting survivin, an anti-apoptotic protein that is highly overexpressed in cancer. SPION physical properties, including particle size and composition, were characterized at each step of synthesis. Our results showed that the SPION platform is biocompatible and capable of delivering functional antisense oligonucleotides to regulate survivin expression; however, significant refinement of the DNA-to-SPION coupling step is needed. Applied clinically, antisense survivin coupled SPIONs can reduce the required dose of, adverse effects from, and resistance to, current cancer chemotherapy regimens. In contrast to engineered NPs for biomedical applications, where real-world exposures would involve careful control of both exposure time- and dose, occupational NP exposures are variable, chronic, and difficult to model in laboratory settings. Chapter 3 focuses on identifying the mechanisms behind carbon nanotube (CNT)-induced malignant transformation of bronchial epithelial cells using a chronic in vitro exposure model. We specifically investigated the role of mesothelin (MSLN), a cell-surface protein that is highly overexpressed in many cancers, in the aggressive phenotype noted following chronic, low-dose CNT exposure. MSLN knockdown resulted in significantly decreased invasion, migration, colonies on soft agar, and tumor sphere formation. In vivo, MSLN knockdown cells formed smaller primary tumors and less metastases. The mechanism by which MSLN contributes to these more aggressive behaviors was investigated using Ingenuity Pathway Analysis, which predicted that increased MSLN could induce cyclin E, a cell cycle regulator known to be associated with human cancer. We found that MSLN knockdown cells had decreased cyclin E, and their proliferation rate was reverted to nearly that of untransformed cells. Cell cycle analysis results were consistent with the decreased rate of proliferation. Together, our results indicate a novel role of MSLN in the malignant transformation of bronchial epithelial cells following CNT exposure, suggesting its utility as a potential biomarker and drug target for CNT-induced malignancies. As demonstrated by the two studies presented here, NPs have the potential to function as both cancer therapeutics and carcinogens. Careful evaluation of toxicity, ensuring that appropriate doses, assays, exposure routes, and endpoints are used, is imperative. Elucidating the physical properties and functionalization that contribute to toxicity, and the mechanisms of that toxicity, will allow NP benefits to be fully exploited while minimizing the risk of widespread, detrimental public health effects.

Targeted Nanoparticle Tested in Patients with Cancer

Cancer.gov

By packaging molecules of the chemotherapy drug docetaxel in nanoparticles, researchers aim to deliver a high dose directly to tumors and reduce the drug's toxicity. A trial to test the targeted nanoparticle is underway in humans.

Transformable liquid-metal nanomedicine

PubMed Central

Lu, Yue; Hu, Quanyin; Lin, Yiliang; Pacardo, Dennis B.; Wang, Chao; Sun, Wujin; Ligler, Frances S.; Dickey, Michael D.; Gu, Zhen

2015-01-01

To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core–shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity. PMID:26625944

Enhanced biocompatibility of ZnS:Mn quantum dots encapsulated with Aloe vera extract for therapeutic applications

NASA Astrophysics Data System (ADS)

Anilkumar, M.; Bindu, K. R.; Sneha Saj, A.; Anila, E. I.

2016-08-01

Toxicity of nanoparticles remains to be a major issue in their application to the biomedical field. Aloe vera (AV) is one of the most widely exploited medicinal plants that have a multitude of amazing properties in the field of medicine. Methanol extract of Aloe vera can be used as a novel stabilising agent for quantum dots to reduce toxicity. We report the synthesis, structural characterization, antibacterial activity and cytotoxicity studies of ZnS:Mn quantum dots synthesized by the colloidal precipitation method, using methanol extract of Aloe vera (AVME) as the capping agent. The ZnS:Mn quantum dots capped with AVME exhibit superior performances in biocompatibility and antibacterial activity compared with ZnS:Mn quantum dots without encapsulation. Project supported by the Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India.

Transformable liquid-metal nanomedicine

NASA Astrophysics Data System (ADS)

Lu, Yue; Hu, Quanyin; Lin, Yiliang; Pacardo, Dennis B.; Wang, Chao; Sun, Wujin; Ligler, Frances S.; Dickey, Michael D.; Gu, Zhen

2015-12-01

To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core-shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity.

Impact of water chemistry on the particle-specific toxicity of copper nanoparticles to Daphnia magna.

PubMed

Xiao, Yinlong; Peijnenburg, Willie J G M; Chen, Guangchao; Vijver, Martina G

2018-01-01

Toxicity of metallic nanoparticle suspensions (NP (total) ) is generally assumed to result from the combined effect of the particles present in suspensions (NP (particle) ) and their released ions (NP (ion) ). Evaluation and consideration of how water chemistry affects the particle-specific toxicity of NP (total) are critical for environmental risk assessment of nanoparticles. In this study, it was found that the toxicity of Cu NP (particle) to Daphnia magna, in line with the trends in toxicity for Cu NP (ion) , decreased with increasing pH and with increasing concentrations of divalent cations and dissolved organic carbon (DOC). Without the addition of DOC, the toxicity of Cu NP (total) to D. magna at the LC50 was driven mainly by Cu NP (ion) (accounting for ≥53% of the observed toxicity). However, toxicity of Cu NP (total) in the presence of DOC at a concentration ranging from 5 to 50mg C/L largely resulted from the NP (particle) (57%-85%), which could be attributable to the large reduction of the concentration of Cu NP (ion) and the enhancement of the stability of Cu NP (particle) when DOC was added. Our results indicate that water chemistry needs to be explicitly taken into consideration when evaluating the role of NP (particle) and NP (ion) in the observed toxicity of NP (total) . Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of AL2O3 and TiO2 nanoparticles on aquatic organisms

NASA Astrophysics Data System (ADS)

Gosteva, I.; Morgalev, Yu; Morgaleva, T.; Morgalev, S.

2015-11-01

Environmental toxicity of aqueous disperse systems of nanoparticles of binary compounds of titanium dioxides (with particle size Δ50=5 nm, Δ50=50 nm, Δ50=90 nm), aluminum oxide alpha-forms (Δ50=7 nm and Δ50=70 nm) and macro forms (TiO2 Δ50=350 nm, Al2O3 A50=4000 nm) were studied using biological testing methods. The bioassay was performed using a set of test organisms representing the major trophic levels. We found the dependence of the toxic effect concentration degree of nTiO2 and nAl2O3 on the fluorescence of the bacterial biosensor "Ekolyum", the chemotactic response of ciliates Paramecium caudatum, the growth of unicellular algae Chlorella vulgaris Beijer and mortality of entomostracans Daphnia magna Straus. We revealed the selective dependence of nTiO2 and nAl2O3 toxicity on the size, concentration and chemical nature of nanoparticles. The minimal concentration causing an organism's response on nTiO2 and nAl2O3 effect depends on the type of the test- organism and the test reaction under study. We specified L(E)C50 and acute toxicity categories for all the studied nanoparticles. We determined that nTiO2 (Δ50=5 nm) belong to the category «Acute toxicity 1», nTiO2 (A50=90 nm) and nAl2O3 (Δ50=70 nm) - to the category «Acute toxicity 2», nAl2O3 (Δ50=7 nm) - to the category «Acute toxicity 3». No acute toxicity was registered for nTiO2 (Δ50=50 nm) and macro form TiO2.

Engineered nanomaterials in food: implications for food safety and consumer health.

PubMed

Martirosyan, Alina; Schneider, Yves-Jacques

2014-05-28

From the current state-of-the-art, it is clear that nanotechnology applications are expected to bring a range of benefits to the food sector aiming at providing better quality and conservation. In the meantime, a growing number of studies indicate that the exposure to certain engineered nanomaterials (ENMs) has a potential to lead to health complications and that there is a need for further investigations in order to unravel the biological outcomes of nanofood consumption. In the current review, we summarize the existing data on the (potential) use of ENMs in the food industry, information on the toxicity profiles of the commonly applied ENMs, such as metal (oxide) nanoparticles (NPs), address the potential food safety implications and health hazards connected with the consumption of nanofood. A number of health complications connected with the human exposure to ENMs are discussed, demonstrating that there is a real basis for the arisen concern not only connected with the gut health, but also with the potency to lead to systemic toxicity. The toxicological nature of hazard, exposure levels and risk to consumers from nanotechnology-derived food are on the earliest stage of investigation and this review also highlights the major gaps that need further research and regulation.

Current understanding of the toxicological risk posed to the fetus following maternal exposure to nanoparticles.

PubMed

Zhang, Yanli; Wu, Junrong; Feng, Xiaoli; Wang, Ruolan; Chen, Aijie; Shao, Longquan

2017-12-01

With the broad use of nanotechnology, the number and variety of nanoparticles that humans can be exposed to has further increased. Consequently, there is growing concern about the potential effect of maternal exposure to various nanoparticles during pregnancy on a fetus. However, the nature of this risk is not fully known. Areas covered: In this review, materno-fetal transfer of nanoparticles through the placenta is described. Both prenatal and postnatal adverse effects, such as fetal resorption, malformation and injury to various organs in mice exposed to nanoparticles are reviewed. The potential mechanisms of toxicity are also discussed. Expert opinion: The toxicology and safe application of recently developed nanoparticles has attracted much attention in the past few years. Although many studies have demonstrated the toxicology of nanoparticles in various species, only a small number of studies have examined the effect on a fetus after maternal exposure to nanoparticles. This is particularly important, because the developing fetus is especially vulnerable to the toxic effects of nanoparticles during fetal development due to the unique physical stage of the fetus. Nanoparticles may directly or indirectly impair fetal development and growth after maternal exposure to nanoparticles.

Kinetics and pathogenesis of intracellular magnetic nanoparticle cytotoxicity

NASA Astrophysics Data System (ADS)

Giustini, Andrew J.; Gottesman, Rachel E.; Petryk, A. A.; Rauwerdink, A. M.; Hoopes, P. Jack

2011-03-01

Magnetic nanoparticles excited by alternating magnetic fields (AMF) have demonstrated effective tumor-specific hyperthermia. This treatment is effective as a monotherapy as well as a therapeutic adjuvant to chemotherapy and radiation. Iron oxide nanoparticles have been shown, so far, to be non-toxic, as are the exciting AMF fields when used at moderate levels. Although higher levels of AMF can be more effective, depending on the type of iron oxide nanoparticles use, these higher field strengths and/or frequencies can induce normal tissue heating and toxicity. Thus, the use of nanoparticles exhibiting significant heating at low AMF strengths and frequencies is desirable. Our preliminary experiments have shown that the aggregation of magnetic nanoparticles within tumor cells improves their heating effect and cytotoxicity per nanoparticle. We have used transmission electron microscopy to track the endocytosis of nanoparticles into tumor cells (both breast adenocarcinoma (MTG-B) and acute monocytic leukemia (THP-1) cells). Our preliminary results suggest that nanoparticles internalized into tumor cells demonstrate greater cytotoxicity when excited with AMF than an equivalent heat dose from excited external nanoparticles or cells exposed to a hot water bath. We have also demonstrated that this increase in SAR caused by aggregation improves the cytotoxicity of nanoparticle hyperthermia therapy in vitro.

Random Walk of Single Gold Nanoparticles in Zebrafish Embryos Leading to Stochastic Toxic Effects on Embryonic Developments

PubMed Central

Browning, Lauren M.; Lee, Kerry J.; Huang, Tao; Nallathamby, Prakash D.; Lowman, Jill E.; Xu, Xiao-Hong Nancy

2010-01-01

We have synthesized and characterized stable (non-aggregation, non-photobleaching and non-blinking), nearly monodisperse and highly-purified Au nanoparticles, and used them to probe transport of cleavage-stage zebrafish embryos and to study their effects on embryonic development in real time. We found that single Au nanoparticles (11.6 ± 0.9 nm in diameter) passively diffused into chorionic space of the embryos via their chorionic-pore-canals and continued their random-walk through chorionic space and into inner mass of embryos. Diffusion coefficients of single nanoparticles vary dramatically (2.8×10-11 to 1.3×10-8 cm2/s) as nanoparticles diffuse through various parts of embryos, suggesting highly diverse transport barriers and viscosity gradients of embryos. The amount of Au nanoparticles accumulated in embryos increase with its concentration. Interestingly, their effects on embryonic development are not proportionally related to the concentration. Majority of embryos (74% on average) incubated chronically with 0.025-1.2 nM Au nanoparticles for 120 h developed to normal zebrafish, with some (24%) being dead and few (2%) deformed. We developed a new approach to image and characterize individual Au nanoparticles embedded in tissues using histology sample preparation methods and LSRP spectra of single nanoparticles. We found that Au nanoparticles in various parts of normally developed and deformed zebrafish, suggesting that random-walk of nanoparticles in embryos during their development might have led to stochastic effects on embryonic development. These results show that Au nanoparticles are much more biocompatible (less toxic) to the embryos than Ag nanoparticles that we reported previously, suggesting that they are better suited as biocompatible probes for imaging embryos in vivo. The results provide powerful evidences that biocompatibility and toxicity of nanoparticles highly depend on their chemical properties, and the embryos can serve as effective in-vivo assays to screen their biocompatibility. PMID:20644873

Safety issues associated with the use of nanoparticles in human body.

PubMed

Sufian, Mian Muhammad; Khattak, Jabar Zaman Khan; Yousaf, Shahzad; Rana, Muhammad Suleman

2017-09-01

Nanotechnology has transformed the world by the introduction of a distinctive class of materials and products in a wide array of fields. It has contributed to the production of innovative materials and devices. Having unique advantages and domestic along with industrial applications, however, has raised the issue of safety for consumers, producers and environment. Having a comparative smaller dimension and other exclusive properties, nanoparticles have the ability to harm human body by interacting through various mechanisms. Here, we endeavoured to review and discuss the characteristics of nanoparticles relevant to their toxicity, conceivable exposure routes of nanoparticles to human body like skin contact, inhalation, and ingestion, and the basic approaches which can aid to control human exposures to toxic nanoparticles have been discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-Engineered Nanoparticles of C60

PubMed Central

Deguchi, Shigeru; Mukai, Sada-atsu; Sakaguchi, Hide; Nonomura, Yoshimune

2013-01-01

We discovered that rubbing bulk solids of C60 between fingertips generates nanoparticles including the ones smaller than 20 nm. Considering the difficulties usually associated with nanoparticle production by pulverisation, formation of nanoparticles by such a mundane method is unprecedented and noteworthy. We also found that nanoparticles of C60 could be generated from bulk solids incidentally without deliberate engineering of any sort. Our findings imply that there exist highly unusual human exposure routes to nanoparticles of C60, and elucidating formation mechanisms of nanoparticles is crucial in assessing their environmental impacts. PMID:23807024

Synthesis and Characterization of Environmentally Benign Nanoparticles

EPA Science Inventory

There has been a growing interest in replacing current non-biodegradable and toxic nanosystems with environmentally benign biopolymer based ones to minimize post-utilization hazards due to uncontrolled accumulation of nanoparticles in the environment. Lignin based nanoparticles (...

Hydrophobically modified polysaccharide-based on polysialic acid nanoparticles as carriers for anticancer drugs.

PubMed

Jung, Bom; Shim, Man-Kyu; Park, Min-Ju; Jang, Eun Hyang; Yoon, Hong Yeol; Kim, Kwangmeyung; Kim, Jong-Ho

2017-03-30

This study presented the development of hydrophobically modified polysialic acid (HPSA) nanoparticles, a novel anticancer drug nanocarrier that increases therapeutic efficacy without causing nonspecific toxicity towards normal cells. HPSA nanoparticles were prepared by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)/N-hydroxysuccinimide (NHS) coupling between N-deacetylated polysialic acid (PSA) and 5β-cholanic acid. The physicochemical characteristics of HPSA nanoparticles (zeta-potential, morphology and size) were measured, and in vitro cytotoxicity and cellular uptake of PSA and HPSA nanoparticles were tested in A549 cells. In vivo cancer targeting of HPSA nanoparticles was evaluated by labeling PSA and HPSA nanoparticles with Cy5.5, a near-infrared fluorescent dye, for imaging. HPSA nanoparticles showed improved cancer-targeting ability compared with PSA. Doxorubicin-loaded HPSA (DOX-HPSA) nanoparticles were prepared using a simple dialysis method. An analysis of the in vitro drug-release profile and drug-delivery behavior showed that DOX was effectively released from DOX-HPSA nanoparticles. In vivo cancer therapy with DOX-HPSA nanoparticles in mice showed antitumor effects that resembled those of free DOX. Moreover, DOX-HPSA nanoparticles had low toxicity toward other organs, reflecting their tumor-targeting property. Hence, HPSA nanoparticles are considered a potential nanocarrier for anticancer agents. Copyright © 2017 Elsevier B.V. All rights reserved.

[Nanotechnology--possibilities and hazards].

PubMed

Snopczyński, Tomasz; Góralczyk, Katarzyna; Czaja, Katarzyna; Struciński, Paweł; Hernik, Agnieszka; Korcz, Wojciech; Ludwicki, Jan K

2009-01-01

Nanoparticles are the objects with at least one demension smaller than 100 nm. Nanoparticles exist in nature or can be produced by human activities, intentionally or unintentionally. Nanotechnology is an emerging science involving manipulation of matter at nanometer scale. Nanoparticles find numerous applications in many fields, starting with electronics, throught medicine, cosmetology, and ending with automotive industry and construction industry. Depending on the use of nanoparticles, the routes of exposure may be inhalation, dermal, oral or parenteral. Nanoparticles have a greater active surface area per unit mass than larger particles. Together with an increase of surface area, toxicity and potential health effects may also increase. Toxicity of nanoparticles depend on many factors, for example: size, shape, chemical composition, solubility, surface area and surface charge. Risk assessment related to human health, should be integrated at all stages of the life cycle of the nanotechnology, starting at the point of conception and including research and development, manufacturing, distribution, use and disposal or recycling.

Using Gold Nanoparticles To Disrupt the Tumor Microenvironment: An Emerging Therapeutic Strategy.

PubMed

Melamed, Jilian R; Riley, Rachel S; Valcourt, Danielle M; Day, Emily S

2016-12-27

Gold nanoparticles have received much attention recently as carriers for anticancer drugs and therapeutic oligonucleotides, but little research has investigated their potential to act as stand-alone therapeutics. Previous studies interrogating their short- and long-term systemic toxicity have found that although gold nanoparticles accumulate within and clear slowly from the liver and spleen, they do not appear to exert toxic effects in these organs. Interestingly, gold nanoparticles innately exhibit the ability to modulate the tumor microenvironment specifically by interfering with crosstalk between tumor cells and stromal cells. In this issue of ACS Nano, Mukherjee and colleagues demonstrate that bare gold nanoparticles can disturb crosstalk between pancreatic stellate cells and pancreatic cancer cells by modulating the cellular secretome to reduce the growth of desmoplastic tissue and inhibit tumor growth. In this Perspective, we highlight opportunities for anticancer targeting within the tumor microenvironment and discuss gold nanoparticles as potential mediators of microenvironment-targeted therapy.

Phototoxicity of TiO2 nanoparticles to zebrafish (Danio rerio) is dependent on life stage.

PubMed

Ma, Hongbo; Diamond, Stephen A

2013-09-01

Zebrafish embryos have been used increasingly to evaluate nanomaterial toxicity. The present study compared phototoxicity of TiO2 nanoparticles with zebrafish at 4 life stages (embryos, yolk-sac larvae, free-swimming larvae, and juvenile) under simulated sunlight using the 96-h standard toxicity assay. Yolk-sac larvae were found to be the most sensitive to TiO2 phototoxicity, suggesting that the widely used zebrafish embryo test may not fully or accurately predict hazard and risk of these nanoparticles to small fish. Copyright © 2013 SETAC.

Safety assessment of nanoparamagnetic contrast agents with different coatings for molecular MRI

NASA Astrophysics Data System (ADS)

Azizian, Gholamreza; Riyahi-Alam, Nader; Haghgoo, Soheila; Saffari, Mojtaba; Zohdiaghdam, Reza; Gorji, Ensieh

2013-04-01

Despite the wide application of gadolinium as a contrast agent for magnetic resonance imaging (MRI), there is a serious lack of information on its toxicity. Gadolinium and gadolinium oxide (Gd-oxide) are used as contrast agents for magnetic resonance imaging (MRI). There are methods for reducing toxicity of these materials, such as core nanoparticles coating or conjugating. Therefore, for toxicity evaluation, we compared the viability of commercial contrast agents in MRI (Gd-DTPA) and three nanoparticles with the same core Gd2O3 and small particulate gadolinium oxide or SPGO (< 40 nm) but different coatings of diethyleneglycol (DEG) as Gd2O3-DEG and methoxy polyethylene glycol-silane (mPEG-silane: 550 and 2000 Dalton) as SPGO-mPEG-silane550 and SPGO-mPEG-silane2000, respectively, in the SK-MEL3 cell line, by light microscopy, MTT assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, and the LDH assay detecting lactate dehydrogenase activity. The viability values were not statistically different between the three nanoparticles and Gd-DTPA. The MTT and LDH assay results showed that Gd2O3-DEG nanoparticles were more toxic than Gd-DTPA and other nanoparticles. Also, SPGO-mPEG-silane2000 was more biocompatible than other nanoparticles. The obtained results did not show any significant increase in cytotoxicity of the nanoparticles and Gd-DTPA, neither dose-dependent nor time-dependent. Therefore, DEG and PEG, due to their considerable properties and irregular sizes (different molecular weights), were selected as the useful surface covering materials of nanomagnetic particles that could reveal noticeable relaxivity and biocompatibility characteristics.

