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1

Altering iron oxide nanoparticle surface properties induce cortical neuron cytotoxicity.  

PubMed

Superparamagnetic iron oxide nanoparticles, with diameters in the range of a few tens of nanometers, display the ability to cross the blood-brain barrier and are envisioned as diagnostic and therapeutic tools in neuro-medicine. However, despite the numerous applications being explored, insufficient information is available on their potential toxic effect on neurons. While iron oxide has been shown to pose a decreased risk of toxicity, surface functionalization, often employed for targeted delivery, can significantly alter the biological response. This aspect is addressed in the present study, which investigates the response of primary cortical neurons to iron oxide nanoparticles with coatings frequently used in biomedical applications: aminosilane, dextran, and polydimethylamine. Prior to administering the particles to neuronal cultures, each particle type was thoroughly characterized to assess the (1) size of individual nanoparticles, (2) concentration of the particles in solution, and (3) agglomeration size and morphology. Culture results show that polydimethylamine functionalized nanoparticles induce cell death at all concentrations tested by swift and complete removal of the plasma membrane. Aminosilane coated particles affected metabolic activity only at higher concentrations while leaving the membrane intact, and dextran-coated nanoparticles partially altered viability at higher concentrations. These findings suggest that nanoparticle characterization and primary cell-based cytotoxicity evaluation should be completed prior to applying nanomaterials to the nervous system. PMID:22111864

Rivet, Christopher J; Yuan, Yuan; Borca-Tasciuc, Diana-Andra; Gilbert, Ryan J

2011-12-06

2

Gold nanoparticles induce cytotoxicity in the alveolar type-II cell lines A549 and NCIH441  

Microsoft Academic Search

BACKGROUND: During the last years engineered nanoparticles (NPs) have been extensively used in different technologies and consequently many questions have arisen about the risk and the impact on human health following exposure to nanoparticles. Nevertheless, at present knowledge about the cytotoxicity induced by NPs is still largely incomplete. In this context, we have investigated the cytotoxicity induced by gold nanoparticles

Chiara Uboldi; Daniele Bonacchi; Giada Lorenzi; M Iris Hermanns; Christine Pohl; Giovanni Baldi; Ronald E Unger; C James Kirkpatrick

2009-01-01

3

Exposure to ZnO nanoparticles induces oxidative stress and cytotoxicity in human colon carcinoma cells  

SciTech Connect

Engineered nanoparticles offer great promise in many industrial and biomedical applications, however little information is available about gastrointestinal toxicity. The purpose of this study was to assess the cytotoxicity, oxidative stress, apoptosis and proinflammatory mediator release induced by ZnO nanoparticles on human colon carcinoma LoVo cells. The biological activity of these particles was related to their physico-chemical characteristics. The physico-chemical characteristics were evaluated by analytical electron microscopy. The cytotoxicity was determined by growth curves and water-soluble tetrazolium assay. The reactive oxygen species production, cellular glutathione content, changes of mitochondrial membrane potential and apoptosis cell death were quantified by flow cytometry. The inflammatory cytokines were evaluated by enzyme-linked immunoadsorbent assay. Treatment with ZnO (5 {mu}g/cm{sup 2} corresponding to 11.5 {mu}g/ml) for 24 h induced on LoVo cells a significant decrease of cell viability, H{sub 2}O{sub 2}/OH{center_dot} increase, O2{sup -{center_dot}} and GSH decrease, depolarization of inner mitochondrial membranes, apoptosis and IL-8 release. Higher doses induced about 98% of cytotoxicity already after 24 h of treatment. The experimental data show that oxidative stress may be a key route in inducing the cytotoxicity of ZnO nanoparticles in colon carcinoma cells. Moreover, the study of the relationship between toxicological effects and physico-chemical characteristics of particles suggests that surface area does not play a primary role in the cytotoxicity.

De Berardis, Barbara; Civitelli, Gabriele; Condello, Maria; Lista, Pasquale; Pozzi, Roberta; Arancia, Giuseppe [Department of Technology and Health, Italian National Institute of Health, Viale Regina Elena 299, 00161 Rome (Italy); Meschini, Stefania, E-mail: stefania.meschini@iss.i [Department of Technology and Health, Italian National Institute of Health, Viale Regina Elena 299, 00161 Rome (Italy)

2010-08-01

4

Radiofrequency field-induced thermal cytotoxicity in cancer cells treated with fluorescent nanoparticles  

PubMed Central

Background Non-ionizing radiation, such as radiofrequency (RF) field and near infrared laser, induces thermal cytotoxicity in cancer cells treated with gold nanoparticles (AuNP). Quantum dots (QD) are fluorescent semiconducting nanoparticles that we hypothesize will induce similar injury following RF field irradiation. Methods AuNP and two types of QD (cadmium-selenide and indium-gallium-phosphide) conjugated to cetuximab (C225), a monoclonal antibody against human epidermal growth factor receptor (EGFR-1), demonstrated concentration-dependent heating in a RF field. We investigated the effect of RF field exposure after targeted nanoparticle treatment in a co-culture of two human cancer cell lines that have differential EGFR-1 expression (a high expressing pancreatic carcinoma, Panc-1, and a low expressing breast carcinoma, Cama-1). Results RF exposed Panc-1 or Cama-1 cells not containing AuNP or QD had a viability greater than 92%. The viability of Panc-1 cells exposed to the RF field after treatment with 50 nM Au-C225 was 39.4% ± 8.3% without injury to bystander Cama-1 cells (viability was 93.7% ± 1.0%, p ~ 0.0006). Panc-1 cells treated with targeted Cd-Se QD were only 47.5% viable after RF field exposure (p < 0.0001 compared to RF only Panc-1 control cells). Targeted InGaP QD decreased Panc-1 viability to 58.2% ± 3.4% after RF field exposure (p ~ 0.0004 compared to Cama-1 and Panc-1 controls). Conclusion We selectively induced RF field cytotoxicity in Panc-1 cells without injury to bystander Cama-1 cells utilizing EGFR-1 targeted nanoparticles, and demonstrated an interesting bifunctionality of fluorescent nanoparticles as agents for both cancer cell imaging and treatment.

Glazer, Evan S.; Curley, Steven A.

2010-01-01

5

Copper Oxide Nanoparticles Induce Oxidative Stress and Cytotoxicity in Airway Epithelial Cells  

PubMed Central

Metal oxide nanoparticles are often used as industrial catalysts and elevated levels of these particles have been clearly demonstrated at sites surrounding factories. To date, limited toxicity data on metal oxide nanoparticles are available. To understand the impact of these airborne pollutants on the respiratory system, airway epithelial (HEp-2) cells were exposed to increasing doses of silicon oxide (SiO2), ferric oxide (Fe2O3) and copper oxide (CuO) nanoparticles, the leading metal oxides found in ambient air surrounding factories. CuO induced the greatest amount of cytotoxicity in a dose dependent manner; while even high doses (400 µg/cm2) of SiO2 and Fe2O3 were non-toxic to HEp-2 cells. Although all metal oxide nanoparticles were able to generate ROS in HEp-2 cells, CuO was better able to overwhelm antioxidant defenses (e.g. catalase and glutathione reductase). A significant increase in the level of 8-isoprostanes and in the ratio of GSSG to total glutathione in cells exposed to CuO suggested that ROS generated by CuO induced oxidative stress in HEp-2 cells. Co-treatment of cells with CuO and the antioxidant resveratrol increased cell viability suggesting that oxidative stress may be the cause of the cytotoxic effect of CuO. These studies demonstrated that there is a high degree of variability in the cytotoxic effects of metal oxides, that this variability is not due to the solubility of the transition metal, and that this variability appears to involve sustained oxidative stress possibly due to redox cycling.

Fahmy, Baher; Cormier, Stephania A.

2009-01-01

6

Gold Nanoparticles Cytotoxicity  

NASA Astrophysics Data System (ADS)

Over the last two decades gold nanoparticles (AuNPs) have been used for many scientific applications and have attracted attention due to the specific chemical, electronic and optical size dependent properties that make them very promising agents in many fields such as medicine, imagine techniques and electronics. More specifically, biocompatible gold nanoparticles have a huge potential for use as the contrast augmentation agent in X-ray Computed Tomography and Photo Acoustic Tomography for early tumor diagnostic as well these nanoparticles are extensively researched for enhancing the targeted cancer treatment effectiveness such as photo-thermal and radiotherapy. In most biomedical applications biocompatible gold nanoparticles are labeled with specific tumor or other pathology targeting antibodies and used for site specific drug delivery. However, even though gold nanoparticles poses very high level of anti cancer properties, the question of their cytotoxicity ones they are released in normal tissue has to be researched. Moreover, the huge amount of industrially produced gold nanoparticles raises the question of these particles being a health hazard, since the penetration is fairly easy for the "nano" size substances. This study focuses on the effect of AuNPs on a human skin tissue, since it is fall in both categories -- the side effects for biomedical applications and industrial workers and users' exposure during production and handling. Therefore, in the present project, gold nanoparticles stabilized with the biocompatible agent citric acid were generated and characterized by Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). The cytotoxic effect of AuNPs release to healthy skin tissue was modeled on 3 different cell types: human keratinocytes, human dermal fibroblasts, and human adipose derived stromal (ADS) cells. The AuNPs localization inside the cell was found to be cell type dependent. Overall cytotoxicity was found to be dependent on time, concentration and nanoparticle size. Additionally, the question of cell recovery once the source of AuNPs is removed was investigated in the present work. It was found that full cell functions recovery is possible after removing the source of nanoparticles.

Mironava, Tatsiana

7

Cytotoxic Effects of Fucoidan Nanoparticles against Osteosarcoma.  

PubMed

In this study, we analyzed the size-dependent bioactivities of fucoidan by comparing the cytotoxic effects of native fucoidan and fucoidan lipid nanoparticles on osteosarcoma in vitro and in vivo. In vitro experiments indicated that nanoparticle fucoidan induced apoptosis of an osteosarcoma cell line more efficiently than native fucoidan. The more potent effects of nanoparticle fucoidan, relative to native fucoidan, were confirmed in vivo using a xenograft osteosarcoma model. Caco-2 cell transport studies showed that permeation of nanoparticle fucoidan was higher than native fucoidan. The higher bioactivity and superior bioavailability of nanoparticle fucoidan could potentially be utilized to develop novel therapies for osteosarcoma. PMID:24177673

Kimura, Ryuichiro; Rokkaku, Takayoshi; Takeda, Shinji; Senba, Masachika; Mori, Naoki

2013-10-30

8

Gold nanoparticles induce cytotoxicity in the alveolar type-II cell lines A549 and NCIH441  

PubMed Central

Background During the last years engineered nanoparticles (NPs) have been extensively used in different technologies and consequently many questions have arisen about the risk and the impact on human health following exposure to nanoparticles. Nevertheless, at present knowledge about the cytotoxicity induced by NPs is still largely incomplete. In this context, we have investigated the cytotoxicity induced by gold nanoparticles (AuNPs), which differed in size and purification grade (presence or absence of sodium citrate residues on the particle surface) in vitro, in the human alveolar type-II (ATII)-like cell lines A549 and NCIH441. Results We found that the presence of sodium citrate residues on AuNPs impaired the viability of the ATII-like cell lines A549 and NCIH441. Interestingly, the presence of an excess of sodium citrate on the surface of NPs not only reduced the in vitro viability of the cell lines A549 and NCIH441, as shown by MTT assay, but also affected cellular proliferation and increased the release of lactate dehydrogenase (LDH), as demonstrated by Ki-67 and LDH-release assays respectively. Furthermore, we investigated the internalization of AuNPs by transmission electron microscopy (TEM) and we observed that particles were internalized by active endocytosis in the cell lines A549 and NCIH441 within 3 hr. In addition, gold particles accumulated in membrane-bound vesicles and were not found freely dispersed in the cytoplasm. Conclusion Our data suggest that the presence of contaminants, such as sodium citrate, on the surface of gold nanoparticles might play a pivotal role in inducing cytotoxicity in vitro, but does not influence the uptake of the particles in human ATII-like cell lines.

Uboldi, Chiara; Bonacchi, Daniele; Lorenzi, Giada; Hermanns, M Iris; Pohl, Christine; Baldi, Giovanni; Unger, Ronald E; Kirkpatrick, C James

2009-01-01

9

Real-time cell-microelectronic sensing of nanoparticle-induced cytotoxic effects.  

PubMed

We report a real-time cell analysis (RTCA) sensing method of 96 electronic microwells for profiling the cytotoxicity of nanoparticles on different cell lines. The method consists of 96 microwells embedded with microelectrodes (96x E-plate) to measure impedance changes of adherent cell lines. When the testing cells change in population, adhesion, and/or morphology, the impedance at the cell-electrode interface changes to provide real-time monitoring of overall cell status. To demonstrate this technique, we used three cell lines as sensing probes: two human lung carcinoma cell lines, A549 and SK-MES-1, and a normal mammalian cell line, CHO-K1. We tested two well-characterized nanoparticles: nano-titanium dioxide (nTiO2) and nano-silver (nAg). The three cell lines were separately seeded into 96x E-plates and treated with varying concentrations of nanoparticles (0.078-160 ?g mL(-1)). This method provides dynamic cell response profiles and temporal IC50 histograms, showing concentration-, time-, particle-, and cell-dependent cytotoxicity. The 24 h and 48 h IC50 values of nAg obtained using both the RTCA and the neutral red uptake (NRU) assays were in good agreement, validating the RTCA technique. The RTCA assay does not suffer interference from nTiO2, whereas the NRU assay cannot be used due to severe interference from nTiO2. A cytostatic response was observed in CHO-K1 cells after 24 h exposure to 40 ?g mL(-1) nTiO2, which was correlated with S-phase cell cycle arrest based on cell cycle analysis using flow cytometry. This suggests that the shapes of the response curves provide indicative information, directing further studies into the mode of action of the toxicant. Advantages of the RTCA technique over traditional colorimetric assays for screening the cytotoxicity of nanoparticles include minimizing interference, qualitative and quantitative cytotoxicity data, and the capability of real-time and high-throughput measurements. PMID:23856233

Moe, Birget; Gabos, Stephan; Li, Xing-Fang

2013-06-18

10

Oxidative stress contributes to cobalt oxide nanoparticles-induced cytotoxicity and DNA damage in human hepatocarcinoma cells  

PubMed Central

Background Cobalt oxide nanoparticles (Co3O4NPs) are increasingly recognized for their utility in biological applications, magnetic resonance imaging, and drug delivery. However, little is known about the toxicity of Co3O4NPs in human cells. Methods We investigated the possible mechanisms of genotoxicity induced by Co3O4NPs in human hepatocarcinoma (HepG2) cells. Cell viability, reactive oxygen species (ROS), glutathione, thiobarbituric acid reactive substance, apoptosis, and DNA damage were assessed in HepG2 cells after Co3O4NPs and Co2+ exposure. Results Co3O4NPs elicited a significant (P < 0.01) reduction in glutathione with a concomitant increase in lipid hydroperoxide, ROS generation, superoxide dismutase, and catalase activity after 24- and 48-hour exposure. Co3O4NPs had a mild cytotoxic effect in HepG2 cells; however, it induced ROS and oxidative stress, leading to DNA damage, a probable mechanism of genotoxicity. The comet assay showed a statistically significant (P < 0.01) dose- and time-related increase in DNA damage for Co3O4NPs, whereas Co2+ induced less change than Co3O4NPs but significantly more than control. Conclusion Our results demonstrated that Co3O4NPs induced cytotoxicity and genotoxicity in HepG2 cells through ROS and oxidative stress.

Alarifi, Saud; Ali, Daoud; Y, Al Omar Suliman; Ahamed, Maqusood; Siddiqui, Maqsood A; Al-Khedhairy, Abdulaziz A

2013-01-01

11

Size-Dependent Cytotoxicity of Gold Nanoparticles  

Microsoft Academic Search

Gold nanoparticles are widely used in biomedical imaging and diagnos- tic tests. Based on their established use in the laboratory and the chemical stability of Au0, gold nanoparticles were expected to be safe. The recent literature, however, contains conflictingdata reg ardingthe cytotoxicity of gold nanoparticles. Against this background a systematic study of water- soluble gold nanoparticles stabilized by triphenylphosphine derivatives

Yu Pan; Sabine Neuss; Annika Leifert; Monika Fischler; Fei Wen; Ulrich Simon; Günter Schmid; Wolfgang Brandau; Willi Jahnen-Dechent

2007-01-01

12

Comparative study of predictive computational models for nanoparticle-induced cytotoxicity.  

PubMed

With the increasing use of nanomaterials incorporated into consumer products, there is a need for developing approaches to establish "quantitative structure-activity relationships" (QSARs). These relationships could be used to predict various biological responses after exposure to nanomaterials for the purposes of risk analysis. This risk analysis is applicable to manufacturers of nanomaterials in an effort to determine potential hazards. Because metal oxide materials are some of the most widely applicable and studied nanoparticle types for incorporation into cosmetics, food packaging, and paints and coatings, we focused on comparing different approaches for establishing QSARs for this class of materials. Metal oxide nanoparticles are believed, by some, to cause alterations in cellular function due to their size and/or surface area. Others have said that these nanomaterials, because of the oxidized state of the metal, do not induce stress in biological tests systems. This controversy highlights the need to systematically develop structure-activity relationships (i.e., the relationship between physicochemical features to the cellular responses) and tools for predicting potential biological effects after a metal oxide nanomaterial exposure. Here, we attempt to identify a set of properties of two specific metal oxide nanomaterials-TiO(2) and ZnO-that could be used to characterize and predict the induced cellular membrane damage of immortalized human lung epithelial cells. We adopt a mathematical modeling approach that uses the engineered nanomaterial size characterized as a dry nanopowder and the nanomaterial behavior in ultrapure water, phosphate buffer, and cell culture media to predict nanomaterial-induced cellular membrane damage (via lactate dehydrogenase release). Results of these studies provide insights on how engineered nanomaterial features influence cellular responses and thereby outline possible approaches for developing and applying predictive computational models for biological responses caused by exposure to nanomaterials. PMID:20561263

Sayes, Christie; Ivanov, Ivan

2010-11-01

13

Irradiation stability and cytotoxicity of gold nanoparticles for radiotherapy  

PubMed Central

Gold nanoparticles are promising as a kind of novel radiosensitizer in radiotherapy. If gold nanoparticles are shown to have good irradiation stability and biocompatibility, they would play an important role in radiotherapy. In this work, we investigated irradiation effects of gold nanoparticles under 2–10 kR gamma irradiation and cytotoxicity of gold nanoparticles with human K562 cells by using Cell Titre-Glo™ luminescent cell viability assay. The results revealed that gamma irradiation had not induced any obvious instability and size variations in gold nanoparticles. We found that gold nanoparticles showed excellent radiation hardness with an absorbed dose conversation factor of 9.491 rad/R. Meanwhile, the surface plasmon resonance of gold nanoparticles was enhanced obviously after 2–10 kR gamma irradiation. Subsequently, cytotoxicity tests indicated that the extremely high concentration of gold nanoparticles could cause a sharp decrease in K562 cell viability, while the low concentration of gold nanoparticles had no obvious influence on the cell viability. Our results revealed that gold nanoparticles were stable under high-energy ray irradiation and showed concentration-dependent cytotoxicity.

Zhang, Xiao-Dong; Guo, Mei-Li; Wu, Hong-Ying; Sun, Yuan-Ming; Ding, Yan-Qiu; Feng, Xin; Zhang, Liang-An

2009-01-01

14

Evaluating cell specific cytotoxicity of differentially charged silver nanoparticles.  

PubMed

Silver nanoparticles (AgNPs) are one of the most commercially viable nanotechnological products, nevertheless; safety issues are raised regarding the use of such nanoparticles due to unintentional health and environmental impacts. In the present study, AgNPs were synthesized by chemically reducing silver nitrate alternatively with sodium borohydride, tannic acid, ascorbic acid and sodium citrate. AgNPs synthesized by reduction with tannic acid (TSNPs) and sodium borohydride (BSNPs) exhibited highest and lowest surface potential respectively. Therefore these two types of AgNPs were selected for their toxicity assessment in cellular environment. We treated skin epithelial A431, lung epithelial A549 and murine macrophages RAW264.7 cells with AgNPs over a range of doses (5-100?g/ml). Toxicity was evaluated by measuring changes in cellular morphology, ROS generation, metabolic activity and expression of various stress markers. Interestingly, TSNPs exhibited a higher negative zeta-potential and also higher toxicity. Higher toxicity of TSNPs was attested by dose-dependent increase in cellular disruption and ROS generation. BSNPs showed cytotoxic effect up to the concentration of 50?g/ml and thereafter the cytotoxic effect attenuated. TSNPs induced a dose dependent increase in the expression of stress markers pp38, TNF-? and HSP-70. Our report proposes that cytotoxicity of AgNPs changes with surface potential of nanoparticles and cells type. PMID:22975145

Kaur, Jasmine; Tikoo, Kulbhushan

2012-08-30

15

In Vitro Cytotoxicity of Fluorescent Silica Nanoparticles Hybridized with Aggregation-Induced Emission Luminogens for Living Cell Imaging  

PubMed Central

Fluorescent silica nanoparticles (FSNPs) can provide high-intensity and photostable fluorescent signals as a probe for biomedical analysis. In this study, FSNPs hybridized with aggregation-induced emission (AIE) luminogens (namely FSNP-SD) were successfully fabricated by a surfactant-free sol-gel method. The FSNP-SD were spherical, monodisperse and uniform in size, with an average diameter of approximately 100 nm, and emitted strong fluorescence at the peak of 490 nm. The FSNP-SD selectively stained the cytoplasmic regions and were distributed in the cytoplasm. Moreover, they can stay inside cells, enabling the tacking of cells over a long period of time. The intracellular vesicles and multinucleated cells were increase gradually with the rise of FSNP-SD concentration. Both cell viability and survival only lost less than 20% when the cells were exposed to the high concentration of 100 ?g/mL FSNP-SD. Additionally, the cell apoptosis and intracellular ROS assay indicated that FSNP-SD had no significant toxic effects at the maximum working concentration of 80 ?g/mL. This study demonstrated that the FSNP-SD are promising biocompatible fluorescent probes for living cell imaging.