The reduced bioavailability of copper by nano-TiO₂ attenuates the toxicity to Microcystis aeruginosa.

PubMed

Chen, Jinyuan; Qian, Yi; Li, Herong; Cheng, Yanhong; Zhao, Meirong

2015-08-01

Nano-TiO2 is a widely applied nanoparticle (NPs) and co-exists with other pollutants such as heavy metals in aquatic environments. However, minimal knowledge is available concerning the ecological risk of these mixtures. Our study reported that at no toxic effect concentrations of TiO2 nanoparticles (5 mg/L), the toxicity of Cu ions to the algae Microcystis aeruginosa was significantly attenuated by TiO2 nanoparticles. Specifically, the concentration of photosynthetic pigments (i.e., concentration of Chla) increased 37% when comparing only Cu ions treated and the nano-TiO2-Cu co-incubation. The levels of phycocyanin (PC), allophycocyanin (APC), phycoerythrin (PE), and phycobiliprotein (PBPs) were also recovered at levels ranging from 23 to 35% after 72 h. For oxidative indexes, the decreased activities of the superoxide dismutase (SOD), peroxidase (POD) content, and malondialdehyde (MDA) with the existence of nano-TiO2 displayed a lower level compared to Cu ions treatment only at 24 and 48 h. This toxicity attenuation can be confirmed by subcellular structures because the impairment to cellular membranes and organelles reduced with the presence of nano-TiO2. The potential mechanisms of the antagonism between the nano-TiO2 and Cu ions can be partially attributed to the sorption of copper onto TiO2 nanoparticles, which fitted the Freundlich isotherm (coefficient = 0.967). The decreased bioavailability of Cu ions protected algae cells from being attacked by free Cu ions. Given the abundance of released nanoparticles and unique physicochemical property of nanoparticles, our results elucidated the ecosafety of nanoparticles and co-substrates in aquatic systems.

Melanin nanoparticles derived from a homology of medicine and food for sentinel lymph node mapping and photothermal in vivo cancer therapy.

PubMed

Chu, Maoquan; Hai, Wangxi; Zhang, Zheyu; Wo, Fangjie; Wu, Qiang; Zhang, Zefei; Shao, Yuxiang; Zhang, Ding; Jin, Lu; Shi, Donglu

2016-06-01

The use of non-toxic or low toxicity materials exhibiting dual functionality for use in sentinel lymph node (SLN) mapping and cancer therapy has attracted considerable attention during the past two decades. Herein, we report that the natural black sesame melanin (BSM) extracted from black sesame seeds (Sesamum indicum L.) shows exciting potential for SLN mapping and cancer photothermal therapy. Aqueous solutions of BSM under neutral and alkaline conditions can assemble into sheet-like nanoparticles ranging from 20 to 200 nm in size. The BSM nanoparticles were encapsulated by liposomes to improve their water solubility and the encapsulated and bare BSM nanoparticles were both non-toxic to cells. Furthermore, the liposome-encapsulated BSM nanoparticles (liposome-BSM) did not exhibit any long-term toxicity in mice. The liposome-BSM nanoparticles were subsequently used to passively target healthy and tumor-bearing mice SLNs, which were identified by the black color of the nanoparticles. BSM also strongly absorbed light in the near-infrared (NIR) range, which was rapidly converted to heat energy. Human esophagus carcinoma cells (Eca-109) were killed efficiently by liposome-BSM nanocomposites upon NIR laser irradiation. Furthermore, mouse tumor tissues grown from Eca-109 cells were seriously damaged by the photothermal effects of the liposome-BSM nanocomposites, with significant tumor growth suppression compared with controls. Given that BSM is a safe and nutritious biomaterial that can be easily obtained from black sesame seed, the results presented herein represent an important development in the use of natural biomaterials for clinical SLN mapping and cancer therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Near-infrared light-triggered "on/off" motion of polymer multilayer rockets.

PubMed

Wu, Zhiguang; Lin, Xiankun; Wu, Yingjie; Si, Tieyan; Sun, Jianmin; He, Qiang

2014-06-24

We describe an approach to modulating the on-demand motion of catalytic polymer-based microengines via near-infrared (NIR) laser irradiation. The polymer multilayer motor was fabricated by the template-assisted layer-by-layer assembly and subsequently deposition of platinum nanoparticles inside and a thin gold shell outside. Then a mixed monolayer of a tumor-targeted peptide and an antifouling poly(ethylene glycol) was functionalized on the gold shell. The microengines remain motionless at the critical peroxide concentration (0.1%, v/v); however, NIR illumination on the engines leads to a photothermal effect and thus rapidly triggers the motion of the catalytic engines. Computational modeling explains the photothermal effect and gives the temperature profile accordingly. Also, the photothermal effect can alone activate the motion of the engines in the absence of the peroxide fuel, implying that it may eliminate the use of toxic fuel in the future. The targeted recognition ability and subsequently killing of cancer cells by the photothermal effect under the higher power of a NIR laser were illustrated. Our results pave the way to apply self-propelled synthetic engines in biomedical fields.

Human skin penetration and local effects of topical nano zinc oxide after occlusion and barrier impairment.

PubMed

Leite-Silva, V R; Sanchez, W Y; Studier, H; Liu, D C; Mohammed, Y H; Holmes, A M; Ryan, E M; Haridass, I N; Chandrasekaran, N C; Becker, W; Grice, J E; Benson, H A E; Roberts, M S

2016-07-01

Public health concerns continue to exist over the safety of zinc oxide nanoparticles that are commonly used in sunscreen formulations. In this work, we assessed the effects of two conditions which may be encountered in everyday sunscreen use, occlusion and a compromised skin barrier, on the penetration and local toxicity of two topically applied zinc oxide nanoparticle products. Caprylic/capric triglyceride (CCT) suspensions of commercially used zinc oxide nanoparticles, either uncoated or with a silane coating, were applied to intact and barrier impaired skin of volunteers, without and with occlusion for a period of six hours. The exposure time was chosen to simulate normal in-use conditions. Multiphoton tomography with fluorescence lifetime imaging was used to noninvasively assess zinc oxide penetration and cellular metabolic changes that could be indicative of toxicity. We found that zinc oxide nanoparticles did not penetrate into the viable epidermis of intact or barrier impaired skin of volunteers, without or with occlusion. We also observed no apparent toxicity in the viable epidermis below the application sites. These findings were validated by ex vivo human skin studies in which zinc penetration was assessed by multiphoton tomography with fluorescence lifetime imaging as well as Zinpyr-1 staining and toxicity was assessed by MTS assays in zinc oxide treated skin cryosections. In conclusion, applications of zinc oxide nanoparticles under occlusive in-use conditions to volunteers are not associated with any measurable zinc oxide penetration into, or local toxicity in the viable epidermis below the application site. Copyright © 2016 Elsevier B.V. All rights reserved.

In Vitro Cytotoxicity Assessment of an Orthodontic Composite Containing Titanium-dioxide Nano-particles

PubMed Central

Heravi, Farzin; Ramezani, Mohammad; Poosti, Maryam; Hosseini, Mohsen; Shajiei, Arezoo; Ahrari, Farzaneh

2013-01-01

Background and aims. Incorporation of nano-particles to orthodontic bonding systems has been considered to prevent enamel demineralization around appliances. This study investigated cytotoxicity of Transbond XT adhesive containing 1 wt% titanium dioxide (TiO2) nano-particles. Materials and methods. Ten composite disks were prepared from each of the conventional and TiO2-containg composites and aged for 1, 3, 5, 7 and 14 days in Dulbecco’s Modified Eagle’s Medium (DMEM). The extracts were obtained and exposed to culture media of human gingival fibroblasts (HGF) and mouse L929 fibroblasts. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results. Both adhesives were moderately toxic for HGF cells on the first day of the experiment, but the TiO2-containing adhesive produced significantly lower toxicity than the pure adhesive (P<0.05). No significant differences were found in cell viability percentages between the two groups on the other days (P>0.05). There was a significant reduction in cell toxicity with increasing pre-incubation time (P<0.001). L929 cells showed similar toxicity trends, but lower sensitivity to detect cytotoxicity of dental composites. Conclusion. The orthodontic adhesive containing TiO2 nano-particles indicated comparable or even lower toxicity than its nano-particle-free counterpart, indicating that incorporation of 1 wt% TiO2 nano-particles to the composite structure does not result in additional health hazards compared to that occurring with the pure adhesive. PMID:24578816

Aerosolization and Atmospheric Transformation of Engineered Nanoparticles

NASA Astrophysics Data System (ADS)

Tiwari, Andrea J.

While research on the environmental impacts of engineered nanoparticles (ENPs) is growing, the potential for them to be chemically transformed in the atmosphere has been largely ignored. The overall objective of this work was to assess the atmospheric transformation of carbonaceous nanoparticles (CNPs). The research focuses on C60 fullerene because it is an important member of the carbonaceous nanoparticle (CNP) family and is used in a wide variety of applications. The first specific objective was to review the potential of atmospheric transformations to alter the environmental impacts of CNPs. We described atmospheric processes that were likely to physically or chemically alter aerosolized CNPs and demonstrated their relevance to CNP behavior and toxicity in the aqueous and terrestrial environment. In order to investigate the transformations of CNP aerosols under controlled conditions, we developed an aerosolization technique that produces nano-scale aerosols without using solvents, which can alter the surface chemistry of the aerosols. We demonstrated the technique with carbonaceous (C60) and metal oxide (TiO2, CeO2) nanoparticle powders. All resulting aerosols exhibited unimodal size distributions and mode particle diameters below 100 nm. We used the new aerosolization technique to investigate the reaction between aerosolized C60 and atmospherically realistic levels of ozone (O3) in terms of reaction products, reaction rate, and oxidative stress potential. We identified C60O, C60O2, and C60O3 as products of the C60-O3 reaction. We demonstrated that the oxidative stress potential of C 60 may be enhanced by exposure to O3. We found the pseudo-first order reaction rate to be 9 x 10-6 to 2 x 10 -5 s-1, which is several orders of magnitude lower than the rate for several PAH species under comparable conditions. This research has demonstrated that a thorough understanding of atmospheric chemistry of ENPs is critical for accurate prediction of their environmental impacts. It has also enabled future research in that vein by developing a novel technique to produce nanoscale aerosols from nanoparticle powders. Results of this research will help guide the formulation of appropriate environmental policy concerning the regulation of ENPs.

Developmental toxicity of Japanese medaka embryos by silver nanoparticles and released ions in the presence of humic acid.

PubMed

Kim, Jun Y; Kim, Ki-Tae; Lee, Byeong G; Lim, Byung J; Kim, Sang D

2013-06-01

The final destination point of nanoparticles is the environment, where they remain a long period; therefore, a deep understanding of the relationship between nanoparticles and the environmental factors is required. Japanese medaka embryos were exposed to two differently prepared AgNPs: freshly prepared AgNPs and aged AgNPs. With these two AgNP preparations, we studied the impacts of humic acid in terms of embryonic toxicity, as well as the behavior of AgNPs. Aged AgNPs exhibited a lower lethal concentration (LC50) value (1.44mg/L) compared to fresh AgNPs (3.53mg/L) through 96h acute toxicity tests, due to the release of silver ions, as confirmed by kinetic analysis. The presence of humic acids considerably reduced the toxicity of aged AgNPs due to complexation with silver ions. Agglomeration, induced by interactions with humic acid, might reduce the bioavailability of AgNPs to Japanese medaka embryos. This study demonstrates that aged AgNPs releasing more silver ions are more toxic than fresh AgNPs, and humic acids play a role in reducing the toxicity of aged AgNPs. Copyright © 2013 Elsevier Inc. All rights reserved.

Lung toxicities of core–shell nanoparticles composed of carbon, cobalt, and silica

PubMed Central

Al Samri, Mohammed T; Silva, Rafael; Almarzooqi, Saeeda; Albawardi, Alia; Othman, Aws Rashad Diab; Al Hanjeri, Ruqayya SMS; Al Dawaar, Shaikha KM; Tariq, Saeed; Souid, Abdul-Kader; Asefa, Tewodros

2013-01-01

We present here comparative assessments of murine lung toxicity (biocompatibility) after in vitro and in vivo exposures to carbon (C–SiO2-etched), carbon–silica (C–SiO2), carbon–cobalt–silica (C–Co–SiO2), and carbon–cobalt oxide–silica (C–Co3O4–SiO2) nanoparticles. These nanoparticles have potential applications in clinical medicine and bioimaging, and thus their possible adverse events require thorough investigation. The primary aim of this work was to explore whether the nanoparticles are biocompatible with pneumatocyte bioenergetics (cellular respiration and adenosine triphosphate content). Other objectives included assessments of caspase activity, lung structure, and cellular organelles. Pneumatocyte bioenergetics of murine lung remained preserved after treatment with C–SiO2-etched or C–SiO2 nanoparticles. C–SiO2-etched nanoparticles, however, increased caspase activity and altered lung structure more than C–SiO2 did. Consistent with the known mitochondrial toxicity of cobalt, both C–Co–SiO2 and C–Co3O4–SiO2 impaired lung tissue bioenergetics. C–Co–SiO2, however, increased caspase activity and altered lung structure more than C–Co3O4–SiO2. The results indicate that silica shell is essential for biocompatibility. Furthermore, cobalt oxide is the preferred phase over the zerovalent Co(0) phase to impart biocompatibility to cobalt-based nanoparticles. PMID:23658487

Inhalation exposure study of titanium dioxide nanoparticles with a primary particle size of 2 to 5 nm.

PubMed

Grassian, Vicki H; O'shaughnessy, Patrick T; Adamcakova-Dodd, Andrea; Pettibone, John M; Thorne, Peter S

2007-03-01

Nanotechnology offers great promise in many industrial applications. However, little is known about the health effects of manufactured nanoparticles, the building blocks of nanomaterials. Titanium dioxide (TiO(2)) nanoparticles with a primary size of 2-5 nm have not been studied previously in inhalation exposure models and represent some of the smallest manufactured nanoparticles. The purpose of this study was to assess the toxicity of these nanoparticles using a murine model of lung inflammation and injury. The properties of TiO(2) nanoparticles as well as the characteristics of aerosols of these particles were evaluated. Mice were exposed to TiO(2) nanoparticles in a whole-body exposure chamber acutely (4 hr) or subacutely (4 hr/day for 10 days). Toxicity in exposed mice was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase (LDH) activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid. Lungs were also evaluated for histopathologic changes Mice exposed acutely to 0.77 or 7.22 mg/m(3) nanoparticles demonstrated minimal lung toxicity or inflammation. Mice exposed subacutely (8.88 mg/m(3)) and necropsied immediately and at week 1 or 2 postexposure had higher counts of total cells and alveolar macrophages in the BAL fluid compared with sentinels. However, mice recovered by week 3 postexposure. Other indicators were negative. Mice subacutely exposed to 2-5 nm TiO(2) nanoparticles showed a significant but moderate inflammatory response among animals at week 0, 1, or 2 after exposure that resolved by week 3 postexposure.

Development of screening assays for nanoparticle toxicity assessment in human blood: preliminary studies with charged Au nanoparticles.

PubMed

Love, Sara A; Thompson, John W; Haynes, Christy L

2012-09-01

As nanoparticles have found increased use in both consumer and medical applications, corresponding increases in possible exposure to humans necessitate studies examining the impacts of these nanomaterials in biological systems. This article examines the effects of approximately 30-nm-diameter gold nanoparticles, with positively and negatively charged surface coatings in human blood. Here, we study the exposure effects, with up to 72 h of exposure to 5, 15, 25 and 50 µg/ml nanoparticles on hemolysis, reactive oxygen species (ROS) generation and platelet aggregation in subsets of cells from human blood. Assessing viability with hemolysis, results show significant changes in a concentration-dependent fashion. Rates of ROS generation were investigated using the dichlorofluorscein diacetate-based assay as ROS generation is a commonly suspected mechanism of nanoparticle toxicity; herein, ROS was not a significant factor. Optical monitoring of platelet aggregation revealed that none of the examined nanoparticles induced aggregation upon short-term exposure.

Novel biocompatible hydrogel nanoparticles: generation and size-tuning of nanoparticles by the formation of micelle templates obtained from thermo-responsive monomers mixtures

NASA Astrophysics Data System (ADS)

Khandadash, Raz; Machtey, Victoria; Shainer, Inbal; Gottlieb, Hugo E.; Gothilf, Yoav; Ebenstein, Yuval; Weiss, Aryeh; Byk, Gerardo

2014-12-01

Biocompatible hydrogel nanoparticles are prepared by polymerization and cross-linking of N-isopropyl acrylamide in a micelle template formed by block copolymers macro-monomers at high temperature. Different monomer ratios form, at high temperature, well-defined micelles of different sizes which are further polymerized leading to nanoparticles with varied sizes from 20 to 390 nm. Physico-chemical characterization of the nanoparticles demonstrates their composition and homogeneity. The NPs were tested in vitro and in vivo biocompatibility assays, and their lack of toxicity was proven. The NPs can be labeled with fluorescent probes, and their intracellular fate can be visualized and quantified using confocal microscopy. Their uptake by live stem cells and distribution in whole developing animals is reported. On the basis of our results, a mechanism of nanoparticle formation is suggested. The lack of toxicity makes these nanoparticles especially attractive for biological applications such as screening and bio-sensing.

Biogenic silver nanoparticles based on trichoderma harzianum: synthesis, characterization, toxicity evaluation and biological activity

NASA Astrophysics Data System (ADS)

Guilger, Mariana; Pasquoto-Stigliani, Tatiane; Bilesky-Jose, Natália; Grillo, Renato; Abhilash, P. C.; Fraceto, Leonardo Fernandes; Lima, Renata De

2017-03-01

White mold is an agricultural disease caused by the fungus Sclerotinia sclerotiorum, which affects important crops. There are different ways of controlling this organism, but none provides inhibition of its resistance structures (sclerotia). Nanotechnology offers promising applications in agricultural area. Here, silver nanoparticles were biogenically synthesized using the fungus Trichoderma harzianum and characterized. Cytotoxicity and genotoxicity were evaluated, and the nanoparticles were initially tested against white mold sclerotia. Their effects on soybean were also investigated with no effects observed. The nanoparticles showed potential against S. sclerotiorum, inhibiting sclerotia germination and mycelial growth. Nanoparticle characterization data indicated spherical morphology, satisfactory polydispersity and size distribution. Cytotoxicity and genotoxicity assays showed that the nanoparticles caused both the effects, although, the most toxic concentrations were above those applied for white mold control. Given the potential of the nanoparticles against S. sclerotiorum, we conclude that this study presents a first step for a new alternative in white mold control.

Monitoring the Environmental Impact of TiO2 Nanoparticles Using a Plant-Based Sensor Network

PubMed Central

Lenaghan, Scott C.; Li, Yuanyuan; Zhang, Hao; Burris, Jason N.; Stewart, C. Neal; Parker, Lynne E.; Zhang, Mingjun

2016-01-01

The increased manufacturing of nanoparticles for use in cosmetics, foods, and clothing necessitates the need for an effective system to monitor and evaluate the potential environmental impact of these nanoparticles. The goal of this research was to develop a plant-based sensor network for characterizing, monitoring, and understanding the environmental impact of TiO2 nanoparticles. The network consisted of potted Arabidopsis thaliana with a surrounding water supply, which was monitored by cameras attached to a laptop computer running a machine learning algorithm. Using the proposed plant sensor network, we were able to examine the toxicity of TiO2 nanoparticles in two systems: algae and terrestrial plants. Increased terrestrial plant growth was observed upon introduction of the nanoparticles, whereas algal growth decreased significantly. The proposed system can be further automated for high-throughput screening of nanoparticle toxicity in the environment at multiple trophic levels. The proposed plant-based sensor network could be used for more accurate characterization of the environmental impact of nanomaterials. PMID:28458617

Delivery of disulfiram into breast cancer cells using folate-receptor-targeted PLGA-PEG nanoparticles: in vitro and in vivo investigations.

PubMed

Fasehee, Hamidreza; Dinarvand, Rassoul; Ghavamzadeh, Ardeshir; Esfandyari-Manesh, Mehdi; Moradian, Hanieh; Faghihi, Shahab; Ghaffari, Seyed Hamidollah

2016-04-21

A folate-receptor-targeted poly (lactide-co-Glycolide) (PLGA)-Polyethylene glycol (PEG) nanoparticle is developed for encapsulation and delivery of disulfiram into breast cancer cells. After a comprehensive characterization of nanoparticles, cell cytotoxicity, apoptosis induction, cellular uptake and intracellular level of reactive oxygen species are analyzed. In vivo acute and chronic toxicity of nanoparticles and their efficacy on inhibition of breast cancer tumor growth is studied. The folate-receptor-targeted nanoparticles are internalized into the cells, induce reactive oxygen species formation, induce apoptosis and inhibit cell proliferation more efficiently compared to the untargeted nanoparticles. The acute and toxicity test show the maximum dose of disulfiram equivalent of nanoparticles for intra-venous injection is 6 mg/kg while show significant decrease in the breast cancer tumor growth rate. It is believed that the developed formulation could be used as a potential vehicle for successful delivery of disulfiram, an old and inexpensive drug, into breast cancer cells and other solid tumors.

Testing Silver Nanoparticle Toxicity Using the Ammonia Oxidizing Bacteria Nitrosomonas Europaea and a High-throughput Assay

NASA Astrophysics Data System (ADS)

Semprini, L.; Bartow, S.; Radniecki, T.

2012-04-01

Understanding the toxicity of nanoparticles on ecologically significant wastewater microbiota, specifically ammonia oxidizing bacteria (AOB), is critical due to the exponential increase in commercialization of nanoparticles as well as the sensitivity of AOB to inhibitors. A high-throughput activity assay was developed to rapidly screen for nanoparticle toxicity on AOB, using a multi-well plate method and AOB Nitrosomonas Europaea. This method demonstrated good agreement with previously established batch bottle assays utilizing both silver ions (Ag+) and nanoparticles (Ag-NPs) as nitrification inhibitors. The method was used to study the inhibition of Ag+ and Ag-NPs (20 nm) on the nitrification by N. Europaea cells grown in fill-and-draw reactors compared exponentially grown batch cells. Results indicate longer hydraulic residence times increased some protection against inhibition as measured by the production of nitrite over a three hour assay. The cells were more sensitive to Ag+ than Ag-NP, which is consistent with our past observations. Studies are currently being conducted to determine the effects that the presence of humic acid and cations on the inhibition and toxicity. Our initial results show that the presence of Mg++ provides protect from Ag-NP inhibition, which partly results from the aggregation of the Ag-NP and a decrease in the rate of oxidation of the Ag-NP to Ag+. The presence of humic acid also provides for some protection from Ag-NP inhibition.

Impacts of select organic ligands on the colloidal stability, dissolution dynamics, and toxicity of silver nanoparticles.

PubMed

Pokhrel, Lok R; Dubey, Brajesh; Scheuerman, Phillip R

2013-11-19

Key understanding of potential transformations that may occur on silver nanoparticle (AgNP) surface upon interaction with naturally ubiquitous organic ligands (e.g., -SH (thoil), humic acid, or -COO (carboxylate)) is limited. Herein we investigated how dissolved organic carbon (DOC), -SH (in cysteine, a well-known Ag(+) chelating agent), and -COO (in trolox, a well-known antioxidant) could alter the colloidal stability, dissolution rate, and toxicity of citrate-functionalized AgNPs (citrate-AgNPs) against a keystone crustacean Daphnia magna. Cysteine, DOC, or trolox amendment of citrate-AgNPs differentially modified particle size, surface properties (charge, plasmonic spectra), and ion release dynamics, thereby attenuating (with cysteine or trolox) or promoting (with DOC) AgNP toxicity. Except with DOC amendment, the combined toxicity of AgNPs and released Ag under cysteine or trolox amendment was lower than of AgNO3 alone. The results of this study show that citrate-AgNP toxicity can be associated with oxidative stress, ion release, and the organism biology. Our evidence suggests that specific organic ligands available in the receiving waters can differentially surface modify AgNPs and alter their environmental persistence (changing dissolution dynamics) and subsequently the toxicity; hence, we caveat to generalize that surface modified nanoparticles upon environmental release may not be toxic to receptor organisms.

Silver nanoparticle induced cytotoxicity, oxidative stress, and DNA damage in CHO cells

NASA Astrophysics Data System (ADS)

Awasthi, Kumud Kant; Awasthi, Anjali; Kumar, Narender; Roy, Partha; Awasthi, Kamlendra; John, P. J.

2013-09-01

Silver nanoparticles (Ag NPs) are being used increasingly in wound dressings, catheters, and in various household products due to their antimicrobial activity. The present study reports the toxicity evaluation of synthesized and well characterized Ag NPs using Chinese hamster ovary (CHO) cells. The UV-Vis spectroscopy reveals the formation of silver nanoparticles by exhibiting the typical surface plasmon absorption maxima at 408-410 nm. Transmission electron microscopy (TEM) reveals that the average diameter of silver nanoparticles is about 5.0 ± 1.0 nm and that they have spherical shape. Cell visibility and cell viability percentage show dose-dependent cellular toxicity of Ag NPs. The half maximal inhibitory concentration (IC50) for CHO cells is 68.0 ± 2.65 μg/ml after 24 h Ag NPs exposure. Toxicity evaluations, including cellular morphology, mitochondrial function (MTT assay), reactive oxygen species (ROS), and DNA fragmentation assay (Ladder pattern) were assessed in unexposed CHO cells (control) and the cells exposed to Ag NPs concentrations of 15, 30, and 60 μg/ml for 24 h. The findings may assist in the designing of Ag NPs for various applications and provide insights into their toxicity.

Comparative in vivo assessment of the subacute toxicity of gold and silver nanoparticles

NASA Astrophysics Data System (ADS)

Rathore, Mansee; Mohanty, Ipseeta Ray; Maheswari, Ujjwala; Dayal, Navami; Suman, Rajesh; Joshi, D. S.

2014-04-01

In spite of the projected therapeutic potentials of gold nanoparticles (GNP) and silver nanoparticles (SNP), very limited data are available on the interaction of nanoparticles with the biological systems. The present investigation was designed to evaluate as well as compare the subacute toxicity of GNP and SNP. Stable suspensions of GNP and SNP with mean particle diameter 10 and 25 nm, respectively, were prepared. Wistar rats were orally fed SNP (3 mg/kg) or GNP (20 μg/kg), once a day for 21 days. Biochemical indices (creatinine phosphokinase-MB, urea, blood urea nitrogen, aspartate transaminase, alkaline alanine transferase) and histopathological features of the liver, heart, brain, lungs, and kidney were evaluated for signs of toxicity. A significant decline in hepatic and renal function in the GNP treated group was observed as compared to SNP. GNP was found to be relatively more toxic on the lungs and SNP on the myocardial tissue as compared to SNP and GNP treatments, respectively. Interestingly, neither SNP nor GNP adversely affected the basal architecture of the brain as compared to sham. The present study demonstrated that GNP was significantly more noxious on the liver and kidney as compared with SNP.

Rare-earth Nanoparticle-induced Cytotoxicity on Spatial Cognition Memory of Mouse Brain.

PubMed

Lin, Cai-Hou; Liu, Gui-Fen; Chen, Jing; Chen, Yan; Lin, Ru-Hui; He, Hong-Xing; Chen, Jian-Ping

2017-11-20

Luminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure. Adult ICR mice were randomly divided into seven groups, including control group (receiving 0.9% normal saline) and six experimental groups (10 mice in each group). Luminescent rare-earth-based nanoparticles were synthesized by a reported co-precipitation method. Two different sizes of the nanoparticles were obtained, and then exposed to ICR mice through caudal vein injection at 0.5, 1.0, and 1.5 mg/kg body weight in each day for 7 days. Next, a Morris water maze test was employed to evaluate impaired behaviors of their spatial recognition memory. Finally, histopathological examination was implemented to study how the nanoparticles can affect the brain tissue of the ICR mice. Two different sizes of rare-earth nanoparticles have been successfully obtained, and their physical properties including luminescence spectra and nanoparticle sizes have been characterized. In these experiments, the rare-earth nanoparticles were taken up in the mouse liver using the magnetic resonance imaging characterization. Most importantly, the experimental results of the Morris water maze tests and histopathological analysis clearly showed that rare-earth nanoparticles could induce toxicity on mouse brain and impair the behaviors of spatial recognition memory. Finally, the mechanism of adenosine triphosphate quenching by the rare-earth nanoparticles was provided to illustrate the toxicity on the mouse brain. This study suggested that long-term exposure of high-dose bare rare-earth nanoparticles caused an obvious damage on the spatial recognition memory in the mice.

Enhanced Intratumoral Delivery of SN38 as a Tocopherol Oxyacetate Prodrug Using Nanoparticles in a Neuroblastoma Xenograft Model.

PubMed

Nguyen, Ferro; Alferiev, Ivan; Guan, Peng; Guerrero, David T; Kolla, Venkatadri; Moorthy, Ganesh S; Chorny, Michael; Brodeur, Garrett M

2018-06-01

Purpose: Currently, <50% of high-risk pediatric solid tumors like neuroblastoma can be cured, and many survivors experience serious or life-threatening toxicities, so more effective, less toxic therapy is needed. One approach is to target drugs to tumors using nanoparticles, which take advantage of the enhanced permeability of tumor vasculature. Experimental Design: SN38, the active metabolite of irinotecan (CPT-11), is a potent therapeutic agent that is readily encapsulated in polymeric nanoparticles. Tocopherol oxyacetate (TOA) is a hydrophobic mitocan that was linked to SN38 to significantly increase hydrophobicity and enhance nanoparticle retention. We treated neuroblastomas with SN38-TOA nanoparticles and compared the efficacy with the parent prodrug CPT-11 using a mouse xenograft model. Results: Nanoparticle treatment induced prolonged event-free survival (EFS) in most mice, compared with CPT-11. This was shown for both SH-SY5Y and IMR-32 neuroblastoma xenografts. Enhanced efficacy was likely due to increased and sustained drug levels of SN38 in the tumor compared with conventional CPT-11 delivery. Interestingly, when recurrent CPT-11-treated tumors were re-treated with SN38-TOA nanoparticles, the tumors transformed from undifferentiated neuroblastomas to maturing ganglioneuroblastomas. Furthermore, these tumors were infiltrated with Schwann cells of mouse origin, which may have contributed to the differentiated histology. Conclusions: Nanoparticle delivery of SN38-TOA produced increased drug delivery and prolonged EFS compared to conventional delivery of CPT-11. Also, lower total dose and drug entrapment in nanoparticles during circulation should decrease toxicity. We propose that nanoparticle-based delivery of a rationally designed prodrug is an attractive approach to enhance chemotherapeutic efficacy in pediatric and adult tumors. Clin Cancer Res; 24(11); 2585-93. ©2018 AACR . ©2018 American Association for Cancer Research.

About the Sterilization of Chitosan Hydrogel Nanoparticles

PubMed Central

Galante, Raquel; Rediguieri, Carolina F.; Kikuchi, Irene Satiko; Vasquez, Pablo A. S.; Colaço, Rogério; Pinto, Terezinha J. A.

2016-01-01

In the last years, nanostructured biomaterials have raised a great interest as platforms for delivery of drugs, genes, imaging agents and for tissue engineering applications. In particular, hydrogel nanoparticles (HNP) associate the distinctive features of hydrogels (high water uptake capacity, biocompatibility) with the advantages of being possible to tailor its physicochemical properties at nano-scale to increase solubility, immunocompatibility and cellular uptake. In order to be safe, HNP for biomedical applications, such as injectable or ophthalmic formulations, must be sterile. Literature is very scarce with respect to sterilization effects on nanostructured systems, and even more in what concerns HNP. This work aims to evaluate the effect and effectiveness of different sterilization methods on chitosan (CS) hydrogel nanoparticles. In addition to conventional methods (steam autoclave and gamma irradiation), a recent ozone-based method of sterilization was also tested. A model chitosan-tripolyphosphate (TPP) hydrogel nanoparticles (CS-HNP), with a broad spectrum of possible applications was produced and sterilized in the absence and in the presence of protective sugars (glucose and mannitol). Properties like size, zeta potential, absorbance, morphology, chemical structure and cytotoxicity were evaluated. It was found that the CS-HNP degrade by autoclaving and that sugars have no protective effect. Concerning gamma irradiation, the formation of agglomerates was observed, compromising the suspension stability. However, the nanoparticles resistance increases considerably in the presence of the sugars. Ozone sterilization did not lead to significant physical adverse effects, however, slight toxicity signs were observed, contrarily to gamma irradiation where no detectable changes on cells were found. Ozonation in the presence of sugars avoided cytotoxicity. Nevertheless, some chemical alterations were observed in the nanoparticles. PMID:28002493

Suppressing iron oxide nanoparticle toxicity by vascular targeted antioxidant polymer nanoparticles.

PubMed

Cochran, David B; Wattamwar, Paritosh P; Wydra, Robert; Hilt, J Zach; Anderson, Kimberly W; Eitel, Richard E; Dziubla, Thomas D

2013-12-01

The biomedical use of superparamagnetic iron oxide nanoparticles has been of continued interest in the literature and clinic. Their ability to be used as contrast agents for imaging and/or responsive agents for remote actuation makes them exciting materials for a wide range of clinical applications. Recently, however, concern has arisen regarding the potential health effects of these particles. Iron oxide toxicity has been demonstrated in in vivo and in vitro models, with oxidative stress being implicated as playing a key role in this pathology. One of the key cell types implicated in this injury is the vascular endothelial cells. Here, we report on the development of a targeted polymeric antioxidant, poly(trolox ester), nanoparticle that can suppress oxidative damage. As the polymer undergoes enzymatic hydrolysis, active trolox is locally released, providing a long term protection against pro-oxidant agents. In this work, poly(trolox) nanoparticles are targeted to platelet endothelial cell adhesion molecules (PECAM-1), which are able to bind to and internalize in endothelial cells and provide localized protection against the cytotoxicity caused by iron oxide nanoparticles. These results indicate the potential of using poly(trolox ester) as a means of mitigating iron oxide toxicity, potentially expanding the clinical use and relevance of these exciting systems. Copyright © 2013 Elsevier Ltd. All rights reserved.

Naturally occurring proteinaceous nanoparticles in Coptidis Rhizoma extract act as concentration-dependent carriers that facilitate berberine absorption

PubMed Central

Ma, Bing-Liang; Yin, Chun; Zhang, Bo-Kai; Dai, Yan; Jia, Yi-Qun; Yang, Yan; Li, Qiao; Shi, Rong; Wang, Tian-Ming; Wu, Jia-Sheng; Li, Yuan-Yuan; Lin, Ge; Ma, Yue-Ming

2016-01-01

Pharmacological activities of some natural products diminish and even disappear after purification. In this study, we explored the mechanisms underlying the decrease of acute oral toxicity of Coptidis Rhizoma extract after purification. The water solubility, in vitro absorption, and plasma exposure of berberine (the major active compound) in the Coptidis Rhizoma extract were much better than those of pure berberine. Scanning electron microscopy, laser scanning confocal microscopy (LSCM), and dynamic light scattering experiments confirmed that nanoparticles attached to very fine precipitates existed in the aqueous extract solution. The LSCM experiment showed that the precipitates were absorbed with the particles by the mouse intestine. High-speed centrifugation of the extract could not remove the nanoparticles and did not influence plasma exposure or acute oral toxicity. However, after extract dilution, the attached precipitates vanished, although the nanoparticles were preserved, and there were no differences in the acute oral toxicity and plasma exposure between the extract and pure berberine. The nanoparticles were then purified and identified as proteinaceous. Furthermore, they could absorb co-dissolved berberine. Our results indicate that naturally occurring proteinaceous nanoparticles in Coptidis Rhizoma extract act as concentration-dependent carriers that facilitate berberine absorption. These findings should inspire related studies in other natural products. PMID:26822920

Interaction and cellular uptake of surface-modified carbon dot nanoparticles by J774.1 macrophages

PubMed Central

Thoo, Lester; Fahmi, Mochamad Z; Zulkipli, Ihsan N; Keasberry, Natasha

2017-01-01

Carbon dot (Cdot) nanoparticles are an emerging class of carbon nanomaterials with a promising potential for drug delivery and bio imaging applications. Although the interaction between Cdots and non-immune cell types has been well studied, Cdot interactions with macrophages have not been investigated. Exposure of Cdot nanoparticles to J774.1 cells, a murine macrophage cell line, resulted in minimal toxicity, where notable toxicity was only seen with Cdot concentrations higher than 0.5 mg/ml. Flow cytometric analysis revealed that Cdots prepared from citric acid were internalized at significantly higher levels by macrophages compared with those prepared from bamboo leaves. Interestingly, macrophages preferentially took up phenylboronic acid (PB)-modified nanoparticles. By fluorescence microscopy, strong blue light-specific punctate Cdot fluorescence resembling Cdot structures in the cytosolic space was mostly observed in J774.1 macrophages exposed to PB-modified nanoparticles and not unmodified Cdot nanoparticles. PB binds to sialic acid residues that are overexpressed on diseased cell surfaces. Our findings demonstrate that PB-conjugated Cdots can be taken up by macrophages with low toxicity and high efficiency. These modified Cdots can be used to deliver drugs to suppress or eliminate aberrant immune cells such as macrophages associated with tumors such as tumor-associated macrophages. PMID:29204100

Toxicity, toxicokinetics and biodistribution of dextran stabilized Iron oxide Nanoparticles for biomedical applications.

PubMed

Remya, N S; Syama, S; Sabareeswaran, A; Mohanan, P V

2016-09-10

Advancement in the field of nanoscience and technology has alarmingly raised the call for comprehending the potential health effects caused by deliberate or unintentional exposure to nanoparticles. Iron oxide magnetic nanoparticles have an increasing number of biomedical applications and hence a complete toxicological profile of the nanomaterial is therefore a mandatory requirement prior to its intended usage to ensure safety and to minimize potential health hazards upon its exposure. The present study elucidates the toxicity of in house synthesized Dextran stabilized iron oxide nanoparticles (DINP) in a regulatory perspective through various routes of exposure, its associated molecular, immune, genotoxic, carcinogenic effects and bio distribution profile. Synthesized ferrite nanomaterials were successfully coated with dextran (<25nm) and were physicochemically characterized and subjected to in vitro and in vivo toxicity evaluations. The results suggest that surface coating of ferrite nanoparticles with dextran helps in improvising particle stability in biological environments. The nanoparticles do not seem to induce oxidative stress mediated toxicological effects, nor altered physiological process or behavior changes or visible pathological lesions. Furthermore no anticipated health hazards are likely to be associated with the use of DINP and could be concluded that the synthesized DINP is nontoxic/safe to be used for biomedical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Silver-doped calcium phosphate nanoparticles: synthesis, characterization, and toxic effects toward mammalian and prokaryotic cells.

PubMed

Peetsch, Alexander; Greulich, Christina; Braun, Dieter; Stroetges, Christian; Rehage, Heinz; Siebers, Bettina; Köller, Manfred; Epple, Matthias

2013-02-01

Spherical silver-doped calcium phosphate nanoparticles were synthesized in a co-precipitation route from calcium nitrate/silver nitrate and ammonium phosphate in a continuous process and colloidally stabilized by carboxymethyl cellulose. Nanoparticles with 0.39 wt% silver content and a diameter of about 50-60 nm were obtained. The toxic effects toward mammalian and prokaryotic cells were determined by viability tests and determination of the minimal inhibitory and minimal bactericidal concentrations (MIC and MBC). Three mammalian cells lines, i.e. human mesenchymal stem cells (hMSC) and blood peripheral mononuclear cells (PBMC, monocytes and T-lymphocytes), and two prokaryotic strains, i.e. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were used. Silver-doped calcium phosphate nanoparticles and silver acetate showed similar effect toward mammalian and prokaryotic cells with toxic silver concentrations in the range of 1-3 μg mL(-1). Copyright © 2012 Elsevier B.V. All rights reserved.

Control of Dielectric Constant and Anti-Bacterial Activity of PVA-PEG/x-SnO2 Nanofiber

NASA Astrophysics Data System (ADS)

Diantoro, M.; Sari, L. A.; Istirohah, T.; Kusumawati, A. D.; Nasikhudin; Sunaryono

2018-05-01

Research in the utilization of organic natural materials for electronic devices and for the biological application becoming extensively studied. We report a comprehensive review of the role of SnO2 nanoparticle and the effect of light intensity on toxicity properties, antibacterial activity, microstructure and electrical properties of PVA-PEG nanofiber films. The PVA-PEG/SnO2 nanofiber structure has been successfully fabricated on the ITO-glass substrate. Characterization was performed on samples using FTIR, XRD, SEM, toxicity and antibacterial tests, as well as LCR measurement. The presence of various light intensities has also measured the dielectric constant. The addition of SnO2 nanoparticle influenced the structure of the PVA-PEG/SnO2 nanofiber bonding functional group indicated by the appearance of Sn-O-Sn peaks at 648.08 cm-1 and 958 cm-1 wavenumbers. The addition of SnO2 nanoparticles affects the grain size of SnO2. Addition of SnO2 nanoparticles increases the detected toxicity voltage but is still below the threshold. It means the compound is not toxic, or safe to use in the body. The film lacks the antibacterial power of S. Aurelius. The addition of nanoparticles SnO2 increases the dielectric constant but decreases with increasing frequency of input voltage and the intensity of light employed to PVA-PEG/SnO2 nanofiber. The application of the light intensity reduces the dielectric constant of the PVA-PEG/SnO2 nanofiber in all nanoparticle doping ranges.

Emerging patterns for engineered nanomaterials in the environment: a review of fate and toxicity studies

NASA Astrophysics Data System (ADS)

Garner, Kendra L.; Keller, Arturo A.