Xia, Yun; Li, Min; Peng, Tao; Zhang, Weijie; Xiong, Jun; Hu, Qinggang; Song, Zifang; Zheng, Qichang

2013-01-01

16

Copper(ii) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response  

NASA Astrophysics Data System (ADS)

The potential toxic effects of two types of copper(ii) oxide (CuO) nanoparticles (NPs) with different specific surface areas, different shapes (rod or spheric), different sizes as raw materials and similar hydrodynamic diameter in suspension were studied on human hepatocarcinoma HepG2 cells. Both CuO NPs were shown to be able to enter into HepG2 cells and induce cellular toxicity by generating reactive oxygen species. CuO NPs increased the abundance of several transcripts coding for pro-inflammatory interleukins and chemokines. Transcriptomic data, siRNA knockdown and DNA binding activities suggested that Nrf2, NF-?B and AP-1 were implicated in the response of HepG2 cells to CuO NPs. CuO NP incubation also induced activation of MAPK pathways, ERKs and JNK/SAPK, playing a major role in the activation of AP-1. In addition, cytotoxicity, inflammatory and antioxidative responses and activation of intracellular transduction pathways induced by rod-shaped CuO NPs were more important than spherical CuO NPs. Measurement of Cu2+ released in cell culture medium suggested that Cu2+ cations released from CuO NPs were involved only to a small extent in the toxicity induced by these NPs on HepG2 cells.The potential toxic effects of two types of copper(ii) oxide (CuO) nanoparticles (NPs) with different specific surface areas, different shapes (rod or spheric), different sizes as raw materials and similar hydrodynamic diameter in suspension were studied on human hepatocarcinoma HepG2 cells. Both CuO NPs were shown to be able to enter into HepG2 cells and induce cellular toxicity by generating reactive oxygen species. CuO NPs increased the abundance of several transcripts coding for pro-inflammatory interleukins and chemokines. Transcriptomic data, siRNA knockdown and DNA binding activities suggested that Nrf2, NF-?B and AP-1 were implicated in the response of HepG2 cells to CuO NPs. CuO NP incubation also induced activation of MAPK pathways, ERKs and JNK/SAPK, playing a major role in the activation of AP-1. In addition, cytotoxicity, inflammatory and antioxidative responses and activation of intracellular transduction pathways induced by rod-shaped CuO NPs were more important than spherical CuO NPs. Measurement of Cu2+ released in cell culture medium suggested that Cu2+ cations released from CuO NPs were involved only to a small extent in the toxicity induced by these NPs on HepG2 cells. Electronic supplementary information (ESI) available: Additional tables and figures supporting the information presented in the manuscript. See DOI: 10.1039/c2nr31785k

Piret, Jean-Pascal; Jacques, Diane; Audinot, Jean-Nicolas; Mejia, Jorge; Boilan, Emmanuelle; Noël, Florence; Fransolet, Maude; Demazy, Catherine; Lucas, Stéphane; Saout, Christelle; Toussaint, Olivier

2012-10-01

17

Cytotoxicity of Phenol Red in Toxicity Assays for Carbon Nanoparticles  

PubMed Central

To explore the novel properties of carbon nanoparticles (CNPs) in nanotoxicity assays, the adsorption of phenol red (a pH indicator for culture medium) by multi-walled carbon nanotubes (MWNTs) and three kinds of carbon blacks (CBs) with nanosize, and its effects on cytotoxicity were studied. Results indicated that the phenol red adsorbed and delivered into cells by CBs was responsible for the toxicity to Hela cells in the medium without serum. The cellular uptake of phenol red was verified using 125I-labeling techniques. The size-dependent cytotoxicity of CBs was found to closely correlate to adsorption of phenol red, cellular uptake of phenol red-CB complexes and the amount of phenol red delivered into the cells by CBs. Although the CBs were either nontoxic or slightly toxic, as vehicles of phenol red, they played an essential role in the cytotoxicity induced by phenol red. However, MWNTs showed an intrinsic cytotoxicity independent of phenol red. The implications associated with these findings are discussed.

Zhu, Ying; Zhang, Xiaoyong; Zhu, Jianhua; Zhao, Qunfen; Li, Yuguo; Li, Wenxin; Fan, Chunhai; Huang, Qing

2012-01-01

18

Comparison of iron oxide nanoparticle and waterbath hyperthermia cytotoxicity  

NASA Astrophysics Data System (ADS)

The development of medical grade iron oxide nanoparticles (IONP) has renewed interest in hyperthermia cancer therapy. Because of their modifiable size and heating capabilities under an AC magnetic field (alternating magnetic field, AMF), IONPs have the potential to damage or kill cells in a manner more therapeutically efficient than previous hyperthermia techniques. The use of IONPs in hyperthermia cancer therapy has prompted numerous questions regarding the cytotoxic mechanism associated with IONP heat therapy and if such mechanism is different (more or less effective) with respect to conventional hyperthermia techniques. In this in vitro study, we determine the immediate and long-term (24 hours) cytotoxic effects of isothermal IONP hyperthermia treatment versus a conventional global heating technique (water bath). Using the same heating time and temperature we showed significantly greater cytotoxicity in IONP-heated cells as opposed to water bath-treated cells. We postulate that the difference in treatment efficacy is due to the spatial relationship of particle-induced thermal damage within cells. Although the exact mechanism is still unclear, it appears likely that intracellular IONPs have to achieve a very high temperature in order to heat the surrounding environment; therefore it is reasonable to assume that particles localized to specific areas of the cell such as the membrane can deliver exacerbated injury to those areas. In this experiment, although detectable global temperature for the particle-heated cells stands comparable to the conventional heat treatment, particle-induced cell death is higher. From the results of this study, we propose that the mechanism of IONP hyperthermia renders enhanced cytotoxicity compared to conventional waterbath hyperthermia at the same measured thermal dose.

Ogden, J. A.; Tate, J. A.; Strawbridge, R. R.; Ivkov, R.; Hoopes, P. J.

2009-02-01

19

Evaluation of cytotoxicity of polypyrrole nanoparticles synthesized by oxidative polymerization.  

PubMed

Polypyrrole (Ppy) is known as biocompatible material, which is used in some diverse biomedical applications and seeming to be a very promising for advanced biotechnological applications. In order to increase our understanding about biocompatibility of Ppy, in this study pure Ppy nanoparticles (Ppy-NPs) of fixed size and morphology were prepared by one-step oxidative polymerization and their cyto-compatibility was evaluated. The impact of different concentration of Ppy nanoparticles on primary mouse embryonic fibroblasts (MEF), mouse hepatoma cell line (MH-22A), and human T lymphocyte Jurkat cell line was investigated. Cell morphology, viability/proliferation after the treatment by Ppy nanoparticles was evaluated. Obtained results showed that Ppy nanoparticles at low concentrations are biocompatible, while at high concentrations they became cytotoxic for Jurkat, MEF and MH-22A cells, and it was found that cytotoxic effect is dose-dependent. PMID:23454454

Vaitkuviene, Aida; Kaseta, Vytautas; Voronovic, Jaroslav; Ramanauskaite, Giedre; Biziuleviciene, Gene; Ramanaviciene, Almira; Ramanavicius, Arunas

2013-02-08

20

Synthesis and cytotoxicity evaluation of novel acylated starch nanoparticles.  

PubMed

Starch nanoparticles (StNPs) were acylated under ambient conditions to obtain various nanosized derivatives formed stable suspension in water and soluble in organic solvents. The degree of substitution (DS) was determined using (1)H NMR technique. The cytotoxicity potential of the derivatised StNPs was evaluated in mouse embryonic fibroblast (3T3L1) cells and A549 tumor cell line using MTT cell viability assay. Other parameters that determine the oxidative stress viz., reactive oxygen species (ROS) generation, intracellular reduced glutathione (GSH), superoxide generation and acridine orange/ethidium bromide staining were also investigated. The present study led to the conclusion that cytotoxic activity of acylated starch nanoparticles was dependent on their dosage, DS and type of substitution. The non-toxic nature in non-cancerous cells reveals that the nanoparticles (NPs) can be used for cancer therapy and drug delivery. The nanoparticles also offered reasonable binding propensity with CT-DNA. PMID:23247257

Thakore, Sonal; Valodkar, Mayur; Soni, Jigar Y; Vyas, Komal; Jadeja, Rajendrasinh N; Devkar, Ranjitsinh V; Rathore, Puran Singh

2012-10-13

21

Imaging carbon nanoparticles and related cytotoxicity  

NASA Astrophysics Data System (ADS)

Carbon-based nanoparticles have attracted significant attention due to their unique physical, chemical, and electrical properties. Numerous studies have been published on carbon nanoparticle toxicity; however, the results remain contradictory. An ideal approach is to combine a cell viability assay with nanometer scale imaging to elucidate the detailed physiological and structural effects of cellular exposure to nanoparticles. We have developed and applied a combination of advanced microscopy techniques to image carbon nanoparticles within cells. Specifically, we have used EFTEM, HAADF-STEM, and tomography and confocal microscopy to generate 3-D images enabling determination of nanoparticle spatial distribution in a cell. With these techniques, we can differentiate between the carbon nanoparticles and the cell in both stained and unstained sections. We found carbon nanoparticles (C60, single-walled carbon nanotubes (SWNT), and multi-walled carbon nanotubes (MWNT)) within the cytoplasm, lysosomes, and nucleus of human monocyte-derived macrophage cells (HMM). C60 aggregated along the plasma and nuclear membrane while MWNTs and SWNTs were seen penetrating the plasma and nuclear membranes. Both the Neutral Red (NR) assay and ultra-stuctural analysis showed an increase in cell death after exposure to MWNTs and SWNTs. SWNTs were more toxic than MWNTs. For both MWNTs and SWNTs, we correlated uptake of the nanoparticles with a significant increase in necrosis. In conclusion, high resolution imaging studies provide us with significant insight into the localised interactions between carbon nanoparticles and cells. Viability assays alone only provide a broad toxicological picture of nanoparticle effects on cells whereas the high resolution images associate the spatial distributions of the nanoparticles within the cell with increased incidence of necrosis. This combined approach will enable us to probe the mechanisms of particle uptake and subsequent chemical changes within the cell, essential for identifying the toxicological profiles of carbon nanoparticles.

Cheng, C.; Porter, A. E.; Muller, K.; Koziol, K.; Skepper, J. N.; Midgley, P.; Welland, M.

2009-02-01

22

The Influences of Cell Type and ZnO Nanoparticle Size on Immune Cell Cytotoxicity and Cytokine Induction  

NASA Astrophysics Data System (ADS)

Nanotechnology represents a new and enabling platform that promises to provide a range of innovative technologies for biological applications. ZnO nanoparticles of controlled size were synthesized, and their cytotoxicity toward different human immune cells evaluated. A differential cytotoxic response between human immune cell subsets was observed, with lymphocytes being the most resistant and monocytes being the most susceptible to ZnO nanoparticle-induced toxicity. Significant differences were also observed between previously activated memory lymphocytes and naive lymphocytes, indicating a relationship between cell-cycle potential and nanoparticle susceptibility. Mechanisms of toxicity involve the generation of reactive oxygen species, with monocytes displaying the highest levels, and the degree of cytotoxicity dependent on the extent of nanoparticle interactions with cellular membranes. An inverse relationship between nanoparticle size and cytotoxicity, as well as nanoparticle size and reactive oxygen species production was observed. In addition, ZnO nanoparticles induce the production of the proinflammatory cytokines, IFN-?, TNF-?, and IL-12, at concentrations below those causing appreciable cell death. Collectively, these results underscore the need for careful evaluation of ZnO nanoparticle effects across a spectrum of relevant cell types when considering their use for potential new nanotechnology-based biological applications.

Hanley, Cory; Thurber, Aaron; Hanna, Charles; Punnoose, Alex; Zhang, Jianhui; Wingett, Denise G.

2009-12-01

23

The Influences of Cell Type and ZnO Nanoparticle Size on Immune Cell Cytotoxicity and Cytokine Induction  

PubMed Central

Nanotechnology represents a new and enabling platform that promises to provide a range of innovative technologies for biological applications. ZnO nanoparticles of controlled size were synthesized, and their cytotoxicity toward different human immune cells evaluated. A differential cytotoxic response between human immune cell subsets was observed, with lymphocytes being the most resistant and monocytes being the most susceptible to ZnO nanoparticle-induced toxicity. Significant differences were also observed between previously activated memory lymphocytes and naive lymphocytes, indicating a relationship between cell-cycle potential and nanoparticle susceptibility. Mechanisms of toxicity involve the generation of reactive oxygen species, with monocytes displaying the highest levels, and the degree of cytotoxicity dependent on the extent of nanoparticle interactions with cellular membranes. An inverse relationship between nanoparticle size and cytotoxicity, as well as nanoparticle size and reactive oxygen species production was observed. In addition, ZnO nanoparticles induce the production of the proinflammatory cytokines, IFN-?, TNF-?, and IL-12, at concentrations below those causing appreciable cell death. Collectively, these results underscore the need for careful evaluation of ZnO nanoparticle effects across a spectrum of relevant cell types when considering their use for potential new nanotechnology-based biological applications.

2009-01-01

24

Cytotoxicity of metal and semiconductor nanoparticles indicated by cellular micromotility.  

PubMed

In the growing field of nanotechnology, there is an urgent need to sensitively determine the toxicity of nanoparticles since many technical and medical applications are based on controlled exposure to particles, that is, as contrast agents or for drug delivery. Before the in vivo implementation, in vitro cell experiments are required to achieve a detailed knowledge of toxicity and biodegradation as a function of the nanoparticles' physical and chemical properties. In this study, we show that the micromotility of animal cells as monitored by electrical cell-substrate impedance analysis (ECIS) is highly suitable to quantify in vitro cytotoxicity of semiconductor quantum dots and gold nanorods. The method is validated by conventional cytotoxicity testing and accompanied by fluorescence and dark-field microscopy to visualize changes in the cytoskeleton integrity and to determine the location of the particles within the cell. PMID:19206269

Tarantola, Marco; Schneider, David; Sunnick, Eva; Adam, Holger; Pierrat, Sebastien; Rosman, Christina; Breus, Vladimir; Sönnichsen, Carsten; Basché, Thomas; Wegener, Joachim; Janshoff, Andreas

2009-01-27

25

The effect of static magnetic fields on the aggregation and cytotoxicity of magnetic nanoparticles.  

PubMed

Biomedical applications of magnetic nanoparticles (MNP), including superparamagnetic nanoparticles, have expanded dramatically in recent years. Systematic and standardized cytotoxicity assessment to ensure the biosafety and biocompatibility of those applications is compulsory. We investigated whether exposure to static magnetic field (SMF) from e.g. magnetic resonance imaging (MRI) could affect the cytotoxicity of superparamagnetic iron oxide (SPIO) nanoparticles using mouse hepatocytes and ferucarbotran, a liver-selective MRI contrast agent as a model system. We show that while the SPIO satisfied the conventional cytotoxicity assessment, clinical doses combined with SMF exposure exerts synergistic adverse effects such as reduced cell viability, apoptosis, and cell cycle aberrations on hepatocytes in vitro and in vivo. Concomitant treatments with the SPIO and SMF generated SPIO aggregates, which demonstrated enhanced cellular uptake, was sufficient to induce the cytotoxicity without further SMF, emphasizing that the SPIO aggregates were the predominant source of the cytotoxicity. Interestingly, the apoptotic effect was dependent on levels of reactive oxygen species (ROS) and SPIO uptake while the reduced cell viability was independent of these factors. Moreover, long-term monitoring showed a significant increase in multinuclear giant cells in the cells concomitantly treated with the SPIO and SMF compared with the control. The results demonstrate that the SPIO produces unidentified cytotoxicity on liver in the presence of SMF and the SPIO aggregates predominantly exert the effect. Since aggregation of MNP in biological milieu in the presence of strong SMF is inevitable, a fundamentally different approach to surface fabrication is essential to increase the biocompatibility of MNP. PMID:21911251

Bae, Ji-Eun; Huh, Man-Il; Ryu, Byung-Kyu; Do, Ji-Yeon; Jin, Seong-Uk; Moon, Myung-Jin; Jung, Jae-Chang; Chang, Yongmin; Kim, Eungseok; Chi, Sung-Gil; Lee, Gang-Ho; Chae, Kwon-Seok

2011-09-10

26

Evaluation of cytotoxic, genotoxic and inflammatory responses of nanoparticles from photocopiers in three human cell lines  

PubMed Central

Background Photocopiers emit nanoparticles with complex chemical composition. Short-term exposures to modest nanoparticle concentrations triggered upper airway inflammation and oxidative stress in healthy human volunteers in a recent study. To further understand the toxicological properties of copier-emitted nanoparticles, we studied in-vitro their ability to induce cytotoxicity, pro-inflammatory cytokine release, DNA damage, and apoptosis in relevant human cell lines. Methods Three cell types were used: THP-1, primary human nasal- and small airway epithelial cells. Following collection in a large volume photocopy center, nanoparticles were extracted, dispersed and characterized in the cell culture medium. Cells were doped at 30, 100 and 300 ?g/mL administered doses for up to 24 hrs. Estimated dose delivered to cells, was ~10% and 22% of the administered dose at 6 and 24 hrs, respectively. Gene expression analysis of key biomarkers was performed using real time quantitative PCR (RT-qPCR) in THP-1 cells at 5 ?g nanoparticles/mL for 6-hr exposure for confirmation purposes. Results Multiple cytokines, GM-CSF, IL-1?, IL-6, IL-8, IFN?, MCP-1, TNF-? and VEGF, were significantly elevated in THP-1 cells in a dose-dependent manner. Gene expression analysis confirmed up-regulation of the TNF-? gene in THP-1 cells, consistent with cytokine findings. In both primary epithelial cells, cytokines IL-8, VEGF, EGF, IL-1?, TNF-?, IL-6 and GM-CSF were significantly elevated. Apoptosis was induced in all cell lines in a dose-dependent manner, consistent with the significant up-regulation of key apoptosis-regulating genes P53 and Casp8 in THP-1 cells. No significant DNA damage was found at any concentration with the comet assay. Up-regulation of key DNA damage and repair genes, Ku70 and Rad51, were also observed in THP-1 cells, albeit not statistically significant. Significant up-regulation of the key gene HO1 for oxidative stress, implicates oxidative stress induced by nanoparticles. Conclusions Copier-emitted nanoparticles induced the release of pro-inflammatory cytokines, apoptosis and modest cytotoxicity but no DNA damage in all three-human cell lines. Taken together with gene expression data in THP-1 cells, we conclude that these nanoparticles are directly responsible for inflammation observed in human volunteers. Further toxicological evaluations of these nanoparticles, including across different toner formulations, are warranted.

2013-01-01

27

Biosynthesized silver nanoparticles by ethanolic extracts of Phytolacca decandra, Gelsemium sempervirens, Hydrastis canadensis and Thuja occidentalis induce differential cytotoxicity through G2/M arrest in A375 cells.  

PubMed

The capability of crude ethanolic extracts of certain medicinal plants like Phytolacca decandra, Gelsemium sempervirens, Hydrastis canadensis and Thuja occidentalis used as homeopathic mother tinctures in precipitating silver nanoparticles from aqueous solution of silver nitrate has been explored. Nanoparticles thus precipitated were characterized by spectroscopic, dynamic light scattering, X-ray diffraction, atomic force and transmission electron microscopic analyses. The drug-DNA interactions of silver nanoparticles were analyzed from data of circular dichroism spectroscopy and melting temperature profiles using calf thymus DNA (CT-DNA) as target. Biological activities of silver nanoparticles of different origin were then tested to evaluate their effective anti-proliferative and anti-bacterial properties, if any, by exposing them to A375 skin melanoma cells and to Escherichia coli C, respectively. Silver nanoparticles showed differences in their level of anti-cancer and anti-bacterial potentials. The nanoparticles of different origin interacted differently with CT-DNA, showing differences in their binding capacities. Particle size differences of the nanoparticles could be attributed for causing differences in their cellular entry and biological action. The ethanolic extracts of these plants had not been tested earlier for their possible efficacies in synthesizing nanoparticles from silver nitrate solution that had beneficial biological action, opening up a possibility of having therapeutic values in the management of diseases including cancer. PMID:23010037

Das, Sreemanti; Das, Jayeeta; Samadder, Asmita; Bhattacharyya, Soumya Sundar; Das, Durba; Khuda-Bukhsh, Anisur Rahman

2012-07-17

28

The mechanism of asbestos-induced cytotoxicity  

SciTech Connect

Crocidolite asbestos fibers constitute a serious environmental pollutant capable of causing pleural scarring and cancer. This thesis addresses three questions: (1) what is the mechanism of asbestos-induced cytotoxicity in vitro and in vivo (2) What is the influence of fiber size on cytotoxicity in vitro and in vivo (3) What is the chronic response of the peritoneal cavity to asbestos fibers of varying lengths Macrophages release reactive oxygen metabolites when exposed to crocidolite in vitro or in vivo. Crocidolite-induced cytotoxicity is prevented with superoxide dismutase (SOD) and catalase. In addition, presoaking crocidolite fibers in deferoxamine, prevents cytotoxicity in vitro and in vivo. In vitro, macrophages exposed to crocidolite also lose mitochondrial membrane potential and undergo lipid peroxidation. Neither of these changes in itself, however, is responsible for macrophage death. We also examined the role of crocidolite fiber size in cytoxicity. Both long and short crocidolite fibers are toxic to macrophages in vitro via an oxidant dependent mechanism. Within the periotoneal cavity long crocidolite fibers are acutely cytotoxic and inflammatory while short fibers are not. Weekly intraperitoneal injections of long and native crocidolite asbestos fibers produced mesotheliomas in 20-40% of mice after 35-50 weeks. Neoplastic and preneoplastic cells were obtained from these mice, cultured, and characterized for in vitro transformation and in vivo tumorigenicity.

Goodglick, L.A.

1988-01-01

29

Intracellular mechanisms of aminoglycoside-induced cytotoxicity  

PubMed Central

Since introduction into clinical practice over 60 years ago, aminoglycoside antibiotics remain important drugs in the treatment of bacterial infections, cystic fibrosis and tuberculosis. However, the ototoxic and nephrotoxic properties of these drugs are still a major clinical problem. Recent advances in molecular biology and biochemistry have begun to uncover the intracellular actions of aminoglycosides that lead to cytotoxicity. In this review, we discuss intracellular binding targets of aminoglycosides, highlighting specific aminoglycoside-binding proteins (HSP73, calreticulin and CLIMP-63) and their potential for triggering caspases and Bcl-2 signalling cascades that are involved in aminoglycoside-induced cytotoxicity. We also discuss potential strategies to reduce aminoglycoside cytotoxicity, which are necessary for greater bactericidal efficacy during aminoglycoside pharmacotherapy.

Karasawa, Takatoshi; Steyger, Peter S.

2013-01-01

30

Cytotoxicity and cell interaction studies of bioadhesive poly(anhydride) nanoparticles for oral antigen/drug delivery.  

PubMed

The use of bioadhesive polymers as nanodevices has emerged as a promising strategy for oral delivery of therapeutics. In this regard, poly(anhydride) nanoparticles have shown great potential for oral drug delivery and vaccine purposes. However, despite extensive research into the biomedical and pharmaceutical applications of poly(anhydride) nanoparticles, there are no studies to evaluate the interaction of these nanoparticles at a cellular level. Therefore, the main objectives of this study were to evaluate the cytotoxicity as well as the cell interaction of different poly(anhydride) nanoparticles: conventional (NP), nanoparticles containing 2-hydroxypropyl-beta-cyclodextrin (NP-HPCD) and nanoparticles coated with poly(ethylene glycol) 6000 (PEG-NP). For this purpose, nanoparticles were prepared by solvent displacement method and labelled with BSA-FITC. Nanoparticles displayed a size about 175 nm with negative surface charge. Cytotoxicity studies were developed by MTS and LDH assays in HepG2 and Caco-2 cells. Results showed that only in HepG2 cells, NP and NP-HPCD induced significant cytotoxicity at the highest concentrations (1 and 2 mg/mL) and incubation times (48 and 72 h) tested. Studies to discriminate between cytoadhesion and cytoinvasion were performed at 4 degrees C and 37 degrees C in Caco-2 cell line as intestinal cell model. Nanoparticles showed cytoadhesion to the cell surface but not internalization; PEG-NP was the most bioadhesive followed by NP-HPCD and NP as demonstrated by flow cytometry. Finally, cellular localization of particles by fluorescence confocal microscopy confirmed the association of these nanoparticles with cells. Thus, this study demonstrated the safety of NP, NP-HPCD and PEG-NP at cellular level and its bioadhesive properties within cells. PMID:24059088

Ojer, Patricia; Neutsch, Lukas; Gabor, Franz; Irache, Juan Manuel; López de Cerain, Adela

2013-11-01

31

In vitro evaluation of cytotoxicity of engineered metal oxide nanoparticles.  