2014-08-01

A comprehensive assessment of the environmental risks posed by engineered nanomaterials (ENMs) entering the environment is necessary, due in part to the recent predictions of ENM release quantities and because ENMs have been identified in waste leachate. The technical complexity of measuring ENM fate and transport processes in all environments necessitates identifying trends in ENM processes. Emerging information on the environmental fate and toxicity of many ENMs was collected to provide a better understanding of their environmental implications. Little research has been conducted on the fate of ENMs in the atmosphere; however, most studies indicate that ENMs will in general have limited transport in the atmosphere due to rapid settling. Studies of ENM fate in realistic aquatic media indicates that in general, ENMs are more stable in freshwater and stormwater than in seawater or groundwater, suggesting that transport may be higher in freshwater than in seawater. ENMs in saline waters generally sediment out over the course of hours to days, leading to likely accumulation in sediments. Dissolution is significant for specific ENMs (e.g., Ag, ZnO, copper ENMs, nano zero-valent iron), which can result in their transformation from nanoparticles to ions, but the metal ions pose their own toxicity concerns. In soil, the fate of ENMs is strongly dependent on the size of the ENM aggregates, groundwater chemistry, as well as the pore size and soil particle size. Most groundwater studies have focused on unfavorable deposition conditions, but that is unlikely to be the case in many natural groundwaters with significant ionic strength due to hardness or salinity. While much still needs to be better understood, emerging patterns with regards to ENM fate, transport, and exposure combined with emerging information on toxicity indicate that risk is low for most ENMs, though current exposure estimates compared with current data on toxicity indicates that at current production and release levels, exposure to Ag, nZVI, and ZnO may cause toxicity to freshwater and marine species.

The effect of nanoparticle degradation on amphiphilic polymer-coated quantum dot toxicity: the importance of particle functionality assessment in toxicology [corrected].

PubMed

Soenen, Stefaan J; Montenegro, José-Maria; Abdelmonem, Abuelmagd M; Manshian, Bella B; Doak, Shareen H; Parak, Wolfgang J; De Smedt, Stefaan C; Braeckmans, Kevin

2014-02-01

Colloidal semiconductor nanoparticles (quantum dots) have attracted a lot of interest in technological and biomedical research, given their potent fluorescent properties. However, the use of heavy-metal-containing nanoparticles remains an issue of debate. The possible toxic effects of quantum dots remain a hot research topic and several questions such as possible intracellular degradation of quantum dots and the effect thereof on both cell viability and particle functionality remain unresolved. In the present work, amphiphilic polymer [corrected] coated CdSe/ZnS quantum dots were synthesized and characterized, after which their effects on cultured cells were evaluated using a multiparametric setup. The data reveal that the quantum dots are taken up through endocytosis and when exposed to the low pH of the endosomal structures, they partially degrade and release cadmium ions, which lowers their fluorescence intensity and augments particle toxicity. Using the multiparametric method, the quantum dots were evaluated at non-toxic doses in terms of their ability to visualize labeled cells for longer time periods. The data revealed that comparing different particles in terms of their applied dose is challenging, likely due to difficulties in obtaining accurate nanoparticle concentrations, but evaluating particle toxicity in terms of their biological functionality enables an easy and straightforward comparison. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Gadolinium-Doped Gallic Acid-Zinc/Aluminium-Layered Double Hydroxide/Gold Theranostic Nanoparticles for a Bimodal Magnetic Resonance Imaging and Drug Delivery System.

PubMed

Sani Usman, Muhammad; Hussein, Mohd Zobir; Fakurazi, Sharida; Masarudin, Mas Jaffri; Ahmad Saad, Fathinul Fikri

2017-08-31

We have developed gadolinium-based theranostic nanoparticles for co-delivery of drug and magnetic resonance imaging (MRI) contrast agent using Zn/Al-layered double hydroxide as the nanocarrier platform, a naturally occurring phenolic compound, gallic acid (GA) as therapeutic agent, and Gd(NO₃)₃ as diagnostic agent. Gold nanoparticles (AuNPs) were grown on the system to support the contrast for MRI imaging. The nanoparticles were characterized using techniques such as Hi-TEM, XRD, ICP-ES. Kinetic release study of the GA from the nanoparticles showed about 70% of GA was released over a period of 72 h. The in vitro cell viability test for the nanoparticles showed relatively low toxicity to human cell lines (3T3) and improved toxicity on cancerous cell lines (HepG2). A preliminary contrast property test of the nanoparticles, tested on a 3 Tesla MRI machine at various concentrations of GAGZAu and water (as a reference) indicates that the nanoparticles have a promising dual diagnostic and therapeutic features to further develop a better future for clinical remedy for cancer treatment.

Role of nanomaterial physicochemical properties on fate and toxicity in bacteria and plants

NASA Astrophysics Data System (ADS)

Slomberg, Danielle

Nanomaterials, defined as those having at least one dimension <100 nm, are ubiquitous in nature. However, engineered nanomaterials have gained increasing attention for use in drug-delivery applications and consumer goods. Examination of nanomaterial toxicity, both beneficial (e.g., drug delivery to bacterial pathogens) and detrimental (e.g., death of terrestrial plants), thus warranted. Herein, I present the evaluation of nitric oxide-releasing nanomaterial toxicity to bacteria and silica particle toxicity to plants as a function of nanomaterial physicochemical properties. Nanomaterial toxicity toward planktonic (i.e., free-floating) Pseudomonas aeruginosa and Staphylococcus aureus bacteria was evaluated as a function of scaffold size, shape, and exterior functionality using nitric oxide-releasing (NO) silica particles, dendrimers, and chitosan oligosaccharides. Improved bactericidal efficacy was observed for silica particles with decreased size and increased aspect ratio (i.e., rod-like) due to improved particle-cell interactions. Likewise, better nanomaterial-bacteria association and biocidal action was noted for more hydrophobic NO-releasing dendrimers and chitosan oligosaccharides. Planktonic bacterial killing was not dependent on chitosan molecular weight due to rapid association between the cationic scaffolds and negatively-charged bacterial cell membranes. Given the importance of nanomaterial physicochemical properties in planktonic bacterial killing, the NO-releasing scaffolds were also evaluated against clinically-relevant bacterial biofilms. Similar to planktonic studies, smaller particle sizes proved more efficient in delivering NO throughout the biofilm. Particles with rod-like shape also eradicated biofilms more effectively. The role of NO-releasing dendrimer and chitosan oligosaccharide hydrophobicity was prominent in scaffold diffusion through the biofilm and subsequent NO delivery, with hydrophobic functionalities generally exhibiting better bacterial association. Lastly, biofilm eradication was more effective for NO-releasing dendrimers exhibiting sustained NO-release compared to delivery of NO via an intial burst. Phytotoxicity and uptake of silica nanoparticles was evaluated for the plant, Arabidopsis thaliana, as a function of particle size, surface composition, and shape (i.e., spherical versus rod-like particles). Overall, the silica nanoparticles examined were found to be relatively non-toxic to A. thaliana plants when pH effects were mitigated. Size-dependent uptake of the silica particles was observed; however no shape-dependent uptake was noted at the low exposure concentration examined.

Synthesis, characterization and toxicological evaluation of maltodextrin capped cadmium sulfide nanoparticles in human cell lines and chicken embryos

PubMed Central

2012-01-01

Background Semiconductor Quantum dots (QDs) have become quite popular thanks to their properties and wide use in biological and biomedical studies. However, these same properties entail new challenges in understanding, predicting, and managing potential adverse health effects following exposure. Cadmium and selenium, which are the major components of the majority of quantum dots, are known to be acutely and chronically toxic to cells and organisms. Protecting the core of nanoparticles can, to some degree, control the toxicity related to cadmium and selenium leakage. Results This study successfully synthesized and characterized maltodextrin coated cadmium sulfide semiconductor nanoparticles. The results show that CdS-MD nanoparticles are cytotoxic and embryotoxic. CdS-MD nanoparticles in low concentrations (4.92 and 6.56 nM) lightly increased the number of HepG2 cell. A reduction in MDA-MB-231 cells was observed with concentrations higher than 4.92 nM in a dose response manner, while Caco-2 cells showed an important increase starting at 1.64 nM. CdS-MD nanoparticles induced cell death by apoptosis and necrosis in MDA-MD-231 cells starting at 8.20 nM concentrations in a dose response manner. The exposure of these cells to 11.48-14.76 nM of CdS-MD nanoparticles induced ROS production. The analysis of cell proliferation in MDA-MB-231 showed different effects. Low concentrations (1.64 nM) increased cell proliferation (6%) at 7 days (p < 0.05). However, higher concentrations (>4.92 nM) increased cell proliferation in a dose response manner (15-30%) at 7 days. Exposures of chicken embryos to CdS-MD nanoparticles resulted in a dose-dependent increase in anomalies that, starting at 9.84 nM, centered on the heart, central nervous system, placodes, neural tube and somites. No toxic alterations were observed with concentrations of < 3.28 nM, neither in cells nor chicken embryos. Conclusions Our results indicate that CdS-MD nanoparticles induce cell death and alter cell proliferation in human cell lines at concentrations higher than 4.92 nM. We also demonstrated that they are embryotoxic. However, no toxic effects were observed with doses lower than 3.28 nM in neither cells nor chicken embryos. The CdS-MD nanoparticles used in this study can be potentially used in bio-imaging applications. However, further studies using mammalian species are required in order to discard more toxic effects. PMID:23270407

Effect of capping agents on the cytotoxicity of silver nanoparticles in human normal and cancer skin cell lines

NASA Astrophysics Data System (ADS)

Netchareonsirisuk, Ponsawan; Puthong, Songchan; Dubas, Stephan; Palaga, Tanapat; Komolpis, Kittinan

2016-11-01

Silver nanoparticles (AgNPs) are among the most widely used nanomaterials in medical and consumer products. However, safety in the uses of AgNPs is still controversial. The toxicity of AgNPs toward various cell types has been reported to depend on the surface properties of the nanoparticles. In this study, the effect of AgNPs with the average size of 5-15 nm on the viability of the CCD-986SK human normal skin fibroblast cell line and A375 human malignant melanoma cell line was evaluated. Comparative toxicity studies, based on MTT assay, were performed by using either sodium alginate or poly (4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSMA) as capping agent in the nanoparticle preparation. The cytotoxicity tests revealed that AgNO3 alone was highly toxic to both cell types while both alginate and PSSMA alone were not toxic. AgNPs capped with alginate were selectively toxic to the cancer cell line but not to the normal cell line while AgNPs capped with PSSMA were toxic to both cancer and normal cell lines. Judging from the 50 % inhibition concentration (IC50), it was found that the cancer cell line was more sensitive to AgNPs than the normal cell line. Study on the mode of cell death by annexin V and propidium iodide staining revealed that AgNPs induced more apoptotic cell death (84-90 %) than necrosis (8-12 %) in the skin cancer cell line. These results suggest that the toxicity of AgNPs depended on the type of capping agent and the type of cell line.

SiC nanoparticles cyto- and genotoxicity to Hep-G2 cells

NASA Astrophysics Data System (ADS)

Barillet, Sabrina; Jugan, Mary-Line; Simon-Deckers, Angélique; Leconte, Yann; Herlin-Boime, Nathalie; Mayne-l'Hermite, Martine; Reynaud, Cécile; Carrière, Marie

2009-05-01

While emerging nanotechnologies have seen significant development in recent years, knowledge on exposure levels as well as data on toxicity of nanoparticles are still quite limited. Indeed, there is a general agreement that development of nanotechnologies may lead to considerable dissemination of nanoparticles in the environment. Nevertheless, questions relative to toxicity versus innocuousness of such materials still remain. Our present study has thus been carried out with the purpose of assessing some aspects of toxicological capacities of three kinds of nano-sized particles: TiO2 and SiC nanoparticles, as well as multi-walled carbon nanotubes (CNT). In order to address the question of their potential toxicity toward living cells, we chose several cellular models. Assuming inhalation as the most probable exposure scenario, we used A549 alveolar epithelial cells as a model for mammalian primary target organ (lung). Furthermore, we considered that nanoparticles that would deposit into the pulmonary system may be translocated to the circulatory system. Thus, we decided to study the effect of nanoparticles on potentially secondary target organs: liver (WIF-B9, Can-10, HepG2) and kidneys (NRK-52E, LLC-PK1). Herein, we will focus our attention on results obtained on the HepG2 cell line exposed to SiC nanoparticles. Scarce literature exists on SiC nanotoxicology. According to the authors that have already carried out studies on this particular nanoparticle, it would seem that SiC nanoparticles do not induce cytotoxicity. That is one of the reasons of the potential use of these nanoparticles as biological labels [1]. We thus were interested in acquiring more data on biological effects induced by SiC nanoparticles. Furthermore, one of the particular aspects of the present study lies in the fact that we tried to specify the influence of physico-chemical characteristics of nanoparticles on toxicological endpoints (cytotoxicity and genotoxicity).

Chronic TiO2 nanoparticle exposure to a benthic organism, Hyalella azteca: Impact of solar UV radiation and material surface coatings on toxicity

EPA Science Inventory

The present study examined the chronic toxicity of TiO2 nanoparticles (nano-TiO2) to a representative benthic species, Hyalella azteca, using an industry standard, P25, and a coated nano-TiO2 used in commercial products. There is limited information on the chronic effects of nano...

Shape-Related Toxicity of Titanium Dioxide Nanofibres

PubMed Central

Allegri, Manfredi; Bianchi, Massimiliano G.; Chiu, Martina; Varet, Julia; Costa, Anna L.; Ortelli, Simona; Blosi, Magda; Bussolati, Ovidio; Poland, Craig A.; Bergamaschi, Enrico

2016-01-01

Titanium dioxide (TiO2) nanofibres are a novel fibrous nanomaterial with increasing applications in a variety of fields. While the biological effects of TiO2 nanoparticles have been extensively studied, the toxicological characterization of TiO2 nanofibres is far from being complete. In this study, we evaluated the toxicity of commercially available anatase TiO2 nanofibres using TiO2 nanoparticles (NP) and crocidolite asbestos as non-fibrous or fibrous benchmark materials. The evaluated endpoints were cell viability, haemolysis, macrophage activation, trans-epithelial electrical resistance (an indicator of the epithelial barrier competence), ROS production and oxidative stress as well as the morphology of exposed cells. The results showed that TiO2 nanofibres caused a cell-specific, dose-dependent decrease of cell viability, with larger effects on alveolar epithelial cells than on macrophages. The observed effects were comparable to those of crocidolite, while TiO2 NP did not decrease cell viability. TiO2 nanofibres were also found endowed with a marked haemolytic activity, at levels significantly higher than those observed with TiO2 nanoparticles or crocidolite. Moreover, TiO2 nanofibres and crocidolite, but not TiO2 nanoparticles, caused a significant decrease of the trans-epithelial electrical resistance of airway cell monolayers. SEM images demonstrated that the interaction with nanofibres and crocidolite caused cell shape perturbation with the longest fibres incompletely or not phagocytosed. The expression of several pro-inflammatory markers, such as NO production and the induction of Nos2 and Ptgs2, was significantly increased by TiO2 nanofibres, as well as by TiO2 nanoparticles and crocidolite. This study indicates that TiO2 nanofibres had significant toxic effects and, for most endpoints with the exception of pro-inflammatory changes, are more bio-active than TiO2 nanoparticles, showing the relevance of shape in determining the toxicity of nanomaterials. Given that several toxic effects of TiO2 nanofibres appear comparable to those observed with crocidolite, the possibility that they exert length dependent toxicity in vivo seems worthy of further investigation. PMID:26999274

A novel near-infrared nanomaterial with high quantum efficiency and its applications in real time in vivo imaging

NASA Astrophysics Data System (ADS)

Cui, X. X.; Fan, Q.; Shi, S. J.; Wen, W. H.; Chen, D. F.; Guo, H. T.; Xu, Y. T.; Gao, F.; Nie, R. Z.; Ford, Harold D.; Tang, Gordon H.; Hou, C. Q.; Peng, B.

2018-05-01

Fluorescence imaging signal is severely limited by the quantum efficiency and emission wavelength. To overcome these challenges, novel NIR-emitting K5NdLi2F10 nanoparticles under NIR excitation was introduced as fluorescence imaging probe for the first time. The photostability of K5NdLi2F10 nanoparticles in the water, phosphate buffer saline, fetal bovine serum and living mice was investigated. The fluorescence signal was detected with depths of 3.5 and 2.0 cm in phantom and pork tissue, respectively. Fluorescence spectrum with a significant signal-to-background ratio of 10:1 was captured in living mice. Moreover, clear NIR images were virtualized for the living mice after intravenous injection. The imaging ability of nanoparticles in tumor-beard mice were evaluated, the enrichment of K5NdLi2F10 nanoparticles in tumor site due to the enhanced permeability and retention effect was confirmed. The systematic studies of toxicity, bio-distribution and in-vivo dynamic imaging suggest that these materials give high biocompatibility and low toxicity. These NIR-emitting nanoparticles with high quantum efficiency, high penetration and low toxicity might facilitate tumor identification in deep tissues more sensitively.

Cytotoxicity evaluation of gold nanoparticles on microalga Dunaliella salina in microplate test system

NASA Astrophysics Data System (ADS)

Chumakov, Daniil; Prilepskii, Artur; Dykman, Lev; Khlebtsov, Boris; Khlebtsov, Nikolai; Bogatyrev, Vladimir

2018-04-01

Gold nanoparticles are intensively studied in biomedicine. Assessment of their biocompatibility is highly important. Currently there is lack of evidence, concerning nanotoxicity of ultrasmall gold nanoparticles < 5 nm. Existing data are rather contradictory. The aim of that study was to evaluate the toxicity of 2 nm colloidal gold, using microalga Dunaliella salina. Cellular barriers of that microalga are very similar to animal cells so it might be considered as a valuable model for nanotoxicity testing. Chlorophyll content as a test-function was used. Spectrophotometric method for chlorophyll determination in vivo in suspensions of D.salina cultures was applied. Calculated EC50 48h value of ionic gold was 25.8 +/- 0.3 mg Au/L. EC50 value of phosphine-stabilized gold nanoclusters was 32.2 +/-1.1 mg Au/L. It was not possible to calculate EC50 for 15 nm citrate gold nanoparticles, as they were non-toxic at all concentrations tested. These results are confirmed by fluorescent -microscopic monitoring of the same probes. It was shown that 10-fold growth of phosphine-stabilized gold nanoparticles (from 2.3 +/- 0.9 nm to 21.1 +/- 7.5 nm) led to 7-fold decrease of their toxicity.

A novel near-infrared nanomaterial with high quantum efficiency and its applications in real time in vivo imaging.

PubMed

Cui, X X; Fan, Q; Shi, S J; Wen, W H; Chen, D F; Guo, H T; Xu, Y T; Gao, F; Nie, R Z; Ford, Harold D; Tang, Gordon H; Hou, C Q; Peng, B

2018-05-18

Fluorescence imaging signal is severely limited by the quantum efficiency and emission wavelength. To overcome these challenges, novel NIR-emitting K 5 NdLi 2 F 10 nanoparticles under NIR excitation was introduced as fluorescence imaging probe for the first time. The photostability of K 5 NdLi 2 F 10 nanoparticles in the water, phosphate buffer saline, fetal bovine serum and living mice was investigated. The fluorescence signal was detected with depths of 3.5 and 2.0 cm in phantom and pork tissue, respectively. Fluorescence spectrum with a significant signal-to-background ratio of 10:1 was captured in living mice. Moreover, clear NIR images were virtualized for the living mice after intravenous injection. The imaging ability of nanoparticles in tumor-beard mice were evaluated, the enrichment of K 5 NdLi 2 F 10 nanoparticles in tumor site due to the enhanced permeability and retention effect was confirmed. The systematic studies of toxicity, bio-distribution and in-vivo dynamic imaging suggest that these materials give high biocompatibility and low toxicity. These NIR-emitting nanoparticles with high quantum efficiency, high penetration and low toxicity might facilitate tumor identification in deep tissues more sensitively.

Decreased Phototoxic Effects of TiO₂ Nanoparticles in Consortium of Bacterial Isolates from Domestic Waste Water

PubMed Central

Mathur, Ankita; Kumari, Jyoti; Parashar, Abhinav; T., Lavanya; Chandrasekaran, N.; Mukherjee, Amitava

2015-01-01

This study is aimed to explore the toxicity of TiO2 nanoparticles at low concentrations (0.25, 0.50 & 1.00 μg/ml); on five bacterial isolates and their consortium in waste water medium both in dark and UVA conditions. To critically examine the toxic effects of nanoparticles and the response mechanism(s) offered by microbes, several aspects were monitored viz. cell viability, ROS generation, SOD activity, membrane permeability, EPS release and biofilm formation. A dose and time dependent loss in viability was observed for treated isolates and the consortium. At the highest dose, after 24h, oxidative stress was examined which conclusively showed more ROS generation & cell permeability and less SOD activity in single isolates as compared to the consortium. As a defense mechanism, EPS release was enhanced in case of the consortium against the single isolates, and was observed to be dose dependent. Similar results were noticed for biofilm formation, which substantially increased at highest dose of nanoparticle exposure. Concluding, the consortium showed more resistance against the toxic effects of the TiO2 nanoparticles compared to the individual isolates. PMID:26496250

An approach for environmental risk assessment of engineered nanomaterials using Analytical Hierarchy Process (AHP) and fuzzy inference rules.