PubMed

The recent advances in nanotechnology and the corresponding popular usage of nanomaterials have resulted in uncertainties regarding their environmental impacts. In this study, we used a systematic approach to study and compare the in vitro cytotoxicity of selected engineered metal oxide nanoparticles to the test organisms--E. coli. Among the seven test nano-sized metal oxides, ZnO, CuO, Al2O3, La2O3, Fe2O3, SnO2 and TiO2, ZnO showed the lowest LD(50) of 21.1 mg/L and TiO2 had the highest LD(50) of 1104.8 mg/L. Data of 14C-glucose mineralization test paralleled the results of bacteria viability test. After regression calculation, the cytotoxicity was found to be correlated with cation charges (R(2) = 0.9785). The higher the cation charge is, the lower the cytotoxicity of the nano-sized metal oxide becomes. To the best of our knowledge, this finding is the first report in nanotoxicology. PMID:19215968

Hu, Xiaoke; Cook, Sean; Wang, Peng; Hwang, Huey-Min

2009-02-12

32

Penetration of lipid membranes by gold nanoparticles: insights into cellular uptake, cytotoxicity, and their relationship.  

PubMed

Nanoparticle penetration into cell membranes is an interesting phenomenon that may have crucial implications on the nanoparticles' biomedical applications. In this paper, a coarse-grained model for gold nanoparticles (AuNPs) is developed (verified against experimental data available) to simulate their interactions with model lipid membranes. Simulations reveal that AuNPs with different signs and densities of surface charges spontaneously adhere to the bilayer surface or penetrate into the bilayer interior. The potential of mean force calculations show that the energy gains upon adhesion or penetration is significant. In the case of penetration, it is found that defective areas are induced across the entire surface of the upper leaflet of the bilayer and a hydrophilic pore that transports water molecules was formed with its surrounding lipids highly disordered. Penetration and its concomitant membrane disruptions can be a possible mechanism of the two observed phenomena in experiments: AuNPs bypass endocytosis during their internalization into cells and cytotoxicity of AuNPs. It is also found that both the level of penetration and membrane disruption increase as the charge density of the AuNP increases, but in different manners. The findings suggest a way of controlling the AuNP-cell interactions by manipulating surface charge densities of AuNPs to achieve designated goals in their biomedical applications, such as striking a balance between their cellular uptake and cytotoxicity in order to achieve optimal delivery efficiency as delivery agents. PMID:20799717

Lin, Jiaqi; Zhang, Hongwu; Chen, Zhen; Zheng, Yonggang

2010-09-28

33

Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects  

PubMed Central

Background The purpose of this study was to investigate the mechanism of noxious effects of amorphous silica nanoparticles on human endothelial cells. Methods Nanoparticle uptake was examined by transmission electron microscopy. Electrochemical nanosensors were used to measure the nitric oxide (NO) and peroxynitrite (ONOO?) released by a single cell upon nanoparticle stimulation. The downstream inflammatory effects were measured by an enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, and flow cytometry, and cytotoxicity was measured by lactate dehydrogenase assay. Results We found that the silica nanoparticles penetrated the plasma membrane and rapidly stimulated release of cytoprotective NO and, to a greater extent, production of cytotoxic ONOO?. The low [NO]/[ONOO?] ratio indicated increased nitroxidative/oxidative stress and correlated closely with endothelial inflammation and necrosis. This imbalance was associated with nuclear factor ?B activation, upregulation of key inflammatory factors, and cell death. These effects were observed in a nanoparticle size-dependent and concentration-dependent manner. Conclusion The [NO]/[ONOO?] imbalance induced by amorphous silica nanoparticles indicates a potentially deleterious effect of silica nanoparticles on vascular endothelium.

Corbalan, J Jose; Medina, Carlos; Jacoby, Adam; Malinski, Tadeusz; Radomski, Marek W

2011-01-01

34

Cytotoxicity and physicochemical properties of hafnium oxide nanoparticles.  

PubMed

Nano-sized hafnium oxide (HfO(2)) particles are being considered for applications within the semiconductor industry. However, little is known about their cytotoxicity. The objective of this work was to assess several HfO(2) nanoparticles (NPs) samples for their acute cytotoxicity. Dynamic light scattering analysis of the samples indicated that the average particle size of the HfO(2) in aqueous dispersions was in the submicron range with a fraction of particles having nano-dimensions. The media used in the toxicity assays decreased or increased the average particle size of HfO(2) NPs due to dispersion or agglomeration. Static time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed numerous surface contaminants on the NPs. Only one HfO(2) sample caused moderate cytotoxicity to human cell lines. The inhibitory sample caused a 50% response in the Live/Dead assay with HaCaT skin cells at 2200 mg L(-1); and a 50% response in the mitochondrial toxicity test at 300 mg L(-1). A microbial inhibition assay based on methanogenic activity also revealed that another HFO(2) sample caused moderate inhibition. The difference in toxicity between samples could not be attributed to size. Instead the difference in toxicity was likely due to differences in the contaminants of the HfO(2). The ToF-SIMS analysis indicated unique signatures of Br and P in the sample toxic to human cell lines suggesting a distinct synthesis was used for that sample which may have been accompanied by inhibitory impurities. The results taken as a whole indicate that HfO(2) itself is relatively non-toxic. PMID:21605889

Field, James A; Luna-Velasco, Antonia; Boitano, Scott A; Shadman, Farhang; Ratner, Buddy D; Barnes, Chris; Sierra-Alvarez, Reyes

2011-05-24

35

Cytotoxical products formation on the nanoparticles heated by the pulsed laser radiation  

NASA Astrophysics Data System (ADS)

Cytotoxical effect of a pulsed laser irradiation in presence of nanoparticles of carbon black, sulphuretted carbon and fullerene-60 on death of human uterus nick cancer HeLa and mice lymphoma P 388 cells was studied in vitro. Bubbles formation as result of "microexplosions" of nanoparticles is one of possible mechanisms of this effect. Other possible mechanism is cytotoxical products formation in result of pyrolysis of nanoparticles and biomaterial which is adjoining. The cytotoxical effect of addition of a supernatant from the carbon nanoparticles suspensions irradiated by the pulsed laser was studied to test this assumption. Analysis using gas chromatograph determined that carbon monoxide is principal gaseous product of such laser pyrolysis. This is known as cytotoxical product. Efficiency of its formation is estimated.

Kogan, Boris Ya.; Titov, Andrey A.; Rakitin, Victor Yu.; Kvacheva, Larisa D.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

2006-03-01

36

Cytotoxicity of hydroxyapatite nanoparticles is shape and cell dependent.  

PubMed

Nanosized hydroxyapatite (nHA) has been proposed as drug delivery vehicles because of its biocompatibility. While the possible risks of nHA inducing inflammation have been highlighted, the specific influence of varying nHA particle morphology is still unclear. In order to establish this understanding, nHA of four different shapes--needle (nHA-ND), plate (nHA-PL), sphere (nHA-SP) and rod (nHA-RD)--were synthesized. The particle effects with the concentration of 10-300 ?g/mL on cytotoxicity, oxygen species generation, production of inflammatory cytokines (TNF-? and IL-6), particle-cell association and cellular uptake were evaluated on BEAS-2B and RAW264.7 cells. Results show that nHA-ND and nHA-PL induced the most significant cell death in BEAS-2B cultures compared to nHA-SP and nHA-RD. Necrosis-apoptosis assay by FITC Annexin V and propidium iodide (PI) staining revealed loss of the majority of BEAS-2B by necrosis. No significant cell death was recorded in RAW264.7 cultures exposed to any of the nHA groups. Correspondingly, no significant differences were observed in TNF-? level for RAW264.7 cells upon incubation with nHA of different shapes. In addition, nHA-RD exhibited a higher degree of particle-cell association and internalization in both BEAS-2B and RAW264.7 cells, compared to nHA-ND. The phenomena suggested that higher particle-cell association and increased cellular uptake of nHA need not result in increased cytotoxicity, indicating the importance of particle shape on cytotoxicity. Specifically, needle- and plate-shaped nHA induced the most significant cell-specific cytotoxicity and IL-6 expression but showed the least particle-cell association. Taken collectively, we demonstrated the shape-dependent effects of nHA on cytotoxicity, inflammatory cytokine expression and particle-cell association. PMID:22415765

Zhao, Xinxin; Ng, SuXiu; Heng, Boon Chin; Guo, Jun; Ma, LwinLwin; Tan, Timothy Thatt Yang; Ng, Kee Woei; Loo, Say Chye Joachim

2012-03-14

37

Rapamycin-induced cytotoxic signal transduction pathway.  

PubMed

We examined the effects of rapamycin on activation, proliferation, and expression of cytotoxic effector molecules in Molt-4 human T lymphocytes. We investigated the effects of rapamycin on cell viability, caspase family protein activities. Western blots of Bcl-2, Bak, p53, p21, p27, Rb, CDK2, and cyclin B1, as well as measurement of reactive oxygen species (ROS) generation and mitochondrial membrane potential transition. Cells were cultured in the presence or absence of rapamycin. Flow cytometric analysis was performed using propidium iodide stain. Viability of Molt-4 cells was decreased by the addition of rapamycin in dose- and time-dependent manners. Rapamycin induced no nuclear fragmentation in Molt-4 cells. Generation of H2O2 in rapamycin-treated Molt-4 cells increased in a time-dependent manner. There were no changes among catalytic activities of caspase proteases. And there was no evidence of expression of Bcl-2, p53, p21, p27, or Rb proteins. G2/M phase cell cycle arrest was identified by flow cytometry. We noted decreased expressions of CDK2 and cyclin B1. We also noted increased Bak protein expression and change in mitochondrial membrane potential transition. In conclusion, rapamycin-induced cytotoxicity was characterized by generation of ROS, which modulated Bak protein expression and mitochondrial dysfunction. G2/M phase cell cycle arrest was achieved by decreased expressions of CDK2 and cyclin B1. PMID:18929849

Choi, S J N; You, H S; Chung, S Y

2008-10-01

38

[Fibers glass induced cytotoxicity and genotoxicity].  

PubMed

Man-made vitrous fibers, have been widely used as a substitute for asbestos, as an insulation material. However the fibrous morphology of MMVFs raises concern about potential health hazard. The aim of our study was to assess cytotoxic and genotoxic effects induced on a human alveolar cell line A549 by exposure to glass wool fibers (GW). Cells were exposed for 72 h to 5, 50, 100 microg/ml of glass wool, after incubation the cell viability was determined by a MTT reduction assay. The genotoxic effect was studies by Comet test. An undamaged cell appeared as a nucleoid and a cell with damaged DNA as a comet. Measurement of Comet parameters: % DNA in the tail, tail length and tail momente (the product of relative tail intensity and lenght, that provides a parameter of DNA damage) were obtained from the analysis. A MTT assay indicated that glass wool caused a decrease in cell viability and this decrease was concentration-dependent. The results of the Comet test for DNA damage detection indicated in cell exposed to glass wool fibers a significant increase of mean TM value. All these results provide that the glass wool fibers can induce cytotoxicity and genotoxicity PMID:18409683

Proietti, L; Giallongo, A; Zakrzewska, A M; Ammoscato, I; Lombardo, L; Frasca, G; Cardile, V

39

[Preparation of superparamagnetic paclitaxel nanoparticles from modified chitosan and their cytotoxicity against malignant brain glioma].  

PubMed

We synthesized the superparamagnetic paclitaxel nanoparticles from modified chitosan tangling around Fe3O4 ferrofluid and taxol, and observed the nanoparticles with transmission electronic microscopy (TEM). Then we evaluated the paramagnetism of the particles by vibration specimen magnetometer (VSM) and tested their cytotoxicity with flow cytometry (FCM). The prepared nanoparticle solution was black without any floccule or sediment and appeared transparent after diluted. The nanoparticles were spherical and dispersed in water with mean diameter of 15 nm under TEM and showed superparamagnetic character. FCM test showed the nanoparticles had significant toxic effects against malignant astrocytoma U251 cell lines, equal to taxol alone. These results showed that the superparamagnetic nanoparticle not only enhanced the solubility of paclitaxel in water, but also was superparamagnetic and cytotoxic, which make suitable tools for magnetic targeting chemotherapy of brain gliomas. PMID:21774213

Zhao, Ming; Li, Anmin; Chang, Jin; Wang, Hanjie; Liang, Shuli; Zhang, Jiajing; Yan, Runmin

2011-06-01

40

Nanoparticles Induced Microscaled Pore Formation on Supported Lipid Bilayer  

NASA Astrophysics Data System (ADS)

Most of recent researches on the cytotoxicity of nanomaterials focused on hydrophilic nanomaterials because of their good dispersion in water, but much less on hydrophobic ones. In this work, we have investigated the effect of semi-hydrophobic nanoparticles (NPs) on the dynamics and morphology of model cell membrane. We have found carboxyl functionalized polystyrene nanoparticles can induce the formation of microscaled pores on neutral supported Egg PC lipid bilayer at the ionic strength range similar to that in the human body with a strong dependence on nanoparticle size and concentration. The hydrophobic interaction between the NP surface and lipid bilayer is accounted for the induced line tension in lipid bilayer; when the tension exceeds a critical value, pores are formed and grow rapidly with dependence on nanoparticle size and ionic strength.

Jing, Benxin; Zhu, Y. Elaine

2011-03-01

41

Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups  

PubMed Central

Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely utilized for the diagnosis and therapy of specific diseases, as magnetic resonance imaging (MRI) contrast agents and drug-delivery carriers, due to their easy transportation to targeted areas by an external magnetic field. For such biomedical applications, SPIONs must have multifunctional characteristics, including optimized size and modified surface. However, the biofunctionality and biocompatibility of SPIONs with various surface functional groups of different sizes have yet to be elucidated clearly. Therefore, it is important to carefully monitor the cytotoxicity and genotoxicity of SPIONs that are surfaced-modified with various functional groups of different sizes. In this study, we evaluated SPIONs with diameters of approximately 10 nm and 100~150 nm, containing different surface functional groups. SPIONs were covered with ?O? groups, so-called bare SPIONs. Following this, they were modified with three different functional groups – hydroxyl (?OH), carboxylic (?COOH), and amine (?NH2) groups – by coating their surfaces with tetraethyl orthosilicate (TEOS), (3-aminopropyl)trimethoxysilane (APTMS), TEOS-APTMS, or citrate, which imparted different surface charges and sizes to the particles. The effects of SPIONs coated with these functional groups on mitochondrial activity, intracellular accumulation of reactive oxygen species, membrane integrity, and DNA stability in L-929 fibroblasts were determined by water-soluble tetrazolium, 2?,7?-dichlorodihydrofluorescein, lactate dehydrogenase, and comet assays, respectively. Our toxicological observations suggest that the functional groups and sizes of SPIONs are critical determinants of cellular responses, degrees of cytotoxicity and genotoxicity, and potential mechanisms of toxicity. Nanoparticles with various surface modifications and of different sizes induced slight, but possibly meaningful, changes in cell cytotoxicity and genotoxicity, which would be significantly valuable in further studies of bioconjugation and cell interaction for drug delivery, cell culture, and cancer-targeting applications.

Hong, Seong Cheol; Lee, Jong Ho; Lee, Jaewook; Kim, Hyeon Yong; Park, Jung Youn; Cho, Johann; Lee, Jaebeom; Han, Dong-Wook

2011-01-01

42

Diuron-induced rat bladder epithelial cytotoxicity.  

PubMed

Diuron, a substituted urea herbicide, is carcinogenic to the rat urinary bladder at high dietary levels (2500 ppm). To further elucidate the mode of action, this study aimed to determine the time course and sequence of bladder cytotoxic and proliferative changes induced by diuron treatment of male Wistar rats. Rats were randomized into two groups (control and 2500 ppm diuron) and treated for 28 days. Ten rats from each group were terminated on each of study days 1, 3, 7, or 28. Scanning electron micro scopy (SEM) showed urothelial cell swelling beginning on day 1, and by day 28, showed extensive necrosis, exfoliation and piling up of cells suggestive of hyperplasia. No difference in the bromo deoxyuridine labeling index was detected. In a second experiment, rats were randomized into control and diuron-treated groups and treated for 7 days or 8 weeks. After 7 days, transmission electron microscopy showed cell degenerative changes and distention of the cytoplasm, organelles, and nuclei characteristic of cytolysis. This resulted in protrusion of the superficial cells into the lumen, corresponding to the cell swelling observed previously by SEM. After 8 weeks, bladders in the diuron-treated group showed an increased incidence of simple hyperplasia by light microscopy (6/10, p < 0.05) compared with controls (0/10) and a significantly different SEM classification. In summary, our results support the hypothesis that urothelial cytotoxicity followed by regenerative cell proliferation are the sequential key events that occur with high-dose diuron exposure in rats. PMID:22923491

Da Rocha, Mitscheli S; Arnold, Lora L; Pennington, Karen L; Muirhead, David; Dodmane, Puttappa R; Anwar, Muhammad M; Battalora, Michael; De Camargo, João Lauro V; Cohen, Samuel M

2012-08-24

43

Effect of Polyethylene Glycol Modification of TiO2 Nanoparticles on Cytotoxicity and Gene Expressions in Human Cell Lines  

PubMed Central

Nanoparticles (NPs) are tiny materials used in a wide range of industrial and medical applications. Titanium dioxide (TiO2) is a type of nanoparticle that is widely used in paints, pigments, and cosmetics; however, little is known about the impact of TiO2 on human health and the environment. Therefore, considerable research has focused on characterizing the potential toxicity of nanoparticles such as TiO2 and on understanding the mechanism of TiO2 NP-induced nanotoxicity through the evaluation of biomarkers. Uncoated TiO2 NPs tend to aggregate in aqueous media, and these aggregates decrease cell viability and induce expression of stress-related genes, such as those encoding interleukin-6 (IL-6) and heat shock protein 70B’ (HSP70B’), indicating that TiO2 NPs induce inflammatory and heat shock responses. In order to reduce their toxicity, we conjugated TiO2 NPs with polyethylene glycol (PEG) to eliminate aggregation. Our findings indicate that modifying TiO2 NPs with PEG reduces their cytotoxicity and reduces the induction of stress-related genes. Our results also suggest that TiO2 NP-induced effects on cytotoxicity and gene expression vary depending upon the cell type and surface modification.

Mano, Sharmy Saimon; Kanehira, Koki; Sonezaki, Shuji; Taniguchi, Akiyoshi

2012-01-01

44

Differential cytotoxicity and particle action of hydroxyapatite nanoparticles in human cancer cells.  

PubMed

Aim: While hydroxyapatite nanoparticles (HAPNs) have been reported to exhibit anticancer effects on several types of human cancer cells, no investigation has been performed to compare their cytotoxicity with different types of cancer cells. The objective of the present study is to investigate the cytotoxic action of HAPNs in different types of human cancer cell and to explore the possible mechanisms involved. Materials & methods: Rod-shaped HAPNs were prepared by the aqueous precipitation method and then labeled with ?uorescein isothiocyanate to visualize the cellular uptake and distribution. Their cytotoxicity to three human carcinoma cell lines (gastric cancer cells [MGC80-3], cervical adenocarcinoma epithelial cells [HeLa] and hepatoma cells [HepG2], as well as to normal human hepatocyte cells [L-02]) was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was characterized by the changes in nuclear morphology with 4',6-diamidino-2-phenylindole staining and by ?ow cytometric analysis with Annexin V-?uorescein isothiocyanate/propidium iodide double staining. Furthermore, the activity of apoptotic proteins (caspase-3, -8 and -9), intracellular reactive oxygen species and glutathione levels were analyzed in HAPN-treated cells. The cellular uptake of HAPNs was studied using flow cytometry analysis, and changes in intracellular calcium levels were investigated using the Ca(2+)-sensitive fluorescent dye, fluo-3 AM. Results: HAPNs significantly inhibited cell proliferation and induced apoptosis of cancer cells with an order of MGC80-3 > HepG2 > HeLa, but had no impact on normal hepatic cells (L-02). The increase in apoptosis was accompanied by the activation of caspase-3 and -9, but not activation of caspase-8. Moreover, HAPN treatment led to reactive oxygen species generation and decreased intracellular glutathione in cancer cells, with the most remarkable reactive oxygen species burst in HeLa cells. The degree of cytotoxicity did not correlate with the cellular uptake efficiency of HAPNs. However, more HAPNs were found inside the nucleus of MGC80-3 cells, and an increase in the intracellular calcium level was observed in all cancer cells, with the highest level also detected in MGC80-3. Conclusion: Varying cytotoxicity of HAPNs was observed in different cancer cell types. Our results suggest that possible mechanisms of cytotoxicity in various types of cancer cells could be different. The elevated calcium concentration and nuclear localization of the particles might be the main mechanism of growth inhibition by HAPNs in cancer cells. Original submitted 18 April 2012; Revised submitted 14 September 2012. PMID:23614636

Tang, Wei; Yuan, Yuan; Liu, Changsheng; Wu, Yuequn; Lu, Xun; Qian, Jiangchao

2013-04-24

45

Mechanisms underlying chlorhexidine-induced cytotoxicity.  

PubMed

Chlorhexidine (CLX) is the most widely used antiseptic for wound and skin disinfection. Despite its potent bactericidal action, skin irritation is observed when it is used topically. This study aimed to evaluate the mechanisms underlying CLX-induced toxicity on human dermal fibroblasts with special emphasis on factors that may mediate or counteract its undesirable effects. Cells were exposed to CLX concentrations of 0.00005-0.025% for 3, 6, 8 or 24 h in the absence or presence of different concentrations of foetal calf serum (FCS) (2, 5 and 10%). Depletion of cell ATP occurred, in a time- and concentration-dependent manner, in all experimental conditions at [CLX] >0.001%. At 24 h of CLX exposure time, the decrease in intracellular ATP was produced from a 10-times lower CLX concentration (0.0001%). Concentrations > or =0.02% produced total loss of ATP. However, cell survival was maintained after CLX treatment for 3 and 8 h and CLX concentrations > or =0.005% were required to produce total cell death. CLX exerted an inhibitory concentration-dependent effect on DNA synthesis from concentrations as low as 0.0001%. Only FCS at 10% appeared to have a cytoprotective action against CLX-induced cytotoxicity. PMID:11566548

Hidalgo, E; Dominguez, C

46

Polyaspartamide derivative nanoparticles with tunable surface charge achieve highly efficient cellular uptake and low cytotoxicity.  

PubMed

Cationic nanocarrier mediated intracellular therapeutic agent delivery acts as a double-edged sword: the carriers promote cellular uptake, but interact nonspecifically and strongly with negatively charged endogenic proteins and cell membranes, which results in aggregates and high cytotoxicity. The present study was aimed at exploring zwitterionic polyaspartamide derivative nanoparticles for efficient intracellular delivery with low cytotoxicity. Poly(aspartic acid) partially grafted tetraethylenepentamine (PASP-pg-TEPA) with different isoelectric points (IEPs) was synthesized. The PASP-pg-TEPA formed zwitterionic nanoparticles with an irregular core and a well-defined shell structure in aqueous medium. Their particle size decreased from about 300 to 80 nm with an increase of the IEP from 7.5 to 9.1. The surface charge of the PASP-pg-TEPA nanoparticles could be tuned from positive to negative with a change of the pH of the medium. The nanoparticles with an IEP above 8.5 exhibited good stability under simulated physiological conditions. It was noted that the zwitterionic PASP-pg-TEPA nanoparticles displayed highly efficient cellular uptake in HeLa cells (approximately 99%) in serum-containing medium and did not adversely affect the cell viability at concentrations up to 1 mg/mL. Furthermore, thermodynamic analysis using isothermal titration calorimetry provided direct evidence that these zwitterionic nanoparticles had low binding affinities for serum protein. Therefore, the zwitterionic PASP-pg-TEPA nanoparticles could overcome limitations of cationic nanocarriers and achieve efficient intracellular delivery with low cytotoxicity. PMID:22770362

Xu, Min; Zhao, Yuefang; Feng, Min

2012-07-25

47

Assessment of cytotoxicity of quantum dots and gold nanoparticles using cell-based impedance spectroscopy.  

PubMed

A continuous online technique based on electric cell-substrate impedance sensing (ECIS) was demonstrated for measuring the concentration and time response function of fibroblastic V79 cells exposed to nanomaterials such as quantum dots (QDs) and fluorescent gold nanoparticles. The half-inhibition concentration, (ECIS50), the required concentration to attain 50% inhibition of the cytotoxic response, was estimated from the response function to ascertain cytotoxicity during the course of measurement. The ECIS50 values agreed well with the results obtained using the standard neutral red assay. Cadmium selenide quantum dots showed direct cytotoxicity with the ECIS assay. For the cadmium telluride quantum dots, significant toxicity could be assigned to free cadmium, although additional toxicity could be attributed to the QDs per se. The QDs synthesized with indium gallium phosphide and the fluorescent gold nanoparticles were not cytotoxic. PMID:18553941

Male, Keith B; Lachance, Bernard; Hrapovic, Sabahudin; Sunahara, Geoff; Luong, John H T

2008-06-14

48

Cytotoxicity of TiO? nanoparticles and their detoxification in a freshwater system.  

PubMed

In the current study, two aspects concerning (i) the cytotoxicity potential of TiO? nanoparticles (NPs) toward freshwater algal isolate Scenedesmus obliquus and (ii) the potential detoxification of NPs by the microalgae were assessed under light (UV-illumination) and dark conditions at low exposure levels (?1 ?g/mL), using sterile freshwater as the test medium. The statistically significant reduction in cell viability, increase in reactive oxygen species production and membrane permeability (light vs. dark) suggested photo-induced toxicity of TiO? NPs. The electron micrographs demonstrated adsorption of the NPs onto the cell surface and substantiated their internalization/uptake. The fluorescence micrographs and the confocal laser scanning (CLSM) images suggested the absence of a definite/intact nucleus in the light treated cells pointing toward the probable genotoxic effects of NPs. In a separate three cycle experiment, a continuous decrease in the cytotoxicity was observed, whereas, at the end of each cycle only fresh algae were added to the supernatant containing NPs from the previous cycle. The decreasing concentrations of the NPs in the subsequent cycles owing to agglomeration-sedimentation processes exacerbated by the algal interactions played a crucial role in the detoxification. In addition, the exo-polymeric substances produced by the cells could have rendered the available NPs less reactive, thereby, enhancing the detoxification effects. PMID:23680676

Dalai, Swayamprava; Pakrashi, Sunandan; Joyce Nirmala, M; Chaudhri, Apoorvi; Chandrasekaran, N; Mandal, A B; Mukherjee, Amitava

2013-04-24

49

Biosynthesis, characterization and cytotoxic effect of plant mediated silver nanoparticles using Morinda citrifolia root extract.  

PubMed

Silver has been used since time to control bodily infection, prevent food spoilage and heal wounds by preventing infection. The present study aims at an environmental friendly method of synthesizing silver nanoparticles, from the root of Morinda citrifolia; without involving chemical agents associated with environmental toxicity. The obtained nanoparticles were characterized by UV-vis absorption spectroscopy with an intense surface plasmon resonance band at 413 nm clearly reveals the formation of silver nanoparticles. Fourier transmission infra red spectroscopy (FTIR) showed nanopartilces were capped with plant compounds. Field emission-scanning electron microscopy (FE-SEM) and Transmission electron microscopy (TEM) showed that the spherical nature of the silver nanoparticles with a size of 30-55 nm. The X-ray diffraction spectrum XRD pattern clearly indicates that the silver nanoparticles formed in the present synthesis were crystalline in nature. In addition these biologically synthesized nanoparticles were also proved to exhibit excellent cytotoxic effect on HeLa cell. PMID:23434694

Suman, T Y; Radhika Rajasree, S R; Kanchana, A; Elizabeth, S Beena

2013-01-24

50

Kinetics and pathogenesis of intracellular magnetic nanoparticle cytotoxicity  

Microsoft Academic Search

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

Andrew J. Giustini; Rachel E. Gottesman; A. A. Petryk; A. M. Rauwerdink; P. Jack Hoopes

2011-01-01

51

In vitro release behavior and cytotoxicity of doxorubicin-loaded gold nanoparticles in cancerous cells  

Microsoft Academic Search

Doxorubicin (DOX), a common cancer chemotherapeutics, was conjugated to folate-modified thiolated-polyethylene glycol-functionalized\\u000a gold nanoparticles. The in vitro, controlled release behavior of DOX-loaded gold nanoparticles was observed using porous dialysis\\u000a membranes (cut-off = 2 kDa). DOX-loaded gold nanoparticles had higher cytotoxicity for folate-receptor-positive cells (KB\\u000a cells) compared to folate-receptor-negative cells (A549 cells) which were 48 and 62% viable for 10 ?M doxorubicin, respectively.\\u000a This indicates the

B. Asadishad; M. Vossoughi; I. Alamzadeh

2010-01-01

52

Heparin and Carboxymethylchitosan Metal Nanoparticles: An Evaluation of Their Cytotoxicity  

PubMed Central

In the search for noninvasive diagnostic techniques and new therapies, “nanosystems”, which are capable of binding and targeting bioactive molecules, are becoming increasingly important. In this context, biocompatible coatings are gaining interest, not only for their biological effects but also because they are considered capable to mask nanoparticle toxicity. In this work, we have compared the toxicity of nanoparticles coated with heparin and carboxymethylchitosan in the SKOV-3 cell line. Our results indicate that heparin and carboxymethylchitosan coatings do not guarantee the decrease of nanoparticle intrinsic toxicity which is often envisaged. Nonetheless, these coatings provide the opportunity for further functionalization with a variety of biomolecules for their use in theranostics.

Bava, Adriana; Cappellini, Francesca; Pedretti, Elisa; Rossi, Federica; Caruso, Enrico; Vismara, Elena; Chiriva-Internati, Maurizio; Bernardini, Giovanni; Gornati, Rosalba

2013-01-01

53

Glutathione and S-nitrosoglutathione in alginate/chitosan nanoparticles: Cytotoxicity  

NASA Astrophysics Data System (ADS)

Nitric oxide (NO) is involved in several physiological processes, such as the control of vascular tone, the immune response and the wound healing process. Thus, there is a great interest in the development of NO-releasing drugs and in matrices which are able to stabilize and release NO locally in different tissues. Thiols, such as glutathione (GSH), are ready nitrosated to form the NO donors S-nitrosothiols (RSNOs). In this work, GSH, a precursor of the NO donor S-nitrosoglutathione (GSNO), was encapsulated into a mucoadhesive combination of alginate/chitosan nanoparticles. The encapsulated GSH was nitrosated in the alginate/chitosan nanoparticles by adding sodium nitrite, leading to the formation of encapsulated GSNO. The cytotoxicity characterization of the nanoparticles containing either GSH or GSNO showed that these materials were completely non cytotoxic to cellular viability. These results show that this novel nanostructure biomaterial has a great potential to be use in biomedical applications where NO has a therapeutical effect.

Marcato, P. D.; Adami, L. F.; Melo, P. S.; de Paula, L. B.; Durán, N.; Seabra, A. B.

2011-07-01

54

Cytotoxic effects and the mechanism of three types of magnetic nanoparticles on human hepatoma BEL-7402 cells  

NASA Astrophysics Data System (ADS)

The evaluation of the toxicity of magnetic nanoparticles (MNPs) has attracted much attention in recent years. The current study aimed to investigate the cytotoxic effects of Fe3O4, oleic acid-coated Fe3O4 (OA-Fe3O4), and carbon-coated Fe (C-Fe) nanoparticles on human hepatoma BEL-7402 cells and the mechanisms. WST-1 assay demonstrated that the cytotoxicity of three types of MNPs was in a dose-dependent manner. G1 (Fe3O4 and OA-Fe3O4) phase and G2 (C-Fe) phase cell arrests and apoptosis induced by MNPs were detected by flow cytometry analysis. The increase in apoptosis was accompanied with the Bax over-expression, mitochondrial membrane potential decrease, and the release of cytochrome C from mitochondria into cytosol. Moreover, apoptosis was further confirmed by morphological and biochemical hallmarks, such as swollen mitochondria with lysing cristae and caspase-3 activation. Our results revealed that certain concentrations of the three types of MNPs affect BEL-7402 cells viability via cell arrest and inducing apoptosis, and the MNPs-induced apoptosis is mediated through the mitochondrial-dependent pathway. The influence potency of MNPs observed in all experiments would be: C-Fe > Fe3O4 > OA-Fe3O4.

Kai, Wei; Xiaojun, Xu; Ximing, Pu; Zhenqing, Hou; Qiqing, Zhang

2011-07-01

55

Size influences the cytotoxicity of poly (lactic-co-glycolic acid) (PLGA) and titanium dioxide (TiO(2)) nanoparticles.  

PubMed

The aim of this study is to uncover the size influence of poly (lactic-co-glycolic acid) (PLGA) and titanium dioxide (TiO(2)) nanoparticles on their potential cytotoxicity. PLGA and TiO(2) nanoparticles of three different sizes were thoroughly characterized before in vitro cytotoxic tests which included viability, generation of reactive oxygen species (ROS), mitochondrial depolarization, integrity of plasma membrane, intracellular calcium influx and cytokine release. Size-dependent cytotoxic effect was observed in both RAW264.7 cells and BEAS-2B cells after cells were incubated with PLGA or TiO(2) nanoparticles for 24 h. Although PLGA nanoparticles did not trigger significantly lethal toxicity up to a concentration of 300 ?g/ml, the TNF-? release after the stimulation of PLGA nanoparticles should not be ignored especially in clinical applications. Relatively more toxic TiO(2) nanoparticles triggered cell death, ROS generation, mitochondrial depolarization, plasma membrane damage, intracellular calcium concentration increase and size-dependent TNF-? release, especially at a concentration higher than 100 ?g/ml. These cytotoxic effects could be due to the size-dependent interaction between nanoparticles and biomolecules, as smaller particles tend to adsorb more biomolecules. In summary, we demonstrated that the ability of protein adsorption could be an important paradigm to predict the in vitro cytotoxicity of nanoparticles, especially for low toxic nanomaterials such as PLGA and TiO(2) nanoparticles. PMID:22983807

Xiong, Sijing; George, Saji; Yu, Haiyang; Damoiseaux, Robert; France, Bryan; Ng, Kee Woei; Loo, Joachim Say-Chye

2012-09-16

56

Effect of surface properties of silica nanoparticles on their cytotoxicity and cellular distribution in murine macrophages  

PubMed Central

Surface properties are often hypothesized to be important factors in the development of safer forms of nanomaterials (NMs). However, the results obtained from studying the cellular responses to NMs are often contradictory. Hence, the aim of this study was to investigate the relationship between the surface properties of silica nanoparticles and their cytotoxicity against a murine macrophage cell line (RAW264.7). The surface of the silica nanoparticles was either unmodified (nSP70) or modified with amine (nSP70-N) or carboxyl groups (nSP70-C). First, the properties of the silica nanoparticles were characterized. RAW264.7 cells were then exposed to nSP70, nSP70-N, or nSP70-C, and any cytotoxic effects were monitored by analyzing DNA synthesis. The results of this study show that nSP70-N and nSP70-C have a smaller effect on DNA synthesis activity by comparison to unmodified nSP70. Analysis of the intracellular localization of the silica nanoparticles revealed that nSP70 had penetrated into the nucleus, whereas nSP70-N and nSP70-C showed no nuclear localization. These results suggest that intracellular localization is a critical factor underlying the cytotoxicity of these silica nanoparticles. Thus, the surface properties of silica nanoparticles play an important role in determining their safety. Our results suggest that optimization of the surface characteristics of silica nanoparticles will contribute to the development of safer forms of NMs.

2011-01-01

57

Rapamycin-Induced Cytotoxic Signal Transduction Pathway  

Microsoft Academic Search

We examined the effects of rapamycin on activation, proliferation, and expression of cytotoxic effector molecules in Molt-4 human T lymphocytes. We investigated the effects of rapamycin on cell viability, caspase family protein activities. Western blots of Bcl-2, Bak, p53, p21, p27, Rb, CDK2, and cyclin B1, as well as measurement of reactive oxygen species (ROS) generation and mitochondrial membrane potential

S. J. N. Choi; H. S. You; S. Y. Chung

2008-01-01

58

Gellan gum capped silver nanoparticle dispersions and hydrogels: cytotoxicity and in vitro diffusion studies  

NASA Astrophysics Data System (ADS)

The preparation of highly stable water dispersions of silver nanoparticles using the naturally available gellan gum as a reducing and capping agent is reported. Further, exploiting the gel formation characteristic of gellan gum silver nanoparticle incorporated gels have also been prepared. The optical properties, morphology, zeta potential and long-term stability of the synthesized silver nanoparticles were investigated. The superior stability of the gellan gum-silver nanoparticle dispersions against pH variation and electrolyte addition is revealed. Finally, we studied the cytotoxicity of AgNP dispersions in mouse embryonic fibroblast cells (NIH3T3) and also evaluated the in vitro diffusion of AgNP dispersions/gels across rat skin.The preparation of highly stable water dispersions of silver nanoparticles using the naturally available gellan gum as a reducing and capping agent is reported. Further, exploiting the gel formation characteristic of gellan gum silver nanoparticle incorporated gels have also been prepared. The optical properties, morphology, zeta potential and long-term stability of the synthesized silver nanoparticles were investigated. The superior stability of the gellan gum-silver nanoparticle dispersions against pH variation and electrolyte addition is revealed. Finally, we studied the cytotoxicity of AgNP dispersions in mouse embryonic fibroblast cells (NIH3T3) and also evaluated the in vitro diffusion of AgNP dispersions/gels across rat skin. Electronic supplementary information (ESI) available: Time dependent UV-Vis spectral studies revealing the stability of AgNP dispersions and agar plate images displaying the antibacterial activity of AgNPs. See DOI: 10.1039/c1nr10957j

Dhar, S.; Murawala, P.; Shiras, A.; Pokharkar, V.; Prasad, B. L. V.

2012-01-01

59

Role of the Nrf2-heme oxygenase-1 pathway in silver nanoparticle-mediated cytotoxicity.  

PubMed

Silver nanoparticles (nano-Ag) have been widely used in various commercial products including textiles, electronic appliances and biomedical products. However, there remains insufficient information on the potential risk of nano-Ag to human health and environment. In the current study, we have investigated the role of NF-E2-related factor 2 (Nrf2) transcription factor in nano-Ag-induced cytotoxicity. When Nrf2 expression was blocked using interring RNA expression in ovarian carcinoma cell line, nano-Ag treatment showed a substantial decrease in cell viability with concomitant increases in apoptosis and DNA damage compared to the control cells. Target gene analysis revealed that the expression of heme oxygenase-1 (HO-1) was highly elevated by nano-Ag in nonspecific shRNA expressing cells, while Nrf2 knockdown cells (NRF2i) did not increase HO-1 expression. The role of HO-1 in cytoprotection against nano-Ag was reinforced by results using pharmacological inducer of HO-1: cobalt protoporphyrin-mediated HO-1 activation in the NRF2i cells prevented nano-Ag-mediated cell death. Similarly, pharmacological or genetic inhibition of HO-1 in nonspecific control cells exacerbated nano-Ag toxicity. As the upstream signaling mechanism, nano-Ag required the phosphoinositide 3-kinase (PI3K) and p38MAPK signaling cascades for HO-1 induction. The treatment with either PI3K inhibitor or p38MAPK inhibitor suppressed HO-1 induction and intensified nano-Ag-induced cell death. Taken together, these results suggest that Nrf2-dependent HO-1 up-regulation plays a protective role in nano-Ag-induced DNA damage and consequent cell death. In addition, nano-Ag-mediated HO-1 induction is associated with the PI3K and p38MAPK signaling pathways. PMID:22036727

Kang, Su Jin; Ryoo, In-Geun; Lee, Young Joon; Kwak, Mi-Kyoung

2011-10-20

60

Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies.  

PubMed

Superparamagnetic iron oxide nanoparticles have been used for many years as magnetic resonance imaging (MRI) contrast agents or in drug delivery applications. In this study, a novel approach to prepare magnetic polymeric nanoparticles with magnetic core and polymeric shell using inverse microemulsion polymerization process is reported. Poly(ethyleneglycol) (PEG)-modified superparamagnetic iron oxide nanoparticles with specific shape and size have been prepared inside the aqueous cores of AOT/n-Hexane reverse micelles and characterized by various physicochemical means such as transmission electron microscopy (TEM), infrared spectroscopy, atomic force microscopy (AFM), vibrating sample magnetometry (VSM), and ultraviolet/visible spectroscopy. The inverse microemulsion polymerization of a polymerizable derivative of PEG and a cross-linking agent resulted in a stable hydrophilic polymeric shell of the nanoparticles. The results taken together from TEM and AFM studies showed that the particles are spherical in shape with core-shell structure. The average size of the PEG-modified nanoparticles was found to be around 40-50 nm with narrow size distribution. The magnetic measurement studies revealed the superparamagnetic behavior of the nanoparticles with saturation magnetization values between 45-50 electromagnetic units per gram. The cytotoxicity profile of the nanoparticles on human dermal fibroblasts as measured by standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the particles are nontoxic and may be useful for various in vivo and in vitro biomedical applications. PMID:15382647

Gupta, Ajay Kumar; Wells, Stephen

2004-03-01

61

Induction of cytotoxicity and apoptosis in mouse blastocysts by silver nanoparticles  

Microsoft Academic Search

Silver nanoparticles (nanoAg) are antibacterial materials widely used in various products and medical supplies. In this report, we examined the cytotoxic effects of nanoAg on mouse embryos at the blastocyst stage, subsequent embryonic attachment and outgrowth in vitro, and in vivo implantation by embryo transfer. Blastocysts treated with 50?M nanoAg exhibited significantly increased apoptosis and a corresponding decrease in total

Po-Wn Li; Tai-Hung Kuo; Ji-Hao Chang; Jui-Ming Yeh; Wen-Hsiung Chan

2010-01-01

62

Enhanced Growth Inhibition of Osteosarcoma by Cytotoxic Polymerized Liposomal Nanoparticles Targeting the Alcam Cell Surface Receptor  

PubMed Central

Osteosarcoma is the most common primary malignancy of bone in children, adolescents, and adults. Despite extensive surgery and adjuvant aggressive high-dose systemic chemotherapy with potentially severe bystander side effects, cure is attainable in about 70% of patients with localized disease and only 20%–30% of those patients with metastatic disease. Targeted therapies clearly are warranted in improving our treatment of this adolescent killer. However, a lack of osteosarcoma-associated/specific markers has hindered development of targeted therapeutics. We describe a novel osteosarcoma-associated cell surface antigen, ALCAM. We, then, create an engineered anti-ALCAM-hybrid polymerized liposomal nanoparticle immunoconjugate (?-AL-HPLN) to specifically target osteosarcoma cells and deliver a cytotoxic chemotherapeutic agent, doxorubicin. We have demonstrated that ?-AL-HPLNs have significantly enhanced cytotoxicity over untargeted HPLNs and over a conventional liposomal doxorubicin formulation. In this way, ?-AL-HPLNs are a promising new strategy to specifically deliver cytotoxic agents in osteosarcoma.

Federman, Noah; Chan, Jason; Nagy, Jon O.; Landaw, Elliot M.; McCabe, Katelyn; Wu, Anna M.; Triche, Timothy; Kang, HyungGyoo; Liu, Bin; Marks, James D.; Denny, Christopher T.

2012-01-01

63

Role of surface charge in cytotoxicity of charged manganese ferrite nanoparticles towards macrophages.  

PubMed

Amphiphilic surfactants have been used to disperse magnetic nanoparticles in biological media, because they exhibit a dual hydrophobic/hydrophilic affinity that facilitates the formation of a nanoemulsion, within which nanoparticle surfaces can be modified to achieve different physicochemical properties. For the investigation of the interactions of cells with charged magnetic nanoparticles in a biological medium, we selected the nanoemulsion method to prepare water-soluble magnetic nanoparticles using amphiphilic surfactant (polysorbate 80). The hydroxyl groups of polysorbate 80 were modified to carboxyl or amine groups. The chemical structures of carboxylated and aminated polysorbate 80 were confirmed, and water-soluble manganese ferrite nanoparticles (MFNPs) were synthesized with three types of polysorbate 80. Colloidal size, morphology, monodispersity, solubility and T2 relaxivity were found to be similar between the three types of MFNP. However, cationic MFNPs exhibited greater cytotoxicity in macrophages (RAW264.7 cells) and lower cellular membrane effective stiffness than anionic and non-ionic MFNPs. Moreover, cationic MFNPs exhibited large uptake efficiency for RAW264.7 cells compared with anionic or non-ionic MFNPs under the same conditions. Therefore, we propose that surface charge should be a key consideration factor in the design of magnetic nanoparticles for theragnostic applications. PMID:23164999

Yang, Seung-Hyun; Heo, Dan; Park, Jinsung; Na, Sungsoo; Suh, Jin-Suck; Haam, Seungjoo; Park, Sahng Wook; Huh, Yong-Min; Yang, Jaemoon

2012-11-19

64

Mass imaging of iron oxide nanoparticles inside cells for in vitro cytotoxicity.  