PubMed

Topuz, Emel; van Gestel, Cornelis A M

2016-01-01

The usage of Engineered Nanoparticles (ENPs) in consumer products is relatively new and there is a need to conduct environmental risk assessment (ERA) to evaluate their impacts on the environment. However, alternative approaches are required for ERA of ENPs because of the huge gap in data and knowledge compared to conventional pollutants and their unique properties that make it difficult to apply existing approaches. This study aims to propose an ERA approach for ENPs by integrating Analytical Hierarchy Process (AHP) and fuzzy inference models which provide a systematic evaluation of risk factors and reducing uncertainty about the data and information, respectively. Risk is assumed to be the combination of occurrence likelihood, exposure potential and toxic effects in the environment. A hierarchy was established to evaluate the sub factors of these components. Evaluation was made with fuzzy numbers to reduce uncertainty and incorporate the expert judgements. Overall score of each component was combined with fuzzy inference rules by using expert judgements. Proposed approach reports the risk class and its membership degree such as Minor (0.7). Therefore, results are precise and helpful to determine the risk management strategies. Moreover, priority weights calculated by comparing the risk factors based on their importance for the risk enable users to understand which factor is effective on the risk. Proposed approach was applied for Ag (two nanoparticles with different coating) and TiO2 nanoparticles for different case studies. Results verified the proposed benefits of the approach. Copyright © 2016 Elsevier Ltd. All rights reserved.

Excess titanium dioxide nanoparticles on the cell surface induce cytotoxicity by hindering ion exchange and disrupting exocytosis processes.

PubMed

Wang, Yanli; Yao, Chenjie; Li, Chenchen; Ding, Lin; Liu, Jian; Dong, Peng; Fang, Haiping; Lei, Zhendong; Shi, Guosheng; Wu, Minghong

2015-08-14

To date, considerable effort has been devoted to determine the potential toxicity of nanoparticles to cells and organisms. However, determining the mechanism of cytotoxicity induced by different types of nanoparticles remains challenging. Herein, typically low toxicity nanomaterials were used as a model to investigate the mechanism of cytotoxicity induced by low toxicity nanomaterials. We studied the effect of nano-TiO2, nano-Al2O3 and nano-SiO2 deposition films on the ion concentration on a cell-free system simulating the cell membrane. The results showed that the ion concentration of K(+), Ca(2+), Na(+), Mg(2+) and SO4(2-) decreased significantly following filtration of the prepared deposition films. More specifically, at a high nano-TiO2 concentration (200 mg L(-1)) and a long nano-TiO2 deposition time (48 h), the concentration of Na(+) decreased from 2958.01 to 2775.72, 2749.86, 2757.36, and 2719.82 mg L(-1), respectively, for the four types of nano-TiO2 studied. Likewise, the concentration of SO4(2-) decreased from 38.83 to 35.00, 35.80, 35.40, and 35.27 mg L(-1), respectively. The other two kinds of typical low toxicity nanomaterials (nano-Al2O3 and nano-SiO2) have a similar impact on the ion concentration change trend. Adsorption of ions on nanoparticles and the hydrated shell around the ions strongly hindered the ions through the nanoparticle films. The endocytosed nanoparticles could be released from the cells without inducing cytotoxicity. Hindering the ion exchange and disrupting the exocytosis process are the main factors that induce cytotoxicity in the presence of excess nano-TiO2 on the cell surface. The current findings may offer a universal principle for understanding the mechanism of cytotoxicity induced by low toxicity nanomaterials.

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer.

PubMed

Carneiro, Marcella Lemos Brettas; Peixoto, Raphael C A; Joanitti, Graziela A; Oliveira, Ricardo G S; Telles, Luis A M; Miranda-Vilela, Ana L; Bocca, Anamélia L; Vianna, Leonora M S; da Silva, Izabel C R; de Souza, Aparecido R; Lacava, Zulmira G M; Báo, Sônia N

2013-02-16

Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Mice were evaluated with regard to the treatments' toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Regarding the treatments' toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications.

PEGylation of zinc nanoparticles amplifies their ability to enhance olfactory responses to odorant

PubMed Central

Singletary, Melissa; Hagerty, Samantha; Muramoto, Shin; Daniels, Yasmine; MacCrehan, William A.; Stan, Gheorghe; Lau, June W.; Pustovyy, Oleg; Globa, Ludmila; Morrison, Edward E.; Sorokulova, Iryna

2017-01-01

Olfactory responses are intensely enhanced with the addition of endogenous and engineered primarily-elemental small zinc nanoparticles (NPs). With aging, oxidation of these Zn nanoparticles eliminated the observed enhancement. The design of a polyethylene glycol coating to meet storage requirements of engineered zinc nanoparticles is evaluated to achieve maximal olfactory benefit. The zinc nanoparticles were covered with 1000 g/mol or 400 g/mol molecular weight polyethylene glycol (PEG). Non-PEGylated and PEGylated zinc nanoparticles were tested by electroolfactogram with isolated rat olfactory epithelium and odorant responses evoked by the mixture of eugenol, ethyl butyrate and (±) carvone after storage at 278 K (5 oC), 303 K (30 oC) and 323 K (50 oC). The particles were analyzed by atomic force microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and laser Doppler velocimetry. Our data indicate that stored ZnPEG400 nanoparticles maintain physiologically-consistent olfactory enhancement for over 300 days. These engineered Nanoparticles support future applications in olfactory research, sensitive detection, and medicine. PMID:29261701

Development of molecular indicators to track the effects of nanoparticle toxicity in Arabidopsis thaliana

EPA Science Inventory

The emergence of nanotechnology and incorporation of nanoparticles in consumer products necessitates risk assessment from an environmental and health safety standpoint. To date, very few studies have examined nanoparticle effects on terrestrial species, especially plants. Pre...

Integration of micro nano and bio technologies with layer-by-layer self-assembly

NASA Astrophysics Data System (ADS)

Kommireddy, Dinesh Shankar

In the past decade, layer-by-layer (LbL) nanoassembly has been used as a tool for immobilization and surface modification of materials with applications in biology and physical sciences. Often, in such applications, LbL assembly is integrated with various techniques to form functional surface coatings and immobilized matrices. In this work, integration of LbL with microfabrication and microfluidics, and tissue engineering are explored. In an effort to integrate microfabrication with LbL nanoassembly, microchannels were fabricated using soft-lithography and the surface of these channels was used for the immobilization of materials using LbL and laminar flow patterning. Synthesis of poly(dimethyldiallyl ammonium chloride)/poly(styrene sulfonate) and poly(dimethyldiallyl ammonium chloride)/bovine serum albumin microstrips is demonstrated with the laminar flow microfluidic reactor. Resulting micropatterns are 8-10 mum wide, separated with few micron gaps. The width of these microstrips as well as their position in the microchannel is controlled by varying the flow rate, time of interaction and concentration of the individual components, which is verified by numerical simulation. Spatially resolved pH sensitivity was observed by modifying the surface of the channel with a pH sensitive dye. In order to investigate the integration of LbL assembly with tissue engineering, glass substrates were coated with nanoparticle/polyelectrolyte layers, and two different cell types were used to test the applicability of these coatings for the surface modification of medical implants. Titanium dioxide (TiO 2), silicon dioxide, halloysite and montmorillonite nanoparticles were assembled with oppositely charged polyelectrolytes. In-vitro cytotoxicity tests of the nanoparticle substrates on human dermal firbroblasts (HDFs) showed that the nanoparticle surfaces do not have toxic effects on the cells. HDFs retained their phenotype on the nanoparticle coatings, by synthesizing type-I collagen. These cells also showed active proliferation on the nanoparticle substrates. Cells attached on TiO2 substrates showed faster rate of spreading compared with the other types of nanoparticle coatings. Mesenchymal stem cells (MSCs) were used as a second cell type to support and elaborate on the results obtained with the HDFs. Increasing surface roughness was observed with increasing number of layers of TiO2. Tests with a higher number of layers of TiO2, showed an increased attachment, proliferation and faster spreading of the MSCs on a larger number of layers of TiO2.

Nanotechnology meets 3D in vitro models: tissue engineered tumors and cancer therapies.

PubMed

da Rocha, E L; Porto, L M; Rambo, C R

2014-01-01

Advances in nanotechnology are providing to medicine a new dimension. Multifunctional nanomaterials with diagnostics and treatment modalities integrated in one nanoparticle or in cooperative nanosystems are promoting new insights to cancer treatment and diagnosis. The recent convergence between tissue engineering and cancer is gradually moving towards the development of 3D disease models that more closely resemble in vivo characteristics of tumors. However, the current nanomaterials based therapies are accomplished mainly in 2D cell cultures or in complex in vivo models. The development of new platforms to evaluate nano-based therapies in parallel with possible toxic effects will allow the design of nanomaterials for biomedical applications prior to in vivo studies. Therefore, this review focuses on how 3D in vitro models can be applied to study tumor biology, nanotoxicology and to evaluate nanomaterial based therapies. © 2013.

An occupational exposure assessment for engineered nanoparticles used in semiconductor fabrication.

PubMed

Shepard, Michele Noble; Brenner, Sara

2014-03-01

Engineered nanoparticles of alumina, amorphous silica, and ceria are used in semiconductor device fabrication during wafer polishing steps referred to as 'chemical mechanical planarization' (CMP). Some metal oxide nanoparticles can impact the biological response of cells and organ systems and may cause adverse health effects; additional research is necessary to better understand potential risks from nanomaterial applications and occupational exposure scenarios. This study was conducted to assess potential airborne exposures to nanoparticles and agglomerates using direct-reading instruments and filter-based samples to characterize workplace aerosols by particle number, mass, size, composition, and morphology. Sampling was repeated for tasks in three work areas (fab, subfab, wastewater treatment) at a facility using engineered nanoparticles for CMP. Real-time measurements were collected using a condensation particle counter (CPC), optical particle counter, and scanning mobility particle spectrometer (SMPS). Filter-based samples were analyzed for total mass or the respirable fraction, and for specific metals of interest. Additional air sample filters were analyzed by transmission electron microscopy with energy dispersive x-ray spectroscopy (TEM/EDX) for elemental identification and to provide data on particle size, morphology, and concentration. Peak concentrations measured on the CPC ranged from 1 to 16 particles per cubic centimeter (P cm(-3)) for background and from 4 to 74 P cm(-3) during tasks sampled in the fab; from 1 to 60 P cm(-3) for background and from 3 to 84 P cm(-3) for tasks sampled in the subfab; and from 1160 to 45 894 P cm(-3) for background and from 1710 to 45 519 P cm(-3) during wastewater treatment system filter change tasks. Significant variability was seen among the repeated task measurements and among background comparisons in each area. Several data analysis methods were used to compare each set of task and background measurements. Increased concentrations of respirable particles were identified for some tasks sampled in each work area, although of relatively low magnitude and inconsistently among repeated measurements for specific tasks. Measurements with a portable SMPS indicated that nanoparticle number concentrations (channels 11.5-115.5nm) increased above background levels by 3.2 P cm(-3) during CMP tool set-up in the fab area but were not elevated when changing filters for the CMP wastewater treatment system. All results from mass concentration analysis were below the limits of detection. Characterization by TEM/EDX identified structures containing the elements of interest (Al, Si), primarily as agglomerates or aggregates in the 100-1000nm size range. Although health-based occupational exposure limits have not been established for nanoscale alumina, silica, or ceria, the measured concentrations by number and mass were below currently proposed benchmarks or reference values for poorly soluble low-toxicity nanoparticles.

Peptide-MHC-based nanomedicines for autoimmunity function as T-cell receptor microclustering devices

NASA Astrophysics Data System (ADS)

Singha, Santiswarup; Shao, Kun; Yang, Yang; Clemente-Casares, Xavier; Solé, Patricia; Clemente, Antonio; Blanco, Jesús; Dai, Qin; Song, Fayi; Liu, Shang Wan; Yamanouchi, Jun; Umeshappa, Channakeshava Sokke; Nanjundappa, Roopa Hebbandi; Detampel, Pascal; Amrein, Matthias; Fandos, César; Tanguay, Robert; Newbigging, Susan; Serra, Pau; Khadra, Anmar; Chan, Warren C. W.; Santamaria, Pere

2017-07-01

We have shown that nanoparticles (NPs) can be used as ligand-multimerization platforms to activate specific cellular receptors in vivo. Nanoparticles coated with autoimmune disease-relevant peptide-major histocompatibility complexes (pMHC) blunted autoimmune responses by triggering the differentiation and expansion of antigen-specific regulatory T cells in vivo. Here, we define the engineering principles impacting biological activity, detail a synthesis process yielding safe and stable compounds, and visualize how these nanomedicines interact with cognate T cells. We find that the triggering properties of pMHC-NPs are a function of pMHC intermolecular distance and involve the sustained assembly of large antigen receptor microclusters on murine and human cognate T cells. These compounds show no off-target toxicity in zebrafish embryos, do not cause haematological, biochemical or histological abnormalities, and are rapidly captured by phagocytes or processed by the hepatobiliary system. This work lays the groundwork for the design of ligand-based NP formulations to re-program in vivo cellular responses using nanotechnology.

Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides:

NASA Astrophysics Data System (ADS)

Chen, Junping; Patil, Swanand; Seal, Sudipta; McGinnis, James F.

2006-11-01

Photoreceptor cells are incessantly bombarded with photons of light, which, along with the cells' high rate of oxygen metabolism, continuously exposes them to elevated levels of toxic reactive oxygen intermediates (ROIs). Vacancy-engineered mixed-valence-state cerium oxide nanoparticles (nanoceria particles) scavenge ROIs. Our data show that nanoceria particles prevent increases in the intracellular concentrations of ROIs in primary cell cultures of rat retina and, in vivo, prevent loss of vision due to light-induced degeneration of photoreceptor cells. These data indicate that the nanoceria particles may be effective in inhibiting the progression of ROI-induced cell death, which is thought to be involved in macular degeneration, retinitis pigmentosa and other blinding diseases, as well as the ROI-induced death of other cell types in diabetes, Alzheimer's disease, atherosclerosis, stroke and so on. The use of nanoceria particles as a direct therapy for multiple diseases represents a novel strategy and suggests that they may represent a unique platform technology.

Multicomponent polymeric nanoparticles enhancing intracellular drug release in cancer cells.

PubMed

Ahmed, Arsalan; Liu, Sen; Pan, Yutong; Yuan, Shanmei; He, Jian; Hu, Yong

2014-12-10

Three kinds of amphiphilic copolymer, that is, poly(ε-caprolactone)-SS-poly(ethylene glycol) (PCL-SS-PEG), poly(ε-caprolactone)-polyethylenimine (PCL-PEI), and poly(ε-caprolactone)-polyethylenimine-folate (PCL-PEI-Fol) were synthesized and self-assembled into surface engineered hybrid nanoparticles (NPs). Morphological studies elucidated the stable, spherical, and uniform sandwich structure of the NPs. PCL-PEI and PCL-SS-PEG segments have introduced pH and reduction responsive characteristics in these NPs, while PCL-PEI-FA copolymers could provide specific targeting capability to cancer cells. The stimuli responsive capabilities of these NPs were carried out. Negative-to-positive charge reversible property, in response to the pH change, was investigated by zeta potential and nuclear magnetic resonance (NMR) measurements. The structure cleavage, due to redox gradient, was studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM). These NPs showed controlled degradation, better drug release, less toxicity, and effective uptake in MCF-7 breast cancer cells. These multifunctional NPs showed promising potential in the treatment of cancer.

Biofabrication of morphology improved cadmium sulfide nanoparticles using Shewanella oneidensis bacterial cells and ionic liquid: For toxicity against brain cancer cell lines.

PubMed

Wang, Li; Chen, Siyuan; Ding, Yiming; Zhu, Qiang; Zhang, Nijia; Yu, Shuqing

2018-01-01

The present work determines the anticancer activity of bio-mediated synthesized cadmium sulfide nanoparticles using the ionic liquid and bacterial cells (Shewanella oneidensis). Bacterial cells have been exposed to be important resources that hold huge potential as ecofriendly, cost-effective, evading toxic of dangerous chemicals and the alternative of conventional physiochemical synthesis. The Shewanella oneidensis is an important kind of metal reducing bacterium, known as its special anaerobic respiratory and sulfate reducing capacity. The crystalline nature, phase purity and surface morphology of biosynthesized cadmium sulfide nanoparticles were analyzed by Fourier transform infrared spectroscopy, X-ray diffraction, Field emission scanning electron microscopy, Energy dispersive spectroscopy and Transmission electron microscopy. The use of imidazolium based ionic liquids as soft templating agent for controlling self-assembly and crystal growth direction of metal sulfide nanoparticles has also advanced as an important method. The microscopic techniques showed that the nanoparticles are designed on the nano form and have an excellent spherical morphology, due to the self-assembled mechanism of ionic liquid assistance. The antitumor efficiency of the cadmium sulfide nanoparticles was investigated against brain cancer cell lines using rat glioma cell lines. The effectively improved nano-crystalline and morphological structure of CdS nanoparticles in the presence of IL exhibit excellent cytotoxicity and dispersion ability on the cell shape is completely spread out showing a nice toxic environment against cancer cells. The cytotoxicity effect of cadmium sulfide nanoparticles was discussed with a diagrammatic representation. Copyright © 2017. Published by Elsevier B.V.

Silica-coated manganite and Mn-based ferrite nanoparticles: a comparative study focused on cytotoxicity

NASA Astrophysics Data System (ADS)

Kaman, Ondřej; Dědourková, Tereza; Koktan, Jakub; Kuličková, Jarmila; Maryško, Miroslav; Veverka, Pavel; Havelek, Radim; Královec, Karel; Turnovcová, Karolína; Jendelová, Pavla; Schröfel, Adam; Svoboda, Ladislav

2016-04-01

Magnetic oxide nanoparticles provide a fascinating tool for biological research and medicine, serving as contrast agents, magnetic carriers, and core materials of theranostic systems. Although the applications rely mostly on iron oxides, more complex oxides such as perovskite manganites may provide a much better magnetic performance. To assess the risk of their potential use, in vitro toxicity of manganite nanoparticles was thoroughly analysed and compared with another prospective system of Mn-Zn ferrite nanoparticles. Magnetic nanoparticles of La0.63Sr0.37MnO3 manganite were prepared by two distinct methods, namely the molten salt synthesis and the traditional sol-gel route, whereas nanoparticles of Mn0.61Zn0.42Fe1.97O4 ferrite, selected as a comparative material, were synthesized by a new procedure under hydrothermal conditions. Magnetic cores were coated with silica and, moreover, several samples of manganite nanoparticles with different thicknesses of silica shell were prepared. The size-fractionated and purified products were analysed using transmission electron microscopy, dynamic light scattering, measurement of the zeta-potential dependence on pH, IR spectroscopy, and SQUID magnetometry. The silica-coated products with accurately determined concentration by atomic absorption spectroscopy were subjected to a robust evaluation of their cytotoxicity by four different methods, including detailed analysis of the concentration dependence of toxicity, analysis of apoptosis, and experiments on three different cell lines. The results, comparing two manganese-containing systems, clearly indicated superior properties of the Mn-Zn ferrite, whose silica-coated nanoparticles show very limited toxic effects and thus constitute a promising material for bioapplications.

Cytotoxicity of TiO{sub 2} nanoparticles towards freshwater sediment microorganisms at low exposure concentrations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumari, Jyoti; Kumar, Deepak; Mathur, Ankita

2014-11-15

There is a persistent need to assess the effects of TiO{sub 2} nanoparticles on the aquatic ecosystem owing to their increasing usage in consumer products and risk of environmental release. The current study is focused on TiO{sub 2} nanoparticle-induced acute toxicity at sub-ppm level (≤1 ppm) on the three different freshwater sediment bacterial isolates and their consortium under two different irradiation (visible light and dark) conditions. The consortium of the bacterial isolates was found to be less affected by the exposure to the nanoparticles compared to the individual cells. The oxidative stress contributed considerably towards the cytotoxicity under both lightmore » and dark conditions. A statistically significant increase in membrane permeability was noted under the dark conditions as compared to the light conditions. The optical and fluorescence microscopic images showed aggregation and chain formation of the bacterial cells, when exposed to the nanoparticles. The electron microscopic (SEM, TEM) observations suggested considerable damage of cells and bio-uptake of nanoparticles. The exopolysaccrides (EPS) production and biofilm formation were noted to increase in the presence of the nanoparticles, and expression of the key genes involved in biofilm formation was studied by RT-PCR. - Highlights: • Toxicity of NPs towards freshwater sediment bacteria at sub-ppm concentrations. • Decreased toxicity of the nanoparticles in the consortium of microorganisms. • Enhanced bacterial resistance through EPS and biofilm formation in the presence of NPs. • Considerable surface damage of cells and internalization of NPs. • Gene expression analyses related to biofilm formation in the presence of NPs.« less

Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

NASA Astrophysics Data System (ADS)

Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro; Shimada, Manabu; Kubo, Masaru; Yamamoto, Kazuhiro; Kitajima, Shinichi; Kuroda, Etsushi; Kawaguchi, Kenji; Sasaki, Takeshi

2015-11-01

We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO2) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO2 nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO2 nanoparticles (2, 10 mg/m3, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO2 nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO2 nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO2 nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO2 nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

Evaluation of the effect of valence state on cerium oxide nanoparticle toxicity following intratracheal instillation in rats

PubMed Central

Dunnick, Katherine M.; Morris, Anna M.; Badding, Melissa A.; Barger, Mark; Stefaniak, Aleksandr B.; Sabolsky, Edward M.; Leonard, Stephen S.

2016-01-01

Cerium (Ce) is becoming a popular metal for use in electrochemical applications. When in the form of cerium oxide (CeO2), Ce can exist in both 3 + and 4 + valence states, acting as an ideal catalyst. Previous in vitro and in vivo evidence have demonstrated that CeO2 has either anti- or pro-oxidant properties, possibly due to the ability of the nanoparticles to transition between valence states. Therefore, we chose to chemically modify the nanoparticles to shift the valence state toward 3+. During the hydrothermal synthesis process, 10 mol% gadolinium (Gd) and 20 mol% Gd, were substituted into the lattice of the CeO2 nanoparticles forming a perfect solid solution with various A-site valence states. These two Gd-doped CeO2 nanoparticles were compared to pure CeO2 nanoparticles. Preliminary characteristics indicated that doping results in minimal size and zeta potential changes but alters valence state. Following characterization, male Sprague-Dawley rats were exposed to 0.5 or 1.0 mg/kg nanoparticles via a single intratracheal instillation. Animals were sacrificed and bronchoalveolar lavage fluid and various tissues were collected to determine the effect of valence state and oxygen vacancies on toxicity 1-, 7-, or 84-day post-exposure. Results indicate that damage, as measured by elevations in lactate dehydrogenase, occurred within 1-day post-exposure and was sustained 7-day post-exposure, but subsided to control levels 84-day post-exposure. Furthermore, no inflammatory signaling or lipid peroxidation occurred following exposure with any of the nanoparticles. Our results implicate that valence state has a minimal effect on CeO2 nanoparticle toxicity in vivo. PMID:26898289

Ectopic Bone Matrix Mineralization: Unveiling the Osteoinductive Nature of Crab Cuticle

NASA Astrophysics Data System (ADS)

Omokanwaye, Tiffany Suella

Engineered nanomaterials are increasingly used in a variety of industrial processes and consumer products. Numerous studies have reported toxicity of different NPs during the last years. Thus, there are growing concerns about the potential impacts to the health and environment of engineered nanoparticles (NPs). However, some methodological problems complicate the interpretation of nanotoxicity studies. On the one hand, some NPs have shown to interfere with classical toxicity assays based on colorimetric or fluorescent measurements. On the other hand, most NPs tend to aggregate in media used in toxicity tests, which complicates the interpretation of the toxicity results. The first objective of this dissertation was to evaluate a novel impedance-based and label-free real time cell analyzer (RTCA) as a high throughput method for screening the cytotoxicity of nanoparticles and to validate the RTCA results using a conventional cytotoxicity test (MTT). Several inorganic NPs were tested for potential cytotoxicity to human bronchial epithelial cells (16HBE14o-). In general, there was a good correlation in cytotoxicity measurements between the two methods. Moreover, none of the NPs tested showed interference with the impedance measurements performed by the RTCA system. The results demonstrate the potential and validity of the impedance-based RTCA technique to rapidly screen for NP toxicity. The second objective of this dissertation was to assess the toxicity of different inorganic NPs to the eukaryotic cell model Saccharomyces cerevisiae, and to test the influence of NP aggregation state in their toxicity. Nanotoxicity was assessed by monitoring oxygen consumption in batch cultures and by analysis of cell membrane integrity. Mn2O3 NPs showed the highest inhibition of O2 consumption and cell membrane damage, while the other NPs caused low or no toxicity to the yeast. Most NPs showed high tendency to aggregate in the assay medium, so a non-toxic dispersant was used to improve NP stability. In contrast to aggregated CeO2 NPs, dispersed CeO 2 NPs showed toxicity to the yeast. However, dispersant supplementation decreased the inhibition caused by Mn2O3 NPs at low concentrations, which could indicate that dispersant association with the particles may have an impact on the interaction between the NPs and the cells. The proven toxicity of some NPs raises concerns about their environmental fate. Municipal and industrial wastewaters are considered primary sources of NPs to the environment. However, information on the behavior and impact of NPs on wastewater treatment processes is very limited. A third objective of this dissertation was to evaluate the fate and long-term effect of ZnO and CuO NPs during wastewater treatment in high-rate anaerobic bioreactors. Laboratory-scale upflow anaerobic sludge blanket (UASB) reactors were fed with synthetic wastewater containing NPs for extended periods of time (> 90 d). Extensive removal (62-82%) of ZnO and CuO NPs was observed during wastewater treatment in the UASB reactors. Scanning electron microscopy and chemical analysis confirmed that NPs were associated with the anaerobic sludge. While short-term exposure to low levels of ZnO and CuO NPs only caused minor inhibition to methanogenesis, extended exposure to NPs accumulated in the sludge bed led to a gradual and partial inhibitory response in the reactors. The inhibitory effect was also evident in the decline in the acetoclastic methanogenic activity of the biomass.

Genotoxicity of Silver Nanoparticles in Vicia faba: A Pilot Study on the Environmental Monitoring of Nanoparticles

PubMed Central

Patlolla, Anita K.; Berry, Ashley; May, LaBethani; Tchounwou, Paul B.

2012-01-01

The use of silver nanoparticles (AgNPs) in commercial products has increased significantly in recent years. Although there have been some attempts to determine the toxic effects of AgNPs in mammalian and human cell-lines, there is little information on plants which play a vital role in ecosystems. The study reports the use of Vicia faba root-tip meristem to investigate the genotoxicity of AgNPs under modified GENE-TOX test conditions. The root tip cells of V. faba were treated with four different concentrations of engineered AgNPs dispersion to study toxicological endpoints such as mitotic index (MI), chromosomal aberrations (CA) and micronucleus induction (MN). For each concentration, five sets of microscopy observations were carried out. The results demonstrated that AgNPs exposure significantly increased (p < 0.05) the number of chromosomal aberrations, micronuclei, and decreased the MI in exposed groups compared to control. From this study we infer that AgNPs might have penetrated the plant system and may have impaired mitosis causing CA and MN. The results of this study demonstrate that AgNPs are genotoxic to plant cells. Since plant assays have been integrated as a genotoxicity component in risk assessment for detection of environmental mutagens, they should be given full consideration when evaluating the overall toxicological impact of the nanoparticles in the environment. PMID:22754463

Genotoxicity of silver nanoparticles in Vicia faba: a pilot study on the environmental monitoring of nanoparticles.

PubMed

Patlolla, Anita K; Berry, Ashley; May, LaBethani; Tchounwou, Paul B

2012-05-01

The use of silver nanoparticles (AgNPs) in commercial products has increased significantly in recent years. Although there have been some attempts to determine the toxic effects of AgNPs in mammalian and human cell-lines, there is little information on plants which play a vital role in ecosystems. The study reports the use of Vicia faba root-tip meristem to investigate the genotoxicity of AgNPs under modified GENE-TOX test conditions. The root tip cells of V. faba were treated with four different concentrations of engineered AgNPs dispersion to study toxicological endpoints such as mitotic index (MI), chromosomal aberrations (CA) and micronucleus induction (MN). For each concentration, five sets of microscopy observations were carried out. The results demonstrated that AgNPs exposure significantly increased (p < 0.05) the number of chromosomal aberrations, micronuclei, and decreased the MI in exposed groups compared to control. From this study we infer that AgNPs might have penetrated the plant system and may have impaired mitosis causing CA and MN. The results of this study demonstrate that AgNPs are genotoxic to plant cells. Since plant assays have been integrated as a genotoxicity component in risk assessment for detection of environmental mutagens, they should be given full consideration when evaluating the overall toxicological impact of the nanoparticles in the environment.

Engineering safer-by-design, transparent, silica-coated ZnO nanorods with reduced DNA damage potential

PubMed Central

Sotiriou, Georgios A.; Watson, Christa; Murdaugh, Kimberly M.; Darrah, Thomas H.; Pyrgiotakis, Georgios; Elder, Alison; Brain, Joseph D.; Demokritou, Philip

2014-01-01

Zinc oxide (ZnO) nanoparticles absorb UV light efficiently while remaining transparent in the visible light spectrum rendering them attractive in cosmetics and polymer films. Their broad use, however, raises concerns regarding potential environmental health risks and it has been shown that ZnO nanoparticles can induce significant DNA damage and cytotoxicity. Even though research on ZnO nanoparticle synthesis has made great progress, efforts on developing safer ZnO nanoparticles that maintain their inherent optoelectronic properties while exhibiting minimal toxicity are limited. Here, a safer-by-design concept was pursued by hermetically encapsulating ZnO nanorods in a biologically inert, nanothin amorphous SiO2 coating during their gas-phase synthesis. It is demonstrated that the SiO2 nanothin layer hermetically encapsulates the core ZnO nanorods without altering their optoelectronic properties. Furthermore, the effect of SiO2 on the toxicological profile of the core ZnO nanorods was assessed using the Nano-Cometchip assay by monitoring DNA damage at a cellular level using human lymphoblastoid cells (TK6). Results indicate significantly lower DNA damage (>3 times) for the SiO2-coated ZnO nanorods compared to uncoated ones. Such an industry-relevant, scalable, safer-by-design formulation of nanostructured materials can liberate their employment in nano-enabled products and minimize risks to the environment and human health. PMID:24955241

Excess titanium dioxide nanoparticles on the cell surface induce cytotoxicity by hindering ion exchange and disrupting exocytosis processes

NASA Astrophysics Data System (ADS)

Wang, Yanli; Yao, Chenjie; Li, Chenchen; Ding, Lin; Liu, Jian; Dong, Peng; Fang, Haiping; Lei, Zhendong; Shi, Guosheng; Wu, Minghong

2015-07-01

To date, considerable effort has been devoted to determine the potential toxicity of nanoparticles to cells and organisms. However, determining the mechanism of cytotoxicity induced by different types of nanoparticles remains challenging. Herein, typically low toxicity nanomaterials were used as a model to investigate the mechanism of cytotoxicity induced by low toxicity nanomaterials. We studied the effect of nano-TiO2, nano-Al2O3 and nano-SiO2 deposition films on the ion concentration on a cell-free system simulating the cell membrane. The results showed that the ion concentration of K+, Ca2+, Na+, Mg2+ and SO42- decreased significantly following filtration of the prepared deposition films. More specifically, at a high nano-TiO2 concentration (200 mg L-1) and a long nano-TiO2 deposition time (48 h), the concentration of Na+ decreased from 2958.01 to 2775.72, 2749.86, 2757.36, and 2719.82 mg L-1, respectively, for the four types of nano-TiO2 studied. Likewise, the concentration of SO42- decreased from 38.83 to 35.00, 35.80, 35.40, and 35.27 mg L-1, respectively. The other two kinds of typical low toxicity nanomaterials (nano-Al2O3 and nano-SiO2) have a similar impact on the ion concentration change trend. Adsorption of ions on nanoparticles and the hydrated shell around the ions strongly hindered the ions through the nanoparticle films. The endocytosed nanoparticles could be released from the cells without inducing cytotoxicity. Hindering the ion exchange and disrupting the exocytosis process are the main factors that induce cytotoxicity in the presence of excess nano-TiO2 on the cell surface. The current findings may offer a universal principle for understanding the mechanism of cytotoxicity induced by low toxicity nanomaterials.To date, considerable effort has been devoted to determine the potential toxicity of nanoparticles to cells and organisms. However, determining the mechanism of cytotoxicity induced by different types of nanoparticles remains challenging. Herein, typically low toxicity nanomaterials were used as a model to investigate the mechanism of cytotoxicity induced by low toxicity nanomaterials. We studied the effect of nano-TiO2, nano-Al2O3 and nano-SiO2 deposition films on the ion concentration on a cell-free system simulating the cell membrane. The results showed that the ion concentration of K+, Ca2+, Na+, Mg2+ and SO42- decreased significantly following filtration of the prepared deposition films. More specifically, at a high nano-TiO2 concentration (200 mg L-1) and a long nano-TiO2 deposition time (48 h), the concentration of Na+ decreased from 2958.01 to 2775.72, 2749.86, 2757.36, and 2719.82 mg L-1, respectively, for the four types of nano-TiO2 studied. Likewise, the concentration of SO42- decreased from 38.83 to 35.00, 35.80, 35.40, and 35.27 mg L-1, respectively. The other two kinds of typical low toxicity nanomaterials (nano-Al2O3 and nano-SiO2) have a similar impact on the ion concentration change trend. Adsorption of ions on nanoparticles and the hydrated shell around the ions strongly hindered the ions through the nanoparticle films. The endocytosed nanoparticles could be released from the cells without inducing cytotoxicity. Hindering the ion exchange and disrupting the exocytosis process are the main factors that induce cytotoxicity in the presence of excess nano-TiO2 on the cell surface. The current findings may offer a universal principle for understanding the mechanism of cytotoxicity induced by low toxicity nanomaterials. Electronic supplementary information (ESI) available: Nano-TiO2 characterization; changes in nucleus morphology; apoptosis assay; variations in Ca2+; schematic of the experiment to simulate ion exchange; TEM images; ion concentration change after being filtered through the nano-deposition films; theoretical simulation methods; ROS generation; intercellular communication; the movie shows the process of Na+ in the films. See DOI: 10.1039/c5nr03269e

The influence of dissolved and surface-bound humic acid on the toxicity of TiO₂ nanoparticles to Chlorella sp.

PubMed

Lin, Daohui; Ji, Jing; Long, Zhifeng; Yang, Kun; Wu, Fengchang

2012-09-15

NOM is likely to coat TiO₂ nanoparticles (nano-TiO₂) discharged into the aquatic environment and influence the nanotoxicity to aquatic organisms, which however has not been well investigated. This study explored the influence of nanoparticle surface-bound humic acid (HA, as a model NOM) as well as dissolved HA on the toxicity of nano-TiO₂ to Chlorella sp., with a specific focus on adhesion of the nanoparticles to the algae. Results showed that nano-TiO₂ and the dissolved HA could inhibit the algal growth with an IC₅₀ of 4.9 and 8.4 mg L⁻¹, respectively, while both dissolved and nanoparticle surface-bound HA could significantly alleviate the algal toxicity of nano-TiO₂. IC₅₀ of nano-TiO₂ increased to 18 mg L⁻¹ in the presence of 5 mg L⁻¹ of the dissolved HA and to 48 mg L⁻¹ as the result of surface-saturation by HA. Co-precipitation experiment and transmission electron microscopy observation revealed that both dissolved and nanoparticle surface-bound HA prevented the adhesion of nano-TiO₂ to the algal cells due to the increased electrosteric repulsion. The generation of intracellular reactive oxygen species (ROS) was significantly limited by the dissolved and nanoparticle surface-bound HA. The prevention of adhesion and inhibition of ROS generation could account for the HA-mitigated nanotoxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Electroanalytical Evaluation of Nanoparticles by Nano-impact Electrochemistry

NASA Astrophysics Data System (ADS)

Karimi, Anahita

Applications of engineered nanoparticles in electronics, catalysis, solid oxide fuel cells, medicine and sensing continue to increase. Traditionally, nanoparticle systems are characterized by spectroscopic and microscopic techniques. These methods are cumbersome and expensive, which limit their routine use for screening purposes. Electrochemistry is a powerful, yet underutilized tool, for the detection and classification of nanoparticles. The first part of this dissertation investigates a recently developed electrochemical method -- nanoparticle collision electrochemistry -- for detection and characterization of nanoparticles. Three independent projects have been described to evaluate the use of this technique for characterizing nanoparticle based systems including: conjugation with biomolecules, interaction with environmental contaminants and fundamental investigation of conformational changes of nanoparticle capping ligands. The thesis reports the first use of nano-impact electrochemistry to quantitatively investigate bioconjugation and biomolecular recognition at conductive nanoparticles. Furthermore, we also demonstrate the potential of this method as a single step, reagentless and label-free technique for the ultra-sensitive detection of biomolecular targets. A fundamental study of biorecognition is important for the development of therapeutics and molecular diagnosis probes in the biomedical, biosensing and biotechnology fields. The second project describes the use of this method as a screening tool of particle reactivity. We study the interaction and adsorption of a toxic environmental metalloid (Arsenic) with metal oxide nanoparticles to extract mechanistic, speciation and loading information. We discuss the potential of this approach to complement or replace costly characterization techniques and enable routine study of nanoparticles and their reactivity. In the third project, we use the nano-impact method to study the pH-dependent conformational changes of polymeric capping agents on the surface of silver nanoparticles. Nano-impact elecrochemistry has demonstrated promising results for studying functionality, stability and conformational changes of stabilizing agents. The second part of this thesis explores the use of carbon nanomaterials such as graphene and Pt-doped CeO2 for the rational design of enzyme-conjugated nanostructures for biosensing applications. The dissertation reports fabrication, characterization and properties of hybrid CeO2-based bioelectrocatalytic nanostructure material with PEDOT:PSS [poly(3,4ethylenedioxythiophene):poly-styrene-sulfonic acid] on porous carbon materials as novel materials for designing high performance laccase (Lac) biocathodes and biofuel cells.

Sun light mediated synthesis of gold nanoparticles as carrier for 6-mercaptopurine: Preparation, characterization and toxicity studies in zebrafish embryo model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganeshkumar, Moorthy; Sastry, Thotapalli Parvathaleswara; Sathish Kumar, Muniram

2012-09-15

Highlights: ► Gold nanoparticles prepared using eco-friendly method with good in vitro stability. ► Can be used as drug delivery system. ► Did not show any toxicity in zebrafish embryo. ► More toxic to cancer cells when compared to N-Au-Mp and Mp. -- Abstract: The objective of this study is to synthesize green chemistry based gold nanoparticles by sun light irradiation method. The prepared gold nanoparticles (AuNPs) were modified using folic acid and then coupled with 6-mercaptopurine. These modified nanoparticles were used as a tool for targeted drug delivery to treat laryngeal cancer. In the present study, novel bionanocomposites containingmore » nutrient agar coated gold nano particles (N-AuNPs) coupled with 6-mercaptopurine (drug) (N-AuNPs-Mp), folic acid (ligand) (N-AuNPs-Mp-Fa) and rhodamine (dye) (N-AuNPs-Rd), a fluorescent agent, were prepared and characterized by IR, UV, TEM, Particle size analysis and in vitro stability. The toxicity and fluorescence of N-Au was studied using zebrafish embryo model. The in vitro cytotoxicity of free Mp, N-Au-Mp and N-Au-Mp-Fa against HEp-2 cells was compared and found that the amount of Mp required to achieve 50% of growth of inhibition (IC{sub 50}) was much lower in N-Au-Mp-Fa than in free Mp and N-Au-Mp.« less

Nanoparticles for Site Specific Genome Editing

NASA Astrophysics Data System (ADS)

McNeer, Nicole Ali

Triplex-forming peptide nucleic acids (PNAs) can be used to coordinate the recombination of short 50-60 by "donor DNA" fragments into genomic DNA, resulting in site-specific correction of genetic mutations or the introduction of advantageous genetic modifications. Site-specific gene editing in hematopoietic stem and progenitor cells (HSPCs) could result in treatment or cure of inherited disorders of the blood such as beta-thalassemia. Gene editing in HSPCs and differentiated T cells could help combat HIV/AIDs by modifying receptors, such as CCR5, necessary for R5-tropic HIV entry. However, translation of genome modification technologies to clinical practice is limited by challenges in intracellular delivery, especially in difficult-to-transfect hematolymphoid cells. In vivo gene editing could also provide novel treatment for systemic monogenic disorders such as cystic fibrosis, an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane receptor. Here, we have engineered biodegradable nanoparticles to deliver oligonucleotides for site-specific genome editing of disease-relevant genes in human cells, with high efficiency, low toxicity, and editing of clinically relevant cell types. We designed nanoparticles to edit the human beta-globin and CCR5 genes in hematopoietic cells. We show that poly(lactic-co-glycolic acid) (PLGA) nanoparticles can delivery PNA and donor DNA for site-specific gene modification in human hematopoietic cells in vitro and in vivo in NOD-scid IL2rgammanull mice. Nanoparticles delivered by tail vein localized to hematopoietic compartments in the spleen and bone marrow of humanized mice, resulting in modification of the beta-globin and CCR5 genes. Modification frequencies ranged from 0.005 to 20% of cells depending on the organ and cell type, without detectable toxicity. This project developed highly versatile methods for delivery of therapeutics to hematolymphoid cells and hematopoietic stem cells, and will help to translate gene therapies for diseases of the blood and immune system to clinical practice. In addition, we have expanded the use of this technology to an additional nonhematopoietic model system: correction of the human cystic fibrosis transmembrane receptor gene in human bronchial epithelial cells. The work presented here represents (1) the first use of biodegradable nanoparticles for PNA delivery, (2) the first direct in vivo site-specific genome modification in human cells, and (3) the first use of triplex-PNA technology for site-specific genome editing in cystic fibrosis.

Adsorption and desorption characteristics of arsenic onto ceria nanoparticles

PubMed Central

2012-01-01

The rapid increase in the use of engineered nanoparticles [ENPs] has resulted in an increasing concern over the potential impacts of ENPs on the environmental and human health. ENPs tend to adsorb a large variety of toxic chemicals when they are emitted into the environment, which may enhance the toxicity of ENPs and/or adsorbed chemicals. The study was aimed to investigate the adsorption and desorption behaviors of arsenic on ceria NPs in aqueous solution using batch technique. Results show that the adsorption behavior of arsenic on ceria NPs was strongly dependent on pH and independent of ionic strength, indicating that the electrostatic effect on the adsorption of these elements was relatively not important compared to surface chemical reactions. The adsorption isotherms fitted very well to both the Langmuir and Freundlich models. The thermodynamic parameters (ΔH0, ΔS0, and ΔG0) for the adsorption of arsenic were determined at three different temperatures of 283, 303, and 323 K. The adsorption reaction was endothermic, and the process of adsorption was favored at high temperature. The desorption data showed that desorption hysteresis occurred at the initial concentration studied. High adsorption capacity of arsenic on ceria NPs suggests that the synergistic effects of ceria NPs and arsenic on the environmental systems may exist when they are released into the environment. PMID:22269298

Effect of contact angle, zeta potential and particles size on the in vitro studies of Al2O3 and SiO2 nanoparticles.