PubMed

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging analysis was performed on murine macrophage cells treated with various concentrations of iron oxide (Fe3O4) nanoparticles, which are used as MRI contrast agents. First, murine macrophage cells were seeded on a slide glass for 24 hrs and treated with varying concentrations of Fe3O4 nanoparticles for 24 hrs. To expose a cross section of each cell and obtain a distribution of the nanoparticles inside the cells, the cells were sputtered using Bi ions after which the cross section of each cell was scanned and imaged using the focused cluster ion beam with a spatial resolution of 300 nm. Fe3O4 nanoparticles were found mainly in the cytoplasm region of the cells, not in the nucleus region of cells, suggesting that the uptake of the Fe3O4 nanoparticles were into the cytoplasm of cell, not into the nucleus of cell. Based on these observations, our protocol using mass imaging analysis would be a useful addition to the study of in vitro nanoparticle cytotoxicity. PMID:21446514

Shon, Hyun Kyong; Park, Jungsin; Choi, Inhong; Park, Hyun Min; Moon, Dae Won; Lee, Tae Geol

2011-01-01

65

Cytotoxicity and cellular uptake of tri-block copolymer nanoparticles with different size and surface characteristics  

PubMed Central

Background Polymer nanoparticles (PNP) are becoming increasingly important in nanomedicine and food-based applications. Size and surface characteristics are often considered to be important factors in the cellular interactions of these PNP, although systematic investigations on the role of surface properties on cellular interactions and toxicity of PNP are scarce. Results Fluorescent, monodisperse tri-block copolymer nanoparticles with different sizes (45 and 90 nm) and surface charges (positive and negative) were synthesized, characterized and studied for uptake and cytotoxicity in NR8383 and Caco-2 cells. All types of PNP were taken up by the cells. The positive smaller PNP45 (45 nm) showed a higher cytotoxicity compared to the positive bigger PNP90 (90 nm) particles including reduction in mitochondrial membrane potential (??m), induction of reactive oxygen species (ROS) production, ATP depletion and TNF-? release. The negative PNP did not show any cytotoxic effect. Reduction in mitochondrial membrane potential (??m), uncoupling of the electron transfer chain in mitochondria and the resulting ATP depletion, induction of ROS and oxidative stress may all play a role in the possible mode of action for the cytotoxicity of these PNP. The role of receptor-mediated endocytosis in the intracellular uptake of different PNP was studied by confocal laser scanning microscopy (CLSM). Involvement of size and charge in the cellular uptake of PNP by clathrin (for positive PNP), caveolin (for negative PNP) and mannose receptors (for hydroxylated PNP) were found with smaller PNP45 showing stronger interactions with the receptors than bigger PNP90. Conclusions The size and surface characteristics of polymer nanoparticles (PNP; 45 and 90 nm with different surface charges) play a crucial role in cellular uptake. Specific interactions with cell membrane-bound receptors (clathrin, caveolin and mannose) leading to cellular internalization were observed to depend on size and surface properties of the different PNP. These properties of the nanoparticles also dominate their cytotoxicity, which was analyzed for many factors. The effective reduction in the mitochondrial membrane potential (??m), uncoupling of the electron transfer chain in mitochondria and resulting ATP depletion, induction of ROS and oxidative stress likely all play a role in the mechanisms behind the cytotoxicity of these PNP.

2012-01-01

66

Cellular Targets and Mechanisms in the Cytotoxic Action of Non-biodegradable Engineered Nanoparticles.  

PubMed

The use of nanoparticles (NPs) has improved the quality of many industrial, pharmaceutical, and medical products. Increased surface reactivity, a major reason for the positive effects of NPs, may, on the other hand, also cause adverse biological effects. Almost all non-biodegradable NPs cause cytotoxic effects but employ quite different modes of action. The relation of biodegradable or loaded NPs to cytotoxic mechanism is more difficult to identify because effects may by caused by the particles or degradation products thereof. This review introduces problems of NPs in conventional cytotoxicity testing (changes of particle parameters in biological fluids, cellular dose, cell line and assay selection). Generation of reactive oxygen and nitrogen species by NPs and of metal ions due to dissolution of the NPs is discussed as a cause for cytotoxicity. The effects of NPs on plasma membrane, mitochondria, lysosomes, nucleus, and intracellular proteins as cellular targets for cytotoxicity are summarized. The comparison of the numerous studies on the mechanism of cellular effects shows that, although some common targets have been identified, other effects are unique for particular NPs or groups of NPs. While titanium dioxide NPs appear to act mainly by generation of reactive oxygen and nitrogen species, biological effects of silver and iron oxide are caused by both reactive species and free metal ions. NPs lacking heavy metals, such as carbon nanotubes and polystyrene particles, interfere with cell metabolism mainly by binding to macromolecules. PMID:24160294

Fröhlich, Eleonore

2013-11-01

67

Caffeine augments Alprazolam induced cytotoxicity in human cell lines.  

PubMed

Combined effects of alprazolam (Alp), a member of benzodiazepine group of drugs and caffeine on human cell lines, HeLa and THP1 were investigated in this study. Alp mediated cytotoxicity was enhanced while caffeine was present. The cell death was confirmed by observing morphological changes, LDH assay and membrane anisotropic study. Also such combined effects induced elevated level of ROS and depletion of GSH. The mechanism of cell death induced by simultaneous treatment of Alp and caffeine was associated with the calcium-mediated activation of mu-calpain, release of lysosomal protease cathepsin B, activation of PARP and cleavage of caspase 3. Our results indicate that, Alp alone induces apoptosis in human cells but in the presence of caffeine it augments necrosis in a well-regulated pathway. Thus our observations strongly suggest that, alprazolam and caffeine together produce severe cytotoxicity in human cell lines. PMID:19490937

Saha, Biswarup; Mukherjee, Ananda; Samanta, Saheli; Saha, Piyali; Ghosh, Anup Kumar; Santra, Chitta Ranjan; Karmakar, Parimal

2009-05-31

68

The cytotoxic activity of amorphous silica nanoparticles is mainly influenced by surface area and not by aggregation.  

PubMed

The aggregation state of NP has been a significant source of difficulty for assessing their toxic activity and great efforts have been done to reduce aggregation of and/or to disperse NP in experimental systems. The exact impact of aggregation on toxicity has, however, not been adequately assessed. Here we compared in vitro the cytotoxic activity of stable monodisperse and aggregated silicon-based nanoparticles (SNP) without introducing a dispersing agent that may affect NP properties. SNP aggregates (180 nm) were produced by controlled electrostatic aggregation through addition of KCl to a Ludox SM sol (25 nm) followed by stabilization and extensive dialysis. The size of the preparations was characterized by TEM and DLS; specific surface area and porosity were derived from N(2) sorption measurements. Macrophage (J774) and fibroblast (3T3) cell lines were exposed to monodisperse or aggregate-enriched suspensions of SNP in DMEM in absence of serum. The cytotoxic activity of the different preparations was assessed by the WST1 assay after 24h of exposure. Parameters that determined the cytotoxic activity were traced by comparing the doses of the different preparations that induced half a maximal reduction in WST1 activity (ED(50)) in both cell lines. We found that ED(50) (6-9 ?g/ml and 15-22 ?g/ml, in J774 and 3T3, respectively) were hardly affected upon aggregation, which was consistent with the fact that the specific surface area of the SNP, a significant determinant of their cytotoxic activity, was unaffected upon aggregation (283-331 m(2)/g). Thus studying small aggregated NP could be as relevant as studying disperse primary NP, when aggregates keep the characteristics of NP, i.e. a high specific surface area and a nanosize dimension. This conclusion does, however, not necessarily hold true for other toxicity endpoints for which the determinants may be different and possibly modified by the aggregation process. PMID:21803137

Rabolli, Virginie; Thomassen, Leen C J; Uwambayinema, Francine; Martens, Johan A; Lison, Dominique

2011-07-22

69

Monodisperse nanoparticles via metal induced crystallization  

NASA Astrophysics Data System (ADS)

This paper discusses the self-assembled formation of monodisperse gold-rich nanoparticles and associated crystalline silicon nanostructures. Multilayer films comprising of amorphous Au25Si75 and amorphous silicon were grown via dc magnetron sputtering and subsequently annealed under varying thermal conditions. The films were characterized by electron microscopy before and after the thermal anneal. Thermal decomposition of the multilayer films results in the metal induced crystallization of amorphous silicon, as well as the formation of uniform Au-rich nanoparticles. Further annealing did not alter the size or position of the nanoparticles, indicating that the particles are too small to induce further silicon crystallization. Through thermodynamic modeling, two mechanisms are shown to be viable means for nanoscaled size selection. The first mechanism entails crystallization of Au25Si75 followed by metal induced crystallization of amorphous silicon, while the second utilizes spinodal decomposition of Au25Si75 to select a single nanoparticle radius.

Chandra, A.; Clemens, B. M.

2004-12-01

70

Laser pulse induced gold nanoparticle gratings  

SciTech Connect

We report the results of our experimental investigation of laser induced gold nanoparticle gratings and their optical diffraction properties. A single shot of a pair Nd-YAG laser pulses with the same polarization is directed toward a 6 nm thick gold film on a substrate of polymethyl methacrylate. As a result of the laser illumination, the thin gold film is fragmented into an array of nanoparticles. Through the observation of scanning electron and dark-field optical microscopes, we discovered that the morphology of the gold nanoparticle grating is dependent on the fluence of laser pulse. The spectrum of first order diffraction shows the dependence on the absorbance property due to the presence of the nanoparticles. The ablation of nanothickness thin films via the use of laser pulses may provide a simple and efficient method for the fabrication of nanoscale structures, including two dimensional arrays of nanoparticles.

Hung, W.-C.; Cheng, W.-H. [Institute of Electro-Optical Engineering, National Sun Yat-sen University, Kaohsiung 804, Taiwan (China); Tsai, M.-S.; Chung, W.-C. [Department of Applied Physics, National Chiayi University, Chiayi 600, Taiwan (China); Jiang, I-M. [Department of Physics, National Sun Yat-sen University, Kaohsiung 804, Taiwan (China); Yeh, Pochi [Department of Electrical and Computer Engineering, University of California, Santa Barbara, California 93106-9560 (United States)

2008-08-11

71

Ultrafine titanium dioxide nanoparticles induce cell death in human bronchial epithelial cells  

Microsoft Academic Search

Titanium dioxide (TiO2) nanoparticles (TNPs), once perceived as harmless, have been shown to induce cytotoxicity on various cell types under UV radiation. However, whether TNPs elicit cell death in the absence of UV has not been thoroughly studied. This study aims to investigate the TNPs-induced cell death mechanism in UV-absent condition by examining the reduction of cell viability and apoptotic

Eric Chen; Miguel Ruvalcaba; Lindsey Araujo; Ryan Chapman; Wei-Chun Chin

2008-01-01

72

Cytotoxicity of aluminium oxide nanoparticles towards fresh water algal isolate at low exposure concentrations.  

PubMed

The growing commercial applications had brought aluminium oxide nanoparticles under toxicologists' purview. In the present study, the cytotoxicity of two different sized aluminium oxide nanoparticles (ANP(1), mean hydrodynamic diameter 82.6±22nm and ANP(2), mean hydrodynamic diameter 246.9±39nm) towards freshwater algal isolate Chlorella ellipsoids at low exposure levels (?1?g/mL) using sterile lake water as the test medium was assessed. The dissolution of alumina nanoparticles and consequent contribution towards toxicity remained largely unexplored owing to its presumed insoluble nature. Herein, the leached Al(3+) ion mediated toxicity has been studied along with direct particulate toxicity to bring out the dynamics of toxicity through colloidal stability, biochemical, spectroscopic and microscopic analyses. The mean hydrodynamic diameter increased with time both for ANP(1) [82.6±22nm (0h) to 246.3±59nm (24h), to 1204±140nm (72h)] and ANP(2) [246.9±39nm (0h) to 368.28±48nm (24h), to 1225.96±186nm (72h)] signifying decreased relative abundance of submicron sized particles (<1000nm). The detailed cytotoxicity assays showed a significant reduction in the viability dependent on dose and exposure. A significant increase in ROS and LDH levels were noted for both ANPs at 1?g/mL concentration. The zeta potential and FT-IR analyses suggested surface chemical interaction between nanoparticles and algal cells. The substantial morphological changes and cell wall damage were confirmed through microscopic analyses (SEM, TEM, and CLSM). At 72h, significant Al(3+) ion release in the test medium [0.092?g/mL for ANP(1), and 0.19?g/mL for ANP(2)] was noted, and the resulting suspension containing leached ions caused significant cytotoxicity, revealing a substantial ionic contribution. This study indicates that both the nano-size and ionic dissolution play a significant role in the cytotoxicity of ANPs towards freshwater algae, and the exposure period largely determines the prevalent mode of nano-toxicity. PMID:23454308

Pakrashi, Sunandan; Dalai, Swayamprava; T C, Prathna; Trivedi, Shruti; Myneni, Radhika; Raichur, Ashok M; Chandrasekaran, N; Mukherjee, Amitava

2013-02-08

73

Nanoparticles from lipid-based liquid crystals: emulsifier influence on morphology and cytotoxicity.  

PubMed

Here, monoolein-based nanoparticles (NPs), obtained through fragmentation of bulk liquid crystalline phases, and stabilized by two different emulsifiers, namely, Pluronic F127 (PF127) and lauroylcholine chloride (LCh), are investigated for structural features and for short-term in vitro cytotoxicity. Depending on the emulsifiers, different morphologies of the lipid NPs (cubosomes and liposomes) are obtained, as demonstrated by cryo-TEM images. Although NPs offer many advantages in medical applications and various chemicals used for their preparation are under investigation, so far there are no standardized procedures to evaluate cell biocompatibility. Two different protocols to evaluate the impact of these lipid NPs on biological systems are presented. Results show that nanoparticles stabilized by PF127 (cubosomes) display a relevant toxicity toward different cell lines, whereas those stabilized by LCh (liposomes) affect cell viability at a much lesser extent. PMID:20170140

Murgia, Sergio; Falchi, Angela M; Mano, Miguel; Lampis, Sandrina; Angius, Rossella; Carnerup, Anna M; Schmidt, Judith; Diaz, Giacomo; Giacca, Mauro; Talmon, Yeshayahu; Monduzzi, Maura

2010-03-18

74

Using nano-QSAR to predict the cytotoxicity of metal oxide nanoparticles  

NASA Astrophysics Data System (ADS)

It is expected that the number and variety of engineered nanoparticles will increase rapidly over the next few years, and there is a need for new methods to quickly test the potential toxicity of these materials. Because experimental evaluation of the safety of chemicals is expensive and time-consuming, computational methods have been found to be efficient alternatives for predicting the potential toxicity and environmental impact of new nanomaterials before mass production. Here, we show that the quantitative structure-activity relationship (QSAR) method commonly used to predict the physicochemical properties of chemical compounds can be applied to predict the toxicity of various metal oxides. Based on experimental testing, we have developed a model to describe the cytotoxicity of 17 different types of metal oxide nanoparticles to bacteria Escherichia coli. The model reliably predicts the toxicity of all considered compounds, and the methodology is expected to provide guidance for the future design of safe nanomaterials.

Puzyn, Tomasz; Rasulev, Bakhtiyor; Gajewicz, Agnieszka; Hu, Xiaoke; Dasari, Thabitha P.; Michalkova, Andrea; Hwang, Huey-Min; Toropov, Andrey; Leszczynska, Danuta; Leszczynski, Jerzy

2011-03-01

75

Cytotoxicity of Al2O3 nanoparticles at low exposure levels to a freshwater bacterial isolate.  

PubMed

The cytotoxicity of Al(2)O(3) nanoparticles (NP) at very low exposure levels (1 ?g/mL and less) to a dominant bacterial isolate from freshwater (lake water), Bacillus licheniformis, was examined. Sterile lake water was directly used as a test medium or matrix to simulate the freshwater environment. Exposure to 1 ?g/mL Al(2)O(3) NP for 2 h caused a 17% decrease in cell viability (as determined by plate count and MTT assay). During the test period, the particles were found to be stable against aggregation in the matrix and exerted a nano-size effect on the exposed test organisms. The decrease in cell viability was proven not to be due to the release of Al(3+) ions from the nanoparticles in the dispersion. The zeta potential and FT-IR analyses suggested that the surface charge based attachment of nanoparticles on to the bacterial cell wall was responsible for flocculation leading to toxicity. The cell wall damage confirmed through SEM and the lipid peroxidation assay also contributed toward toxicity. This study warns of possible ecotoxicity of nanoparticles even at environmentally relevant concentrations. However, detailed studies need to be carried out to establish probable mechanistic aspects of this low concentration toxicity phenomenon. PMID:21967630

Pakrashi, Sunandan; Dalai, Swayamprava; Sabat, Debabrat; Singh, Suniti; Chandrasekaran, N; Mukherjee, Amitava

2011-10-14

76

Green synthesis and characterization of selenium nanoparticles and its augmented cytotoxicity with doxorubicin on cancer cells.  

PubMed

Green synthesis of selenium nanoparticles (SeNPs) was achieved by a simple biological procedure using the reducing power of fenugreek seed extract. This method is capable of producing SeNPs in a size range of about 50-150 nm, under ambient conditions. The synthesized nanoparticles can be separated easily from the aqueous sols by a high-speed centrifuge. These selenium nanoparticles were characterized by UV-Vis spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and elemental analysis by X-ray fluorescence spectrometer (XRF). Nanocrystalline SeNPs were obtained without post-annealing treatment. FTIR spectrum confirms the presence of various functional groups in the plant extract, which may possibly influence the reduction process and stabilization of nanoparticles. The cytotoxicity of SeNPs was assayed against human breast-cancer cells (MCF-7). It was found that SeNPs are able to inhibit the cell growth by dose-dependent manner. In addition, combination of SeNPs and doxorubicin shows better anticancer effect than individual treatments. PMID:23446776

Ramamurthy, Ch; Sampath, K S; Arunkumar, P; Kumar, M Suresh; Sujatha, V; Premkumar, K; Thirunavukkarasu, C

2013-02-28

77

Cytotoxity of nanoparticles is influenced by size, proliferation and embryonic origin of the cells used for testing.  

PubMed

Cytotoxicity screening is a common technique in drug compound screening for the identification of adverse cellular effects. Nanoparticles may cause interference in these assays. For the interpretation of cytotoxicity data it is important to study also the influence of other factors like pre-treatment of the nanoparticles, the choice of the cell culture medium and type of cell used for testing. Carboxyl polystyrene particles (CPS, 20-1000 nm) were physicochemically characterized and cytotoxicity assessed with seven screening assays in 20 cell lines, which differed in species, growth pattern, cell size, doubling time, embryonic origin and capacity for phagocytosis. Small CPS acted more cytotoxic in all cell lines, larger CPS only in phagocytic cells. Small differences in cytotoxicity were noted between the screening assays. Growth pattern and cell size determined cytotoxicity more than proliferation rate and embryonic origin of cells. Non-adherent cells, cells of mesenchymal origin and with high proliferation rate may be more susceptible to damage by nanoparticles. PMID:21627401

Fröhlich, Eleonore; Meindl, Claudia; Roblegg, Eva; Griesbacher, Antonia; Pieber, Thomas R

2011-05-31

78

An effective strategy for the synthesis of biocompatible gold nanoparticles using danshensu antioxidant: prevention of cytotoxicity via attenuation of free radical formation.  

PubMed

To suppress the cytotoxicity of gold nanoparticles (AuNPs), danshensu, a naturally occurring polyphenol antioxidant isolated from Chinese herb, was used to provide a fundamental protection layer for AuNPs, to alleviate oxidative stress and as a reducing agent to react with chloroauric acid. Besides danshensu, gum arabic was chosen as an auxiliary stabilising agent to improve the stability of AuNPs against aggregation. As expected, the prepared GA-DS-AuNPs (gum arabic-danshensu-gold nanoparticle) was remarkably stable in various buffer solutions. More interestingly, the GA-DS-AuNPs not only did not show any appreciable cytotoxicity, but also could alleviate the oxidative damage induced by AuNPs. Meanwhile, the ROS/RNS scavenging activities of GA-DS-AuNPs was evaluated by electron spin resonance spectroscopy (ESR), potentiometric nitric oxide (NO) sensor and cell confocal imaging. The results suggest that GA-DS-AuNPs might have effectively reduced the AuNPs-induced cytotoxicity and oxidative stress by downregulation of ROS/NOS production. The GA-DS-AuNPs may provide potential opportunities for the application in nanomedicine and nanobiology. PMID:22313229

Du, Libo; Miao, Xiaoxiang; Jiang, Yugang; Jia, Hongying; Tian, Qiu; Shen, Jiangang; Liu, Yang

2012-02-07

79

Poly(ethylene) glycol-capped silver and magnetic nanoparticles: Synthesis, characterization, and comparison of bactericidal and cytotoxic effects.  

PubMed

Silver and magnetic (Fe3O4) nanoparticles have attracted wide attention as novel antimicrobial agents due to their unique chemical and physical properties. In order to study the comparative effects on antibacterial and animal cytotoxicity, Staphylococcus aureus and NIH 3T3 fibroblasts were used, respectively. Both nanoparticles were synthesized via a novel matrix-mediated method using poly(ethylene) glycol. Formation of silver nanoparticles was confirmed by fluorescence and ultraviolet-visible spectroscopic techniques. The poly(ethylene) glycol-coated silver and Fe3O4 nanoparticles were characterized by scanning electron microscope, transmission electron microscope, zeta potential, particle size analysis, Fourier-transform infrared, X-ray diffraction, and X-ray photoelectron spectroscopy. The antimicrobial results indicate that both poly(ethylene) glycol-coated silver and Fe3O4 nanoparticles inhibited S. aureus growth at the concentrations of 5 and 10?µg/mL at all time points without showing any significant cytotoxicity on NIH 3T3 fibroblasts. The particle size of both the poly(ethylene) glycol-coated silver and Fe3O4 nanoparticles dominated in the range 10-15?nm, obtained by particle size analyzer. The poly(ethylene) glycol coating on the particles showed less aggregation of nanoparticles, as observed by scanning electron microscope and transmission electron microscope. The overall obtained results indicated that these two nanoparticles were stable and could be used to develop a magnetized antimicrobial scaffolds for biomedical applications. PMID:23959858

Mandal, A; Sekar, S; Chandrasekaran, N; Mukherjee, A; Sastry, Tp

2013-08-19

80

Peptide-Induced Antiviral Protection by Cytotoxic T Cells  

NASA Astrophysics Data System (ADS)

A specific antiviral cytotoxic immune response in vivo could be induced by the subcutaneous injection of the T-cell epitope of the lymphocytic choriomeningitis virus (LCMV) nucleoprotein as an unmodified free synthetic peptide (Arg-Pro-Gln-Ala-Ser-Gly-Val-Tyr-Met-Gly-Asn-Leu-Thr-Ala-Gln) emulsified in incomplete Freund's adjuvant. This immunization rendered mice into a LCMV-specific protective state as shown by the inhibition of LCMV replication in spleens of such mice. The protection level of these mice correlated with the ability to respond to the peptide challenge by CD8^+ virus-specific cytotoxic T cells. This is a direct demonstration that peptide vaccines can be antivirally protective in vivo, thus encouraging further search for appropriate mixtures of stable peptides that may be used as T-cell vaccines.

Schulz, Manfred; Zinkernagel, Rolf M.; Hengartner, Hans

1991-02-01

81

BCG induced CD4+ cytotoxic T cells from BCG vaccinated healthy subjects: relation between cytotoxicity and suppression in vitro.  

PubMed

Mycobacterial antigen specific cytotoxic T cells killing antigen-pulsed antigen presenting cells (APC) were induced from peripheral blood mononuclear cells (PBMC) of BCG-vaccinated healthy subjects after activation in vitro with BCG. CD8+ depleted cells were as effective as PBMC, indicating that CD4+ cells play a dominant role in this phenomenon. CD4+ T cell clones raised against BCG also exhibited mycobacterial antigen specific cytotoxicity and suppressed BCG-driven selfproliferation. However, the same clones could either suppress or enhance the proliferation of other T cell clones from the same subject. The possible function in vivo of the cytotoxicity mediated by CD4+ T cells is discussed. PMID:2958195

Mustafa, A S; Godal, T

1987-08-01

82

Cytotoxicity of surface-functionalized silicon and germanium nanoparticles: the dominant role of surface charges  

NASA Astrophysics Data System (ADS)

Although it is frequently hypothesized that surface (like surface charge) and physical characteristics (like particle size) play important roles in cellular interactions of nanoparticles (NPs), a systematic study probing this issue is missing. Hence, a comparative cytotoxicity study, quantifying nine different cellular endpoints, was performed with a broad series of monodisperse, well characterized silicon (Si) and germanium (Ge) NPs with various surface functionalizations. Human colonic adenocarcinoma Caco-2 and rat alveolar macrophage NR8383 cells were used to clarify the toxicity of this series of NPs. The surface coatings on the NPs appeared to dominate the cytotoxicity: the cationic NPs exhibited cytotoxicity, whereas the carboxylic acid-terminated and hydrophilic PEG- or dextran-terminated NPs did not. Within the cationic Si NPs, smaller Si NPs were more toxic than bigger ones. Manganese-doped (1% Mn) Si NPs did not show any added toxicity, which favors their further development for bioimaging. Iron-doped (1% Fe) Si NPs showed some added toxicity, which may be due to the leaching of Fe3+ ions from the core. A silica coating seemed to impart toxicity, in line with the reported toxicity of silica. Intracellular mitochondria seem to be the target for the toxic NPs since a dose-, surface charge- and size-dependent imbalance of the mitochondrial membrane potential was observed. Such an imbalance led to a series of other cellular events for cationic NPs, like decreased mitochondrial membrane potential (??m) and ATP production, induction of ROS generation, increased cytoplasmic Ca2+ content, production of TNF-? and enhanced caspase-3 activity. Taken together, the results explain the toxicity of Si NPs/Ge NPs largely by their surface characteristics, provide insight into the mode of action underlying the observed cytotoxicity, and give directions on synthesizing biocompatible Si and Ge NPs, as this is crucial for bioimaging and other applications in for example the field of medicine.Although it is frequently hypothesized that surface (like surface charge) and physical characteristics (like particle size) play important roles in cellular interactions of nanoparticles (NPs), a systematic study probing this issue is missing. Hence, a comparative cytotoxicity study, quantifying nine different cellular endpoints, was performed with a broad series of monodisperse, well characterized silicon (Si) and germanium (Ge) NPs with various surface functionalizations. Human colonic adenocarcinoma Caco-2 and rat alveolar macrophage NR8383 cells were used to clarify the toxicity of this series of NPs. The surface coatings on the NPs appeared to dominate the cytotoxicity: the cationic NPs exhibited cytotoxicity, whereas the carboxylic acid-terminated and hydrophilic PEG- or dextran-terminated NPs did not. Within the cationic Si NPs, smaller Si NPs were more toxic than bigger ones. Manganese-doped (1% Mn) Si NPs did not show any added toxicity, which favors their further development for bioimaging. Iron-doped (1% Fe) Si NPs showed some added toxicity, which may be due to the leaching of Fe3+ ions from the core. A silica coating seemed to impart toxicity, in line with the reported toxicity of silica. Intracellular mitochondria seem to be the target for the toxic NPs since a dose-, surface charge- and size-dependent imbalance of the mitochondrial membrane potential was observed. Such an imbalance led to a series of other cellular events for cationic NPs, like decreased mitochondrial membrane potential (??m) and ATP production, induction of ROS generation, increased cytoplasmic Ca2+ content, production of TNF-? and enhanced caspase-3 activity. Taken together, the results explain the toxicity of Si NPs/Ge NPs largely by their surface characteristics, provide insight into the mode of action underlying the observed cytotoxicity, and give directions on synthesizing biocompatible Si and Ge NPs, as this is crucial for bioimaging and other applications in for example the field of medicine. Electronic supplementary information (ESI) available: Syn

Bhattacharjee, Sourav; Rietjens, Ivonne M. C. M.; Singh, Mani P.; Atkins, Tonya M.; Purkait, Tapas K.; Xu, Zejing; Regli, Sarah; Shukaliak, Amber; Clark, Rhett J.; Mitchell, Brian S.; Alink, Gerrit M.; Marcelis, Antonius T. M.; Fink, Mark J.; Veinot, Jonathan G. C.; Kauzlarich, Susan M.; Zuilhof, Han

2013-05-01

83

Iron nanoparticles increase 7-ketocholesterol-induced cell death, inflammation, and oxidation on murine cardiac HL1-NB cells  

PubMed Central

Objective: To evaluate the cytotoxicity of iron nanoparticles on cardiac cells and to determine whether they can modulate the biological activity of 7-ketocholesterol (7KC) involved in the development of cardiovascular diseases. Nanoparticles of iron labeled with Texas Red are introduced in cultures of nonbeating mouse cardiac cells (HL1-NB) with or without 7-ketocholesterol 7KC, and their ability to induce cell death, pro-inflammatory and oxidative effects are analyzed simultaneously. Study design: Flow cytometry (FCM), confocal laser scanning microscopy (CLSM), and subsequent factor analysis image processing (FAMIS) are used to characterize the action of iron nanoparticles and to define their cytotoxicity which is evaluated by enhanced permeability to SYTOX Green, and release of lactate deshydrogenase (LDH). Pro-inflammatory effects are estimated by ELISA in order to quantify IL-8 and MCP-1 secretions. Pro-oxidative effects are measured with hydroethydine (HE). Results: Iron Texas Red nanoparticles accumulate at the cytoplasmic membrane level. They induce a slight LDH release, and have no inflammatory or oxidative effects. However, they enhance the cytotoxic, pro-inflammatory and oxidative effects of 7KC. The accumulation dynamics of SYTOX Green in cells is measured by CLSM to characterize the toxicity of nanoparticles. The emission spectra of SYTOX Green and nanoparticles are differentiated, and corresponding factor images specify the possible capture and cellular localization of nanoparticles in cells. Conclusion: The designed protocol makes it possible to show how Iron Texas Red nanoparticles are captured by cardiomyocytes. Interestingly, whereas these fluorescent iron nanoparticles have no cytotoxic, pro-inflammatory or oxidative activities, they enhance the side effects of 7KC.

Kahn, Edmond; Baarine, Mauhamad; Pelloux, Sophie; Riedinger, Jean-Marc; Frouin, Frederique; Tourneur, Yves; Lizard, Gerard

2010-01-01

84

Cytotoxicity of surface-functionalized silicon and germanium nanoparticles: the dominant role of surface charges.  

PubMed

Although it is frequently hypothesized that surface (like surface charge) and physical characteristics (like particle size) play important roles in cellular interactions of nanoparticles (NPs), a systematic study probing this issue is missing. Hence, a comparative cytotoxicity study, quantifying nine different cellular endpoints, was performed with a broad series of monodisperse, well characterized silicon (Si) and germanium (Ge) NPs with various surface functionalizations. Human colonic adenocarcinoma Caco-2 and rat alveolar macrophage NR8383 cells were used to clarify the toxicity of this series of NPs. The surface coatings on the NPs appeared to dominate the cytotoxicity: the cationic NPs exhibited cytotoxicity, whereas the carboxylic acid-terminated and hydrophilic PEG- or dextran-terminated NPs did not. Within the cationic Si NPs, smaller Si NPs were more toxic than bigger ones. Manganese-doped (1% Mn) Si NPs did not show any added toxicity, which favors their further development for bioimaging. Iron-doped (1% Fe) Si NPs showed some added toxicity, which may be due to the leaching of Fe(3+) ions from the core. A silica coating seemed to impart toxicity, in line with the reported toxicity of silica. Intracellular mitochondria seem to be the target for the toxic NPs since a dose-, surface charge- and size-dependent imbalance of the mitochondrial membrane potential was observed. Such an imbalance led to a series of other cellular events for cationic NPs, like decreased mitochondrial membrane potential (??m) and ATP production, induction of ROS generation, increased cytoplasmic Ca(2+) content, production of TNF-? and enhanced caspase-3 activity. Taken together, the results explain the toxicity of Si NPs/Ge NPs largely by their surface characteristics, provide insight into the mode of action underlying the observed cytotoxicity, and give directions on synthesizing biocompatible Si and Ge NPs, as this is crucial for bioimaging and other applications in for example the field of medicine. PMID:23619571

Bhattacharjee, Sourav; Rietjens, Ivonne M C M; Singh, Mani P; Atkins, Tonya M; Purkait, Tapas K; Xu, Zejing; Regli, Sarah; Shukaliak, Amber; Clark, Rhett J; Mitchell, Brian S; Alink, Gerrit M; Marcelis, Antonius T M; Fink, Mark J; Veinot, Jonathan G C; Kauzlarich, Susan M; Zuilhof, Han

2013-04-25

85

Cytotoxicity Induced by Engineered Silver Nanocrystallites is Dependent on Surface Coatings and Cell Types  

SciTech Connect

Due to their unique antimicrobial properties silver nanocrystallites have garnered substantial recognition and are used extensively in biomedical applications such as wound dressing, surgical instruments and as bone substitute material. They are also released into unintended locations such as the environment or biosphere. Therefore it is imperative to understand the potential interactions, fate and transport of nanoparticles with environmental biotic systems. Although numerous factors including the composition, size, shape, surface charge and capping molecule of nanoparticles are known to influence the cell cytotoxicity, our results demonstrate for the first time that surface coatings are a major determinant in eliciting the potential cytotoxicity and cell interactions of silver nanoparticles. In the present investigation, silver nanocrystallites with nearly uniform size and shape distribution but with different surface coatings, imparting overall high negativity to high positivity, were synthesized. These nanoparticles were poly (diallyldimethylammonium) chloride-Ag, biogenic-Ag, colloidal-Ag (uncoated) and oleate-Ag with zeta potentials +45 5 mV, -12 2 mV, -42 5 mV and -45 5 mV respectively; the particles were thoroughly purified so as to avoid false cytotoxicity interpretations. A systematic investigation on the cytotoxic effects, cellular response and membrane damage caused by these four different silver nanoparticles were evaluated using multiple toxicity measurements on mouse macrophage (RAW-264.7) and lung epithelial (C-10) cell lines. From a toxicity perspective, our results clearly indicated that the cytotoxicity was depend on various factors such as synthesis procedure, surface coat or surface charge and the cell-type for the different silver nanoparticles that were investigated. Poly (diallyldimethylammonium) chloride -Ag was found to be the most toxic, followed by biogenic-Ag and oleate-Ag, whereas uncoated-Ag was found to be least toxic to both macrophage and epithelial cells. Also, based on our cytotoxicity interpretations, epithelial cells were found to be more resistant to the silver nanoparticles than the macrophage cells, regardless of the surface coating.

Suresh, Anil K [ORNL; Pelletier, Dale A [ORNL; Wang, Wei [ORNL; Morrell-Falvey, Jennifer L [ORNL; Doktycz, Mitchel John [ORNL

2012-01-01

86

Metabolic profiling reveals disorder of carbohydrate metabolism in mouse fibroblast cells induced by titanium dioxide nanoparticles.  

PubMed

As titanium dioxide (TiO2 ) nanoparticles are widely used commercially, their potential biosafety and metabolic mechanism needs to be fully explained. In this study, the cytotoxicity of homogeneous and weakly aggregated (< 100?nm) TiO2 nanoparticles was investigated by analyzing the changes in metabolite profiles both in mouse fibroblast (L929) cells and their corresponding culture media using gas chromatograph with a time-of-flight mass spectrometry (GC/TOFMS)-based metabolomic strategy. With multivariate statistics analysis, satisfactory separations were observed in principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models. Based on the variable importance in the OPLS-DA models, a series of differential metabolites were identified by comparison between TiO2 nanoparticle-treated L929 cells or their corresponding culture media and the control groups. It was found that the major biochemical metabolism (carbohydrate metabolism) was suppressed in TiO2 nanoparticle-treated L929 cells and their corresponding culture media. These results might account for the serious damage to energy metabolism in mitochondria and the increased cellular oxidation stress in TiO2 nanoparticle-induced L929 cells. These results also suggest that the metabolomic strategy had a great potential in evaluating the cytotoxicity of TiO2 nanoparticles and thus was very helpful in understanding its underlying molecular mechanisms. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22996321

Jin, Chengyu; Liu, Yumin; Sun, Limin; Chen, Tianlu; Zhang, Yinan; Zhao, Aihua; Wang, Xiaoyan; Cristau, Melanie; Wang, Kaisheng; Jia, Wei

2012-09-20

87

In vitro cytotoxicity and genotoxicity studies of titanium dioxide (TiO2) nanoparticles in Chinese hamster lung fibroblast cells.  

PubMed

There are increasing safety concerns about the development and abundant use of nanoparticles. The unique physical and chemical characteristics of titanium dioxide (TiO2) nanoparticles result in different chemical and biological activities compared to their larger micron-sized counterparts, and can subsequently play an important role in influencing toxicity. Therefore, our objective was to investigate the cytotoxicity and genotoxicity of commercially available TiO2 nanoparticles with respect to their selected physicochemical properties, as well as the role of surface coating of these nanoparticles. While all types of tested TiO2 samples decrease cell viability in a mass-based concentration- and size-dependent manner, the polyacrylate-coated nano-TiO2 product was only cytotoxic at higher concentrations. A similar pattern of response was observed for induction of apoptosis/necrosis, and no DNA damage was detected in the polyacrylate-coated nano-TiO2 model. Given the increasing production of TiO2 nanoparticles, toxicological studies should take into account the physiochemical properties of these nanoparticles that may help researchers to develop new nanoparticles with minimum toxicity. PMID:23274916

Hamzeh, Mahsa; Sunahara, Geoffrey I

2012-12-28

88

Laser pulse induced gold nanoparticle gratings  

Microsoft Academic Search

We report the results of our experimental investigation of laser induced gold nanoparticle gratings and their optical diffraction properties. A single shot of a pair Nd-YAG laser pulses with the same polarization is directed toward a 6 nm thick gold film on a substrate of polymethyl methacrylate. As a result of the laser illumination, the thin gold film is fragmented

Wen-Chi Hung; Wood-Hi Cheng; Ming-Shan Tsai; Wei-Chih Chung; I.-Min Jiang; Pochi Yeh

2008-01-01

89

Cytotoxic effects in 3T3-L1 mouse and WI-38 human fibroblasts following 72 hour and 7 day exposures to commercial silica nanoparticles.  

PubMed

The potential toxic effects in murine (3T3-L1) and human (WI-38) fibroblast cell lines of commercially available silica nanoparticles (NPs), Ludox CL (nominal size 21 nm) and CL-X (nominal size of 30 nm) were investigated with particular attention to the effect over long exposure times (the tests were run after 72 h exposure up to 7 days). These two formulations differed in physico-chemical properties and showed different stabilities in the cell culture medium used for the experiments. Ludox CL silica NPs were found to be cytotoxic only at the higher concentrations to the WI-38 cells (WST-1 and LDH assays) but not to the 3T3-L1 cells, whereas the Ludox CL-X silica NPs, which were less stable over the 72 h exposure, were cytotoxic to both cell lines in both assays. In the clonogenic assay both silica NPs induced a concentration dependent decrease in the surviving fraction of 3T3-L1 cells, with the Ludox CL-X silica NPs being more cytotoxic. Cell cycle analysis showed a trend indicating alterations in both cell lines at different phases with both silica NPs tested. Buthionine sulfoximine (?-glutamylcysteine synthetase inhibitor) combined with Ludox CL-X was found to induce a strong decrease in 3T3-L1 cell viability which was not observed for the WI-38 cell line. This study clearly indicates that longer exposure studies may give important insights on the impact of nanomaterials on cells. However, and especially when investigating nanoparticle effects after such long exposure, it is fundamental to include a detailed physico-chemical characterization of the nanoparticles and their dispersions over the time scale of the experiment, in order to be able to interpret eventual impacts on cells. PMID:22705593

St?pnik, Maciej; Arkusz, Joanna; Smok-Pieni??ek, Anna; Bratek-Skicki, Anna; Salvati, Anna; Lynch, Iseult; Dawson, Kenneth A; Gromadzi?ska, Jolanta; De Jong, Wim H; Rydzy?ski, Konrad

2012-06-13

90

Vitamin K3 analogs induce selective tumor cytotoxicity in neuroblastoma.  

PubMed

We investigated the cytotoxicity of eight vitamin K3 (VK3) analogs against neuroblastoma cell lines (IMR-32, LA-N-1, NB-39, and SK-N-SH) and normal cell lines (human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (HDF)) using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. 2-[(2-Methoxy)ethylthio]-3-methyl-1,4-naphthoquinone (VK3-OCH(3)) showed especially potent cytotoxic activities against neuroblastoma cells compared with normal cells. In a Hoechst 33342 staining experiment, apoptotic morphologies characterized by cell shrinkage, nuclear condensation, and nuclear fragmentation were observed in IMR-32 and LA-N-1 cells after 48 h of treatment with 10(-5) M of VK3-OCH(3). To clarify the molecular mechanisms of apoptosis induced by VK3-OCH(3), we examined the expression of apoptosis related proteins using a Proteome Profiler Array and western blotting. Heme oxygenase (HO)-1 was remarkably increased by VK3-OCH(3) compared with the control (173% in IMR-32 and 170% in LA-N-1 at 24 h). Moreover, caveolin-1 was induced by VK3-OCH(3) at 48 h. In addition, VK3-OCH(3) arrested the cell cycle at the G2/M phase in IMR-32 cells. These results suggest that VK3-OCH(3) exhibited a selective antitumor activity via HO-1-related mechanisms. PMID:22466570

Kitano, Toru; Yoda, Hiroyuki; Tabata, Keiichi; Miura, Motofumi; Toriyama, Masaharu; Motohashi, Shigeyasu; Suzuki, Takashi

2012-01-01

91

Monodisperse nanoparticles via metal induced crystallization  

SciTech Connect

This paper discusses the self-assembled formation of monodisperse gold-rich nanoparticles and associated crystalline silicon nanostructures. Multilayer films comprising of amorphous Au{sub 25}Si{sub 75} and amorphous silicon were grown via dc magnetron sputtering and subsequently annealed under varying thermal conditions. The films were characterized by electron microscopy before and after the thermal anneal. Thermal decomposition of the multilayer films results in the metal induced crystallization of amorphous silicon, as well as the formation of uniform Au-rich nanoparticles. Further annealing did not alter the size or position of the nanoparticles, indicating that the particles are too small to induce further silicon crystallization. Through thermodynamic modeling, two mechanisms are shown to be viable means for nanoscaled size selection. The first mechanism entails crystallization of Au{sub 25}Si{sub 75} followed by metal induced crystallization of amorphous silicon, while the second utilizes spinodal decomposition of Au{sub 25}Si{sub 75} to select a single nanoparticle radius.

Chandra, A.; Clemens, B.M. [Department of Materials Science and Engineering, Stanford University, Stanford, California 94305 (United States)

2004-12-01

92

Electron beam induced growth of silver nanoparticles.  

PubMed

An electron beam inducing method for sprouting large quantities of silver nanoparticles on the surface of silver chloride particles is reported. The electron beam driven process was characterized by time-dependent scanning electron microscope (SEM) and energy dispersive spectrum (EDS), allowing for observing several key intermediates in and characteristics of the growth process. Theoretical calculation coupled with experimental observation demonstrated that the growth of silver nanoparticles was mostly related to the current density of electron beam. Decomposition of the silver chloride on the surface of sample was under electron beam irradiation resulted in silver nanoparticles and chlorine. This phenomenon could be useful in developing a novel mechanism for preparation of nanostructures and proposing a reference to avoid image distortion during the characterization of silver compounds under SEM. PMID:22753345

Shi, Guanghua; Bao, Shengxiang; Lai, Weiming; Rao, Zhenzhen; Zhang, Xiaowen; Wang, Zuwen

2012-07-02

93

The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles  

PubMed Central

Many types of nanoparticles (NPs) are tested for use in medical products, particularly in imaging and gene and drug delivery. For these applications, cellular uptake is usually a prerequisite and is governed in addition to size by surface characteristics such as hydrophobicity and charge. Although positive charge appears to improve the efficacy of imaging, gene transfer, and drug delivery, a higher cytotoxicity of such constructs has been reported. This review summarizes findings on the role of surface charge on cytotoxicity in general, action on specific cellular targets, modes of toxic action, cellular uptake, and intracellular localization of NPs. Effects of serum and intercell type differences are addressed. Cationic NPs cause more pronounced disruption of plasma-membrane integrity, stronger mitochondrial and lysosomal damage, and a higher number of autophagosomes than anionic NPs. In general, nonphagocytic cells ingest cationic NPs to a higher extent, but charge density and hydrophobicity are equally important; phagocytic cells preferentially take up anionic NPs. Cells do not use different uptake routes for cationic and anionic NPs, but high uptake rates are usually linked to greater biological effects. The different uptake preferences of phagocytic and nonphagocytic cells for cationic and anionic NPs may influence the efficacy and selectivity of NPs for drug delivery and imaging.

Frohlich, Eleonore

2012-01-01

94

Preparation, characterization and in vitro cytotoxicity of paclitaxel-loaded sterically stabilized solid lipid nanoparticles.  

PubMed

In an effort to develop an alternative formulation of paclitaxel suitable for parenteral administration, paclitaxel-loaded sterically stabilized solid lipid nanoparticles (SLNs) were prepared, characterized and examined for in vitro cytotoxicity. The SLNs, comprising trimyristin (TM) as a solid lipid core and egg phosphatidylcholine and pegylated phospholipid as stabilizers, were prepared using a hot homogenization method. Regardless of paclitaxel loading, the particle sizes and zeta potentials of the prepared SLNs were around 200nm and -38mV, respectively, suggesting that they would be suitable as a parenteral formulation. Cryo-scanning electron microscopy showed that the SLNs were homogeneous and spherical in shape, while differential scanning calorimetry measurement of the melting peak revealed that the TM exists as a solid in our formulation. Paclitaxel was loaded to the solid cores at a w/w ratio of 6%. Gel column chromatography showed that paclitaxel co-eluted with the phospholipids, indicating that paclitaxel was incorporated in the SLNs. An in vitro drug release study showed that paclitaxel was released from the SLNs in a slow but time-dependent manner. Furthermore, treatment of the OVCAR-3 human ovarian cancer cell line and the MCF-7 breast cancer cell line with paclitaxel-loaded SLNs yielded cytotoxicities comparable to those of a commercially available Cremophor EL-based paclitaxel formulation. These results collectively suggest that our optimized SLN formulation may have a potential as alternative delivery system for parenteral administration of paclitaxel. PMID:17257668

Lee, Mi-Kyung; Lim, Soo-Jeong; Kim, Chong-Kook

2007-01-10

95

Titanium Dioxide (TiO2) Nanoparticles Preferentially Induce Cell Death in Transformed Cells in a Bak/Bax-Independent Fashion  

PubMed Central

While the cytotoxic effects of titanium dioxide (TiO2) nanoparticles have been under intense investigation, the molecular mechanisms of this cytotoxicity remain unknown. Here we investigated the influence of oncogenic transformation and a major apoptotic signaling pathway on cellular responses to TiO2 nanoparticles. Isogenic wild-type (WT) and apoptosis-resistant (Bak?/?Bax?/?) cell lines with and without tumorigenic transformation were examined. TiO2 nanoparticles preferentially reduced viability of tumorigenic cells in a dose-dependent fashion compared with their untransformed counterparts. Importantly, the elevated cytotoxicity of TiO2 nanoparticles was independent of a major Bak/Bax-dependent apoptosis pathway. Because transformation does not affect cellular fluid-phase endocytosis or nanoparticle uptake, it is likely that the increased cytotoxicity in tumor cells is due to the interaction between TiO2 nanoparticles and the lysosomal compartment. Overall, our data indicate that TiO2 nanoparticles induce cytotoxicity preferentially in transformed cells independent of a major apoptotic signaling pathway.