PubMed

Karunakaran, Gopalu; Suriyaprabha, Rangaraj; Rajendran, Venkatachalam; Kannan, Narayanasamy

2015-02-01

Currently, nanometal oxides find their role in different biological applications such as tissue engineering, implant and bone replacement materials. Owing to the increased use of nanoparticles, it is necessary to understand their release and toxicity in the biological system. In this regard, three independent studies such as in vitro cytotoxicity, antioxidant activity and biocompatibility of nano- and micrometal oxide particles such as alumina (Al2O3) and silica (SiO2) are evaluated. It is evident from cell viability study that nanoAl2O3 and SiO2 particles are less toxic when compared with microAl2O3 and SiO2 to NIH 3T3 cell lines up to 200 µg/ml. Antioxidant properties of micro- and nanoAl2O3 in terms of radical scavenging percentage for micro- and nanoAl2O3 are 59.1% and 72.1%, respectively, at 100 mg. Similarly, the radical scavenging percentage of nano- and bulk SiO2 are 81.0% and 67.2%, respectively. The present study reveals that the cellular behaviour, interaction and biocompatibility of metal oxides differ with dose, particle size, contact angle and zeta potential. The present study opens up a new strategy to analyse in vitro nanotoxicity.

Investigations of nano-particle toxicity and uptake of Cerium oxide and Titanium dioxide in Arabidopsis thaliana (L.)

EPA Science Inventory

The emergence of nanotechnology and incorporation of nanoparticles in consumer products necessitates risk assessment from an environmental and health safety standpoint. To date, very few studies have examined nanoparticle effects on terrestrial species, especially plants. In ...

A convenient method to prepare emulsified polyacrylate nanoparticles from powders [corrected] for drug delivery applications.

PubMed

Garay-Jimenez, Julio C; Turos, Edward

2011-08-01

We describe a method to obtain purified, polyacrylate nanoparticles in a homogeneous powdered form that can be readily reconstituted in aqueous media for in vivo applications. Polyacrylate-based nanoparticles can be easily prepared by emulsion polymerization using a 7:3 mixture of butyl acrylate and styrene in water containing sodium dodecyl sulfate as a surfactant and potassium persulfate as a water-soluble radical initiator. The resulting emulsions contain nanoparticles measuring 40-50 nm in diameter with uniform morphology, and can be purified by centrifugation and dialysis to remove larger coagulants as well as residual surfactant and monomers associated with toxicity. These purified emulsions can be lyophilized in the presence of maltose (a non-toxic cryoprotectant) to provide a homogeneous dried powder, which can be reconstituted as an emulsion by addition of an aqueous diluent. Dynamic light scattering and microbiological experiments were carried out on the reconstituted nanoparticles. This procedure allows for ready preparation of nanoparticle emulsions for drug delivery applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis.

PubMed

Guo, Ling; Luo, Shi; Du, Zhengwu; Zhou, Meiling; Li, Peiwen; Fu, Yao; Sun, Xun; Huang, Yuan; Zhang, Zhirong

2017-10-12

Mesangial cells-mediated glomerulonephritis is a frequent cause of end-stage renal disease. Here, we show that celastrol is effective in treating both reversible and irreversible mesangioproliferative glomerulonephritis in rat models, but find that its off-target distributions cause severe systemic toxicity. We thus target celastrol to mesangial cells using albumin nanoparticles. Celastrol-albumin nanoparticles crosses fenestrated endothelium and accumulates in mesangial cells, alleviating proteinuria, inflammation, glomerular hypercellularity, and excessive extracellular matrix deposition in rat anti-Thy1.1 nephritis models. Celastrol-albumin nanoparticles presents lower drug accumulation than free celastrol in off-target organs and tissues, thereby minimizing celastrol-related systemic toxicity. Celastrol-albumin nanoparticles thus represents a promising treatment option for mesangioproliferative glomerulonephritis and similar glomerular diseases.Mesangial cell-mediated glomerulonephritis is a frequent cause of kidney disease. Here the authors show that celastrol loaded in albumin nanoparticles efficiently targets mesangial cells, and is effective in rat models.

Non-hazardous anticancerous and antibacterial colloidal 'green' silver nanoparticles.

PubMed

Barua, Shaswat; Konwarh, Rocktotpal; Bhattacharya, Satya Sundar; Das, Pallabi; Devi, K Sanjana P; Maiti, Tapas K; Mandal, Manabendra; Karak, Niranjan

2013-05-01

Poly(ethylene glycol) stabilized colloidal silver nanoparticles were prepared using the reductive potency of the aqueous extract of Thuja occidentalis leaves under ambient conditions. The nanoparticles were well dispersed within a narrow size spectrum (7-14 nm) and displayed characteristic surface plasmon resonance peak at around 420 nm and Bragg's reflection planes of fcc structure. MTT assay revealed the dose-dependent cytocompatibility and toxicity of the nanoparticles with the L929 normal cell line. On the other hand, the antiproliferative action of the nanoparticles was evaluated on HeLa cell (cancerous cells) line. Fluorescence and phase contrast microscopic imaging indicated the appearance of multinucleate stages with aggregation and nuclear membrane disruption of the HeLa cells post treatment with the nanoparticles. The interaction at the prokaryotic level was also assessed via differential antibacterial efficacy against Staphylococcus aureus (MTCC 3160) and Escherichia coli (MTCC 40). Under these perspectives, it is also necessary to observe the environmental impact of the prepared silver nanoparticles. Hence, the dose dependent toxicity of silver nanoparticles was evaluated upon the earthworm species Eisenia fetida. Neither the survival nor the reproduction was affected by the addition of silver nanoparticles up to 1000 ppm. Thus these 'green' silver nanoparticles have promising potential as future materials. Copyright © 2012 Elsevier B.V. All rights reserved.

Towards Environmentally-benign Nanoengineering: Antimicrobial Nanoparticles Based on Silver-infused Lignin Cores

NASA Astrophysics Data System (ADS)

Richter, Alexander Philipp

Engineered nanomaterials are capable of solving challenges in industries important to society such as energy, agriculture, and health care. Antimicrobial silver nanoparticles (AgNPs) are the most widely used nanoparticles by number of commercial products in commerce today. However, the increased introduction of AgNPs in industrial applications may lead to discharge of persistent nanoparticles in the environment and undesired impacts on living organisms. This dissertation will present a new class of antimicrobial environmentallybenign nanoparticles (EbNPs) designed with green chemistry principles, which can serve as highly efficient microbicide substitutes of the AgNPs. The EbNP core is made of biodegradable lignin, and is infused with an optimal amount of silver ions. We report on the fabrication of environmentally benign nanoparticles (EbNPs) using two types of lignin precursors with simple, inexpensive, and non-toxic processes, (i) by employing a solvent exchange precipitation method at room temperature and (ii) by applying an environmentally friendly water-based acid precipitation method. The synthesis of Organosolv (High Purity Lignin) nanoparticles via antisolvent flash precipitation method in water resulted in particles in the size range of 45 to 250 nm in diameter. We investigate the synthesis parameters of Kraft (Indulin AT) lignin nanoparticles by flash precipitation induced by pH drop in ethylene glycol. Furthermore, we evaluate the ionic strength and pH stability of both lignin nanoparticle suspensions and highlight differences in the systems. After silver ion infusion of Indulin AT nanoparticles followed by surface modification, we show that the EbNPs exhibit higher antimicrobial activity towards Gram-negative human pathogens Escherichia coli and Pseudomonas aeruginosa and Gram-positive human pathogens Staphylococcus epidermidis in direct comparison with silver nanoparticles and silver nitrate solution, and that the particles are effective against quaternary ammonium resistant Ralstonia bacteria. The enhanced antimicrobial action is due to highly-biocidal silver ions released from the EbNP matrix at the cell. High-throughput bioactivity screening using mammalian cell and zebrafish embryo assays performed in collaboration with the U.S. Environmental Protection Agency did not reveal increased safety concerns of the EbNPs, when compared to equivalent amount of AgNPs or AgNO3 solution. The silver ion functionalized EbNPs exhibit broad spectrum microbicide action and are capable of neutralizing common gram-negative human pathogens as well as quaternary amineresistant bacteria, while using ten times less silver when compared with conventional AgNPs and AgNO3 aqueous solution. We envisage that the overall environmental impact of silver ion functionalized EbNPs is likely to be significantly smaller when compared to AgNPs. As more general impact, the approach of engineering environmentally-benign lignin-core nanoparticles with matching functionality to persistent nanoparticles illustrates how green chemistry principles including atom economy, use of renewable feedstocks, and design for degradation can be applied to design more sustainable nanomaterials with increased functionality and decreased environmental footprint.

Toxicity assessment of anatase and rutile titanium dioxide nanoparticles: The role of degradation in different pH conditions and light exposure.

PubMed

De Matteis, Valeria; Cascione, Mariafrancesca; Brunetti, Virgilio; Toma, Chiara Cristina; Rinaldi, Rosaria

2016-12-01

Titanium dioxide nanoparticles (TiO 2 NPs), in the two crystalline forms, rutile and anatase, have been widely used in many industrial fields, especially in cosmetics. Therefore, a lot of details about their safety issues have been discussed by the scientific community. Many studies have led to a general agreement about TiO 2 NPs toxicity, in particular for anatase form, but no mechanism details have been proved yet. In this study, data confirm the different toxic potential of rutile and anatase TiO 2 NPs in two cell lines up to 5nM nanoparticles concentration. Moreover, we evaluated the role of titanium ions released by TiO 2 NPs in different conditions, at pH=4.5 (the typical lysosomal compartment pH) and at pH=5.5 (the skin physiological pH) in conditions of darkness and light, to mimic the dermal exposure of cosmetics. Anatase nanoparticles were proner to degradation both in the acidic conditions and at skin pH. Our study demonstrates that pH and sunlight are dominant factors to induce oxidative stress, TiO 2 NPs degradation and toxicity effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of electrostatic interactions in the toxicity of titanium dioxide nanoparticles toward Escherichia coli.

PubMed

Pagnout, Christophe; Jomini, Stéphane; Dadhwal, Mandeep; Caillet, Céline; Thomas, Fabien; Bauda, Pascale

2012-04-01

The increasing production and use of titanium dioxide nanoparticles (NP-TiO(2)) has led to concerns about their possible impact on the environment. Bacteria play crucial roles in ecosystem processes and may be subject to the toxicity of these nanoparticles. In this study, we showed that at low ionic strength, the cell viability of Escherichia coli was more severely affected at pH 5.5 than at pH 7.0 and pH 9.5. At pH 5.5, nanoparticles (positively charged) strongly interacted with the bacterial cells (negatively charged) and accumulated on their surfaces. This phenomenon was observed in a much lower degree at pH 7.0 (NP-TiO(2) neutrally charged and cells negatively charged) and pH 9.5 (both NP-TiO(2) and cells negatively charged). It was also shown that the addition of electrolytes (NaCl, CaCl(2), Na(2)SO(4)) resulted in a gradual reduction of the NP-TiO(2) toxicity at pH 5.5 and an increase in this toxicity at pH 9.5, which was closely related to the reduction of the NP-TiO(2) and bacterial cell electrostatic charges. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Hydrophobic Effect from Conjugated Chemicals or Drugs on In Vivo Biodistribution of RNA Nanoparticles.

PubMed

Jasinski, Daniel L; Yin, Hongran; Li, Zhefeng; Guo, Peixuan

2018-01-01

Liver or other organ accumulation of drugs is one of the major problems that leads to toxicity and side effects in therapy using chemicals or other macromolecules. It has been shown that specially designed RNA nanoparticles can specifically target cancer cells, silence oncogenic genes, and stop cancer growth with little or no accumulation in the liver or other vital organs. It is well known that physical properties of nanoparticles such as size, shape, and surface chemistry affect biodistribution and pharmacokinetic profiles in vivo. This study examined how the hydrophobicity of chemicals conjugated to RNA nanoparticles affect in vivo biodistribution. Weaker organ accumulation was observed for hydrophobic chemicals after they were conjugated to RNA nanoparticles, revealing RNA's ability to solubilize hydrophobic chemicals. It was found that different chemicals conjugated to RNA nanoparticles resulted in the alteration of RNA hydrophobicity. Stronger hydrophobicity induced by chemical conjugates resulted in higher accumulation of RNA nanoparticles in vital organs in mice. This study provides new insights for handling drug insolubility, therapeutic toxicity, and organ clearance in drug development.

Protein Corona Prevents TiO2 Phototoxicity.

PubMed

Garvas, Maja; Testen, Anze; Umek, Polona; Gloter, Alexandre; Koklic, Tilen; Strancar, Janez

2015-01-01

TiO2 nanoparticles have generally low toxicity in the in vitro systems although some toxicity is expected to originate in the TiO2-associated photo-generated radical production, which can however be modulated by the radical trapping ability of the serum proteins. To explore the role of serum proteins in the phototoxicity of the TiO2 nanoparticles we measure viability of the exposed cells depending on the nanoparticle and serum protein concentrations. Fluorescence and spin trapping EPR spectroscopy reveal that the ratio between the nanoparticle and protein concentrations determines the amount of the nanoparticles' surface which is not covered by the serum proteins and is proportional to the amount of photo-induced radicals. Phototoxicity thus becomes substantial only at the protein concentration being too low to completely coat the nanotubes' surface. These results imply that TiO2 nanoparticles should be applied with ligands such as proteins when phototoxic effects are not desired - for example in cosmetics industry. On the other hand, the nanoparticles should be used in serum free medium or any other ligand free medium, when phototoxic effects are desired - as for efficient photodynamic cancer therapy.

Zinc oxide nanoparticles affect carbon and nitrogen mineralization of Phoenix dactylifera leaf litter in a sandy soil.

PubMed

Rashid, Muhammad Imtiaz; Shahzad, Tanvir; Shahid, Muhammad; Ismail, Iqbal M I; Shah, Ghulam Mustafa; Almeelbi, Talal

2017-02-15

We investigated the impact of zinc oxide nanoparticles (ZnO NPs; 1000mgkg -1 soil) on soil microbes and their associated soil functions such as date palm (Phoenix dactylifera) leaf litter (5gkg -1 soil) carbon and nitrogen mineralization in mesocosms containing sandy soil. Nanoparticles application in litter-amended soil significantly decreased the cultivable heterotrophic bacterial and fungal colony forming units (cfu) compared to only litter-amended soil. The decrease in cfu could be related to lower microbial biomass carbon in nanoparticles-litter amended soil. Likewise, ZnO NPs also reduced CO 2 emission by 10% in aforementioned treatment but this was higher than control (soil only). Labile Zn was only detected in the microbial biomass of nanoparticles-litter applied soil indicating that microorganisms consumed this element from freely available nutrients in the soil. In this treatment, dissolved organic carbon and mineral nitrogen were 25 and 34% lower respectively compared to litter-amended soil. Such toxic effects of nanoparticles on litter decomposition resulted in 130 and 122% lower carbon and nitrogen mineralization efficiency respectively. Hence, our results entail that ZnO NPs are toxic to soil microbes and affect their function i.e., carbon and nitrogen mineralization of applied litter thus confirming their toxicity to microbial associated soil functions. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of composition, morphology and size of nanozeolite on its in vitro cytotoxicity.

PubMed

Kihara, Takanori; Zhang, Yahong; Hu, Yuanyuan; Mao, Qiaofan; Tang, Yi; Miyake, Jun

2011-06-01

The extensive applications of nanoparticle materials in biomedical and biotechnological fields trigger the rapid development of nanotoxicology, because nanoparticles are reported to cause more damage than larger ones when human exposure to them. In the present manuscript, we prepared a series of zeolite nanocrystals with different frameworks, sizes, compositions and shapes, and provided the first report on their toxic difference. As our results, the toxicities of zeolite nanoparticles depend on their size, composition and shape when they are exposed to HeLa cells. The pure-silica nanozeolite silicalite-1 displays nontoxicity, but aluminum-containing nanozeolites, such as ZSM-5, LTL, and LTA, show a dose-dependent toxic manner. The different shapes of nanozeolites can lead to different cytotoxicities, while the influences of the surface charge differences of various nanozeolites on their toxicities are unconspicuous. More importantly, caspase-3 activity and LDH released assays showed that the toxic nanozeolites seem to induce cell necrosis rather than cell apoptosis by the damnification for the cell membranes. These results are expected to direct the applications of nanozeolites with different structures and shapes in biomedicine and clinic science. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

77 FR 65863 - Application(s) for Duty-Free Entry of Scientific Instruments

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-31

... characterization of nanoparticles produced by wood, insect sensory receptors, and nanoscale interactions between... instrument will be used to study mammalian cell cultures, and the toxic effects of exposure to nanoparticles of different compositions, size, shape and surface coatings. The interactions of these nanoparticles...

Attenuation of Microbial Stress Due to Nano-Ag and Nano-TiO2 Interactions under Dark Conditions.

PubMed

Wilke, Carolyn M; Tong, Tiezheng; Gaillard, Jean-François; Gray, Kimberly A

2016-10-04

Engineered nanomaterials (ENMs) are incorporated into thousands of commercial products, and their release into environmental systems creates complex mixtures with unknown toxicological outcomes. To explore this scenario, we probe the chemical and toxicological interactions of nanosilver (n-Ag) and nanotitania (n-TiO 2 ) in Lake Michigan water, a natural aqueous medium, under dark conditions. We find that the presence of n-Ag induces a stress response in Escherichia coli, as indicated by a decrease in ATP production observed at low concentrations (in the μg L -1 range), with levels that are environmentally relevant. However, when n-Ag and n-TiO 2 are present together in a mixture, n-TiO 2 attenuates the toxicity of n-Ag at and below 20 μg L -1 by adsorbing Ag + (aq) . We observe, however, that toxic stress cannot be explained by dissolved silver concentrations alone and, therefore, must also depend on silver associated with the nanoscale fraction. Although the attenuating effect of n-TiO 2 on n-Ag's toxicity is limited, this study emphasizes the importance of probing the toxicity of ENM mixtures under environmental conditions to assess how chemical interactions between nanoparticles change the toxicological effects of single ENMs in unexpected ways.

Development and Optimization of Silver Nanoparticle Formulation for Fabrication

DTIC Science & Technology

2015-08-14

Development and Optimization of Silver Nanoparticle Formulation for Fabrication Publication Type: DJournal/ Paper D Book Chapter ~ Tech Report D...leofPublicationorPresentation: Deve l opment and Optimization of Silver Nanoparticle Formulation for Fabrication 3. Author(s): (List authors starting...fabrication process of silver nanoparticl es could improve future silver containing products , which is i mpor tant to l owering toxicity and improving

Gadolinium-Doped Gallic Acid-Zinc/Aluminium-Layered Double Hydroxide/Gold Theranostic Nanoparticles for a Bimodal Magnetic Resonance Imaging and Drug Delivery System

PubMed Central

Sani Usman, Muhammad; Hussein, Mohd Zobir; Fakurazi, Sharida; Ahmad Saad, Fathinul Fikri

2017-01-01

We have developed gadolinium-based theranostic nanoparticles for co-delivery of drug and magnetic resonance imaging (MRI) contrast agent using Zn/Al-layered double hydroxide as the nanocarrier platform, a naturally occurring phenolic compound, gallic acid (GA) as therapeutic agent, and Gd(NO3)3 as diagnostic agent. Gold nanoparticles (AuNPs) were grown on the system to support the contrast for MRI imaging. The nanoparticles were characterized using techniques such as Hi-TEM, XRD, ICP-ES. Kinetic release study of the GA from the nanoparticles showed about 70% of GA was released over a period of 72 h. The in vitro cell viability test for the nanoparticles showed relatively low toxicity to human cell lines (3T3) and improved toxicity on cancerous cell lines (HepG2). A preliminary contrast property test of the nanoparticles, tested on a 3 Tesla MRI machine at various concentrations of GAGZAu and water (as a reference) indicates that the nanoparticles have a promising dual diagnostic and therapeutic features to further develop a better future for clinical remedy for cancer treatment. PMID:28858229

Organically Modified Silica Nanoparticles Are Biocompatible and Can Be Targeted to Neurons In Vivo

PubMed Central

Kumar, Rajiv; Iacobucci, Gary J.; Kuznicki, Michelle L.; Kosterman, Andrew; Bergey, Earl J.; Prasad, Paras N.; Gunawardena, Shermali

2012-01-01

The application of nanotechnology in biological research is beginning to have a major impact leading to the development of new types of tools for human health. One focus of nanobiotechnology is the development of nanoparticle-based formulations for use in drug or gene delivery systems. However most of the nano probes currently in use have varying levels of toxicity in cells or whole organisms and therefore are not suitable for in vivo application or long-term use. Here we test the potential of a novel silica based nanoparticle (organically modified silica, ORMOSIL) in living neurons within a whole organism. We show that feeding ORMOSIL nanoparticles to Drosophila has no effect on viability. ORMOSIL nanoparticles penetrate into living brains, neuronal cell bodies and axonal projections. In the neuronal cell body, nanoparticles are present in the cytoplasm, but not in the nucleus. Strikingly, incorporation of ORMOSIL nanoparticles into the brain did not induce aberrant neuronal death or interfered with normal neuronal processes. Our results in Drosophila indicate that these novel silica based nanoparticles are biocompatible and not toxic to whole organisms, and has potential for the development of long-term applications. PMID:22238611

Acute and subchronic toxicity analysis of surface modified paclitaxel attached hydroxyapatite and titanium dioxide nanoparticles.