Zhu, Yanglong; Eaton, John W.; Li, Chi

2012-01-01

96

The cytotoxicity evaluation of magnetic iron oxide nanoparticles on human aortic endothelial cells  

PubMed Central

One major obstacle for successful application of nanoparticles in medicine is its potential nanotoxicity on the environment and human health. In this study, we evaluated the cytotoxicity effect of dimercaptosuccinic acid-coated iron oxide (DMSA-Fe2O3) using cultured human aortic endothelial cells (HAECs). Our results showed that DMSA-Fe2O3 in the culture medium could be absorbed into HAECs, and dispersed in the cytoplasm. The cytotoxicity effect of DMSA-Fe2O3 on HAECs was dose-dependent, and the concentrations no more than 0.02 mg/ml had little toxic effect which were revealed by tetrazolium dye assay. Meanwhile, the cell injury biomarker, lactate dehydrogenase, was not significantly higher than that from control cells (without DMSA-Fe2O3). However, the endocrine function for endothelin-1 and prostacyclin I-2, as well as the urea transporter function, was altered even without obvious evidence of cell injury in this context. We also showed by real-time PCR analysis that DMSA-Fe2O3 exposure resulted in differential effects on the expressions of pro- and anti-apoptosis genes of HAECs. Meanwhile, it was noted that DMSA-Fe2O3 exposure could activate the expression of genes related to oxidative stress and adhesion molecules, which suggested that inflammatory response might be evoked. Moreover, we demonstrated by in vitro endothelial tube formation that even a small amount of DMSA-Fe2O3 (0.01 and 0.02 mg/ml) could inhibit angiogenesis by the HAECs. Altogether, these results indicate that DMSA-Fe2O3 have some cytotoxicity that may cause side effects on normal endothelial cells.

2013-01-01

97

Ion irradiation induced hollow and sandwiched nanoparticles  

SciTech Connect

We report on the fabrication of hollow and sandwiched nanoparticles by ion irradiation. Ag nanoparticles embedded in silica were irradiated by N{sup +}, Si{sup +}, Ar{sup +}, and Cu{sup +} ions at 300 keV to a fluence of 5x10{sup 16} ions/cm{sup 2}, by Cu{sup +} ions at varying energies from 110 to 500 keV to a fluence of 5x10{sup 16} ions/cm{sup 2}, and by Cu{sup +} ions at 400 keV to fluences varied from 1x10{sup 16} to 1x10{sup 17} ions/cm{sup 2}. The size of the irradiation-induced nanovoids increases with increasing ion mass and energy. The formation of nanovoids depends on the electronic and nuclear energy loss of the irradiation ions. The formation of irradiation-induced sandwiched nanoparticles is because of the capture of knocked-out Ag atoms from nanoshells by nanovoids. The size of the inner nanoparticles within the sandwiched structure increases with increasing fluence.

Ren Feng; Cai Guangxu; Xiao Xiangheng; Fan Lixia; Liu Chang; Fu Dejun; Wang Jianbo; Jiang Changzhong [Key Laboratory of Acoustic and Photonic Materials and Devices of Ministry of Education, Wuhan University, Wuhan 430072 (China) and Department of Physics, Wuhan University, Wuhan 430072 (China)

2008-04-15

98

Effect of seabuckthorn on sodium nitroprusside-induced cytotoxicity in murine macrophages  

Microsoft Academic Search

The present study reports the anti-oxidant activity of alcoholic extracts of leaf and fruit of seabuckthorn (SBT) on nitric oxide (NO) induced cytotoxicity in J-774 macrophages. Sodium nitroprusside (SNP), which generates NO at the concentration of 500 ?g\\/ml, induced cytotoxicity as revealed by decreased neutral red uptake by macrophages. The cytotoxicity of SNP was attributed to enhanced reactive oxygen species (ROS)

S. Geetha; M. Sai Ram; Virendra Singh; G. Ilavazhagan; R. C. Sawhney

2002-01-01

99

Resveratrol Inhibited Hydroquinone-Induced Cytotoxicity in Mouse Primary Hepatocytes  

PubMed Central

Hydroquinone (1,4-benzenediol) has been widely used in clinical situations and the cosmetic industry because of its depigmenting effects. Most skin-lightening hydroquinone creams contain 4%–5% hydroquinone. We have investigated the role of resveratrol in prevention of hydroquinone induced cytotoxicity in mouse primary hepatocytes. We found that 400 µM hydroquinone exposure alone induced apoptosis of the cells and also resulted in a significant drop of cell viability compared with the control, and pretreatment of resveratrol to a final concentration of 0.5 mM 1 h before hydroquinone exposure did not show a significant improvement in the survival rate of the hepatocytes, however, relatively higher concentrations of resveratrol (?1 mM) inhibited apoptosis of the mouse primary hepatocytes and increased cell viability in a dose-dependent manner, and in particular the survival rate of the hepatocytes was recovered from 28% to near 100% by 5 mM resveratrol. Interestingly, pretreatment with resveratrol for longer time (24 h), even in very low concentrations (50 µM, 100 µM), blocked the damage of hydroquinone to the cells. We also observed that resveratrol pretreatment suppressed hydroquinone-induced expression of cytochrome P450 2E1 mRNA dose-dependently. The present study suggests that resveratrol protected the cells against hydroquinone-induced toxicity through its antioxidant function and possibly suppressive effect on the expression of cytochrome P450 2E1.

Wang, Da-Hong; Ootsuki, Yoshie; Fujita, Hirofumi; Miyazaki, Masahiro; Yie, Qinxia; Tsutsui, Ken; Sano, Kuniaki; Masuoka, Noriyoshi; Ogino, Keiki

2012-01-01

100

Effect of seabuckthorn on sodium nitroprusside-induced cytotoxicity in murine macrophages.  

PubMed

The present study reports the anti-oxidant activity of alcoholic extracts of leaf and fruit of seabuckthorn (SBT) on nitric oxide (NO) induced cytotoxicity in J-774 macrophages. Sodium nitroprusside (SNP), which generates NO at the concentration of 500 microg/ml, induced cytotoxicity as revealed by decreased neutral red uptake by macrophages. The cytotoxicity of SNP was attributed to enhanced reactive oxygen species (ROS) production, which in turn resulted in decrease in anti-oxidant levels. Alcoholic leaf and fruit extracts of SBT at the concentration of 500 microg/ml were found to have a significant cytoprotective effect against SNP-induced oxidative stress. These extracts inhibited SNP-induced cytotoxicity, free radical production and maintained the anti-oxidant status identical to that of control cells. The alcoholic fruit extract of SBT was found to have significantly higher anti-oxidant activity than leaf extract against SNP-induced cytotoxicity in murine macrophages. PMID:12481983

Geetha, S; Ram, M Sai; Singh, Virendra; Ilavazhagan, G; Sawhney, R C

2002-11-01

101

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

NASA Astrophysics Data System (ADS)

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.

Ispas, Cristina R.

102

Evaluation of the cytotoxic effect of camptothecin solid lipid nanoparticles on MCF7 cells.  

PubMed

Abstract Camptothecin (CPT) and its analogs exhibit remarkable anti-tumor activity, due to their ability to inhibit DNA topoisomerase I. However, its use is limited by the lack of solubility and stability of the active lactone form. An attractive alternative is the encapsulation of CPT within liposomes. In this study, CPT was incorporated into solid lipid nanoparticles (SLN) based on the triglyceride, Compritol 888 ATO, using supercritical fluid technology without requiring the use of harmful solvents. This drug delivery system was characterized and its cytotoxicity effect was evaluated by measuring MCF7 and MCF10A cell viability as a function of drug loading during a 48-h treatment. Results showed that after 10?h of treatment, MCF7 cells displayed an IC50 of 0.23?±?0.034??M at a 1:5 (CPT:SLN) loading and 0.22?±?0.027??M at a 1:10 loading, whereas MCF10A cells displayed an IC50 of 0.40?±?0.036??M at 1:5 and 0.60?±?0.063??M at 1:10. On the other hand, the IC50 of free CPT was 0.57?±?0.035??M and 1.07?±?0.077??M for MCF7 and MCF10A cells, respectively. Cellular uptake and retention measurements in both cells displayed a two-fold increase when using the SLN formulation. The results from this study showed that the cytotoxic effects of CPT in a SLN formulation improved when compared with those seen with free CPT. The results of this study showed that delivery of CPT as a SLN formulation could be a promising strategy for enhancing its chemotherapeutic effects. PMID:24024505

Acevedo-Morantes, Claudia Y; Acevedo-Morantes, María T; Suleiman-Rosado, David; Ramírez-Vick, Jaime E

2013-09-11

103

Flow-Induced Assembly of Nickel Nanoparticles  

NASA Astrophysics Data System (ADS)

Lead telluride and bismuth telluride exhibit the peak value of about 1 for figure of merit (ZT) of bulk thermoelectric materials; the figure of merit is a measure of efficiency for thermoelectric energy conversion. ZT greater than around 2-3 is necessary for thermoelectric devices to have widespread, practical applications in fields such as regenerative power recovery. Nanoscaled thermoelectric materials have surpassed this criterion, however, the scale-up of these nanostructured materials while maintaining the desired properties has proven to be challenging. Flow-induced assembly of nanoparticles at an air/water interface is a potential candidate to scale-up production of nanostructured thermoelectric materials. Here, we spread nanoparticles on the surface of water using classical techniques developed for Langmuir monolayers. Interfacial shear is produced by an annular Couette flow driven by the constant rotation of an outer cylinder and a stationary inner cylinder. The Reynolds number is large enough to produce strong shearing motion at the interface in order to assemble the particles into a well organized film. These films will subsequently be harvested and stacked accordingly with minimal loss of desired properties. In this paper we investigate flow induced assembly of nickel nanoparticles as a model system.

Russell, Nathan A.; Borca-Tasciuc, Theodorian; Hirsa, Amir H.

2008-07-01

104

Biocompatibility of Fe3O4 nanoparticles evaluated by in vitro cytotoxicity assays using normal, glia and breast cancer cells  

NASA Astrophysics Data System (ADS)

In order to reveal the biocompatibility of Fe3O4 nanoparticles and bipolar surfactant tetramethylammonium 11-aminoundecanoate cytotoxicity tests were performed as a function of concentration from low (0.1 µg ml-1) to higher concentration (100 µg ml-1) using various human glia, human breast cancer and normal cell lines. Cytotoxicity tests for human glia (D54MG, G9T, SF126, U87, U251, U373), human breast cancer (MB157, SKBR3, T47D) and normal (H184B5F5/M10, WI-38, SVGp12) cell lines exhibited almost nontoxicity and reveal biocompatibility of Fe3O4 nanoparticles in the concentration range of 0.1-10 µg ml-1, while accountable cytotoxicity can be seen at 100 µg ml-1. The results of our studies suggest that Fe3O4 nanoparticles coated with bipolar surfactant tetramethylammonium 11-aminoundecanoate are biocompatible and promising for bio-applications such as drug delivery, magnetic resonance imaging and magnetic hyperthermia.

Ankamwar, B.; Lai, T. C.; Huang, J. H.; Liu, R. S.; Hsiao, M.; Chen, C. H.; Hwu, Y. K.

2010-02-01

105

Whole-animal senescent cytotoxic T cell removal using antibodies linked to magnetic nanoparticles.  

PubMed

A major type of unwanted cells that accumulate in aging are anergic cytotoxic T cells. These cells often have virus-specific T cell receptors, as well as other surface markers that distinguish them from their youthful counterparts, and they are thought to play a major role in the decline of the immune system with age. Here we consider two surface markers thought to define these cells in mice, CD8 and Killer cell lectin-like receptor G1 (KLRG1), and a means we developed to remove these cells from the blood of aged C57BL/6 mice. Using antibodies with magnetic nanoparticles linked to their Fc domains, we first developed a method to use magnets to filter out the unwanted cells from the blood and later constructed a device that does this automatically. We demonstrated that this device could reduce the KLRG1-positive CD8 cell count in aged mouse blood by a factor of 7.3 relative to the total CD8 cell compartment, reaching a level typically seen only in very young animals. PMID:20426617

Rebo, Justin; Causey, Keith; Zealley, Ben; Webb, Tim; Hamalainen, Mark; Cook, Brian; Schloendorn, John

106

Proper design of silica nanoparticles combines high brightness, lack of cytotoxicity and efficient cell endocytosis.  

PubMed

Silica-based luminescent nanoparticles (SiNPs) show promising prospects in nanomedicine in light of their chemical properties and versatility. In this study, we have characterized silica core-PEG shell SiNPs derivatized with PEG moieties (NP-PEG), with external amino- (NP-PEG-amino) or carboxy-groups (NP-PEG-carbo), both in cell cultures as well as in animal models. By using different techniques, we could demonstrate that these SiNPs were safe and did not exhibit appreciable cytotoxicity in different relevant cell models, of normal or cancer cell types, growing either in suspension (JVM-2 leukemic cell line and primary normal peripheral blood mononuclear cells) or in adherence (human hepatocarcinoma Huh7 and umbilical vein endothelial cells). Moreover, by multiparametric flow cytometry, we could demonstrate that the highest efficiency of cell uptake and entry was observed with NP-PEG-amino, with a stable persistence of the fluorescence signal associated with SiNPs in the loaded cell populations both in vitro and in vivo settings suggesting this as an innovative method for cell traceability and detection in whole organisms. Finally, experiments performed with the endocytosis inhibitor Genistein clearly suggested the involvement of a caveolae-mediated pathway in SiNP endocytosis. Overall, these data support the safe use of these SiNPs for diagnostic and therapeutic applications. PMID:23851463

Rampazzo, Enrico; Voltan, Rebecca; Petrizza, Luca; Zaccheroni, Nelsi; Prodi, Luca; Casciano, Fabio; Zauli, Giorgio; Secchiero, Paola

2013-09-01

107

Cellular cytotoxicity and in-vivo biodistribution of docetaxel poly(lactide-co-glycolide) nanoparticles.  

PubMed

Docetaxel (DTX) is one of the most effective antineoplastic drugs. However, its current clinical administration, formulated in tween80, causes serious side effects. This study is focused on preparation and evaluation of poly(lactide-co-glycolide) nanoparticles (NPs) containing DTX to remove tween80. Drug encapsulation efficiency, in-vitro drug release, cellular cytotoxicity, and in-vivo biodistribution of NPs in mice after intravenous administration were investigated. The average diameter of the NPs was approximately 172-178 nm with encapsulation efficiency of 68%. A burst release of approximately 30% (w/w) of the loaded drug followed by a sustained release profile was observed. Cellular mortality of the NPs was more than or at least as great as DTX free drug; for example, cell viability measured at 100 nmol/l drug concentration was decreased from 50.9% for DTX free drug to 15.9% for the NP formulation after 48 h incubation with T47D cells. The DTX plasma amount remained at a good level (13% of the initial dose) in the NP formulation compared with the DTX conventional formulation, which is approximately 0.5% of the initial dose, was present in plasma up to 2 h. Poly(lactide-co-glycolide) NPs containing DTX prepared in this study may be regarded as a suitable and superior formulation for the current formulation in the market containing tween80 with improved cancerous cell mortality and biodistribution characteristics. PMID:19809300

Esmaeili, Farnaz; Dinarvand, Rassoul; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Esmaily, Hadi; Atyabi, Fatemeh

2010-01-01

108

Zinc oxide nanoparticles show antidiabetic activity in streptozotocin-induced Types-1 and 2 diabetic rats.  

PubMed

Aim: The correlation of diabetes and an imbalance in zinc homeostasis makes zinc-based therapy an attractive proposition. In this study, zinc oxide nanoparticles were evaluated for antidiabetic effects and safety. Materials & methods: Zinc oxide nanoparticles (1, 3 and 10 mg/kg) were tested for antidiabetic activity in streptozotocin-induced Types-1 and 2 diabetic rats. Single-dose pharmacokinetic study, cytotoxicity, hemolysis, acute and subacute toxicity tests, and mechanism-of-action studies were performed. Results: Oral administration of zinc oxide nanoparticles resulted in significant antidiabetic effects - that is, improved glucose tolerance, higher serum insulin (70%), reduced blood glucose (29%), reduced nonesterified fatty acids (40%) and reduced triglycerides (48%). Nanoparticles were systemically absorbed resulting in elevated zinc levels in the liver, adipose tissue and pancreas. Increased insulin secretion and superoxide dismutase activity were also seen in rat insulinoma (RIN5f) cells. Nanoparticles were safe up to a 300 mg/kg dose in rats. Conclusion: Zinc oxide nanoparticles are a promising antidiabetic agent warranting further studies. Original submitted 9 July 2012; Revised submitted 27 November 2012. PMID:23427863

Umrani, Rinku D; Paknikar, Kishore M

2013-02-21

109

Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells  

Microsoft Academic Search

BACKGROUND: Human rhinoviruses (RV), the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro. METHODS: Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were

Apostolos Bossios; Stelios Psarras; Dimitrios Gourgiotis; Chrysanthi L Skevaki; Andreas G Constantopoulos; Photini Saxoni-Papageorgiou; Nikolaos G Papadopoulos

2005-01-01

110

Protective Effects of Ginkgo biloba Leaf Extracts on Trichloroethylene-Induced Human Keratinocyte Cytotoxicity and Apoptosis  

Microsoft Academic Search

The objective of this study was to assess the protective effects of Ginkgo biloba leaf extracts (EGb) on trichloroethylene (TCE)-induced cytotoxicity and apoptosis in normal human epidermal keratinocytes (NHEK). Cytotoxicity was determined by neutral red uptake, and lipid peroxidation of the cells was assessed by malondialdehyde (MDA) and superoxide dismutase (SOD). Electron microscopy and flow cytometry were used to evaluate

Q.-X. Zhu; T. Shen; D.-Y. Tu; R. Ding; Z.-Z. Liang; X.-J. Zhang

2005-01-01

111

Apoptosis in mesangial cells induced by ionizing radiation and cytotoxic drugs  

Microsoft Academic Search

Apoptosis in mesangial cells induced by ionizing radiation and cytotoxic drugs. Mesangial proliferation contributes to the pathogenesis of many forms of glomerulonephritis. To evaluate the role of apoptosis on the pharmacologic effects of cytotoxic drugs and ionizing radiation, we studied their effects on cultured rat mesangial cells (MC), whose apoptotic response to these drugs is unknown. Mesangial cells were cultured

Dae Ryong Cha; Stella M Feld; Cynthia Nast; Janine LaPage; Sharon G Adler

1996-01-01

112

In vitro evaluation of cellular response induced by manufactured nanoparticles.  

PubMed

"Nanoparticle" is defined as the particles whose diameter in at least one dimension is less than 100 nm. Compared with fine-particles, nanoparticles have large specific surface area. There is a dramatic increase over fine-particles in chemical and physical activities, such as ion release, adsorption ability, and ROS production. These properties are important for industrial use, and many nanoparticles are already used in products familiar to consumers as sunscreens and cosmetics. However, nanoparticle properties beneficial to the industry may also induce biological influences, including toxic activities. Recently, many investigations about the toxicology of nanoparticles have been reported. In the evaluation of nanoparticles toxicity, in vitro studies give us important information, especially in terms of toxic mechanisms. In vitro studies showed that some nanoparticles induce oxidative stress, apoptosis, production of cytokines, and cell death. There are reports that cellular influences of other nanoparticles are small. There are also reports of different results, some with low and some with high influences, for the same nanoparticle. One of the causes of this inconsistency might be a diremption of the living body influence study and the characterization study. Characterization of individual nanoparticles and their dispersions are essential for in vitro evaluation of their biological effects since each nanoparticle shows unique chemical and physical properties. Particularly, the aggregation state and metal ion release ability of nanoparticles affect its cellular influences. Reports concerning the characterization in the in vitro toxicity assessment are increasing. For an accurate risk assessment of nanoparticles, in this review, we outline recent studies of in vitro evaluation of cellular influences induced by nanoparticles. Moreover, we also introduce current studies about the characterization methods of nanoparticles and their dispersions for toxicological evaluation. PMID:22136515

Horie, Masanori; Kato, Haruhisa; Fujita, Katsuhide; Endoh, Shigehisa; Iwahashi, Hitoshi

2011-12-30

113

Cytotoxicity of Gold Nanoparticles with Varying Concentration and Under Low Dose Environmental Radiation on Human Embryonic Kidney 293 Cells (HEK-293)  

NASA Astrophysics Data System (ADS)

Nanomaterials are increasingly being used in medicine. Most research surrounding the health and safety effects of nanomaterials examine the cytotoxicity of nanoparticles alone. Few studies, as this one does, examines the combined effects of nanoparticle concentration and radiation exposure on cytotoxicity to human embryonic kidney 293 cells (HEK-293). Nanoparticles injected in the body are supposed to undergo biodegradation once they are done their specified task, however, some do not and accumulate in the cells (particularly at the liver and kidney) and this causes intracellular changes. Examples of intracellular changes are the disruption of organelle integrity or gene alterations. This will cause the cells to die because the cells are very sensitive to changes in their pH. The experiments reported here focus on the cytotoxicity of gold nanoparticles as a function of varying particle concentrations and also with and without exposure to UV radiation.

Crudup, Shalana; Braender, Bruce; Iftode, Cristina; Dobbins, Tabbetha

2013-03-01

114

Titanium Dioxide (TiO2) Nanoparticles Induce JB6 Cell Apoptosis Through Activation of the Caspase8\\/Bid and Mitochondrial Pathways  

Microsoft Academic Search

Titanium dioxide (TiO2), a commercially important material, is used in a wide variety of products. Although TiO2 is generally regarded as nontoxic, the cytotoxicity, pathogenicity, and carcinogenicity of TiO2 nanoparticles have been recently recognized. The present study investigated TiO2 nanoparticle-induced cell apoptosis and molecular mechanisms involved in this process in a mouse epidermal (JB6) cell line. Using the 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium

Jinshun Zhao; Linda Bowman; Xingdong Zhang; Val Vallyathan; Shih-Houng Young; Vincent Castranova; Min Ding

2009-01-01

115

Involvement of Iysosomal proteolysis in hepatocyte cytotoxicity induced by Cu (II) or Cr (VI)  

NASA Astrophysics Data System (ADS)

Previously we showed that the redox active Cu (II) and Cr (VI) were very powerful at inducing reactive oxygen species (“ROS”) formation in hepatocytes and furthermore “ROS” scavengers prevented Cu (II) and Cr (VI) induced hepatocyte cytotoxicity[1,2]. In the following it is shown that hepatocyte cytotoxicity induced by Cu (II) and Cr(VI) were preceded by lysosomal proteolysis as demonstrated by tyrosine release. Hepatocyte lysosomal proteolysis was also prevented by leupeptin and pepstatin (lysosomal protease inhibitors). Cu(II) and Cr (VI) induced cytotoxicity was also prevented by leupeptin and pepstatin. A marked increase in Cu (II) and Cr (VI) induced hepatocyte toxicity also occurred if the lysosomal toxins gentamicin or aurothioglucose were added at the same time as the Cu (II) and Cr (VI). Furthermore destabilizing lysosomal membranes beforehand by preincubating the hepatocytes with gentamicin or aurothioglucose prevented Cu (II) and Cr (VI) induced hepatocyte cytotoxicity. It is proposed that Cu (II) and Cr (VI) induced cytotoxicity involves lysosomal damage that causes the release of cytotoxic digestive enzymes as a result of lysosomal membrane damage by “ROS".