PubMed

Venkatasubbu, Gopinath Devanand; Ramasamy, S; Gaddam, Pramod Reddy; Kumar, J

2015-01-01

Nanoparticles are widely used for targeted drug delivery applications. Surface modification with appropriate polymer and ligands is carried out to target the drug to the affected area. Toxicity analysis is carried out to evaluate the safety of the surface modified nanoparticles. In this study, paclitaxel attached, folic acid functionalized, polyethylene glycol modified hydroxyapatite and titanium dioxide nanoparticles were used for targeted drug delivery system. The toxicological behavior of the system was studied in vivo in rats and mice. Acute and subchronic studies were carried out. Biochemical, hematological, and histopathological analysis was also done. There were no significant alterations in the biochemical parameters at a low dosage. There was a small change in alkaline phosphatase (ALP) level at a high dosage. The results indicate a safe toxicological profile.

Challenges in realizing selectivity for nanoparticle biodistribution and clearance: lessons from gold nanoparticles.

PubMed

Haute, Desiree Van; Berlin, Jacob M

2017-08-01

The field of nanomedicine has received much attention for its potential to allow for targeted identification and treatment of tumors, while sparing healthy tissue. This promise has yet to be clinically realized; instead nanomedicine has translated into clinical benefit via formulations that improve the pharmacokinetics and toxicity profiles of toxic chemotherapeutic agents. In this perspective, we highlight that several of the defining strategies for using nanoparticles intravenously to target solid tumors have limited supporting data in animal studies. Namely, it does not appear that reducing macrophage (and other cell type) uptake in vitro leads to better biodistribution in vivo, nor does increasing blood circulation time nor active targeting. We suggest instead that the coming decade will primarily see nanoparticles impact immunotherapy and local/pseudolocal cancer therapy.

Sonochemical synthesis of novel magnesium 1,2,4-triazole-1-carbodithioate nanoparticles as antifungals

NASA Astrophysics Data System (ADS)

Gumber, Khushbu; Sidhu, Anjali; Kaur, Robinpreet

2017-04-01

Novel magnesium 1,2,4-triazole-1-carbodithioates were sonochemically synthesized as water-dispersable nanoparticles owing to their water insolubility. The two-step reaction protocol was followed to synthesize the novel triazole ligand system for complexation with magnesium metal due to its low biological toxicity. Different concentrations of Poly Vinyl Pyrrolidine were used to stabilize and standardise the size of nanoparticles, which were characterised by TEM analysis. UV-Visible and infrared spectroscopies were used to analyse the metal ligand interaction, and CHNS analysis was used to propose the structure of the metal complex. The spore germination inhibition technique was used to evaluate the antifungal potential of synthesized nano-complexes against two phytopathogenic test fungi viz . A. alternata and F. moniliforme. The nanoparticles had inflicted moderate in vitro inhibition of fungal growth, which was comparable to standard fungicide Indofil M-45. The in silico toxicity of the compounds was made using the Toxtree analysis software that indicated the compounds belong to class III group of toxicity, which was same as that of commercial standards of DTC.

Edible lipid nanoparticles: digestion, absorption, and potential toxicity.

PubMed

McClements, David Julian

2013-10-01

Food-grade nanoemulsions are being increasingly used in the food and beverage industry to encapsulate, protect, and deliver hydrophobic functional components, such as oil-soluble flavors, colors, preservatives, vitamins, and nutraceuticals. These nanoemulsions contain lipid nanoparticles (radius <100 nm) whose physicochemical characteristics (e.g., composition, dimensions, structure, charge, and physical state) can be controlled by selection of appropriate ingredients and fabrication techniques. Nanoemulsions have a number of potential advantages over conventional emulsions for applications within the food industry: higher stability to particle aggregation and gravitational separation; higher optical transparency; and, increased bioavailability of encapsulated components. On the other hand, there are also some risks associated with consumption of lipid nanoparticles that should be considered before they are widely utilized, such as their ability to alter the fate of bioactive components within the gastrointestinal tract and the potential toxicity of some of the components used in their fabrication (e.g., surfactants and organic solvents). This article provides an overview of the current status of the biological fate and potential toxicity of food-grade lipid nanoparticles suitable for utilization within the food and beverage industry. Copyright © 2013 Elsevier Ltd. All rights reserved.

Deposition of Nanostructured Thin Film from Size-Classified Nanoparticles

NASA Technical Reports Server (NTRS)

Camata, Renato P.; Cunningham, Nicholas C.; Seol, Kwang Soo; Okada, Yoshiki; Takeuchi, Kazuo

2003-01-01

Materials comprising nanometer-sized grains (approximately 1_50 nm) exhibit properties dramatically different from those of their homogeneous and uniform counterparts. These properties vary with size, shape, and composition of nanoscale grains. Thus, nanoparticles may be used as building blocks to engineer tailor-made artificial materials with desired properties, such as non-linear optical absorption, tunable light emission, charge-storage behavior, selective catalytic activity, and countless other characteristics. This bottom-up engineering approach requires exquisite control over nanoparticle size, shape, and composition. We describe the design and characterization of an aerosol system conceived for the deposition of size classified nanoparticles whose performance is consistent with these strict demands. A nanoparticle aerosol is generated by laser ablation and sorted according to size using a differential mobility analyzer. Nanoparticles within a chosen window of sizes (e.g., (8.0 plus or minus 0.6) nm) are deposited electrostatically on a surface forming a film of the desired material. The system allows the assembly and engineering of thin films using size-classified nanoparticles as building blocks.

PST-Gold nanoparticle as an effective anticancer agent with immunomodulatory properties.

PubMed

Joseph, Manu M; Aravind, S R; Varghese, Sheeja; Mini, S; Sreelekha, T T

2013-04-01

Polysaccharide PST001, which is isolated from the seed kernels of Tamarindus indica (Ti), is an antitumor and immunomodulatory compound. Gold nanoparticles have been used for various applications in cancer. In the present report, a novel strategy for the synthesis and stabilization of gold nanoparticles using anticancer polysaccharide PST001 was employed and the nanoparticles' antitumor activity was evaluated. PST-Gold nanoparticles were prepared such that PST001 acted both as a reducing agent and as a capping agent. PST-Gold nanoparticles showed high stability, no obvious aggregation for months and a wide range of pH tolerance. PST-Gold nanoparticles not only retained the antitumor effect of PST001 but also showed an enhanced effect even at a low concentration. It was also found that the nanoparticles exerted their antitumor effects through the induction of apoptosis. In vivo assays on BALB/c mice revealed that PST-Gold nanoparticles exhibited immunomodulatory effects. Evaluation of biochemical, hematological and histopathological features of mice revealed that PST-Gold nanoparticles could be administered safely without toxicity. Using the polysaccharide PST001 for the reduction and stabilization of gold nanoparticles does not introduce any environmental toxicity or biological hazards, and these particles are more effective than the parent polysaccharide. Further studies should be employed to exploit these particles as anticancer agents with imaging properties. Copyright © 2012 Elsevier B.V. All rights reserved.

In vivo uptake and acute immune response to orally administered chitosan and PEG coated PLGA nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Semete, B., E-mail: Bsemete@csir.co.z; Booysen, L.I.J.; Department of Pharmaceutics, North-West University, Potchefstroom Campus, Potchefstroom, 2520

2010-12-01

Nanoparticulate drug delivery systems offer great promise in addressing challenges of drug toxicity, poor bioavailability and non-specificity for a number of drugs. Much progress has been reported for nano drug delivery systems for intravenous administration, however very little is known about the effects of orally administered nanoparticles. Furthermore, the development of nanoparticulate systems necessitates a thorough understanding of the biological response post exposure. This study aimed to elucidate the in vivo uptake of chitosan and polyethylene glycol (PEG) coated Poly, DL, lactic-co-glycolic Acid (PLGA) nanoparticles and the immunological response within 24 h of oral and peritoneal administration. These PLGA nanoparticlesmore » were administered orally and peritoneally to female Balb/C mice, they were taken up by macrophages of the peritoneum. When these particles were fluorescently labelled, intracellular localisation was observed. The expression of pro-inflammatory cytokines IL-2, IL-6, IL-12p70 and TNF-{alpha} in plasma and peritoneal lavage was found to remain at low concentration in PLGA nanoparticles treated mice as well as ZnO nanoparticles during the 24 hour period. However, these were significantly increased in lipopolysaccharide (LPS) treated mice. Of these pro-inflammatory cytokines, IL-6 and IL-12p70 were produced at the highest concentration in the positive control group. The anti-inflammatory cytokines IL-10 and chemokines INF-{gamma}, IL-4, IL-5 remained at normal levels in PLGA treated mice. IL-10 and INF-{gamma} were significantly increased in LPS treated mice. MCP-1 was found to be significantly produced in all groups in the first hours, except the saline treated mice. These results provide the first report to detail the induction of cytokine production by PLGA nanoparticles engineered for oral applications.« less

[Comparative Sensitivity of the Luminescent Photobacterium phosphoreum, Escherichia coli, and Bacillus subtilis Strains to Toxic Effects of Carbon-Based Nanomaterials and Metal Nanoparticles].

PubMed

Deryabina, D G; Efremova, L V; Karimov, I F; Manukhov, I V; Gnuchikh, E Yu; Miroshnikov, S A

2016-01-01

A comparative analysis of the four commercially available and laboratory luminescent sensor strains to the toxic effect of 10 carbon-based nanomatherials (CBNs) and 10 metal nanoparticles (MNPs) was carried out in this study. The bioluminescence inhibition assays with marine Photobacterium phosphoreum and recombinant Escherichia coli strains were varied in minimal toxic concentrations and EC50 values but led to well correlated biotoxicity evaluation for the most active compounds were ranked as Cu > (MgO, CuO) > (fullerenol, graphene oxide). The novel sensor strain Bacillus subtilis EG 168-1 exhibited the highest sensitivity to CBNs and MNPs that increased significantly number of toxic compounds causing the bacterial bioluminescence inhibition effect.

One-to-one comparison of sunscreen efficacy, aesthetics and potential nanotoxicity

NASA Astrophysics Data System (ADS)

Barnard, Amanda S.

2010-04-01

Numerous reports have described the superior properties of nanoparticles and their diverse range of applications. Issues of toxicity, workplace safety and environmental impact have also been a concern. Here we show a theoretical comparison of how the size of titanium dioxide nanoparticles and their concentration in sunscreens can affect efficacy, aesthetics and potential toxicity from free radical production. The simulation results reveal that, unless very small nanoparticles can be shown to be safe, there is no combination of particle size and concentration that will deliver optimal performance in terms of sun protection and aesthetics. Such a theoretical method complements well the experimental approach for identifying these characteristics.

Characteristics of silver nanoparticles in vehicles for biological applications.

PubMed

Kejlová, Kristina; Kašpárková, Věra; Krsek, Daniel; Jírová, Dagmar; Kolářová, Hana; Dvořáková, Markéta; Tománková, Kateřina; Mikulcová, Veronika

2015-12-30

Silver nanoparticles (AgNPs) have been used for decades as anti-bacterial agents in various industrial fields such as cosmetics, health industry, food storage, textile coatings and environmental applications, although their toxicity is not fully recognized yet. Antimicrobial and catalytic activity of AgNPs depends on their size as well as structure, shape, size distribution, and physico-chemical environment. The unique properties of AgNPs require novel or modified toxicological methods for evaluation of their toxic potential combined with robust analytical methods for characterization of nanoparticles applied in relevant vehicles, e.g., culture medium with/without serum and phosphate buffered saline. Copyright © 2015 Elsevier B.V. All rights reserved.

Health risk assessment for nanoparticles: A case for using expert judgment

NASA Astrophysics Data System (ADS)

Kandlikar, Milind; Ramachandran, Gurumurthy; Maynard, Andrew; Murdock, Barbara; Toscano, William A.

2007-01-01

Uncertainties in conventional quantitative risk assessment typically relate to values of parameters in risk models. For many environmental contaminants, there is a lack of sufficient information about multiple components of the risk assessment framework. In such cases, the use of default assumptions and extrapolations to fill in the data gaps is a common practice. Nanoparticle risks, however, pose a new form of risk assessment challenge. Besides a lack of data, there is deep scientific uncertainty regarding every aspect of the risk assessment framework: (a) particle characteristics that may affect toxicity; (b) their fate and transport through the environment; (c) the routes of exposure and the metrics by which exposure ought to be measured; (d) the mechanisms of translocation to different parts of the body; and (e) the mechanisms of toxicity and disease. In each of these areas, there are multiple and competing models and hypotheses. These are not merely parametric uncertainties but uncertainties about the choice of the causal mechanisms themselves and the proper model variables to be used, i.e., structural uncertainties. While these uncertainties exist for PM2.5 as well, risk assessment for PM2.5 has avoided dealing with these issues because of a plethora of epidemiological studies. However, such studies don't exist for the case of nanoparticles. Even if such studies are done in the future, they will be very specific to a particular type of engineered nanoparticle and not generalizable to other nanoparticles. Therefore, risk assessment for nanoparticles will have to deal with the various uncertainties that were avoided in the case of PM2.5. Consequently, uncertainties in estimating risks due to nanoparticle exposures may be characterized as `extreme'. This paper proposes a methodology by which risk analysts can cope with such extreme uncertainty. One way to make these problems analytically tractable is to use expert judgment approaches to study the degree of consensus and/or disagreement between experts on different parts of the exposure-response paradigm. This can be done by eliciting judgments from a wide range of experts on different parts of the risk causal chain. We also use examples to illustrate how studying expert consensus/disagreement helps in research prioritization and budget allocation exercises. The expert elicitation can be repeated over the course of several years, over which time, the state of scientific knowledge will also improve and uncertainties may possibly reduce. Results from expert the elicitation exercise can be used by risk managers or managers of funding agencies as a tool for research prioritization.

Assessing the Risk of Engineered Nanomaterials in the Environment: Development and Application of the nanoFate Model.

PubMed

Garner, Kendra L; Suh, Sangwon; Keller, Arturo A

2017-05-16

We developed a dynamic multimedia fate and transport model (nanoFate) to predict the time-dependent accumulation of metallic engineered nanomaterials (ENMs) across environmental media. nanoFate considers a wider range of processes and environmental subcompartments than most previous models and considers ENM releases to compartments (e.g., urban, agriculture) in a manner that reflects their different patterns of use and disposal. As an example, we simulated ten years of release of nano CeO 2 , CuO, TiO 2 , and ZnO in the San Francisco Bay area. Results show that even soluble metal oxide ENMs may accumulate as nanoparticles in the environment in sufficient concentrations to exceed the minimum toxic threshold in freshwater and some soils, though this is more likely with high-production ENMs such as TiO 2 and ZnO. Fluctuations in weather and release scenario may lead to circumstances where predicted ENM concentrations approach acute toxic concentrations. The fate of these ENMs is to mostly remain either aggregated or dissolved in agricultural lands receiving biosolids and in freshwater or marine sediments. Comparison to previous studies indicates the importance of some key model aspects including climatic and temporal variations, how ENMs may be released into the environment, and the effect of compartment composition on predicted concentrations.

Synthesis and 3D printing of biodegradable polyurethane elastomer by a water-based process for cartilage tissue engineering applications.

PubMed

Hung, Kun-Che; Tseng, Ching-Shiow; Hsu, Shan-Hui

2014-10-01

Biodegradable materials that can undergo degradation in vivo are commonly employed to manufacture tissue engineering scaffolds, by techniques including the customized 3D printing. Traditional 3D printing methods involve the use of heat, toxic organic solvents, or toxic photoinitiators for fabrication of synthetic scaffolds. So far, there is no investigation on water-based 3D printing for synthetic materials. In this study, the water dispersion of elastic and biodegradable polyurethane (PU) nanoparticles is synthesized, which is further employed to fabricate scaffolds by 3D printing using polyethylene oxide (PEO) as a viscosity enhancer. The surface morphology, degradation rate, and mechanical properties of the water-based 3D-printed PU scaffolds are evaluated and compared with those of polylactic-co-glycolic acid (PLGA) scaffolds made from the solution in organic solvent. These scaffolds are seeded with chondrocytes for evaluation of their potential as cartilage scaffolds. Chondrocytes in 3D-printed PU scaffolds have excellent seeding efficiency, proliferation, and matrix production. Since PU is a category of versatile materials, the aqueous 3D printing process developed in this study is a platform technology that can be used to fabricate devices for biomedical applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Engineered Nanomaterials in Food: Implications for Food Safety and Consumer Health

PubMed Central

Martirosyan, Alina; Schneider, Yves-Jacques

2014-01-01

From the current state-of-the-art, it is clear that nanotechnology applications are expected to bring a range of benefits to the food sector aiming at providing better quality and conservation. In the meantime, a growing number of studies indicate that the exposure to certain engineered nanomaterials (ENMs) has a potential to lead to health complications and that there is a need for further investigations in order to unravel the biological outcomes of nanofood consumption. In the current review, we summarize the existing data on the (potential) use of ENMs in the food industry, information on the toxicity profiles of the commonly applied ENMs, such as metal (oxide) nanoparticles (NPs), address the potential food safety implications and health hazards connected with the consumption of nanofood. A number of health complications connected with the human exposure to ENMs are discussed, demonstrating that there is a real basis for the arisen concern not only connected with the gut health, but also with the potency to lead to systemic toxicity. The toxicological nature of hazard, exposure levels and risk to consumers from nanotechnology-derived food are on the earliest stage of investigation and this review also highlights the major gaps that need further research and regulation. PMID:24879486

Polyvinylpyrrolidone and arsenic-induced changes in biological responses of model aquatic organisms exposed to iron-based nanoparticles

NASA Astrophysics Data System (ADS)

Llaneza, Verónica; Rodea-Palomares, Ismael; Zhou, Zuo; Rosal, Roberto; Fernández-Pina, Francisca; Bonzongo, Jean-Claude J.

2016-08-01

The efficiency of zero-valent iron particles used in the remediation of contaminated groundwater has, with the emergence of nanotechnology, stimulated interest on the use of nano-size particles to take advantage of high-specific surface area and reactivity characteristics of nanoparticles (NPs). Accordingly, engineered iron-NPs are among the most widely used nanomaterials for in situ remediation. However, while several ecotoxicity studies have been conducted to investigate the adverse impacts of these NPs on aquatic organisms, research on the implications of spent iron-based NPs is lacking. In this study, a comparative approach is used, in which the biological effects of three iron-based NPs (Fe3O4 and γ-Fe2O3 NPs with particle sizes ranging from 20 to 50 nm, and Fe0-NPs with an average particle size of 40 nm) on Raphidocelis subcapitata (formely known as Pseudokirchneriella subcapitata) and Daphnia magna were investigated using both as-prepared and pollutant-doped Fe-based NPs. For the latter, arsenic (As) was used as example sorbed pollutant. The results show that improved degree of NP dispersion by use of polyvinylpyrrolidone overlapped with both increased arsenic adsorption capacity and toxicity to the tested organisms. For R. subcapitata, Fe-oxide NPs were more toxic than Fe0-NPs, due primarily to differences in the degree of NPs aggregation and ability to produce reactive oxygen species. For the invertebrate D. magna, a similar trend of biological responses was observed, except that sorption of As to Fe0-NPs significantly increased the toxic response when compared to R. subcapitata. Overall, these findings point to the need for research on downstream implications of NP-pollutant complexes generated during water treatment by injection of NPs into aquatic systems.

Influence of titanium dioxide nanoparticles on the toxicity of arsenate in Nannochloropsis maritima.

PubMed

Yang, Fan; Yan, Changzhou

2018-06-13

Interest is growing in the role that nanoparticles play in modifying the biological effects of contaminants. This study aimed to determine whether nano-TiO 2 exhibited pronounced influence on arsenate (As(V)) toxicity levels to the marine microalgae Nannochloropsis maritima. We compared individual and combined toxicity levels of As(V) and nano-TiO 2 by assessing the inhibition percentages of algal growth. Compared to groups treated with As(V) alone, an EC 50 of 53.0 mg/L decreased by 28.8% after the addition of nanoparticles. This enhanced toxicity was attributed to the inhibition of As methylation and the promotion of lipid peroxidation in the presence of nano-TiO 2 . Additionally, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) also showed that algal cells exhibited different degrees of shrinkage, that cell wall were destroyed in the process, and that the photosynthetic apparatus was virtually indiscernible after the addition of nano-TiO 2 . In addition, for low As(V) concentration exposure groups, nano-TiO 2 could alleviate As(V) toxicity to some extent by reducing As sorption onto algal cells and subcellular distribution in organelles, but this alleviation effect could not protect against the combined toxicity (both As(V) and nano-TiO 2 ) effect on N. maritima, which was verified by the higher inhibition percentage of the algal growth rate in the combined exposure group treatment compared to the As(V) exposure treatment alone. Our results suggest that more attention must be paid to the potential impact of nanoparticles on the bioavailability and biotransformation of contaminants in phytoplankton. Copyright © 2018 Elsevier Ltd. All rights reserved.