Pourahmad, J.; O'Brien, P. J.

2003-05-01

116

Functionalized nanoparticles for AMF-induced gene and drug delivery  

NASA Astrophysics Data System (ADS)

The properties and broad applications of nano-magnetic colloids have generated much interest in recent years. Specially, Fe3O4 nanoparticles have attracted a great deal of attention since their magnetic properties can be used for hyperthermia treatment or drug targeting. For example, enhanced levels of intracellular gene delivery can be achieved using Fe3O4 nano-vectors in the presence of an external magnetic field, a process known as 'magnetofection'. The low cytotoxicity, tunable particle size, ease of surface functionalization, and ability to generate thermal energy using an external alternating magnetic field (AMF) are properties have propelled Fe3O4 research to the forefront of nanoparticle research. The strategy of nanoparticle-mediated, AMF-induced heat generation has been used to effect intracellular hyperthermia. One application of this 'magnetic hyperthermia' is heat activated local delivery of a therapeutic effector (e.g.; drug or polynucleotide). This thesis describes the development of a magnetic nano-vector for AMF-induced, heat-activated pDNA and small molecule delivery. The use of heat-inducible vectors, such as heat shock protein ( hsp) genes, is a promising mode of gene therapy that would restrict gene expression to a local region by focusing a heat stimulus only at a target region. We thus aimed to design an Fe3O4 nanoparticle-mediated gene transfer vehicle for AMF-induced localized gene expression. We opted to use 'click' oximation techniques to assemble the magnetic gene transfer vector. Chapter 2 describes the synthesis, characterization, and transfection studies of the oxime ether lipid-based nano-magnetic vectors MLP and dMLP. The synthesis and characterization of a novel series of quaternary ammonium aminooxy reagents (2.1--2.4) is described. These cationic aminooxy compounds were loaded onto nanoparticles for ligation with carbonyl groups and also to impart a net positive charge on the nanoparticle surface. Our studies indicated that the non-toxic magnetoplexes (magnetic nanoparticle + pDNA complex) derived from dMLP deliver pDNA into mammalian cells even without external magnetic assistance. To date, dMLP is the only polymer-free magnetic gene delivery system that can deliver pDNA without any magnetic assistance. Chapter 3 of this thesis outlines the synthesis and characterization of other oxime ether lipids and details studies using derived-lipoplexes. These lipids were evaluated in pDNA and siRNA transfection studies in various mammalian cell lines. This work constitutes the first use of an oxime ether as the linking domain in cationic transfection lipids. These biocompatible oxime ether lipids can be readily assembled by click chemistry through ligation of hydrophobic aldehydes with quaternary ammonium aminooxy salts. Our studies showed that the oxime ether lipids transfected pDNA and siRNA efficiently in MCF-7, H 1792, and in PAR C10 cells comparable to and in some cases better than commercial transfection lipids. Chapter 4 describes the design and characterization of a nano-magnetic delivery system for AMF-induced drug (doxorubicin) release. In efforts to develop a magnetic formulation free from thermosensitive materials, such as hydrogels, we synthesized three nanoparticle-based doxorubicin formulations using charge interactions as the key associative force. To do so, we synthesized and characterized a novel cationic oxime ether conjugate at C-13 of doxorubicin. Our investigation indicated that the positive charge of the oxime ether drug conjugate tended to bind better to the negatively charged nanoparticle than did the other formulations prepared in stepwise manner. Our findings show that the nano-magnetic formulations remained essestially inactive at body temperature (37.5 °C) and released a majority of the cargo only when exposed to an external AMF. Our designed magnetic drug delivery platform is the first example of an AMF-inducible system that does not depend on the inclusion of thermosensitive materials. Finally, we have developed a bioanalytical application of the highly chemosele

Biswas, Souvik

117

Proper design of silica nanoparticles combines high brightness, lack of cytotoxicity and efficient cell endocytosis  

NASA Astrophysics Data System (ADS)

Silica-based luminescent nanoparticles (SiNPs) show promising prospects in nanomedicine in light of their chemical properties and versatility. In this study, we have characterized silica core-PEG shell SiNPs derivatized with PEG moieties (NP-PEG), with external amino- (NP-PEG-amino) or carboxy-groups (NP-PEG-carbo), both in cell cultures as well as in animal models. By using different techniques, we could demonstrate that these SiNPs were safe and did not exhibit appreciable cytotoxicity in different relevant cell models, of normal or cancer cell types, growing either in suspension (JVM-2 leukemic cell line and primary normal peripheral blood mononuclear cells) or in adherence (human hepatocarcinoma Huh7 and umbilical vein endothelial cells). Moreover, by multiparametric flow cytometry, we could demonstrate that the highest efficiency of cell uptake and entry was observed with NP-PEG-amino, with a stable persistence of the fluorescence signal associated with SiNPs in the loaded cell populations both in vitro and in vivo settings suggesting this as an innovative method for cell traceability and detection in whole organisms. Finally, experiments performed with the endocytosis inhibitor Genistein clearly suggested the involvement of a caveolae-mediated pathway in SiNP endocytosis. Overall, these data support the safe use of these SiNPs for diagnostic and therapeutic applications.Silica-based luminescent nanoparticles (SiNPs) show promising prospects in nanomedicine in light of their chemical properties and versatility. In this study, we have characterized silica core-PEG shell SiNPs derivatized with PEG moieties (NP-PEG), with external amino- (NP-PEG-amino) or carboxy-groups (NP-PEG-carbo), both in cell cultures as well as in animal models. By using different techniques, we could demonstrate that these SiNPs were safe and did not exhibit appreciable cytotoxicity in different relevant cell models, of normal or cancer cell types, growing either in suspension (JVM-2 leukemic cell line and primary normal peripheral blood mononuclear cells) or in adherence (human hepatocarcinoma Huh7 and umbilical vein endothelial cells). Moreover, by multiparametric flow cytometry, we could demonstrate that the highest efficiency of cell uptake and entry was observed with NP-PEG-amino, with a stable persistence of the fluorescence signal associated with SiNPs in the loaded cell populations both in vitro and in vivo settings suggesting this as an innovative method for cell traceability and detection in whole organisms. Finally, experiments performed with the endocytosis inhibitor Genistein clearly suggested the involvement of a caveolae-mediated pathway in SiNP endocytosis. Overall, these data support the safe use of these SiNPs for diagnostic and therapeutic applications. Electronic supplementary information (ESI) available: Synthetic procedures, 1H and 13C NMR spectra, TEM and DLS measurements, and absorption and emission spectra. See DOI: 10.1039/c3nr02563b

Rampazzo, Enrico; Voltan, Rebecca; Petrizza, Luca; Zaccheroni, Nelsi; Prodi, Luca; Casciano, Fabio; Zauli, Giorgio; Secchiero, Paola

2013-08-01

118

Antibacterial and Cytotoxic Efficacy of Extracellular Silver Nanoparticles Biofabricated from Chromium Reducing Novel OS4 Strain of Stenotrophomonas maltophilia  

PubMed Central

Biofabricated metal nanoparticles are generally biocompatible, inexpensive, and ecofriendly, therefore, are used preferably in industries, medical and material science research. Considering the importance of biofabricated materials, we isolated, characterized and identified a novel bacterial strain OS4 of Stenotrophomonas maltophilia (GenBank: JN247637.1). At neutral pH, this Gram negative bacterial strain significantly reduced hexavalent chromium, an important heavy metal contaminant found in the tannery effluents and minings. Subsequently, even at room temperature the supernatant of log phase grown culture of strain OS4 also reduced silver nitrate (AgNO3) to generate nanoparticles (AgNPs). These AgNPs were further characterized by UV–visible, Nanophox particle size analyzer, XRD, SEM and FTIR. As evident from the FTIR data, plausibly the protein components of supernatant caused the reduction of AgNO3. The cuboid and homogenous AgNPs showed a characteristic UV-visible peak at 428 nm with average size of ?93 nm. The XRD spectra exhibited the characteristic Bragg peaks of 111, 200, 220 and 311 facets of the face centred cubic symmetry of nanoparticles suggesting that these nanoparticles were crystalline in nature. From the nanoparticle release kinetics data, the rapid release of AgNPs was correlated with the particle size and increasing surface area of the nanoparticles. A highly significant antimicrobial activity against medically important bacteria by the biofabricated AgNPs was also revealed as decline in growth of Staphylococcus aureus (91%), Escherichia coli (69%) and Serratia marcescens (66%) substantially. Additionally, different cytotoxic assays showed no toxicity of AgNPs to liver function, RBCs, splenocytes and HeLa cells, hence these particles were safe to use. Therefore, this novel bacterial strain OS4 is likely to provide broad spectrum benefits for curing chromium polluted sites, for biofabrication of AgNPs and ultimately in the nanoparticle based drug formulation for the treatment of infectious diseases.

Oves, Mohammad; Khan, Mohammad Saghir; Zaidi, Almas; Ahmed, Arham S.; Ahmed, Faheem; Ahmad, Ejaz; Sherwani, Asif; Owais, Mohammad; Azam, Ameer

2013-01-01

119

Cytotoxicity and antibacterial property of titanium alloy coated with silver nanoparticle-containing polyelectrolyte multilayer.  

PubMed

Silver nanoparticle (AgNP) was incorporated into dopamine-modified alginate/chitosan (DAL/CHI) polyelectrolyte multilayer to modify the surface of titanium alloy and improve its antibacterial property. Scanning electron microscopy showed that AgNP with the size of 50 nm embedded in DAL/CHI multilayers homogeneously. X-ray photoelectron spectroscopy analysis indicated that the nanoparticles were silver (0) with peaks at 368.4 and 374.4 eV, respectively. The formation of silver (0) without the addition of reductants was due to the self-polymerization of dopamine, which can reduce the silver cation into neutral metal. The polyelectrolyte multilayer coating enhanced the wettability of titanium alloy and promoted the fibroblast proliferation significantly, which could be attributed to the excellent biocompatibility of DAL/CHI. Despite the slight fall of L929 cell activity after AgNP incorporation, AgNP-DAL/CHI multilayer inhibited the growth of both Escherichia coli and Staphylococcus aureus. The above results demonstrate that dopamine decoration is a simple and effective way to induce the in-situ formation of AgNP within polyelectrolyte multilayer. Furthermore, the AgNP-containing multilayer considerably enhances the antibacterial activity of titanium alloy. The fabrication of AgNP-DAL/CHI multilayer on the surface of titanium implant might have great potential in orthopedic use. PMID:23623101

Zhang, Xinming; Li, Zhaoyang; Yuan, Xubo; Cui, Zhenduo; Bao, Huijing; Li, Xue; Liu, Yunde; Yang, Xianjin

2013-03-14

120

Fluorescent non-porous silica nanoparticles for long-term cell monitoring: Cytotoxicity and particle functionality.  

PubMed

Inorganic nanoparticles such as silica particles offer many exciting possibilities for biomedical applications. However, the possible toxicity of these particles remains an issue of debate that seriously impedes their full exploitation. In the present work, commercially available fluorescent silica nanoparticles 25, 45 and 75nm in diameter optimized for cell labelling (C-Spec® particles) are evaluated with regard to their effects on cultured cells using a novel multiparametric setup. The particles show clear concentration and size-dependent effects, where toxicity is caused by the number and total surface area of cell-associated particles. Cell-associated particles generate a short burst of oxidative stress that, next to inducing cell death, affects cell signalling and impedes cell functionality. For cell labelling purposes, 45nm diameter silica particles were found to be optimally suited and no adverse effects were noticeable at concentrations of 50?gml(-1) or below. At this safe concentration, the particles were found to still allow fluorescence tracking of cultured cells over longer time periods. In conclusion, the data shown here provide a suitable concentration of silica particles for fluorescent cell labelling and demonstrate that at safe levels, silica particles remain perfectly suitable for fluorescent cell studies. PMID:23664886

Soenen, Stefaan J; Manshian, Bella; Doak, Shareen H; De Smedt, Stefaan C; Braeckmans, Kevin

2013-05-09

121

Induction of Potent Antigen-specific Cytotoxic T Cell Response by PLGA-nanoparticles Containing Antigen and TLR Agonist.  

PubMed

Previously we showed that biodegradable nanoparticles containing poly-IC or CpG oligodeoxynucleotide (ODN) together with ovalbumin (OVA) were efficient at inducing MHC-restricted presentation of OVA peptides in dendritic cells. The CTL-inducing activities of the nanoparticles were examined in the present study. Nanoparticles containing poly-IC or CpG ODN together with OVA were prepared using biodegradable polymer poly(D,L-lactic acid-co-glycolic acid), and then were opsonized with mouse IgG. The nanoparticles were injected into the tail vein of mice, and 7 days later the OVA-specific CTL activities were measured using an in vivo CTL assay. Immunization of mice with the nanoparticles containing poly-IC or CpG ODN together with OVA elicited potent OVA-specific CTL activity compared to those containing OVA only. In accordance with these results, nanoparticles containing poly-IC or CpG ODN together with OVA exerted potent antitumor activity in mice that were subcutaneously implanted with EG7.OVA tumor cells. These results show that encapsulation of poly-IC or CpG ODN together with antigen in biodegradable nanoparticles is an effective approach for the induction of potent antigen-specific CTL responses in vivo. PMID:23559898

Lee, Young-Ran; Lee, Young-Hee; Kim, Ki-Hyang; Im, Sun-A; Lee, Chong-Kil

2013-02-28

122

Cytotoxicity of sophorolipid-gellan gum-gold nanoparticle conjugates and their doxorubicin loaded derivatives towards human glioma and human glioma stem cell lines.  

PubMed

Biocompatible gold nanoparticles were synthesized by using a naturally occurring gum--Gellan Gum--as a capping and reducing agent. These were further conjugated with sophorolipids which again were accessed through a biochemical transformation of a fatty acid. The cellular uptake of sophorolipid-conjugated gellan gum reduced gold nanoparticles and their cytotoxicity on human glioma cell line LN-229 and human glioma stem cell line HNGC-2 were investigated. Quite surprisingly even the simple sophorolipid-conjugated gellan gum reduced/capped gold nanoparticles showed greater efficacy in killing the glioma cell lines and, gratifyingly, the glioma stem cell lines also. The cytotoxic effects became more prominent once the anti cancer drug doxorubicin hydrochloride was also conjugated to these gold nanoparticles. PMID:21069248

Dhar, Sheetal; Reddy, E Maheswara; Prabhune, Asmita; Pokharkar, Varsha; Shiras, Anjali; Prasad, B L V

2010-11-11

123

Curcumin reduces ?-synuclein induced cytotoxicity in Parkinson's disease cell model  

Microsoft Academic Search

BACKGROUND: Overexpression and abnormal accumulation of aggregated ?-synuclein (?S) have been linked to Parkinson's disease (PD) and other synucleinopathies. ?S can misfold and adopt a variety of morphologies but recent studies implicate oligomeric forms as the most cytotoxic species. Both genetic mutations and chronic exposure to neurotoxins increase ?S aggregation and intracellular reactive oxygen species (ROS), leading to mitochondrial dysfunction

Min S Wang; Shanta Boddapati; Sharareh Emadi; Michael R Sierks

2010-01-01

124

Weakly Charged Cationic Nanoparticles Induce DNA Bending and Strand Separation  

SciTech Connect

The understanding of interactions between double stranded (ds) DNA and charged nanoparticles will have a broad bearing on many important applications from drug delivery [ 1 4 ] to DNAtemplated metallization. [ 5 , 6 ] Cationic nanoparticles (NPs) can bind to DNA, a negatively charged molecule, through a combination of electrostatic attraction, groove binding, and intercalation. Such binding events induce changes in the conformation of a DNA strand. In nature, DNA wraps around a cylindrical protein assembly (diameter and height of 6 nm) [ 7 ] with an 220 positive charge, [ 8 ] creating the complex known as chromatin. Wrapping and bending of DNA has also been achieved in the laboratory through the binding of highly charged species such as molecular assemblies, [ 9 , 10 ] cationic dendrimers, [ 11 , 12 ] and nanoparticles. [ 13 15 ] The charge of a nanoparticle plays a crucial role in its ability to induce DNA structural changes. If a nanoparticle has a highly positive surface charge density, the DNA is likely to wrap and bend upon binding to the nanoparticle [ 13 ] (as in the case of chromatin). On the other hand, if a nanoparticle is weakly charged it will not induce dsDNA compaction. [ 9 , 10 , 15 ] Consequently, there is a transition zone from extended to compact DNA conformations which depends on the chemical nature of the nanoparticle and occurs for polycations with charges between 5 and 10. [ 9 ] While the interactions between highly charged NPs and DNA have been extensively studied, the processes that occur within the transition zone are less explored.

Railsback, Justin [North Carolina State University; Singh, Abhishek [North Carolina State University; Pearce, Ryan [North Carolina State University; McKnight, Timothy E [ORNL; Collazo, Ramon [North Carolina State University; Sitar, Zlatko [ORNL; Yingling, Yaroslava [North Carolina State University; Melechko, Anatoli Vasilievich [ORNL

2012-01-01

125

Cytotoxicity of solid lipid nanoparticles and nanostructured lipid carriers containing the local anesthetic dibucaine designed for topical application  

NASA Astrophysics Data System (ADS)

Dibucaine (DBC) is powerful long-lasting local anesthetic, but it is also considered fairly toxic to the CNS. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have attracted attention as carriers for drug delivery. The aim of this study was to develop and to evaluate the cytotoxic activity of DBC-loaded SLN and NLC against 3T3 fibroblast and HaCat keratinocyte cells. The SLN and NLC had myristyl myristate and Liponate®GC as their lipid matrices, respectively, plus a surfactant. SLN and NLC were characterized in terms in their diameter, size distribution, surface charge and DBC encapsulation efficiency. The particle size of SLN and NLC were around 234.33 and 166.62 nm, respectively. The polydispersity index was kept below 0.2 for both nanomaterials. Negative surface charges were observed for both nanoparticles, which decreased in the presence of the anesthetic. Encapsulation efficiency reached 76% and 90%, respectively, in SLN and NLC. DBC alone was found to be toxic to 3T3 and HaCat cells in culture. However, NLC and SLN loaded DBC decreased its intrinsic cytotoxic effect against 3T3 and HaCat cells. In conclusion, encapsulation of DBC in SLN and NLC decreased the in vitro toxicity of the local anesthetic, indicating the potential of these nanocarriers for clinical applications.

Barbosa, R. M.; da Silva, C. M. G.; Bella, T. S.; de Araújo, D. R.; Marcato, P. D.; Durán, N.; de Paula, E.

2013-04-01

126

Role of free radicals and metal ions in direct current-induced cytotoxicity.  

PubMed

The purpose of this study was to investigate the mechanism of direct current (DC)-induced cytotoxicity. To test the working hypothesis that electrolysis products are responsible for the DC-induced cytotoxicity, the cytotoxic effects between the direct and indirect DC treatment against human polymorphonuclear cells (PMNs) was compared. The indirect DC treatment (treatment with the culture medium exposed to DC) was comparable in cytotoxicity to the direct DC treatment, suggesting that electrolysis products have an important role in DC-induced cytotoxicity. Metal ions released from different electrodes into the culture medium were quantified by the inductively coupled plasma-mass spectroscopy. Higher concentrations of Ag, Zn, and Ni and chromium were released from Ag, Zn, and stainless steel (St) electrodes, respectively, whereas much lower concentrations of Ni and Ti were released from Ni-Ti electrode. Further, electron spin resonance spectroscopy with spin-trapping agent showed that the direct current with the following metal electrodes generated alkoxyl radical (St and Ni-Ti electrodes), hydrogen radical (Ag and Au electrodes), and both carbon and alkoxyl radicals (Zn electrode), respectively. These results suggest that free radicals and metal ions released from electrodes contribute to the cytotoxicity of DC treatment used for iontophoresis. PMID:16631845

Nakamura, Yuko; Takahashi, Keiso; Satoh, Kazue; Shimetani, Akiko; Sakagami, Hiroshi; Nishikawa, Hirofumi

2006-02-07

127

Apoptosis induced by tungsten carbide-cobalt nanoparticles in JB6 cells involves ROS generation through both extrinsic and intrinsic apoptosis pathways.  

PubMed

In this study, apoptosis and related signaling induced by WC-Co nanoparticles were investigated in JB6 cells and rat lung macrophages. Electron spin resonance (ESR) and fluorescent staining indicated that both WC-Co nanoparticles and fine particles stimulated reactive oxygen species (ROS) generation. Catalase exhibited an inhibitory effect on WC-Co nanoparticle-induced ROS as well as mitochondrial membrane permeability damage. Further study indicated that WC-Co nanoparticles elicited higher cytotoxicity and apoptotic induction than fine particles. Western blot analysis showed activation of proapoptotic factors including Fas, Fas-associated protein with death domain (FADD), caspase 3, 8 and 9, BID and BAX. In addition, both cytochrome c and apoptosis-inducing factor (AIF) were upregulated and released from mitochondria to the cytoplasm. Our findings demonstrate that, on a mass basis, WC-Co nanoparticles exhibit higher cytotoxicity and apoptotic induction than fine particles. Apoptosis induced by WC-Co nanoparticles and fine particles involves both extrinsic and intrinsic apoptosis pathways. PMID:23417053

Zhao, Jinshun; Bowman, Linda; Magaye, Ruth; Leonard, Stephen S; Castranova, Vincent; Ding, Min

2013-02-15

128

Singlet oxygen mediated DNA degradation by copper nanoparticles: potential towards cytotoxic effect on cancer cells  

Microsoft Academic Search

The DNA degradation potential and anti-cancer activities of copper nanoparticles of 4-5 nm size are reported. A dose dependent\\u000a degradation of isolated DNA molecules by copper nanoparticles through generation of singlet oxygen was observed. Singlet oxygen\\u000a scavengers such as sodium azide and Tris [hydroxyl methyl] amino methane were able to prevent the DNA degradation action of\\u000a copper nanoparticles confirming the

Gregor P Jose; Subhankar Santra; Swadhin K Mandal; Tapas K Sengupta

2011-01-01

129

Bismuth induces metallothionein but does not protect against cadmium cytotoxicity in cultured vasular endothelial cells  

SciTech Connect

Cadmium has been shown to be an inducer of cardiovascular lesions such as atherosclerosis and hypertension. The relationship between cadmium exposure and vascular diseases was shown by epidemiological data. We found that cadmium destroys the monolayer of cultured vascular endothelial cells. This suggested that damage of vascular endothelial cells may be an important event of cadmium-induced vascular disorders. Metallothionein induction is postulated to be in general the most important mechanism for protection against cadmium toxicity. However, zinc protects vascular endothelial cells from cadmium cytotoxicity without metallothionein induction; zinc was not an effective inducer of the protein. Recently, we found that bismuth strongly induces metallothionein selectively in vascular endothelial cells. Although zinc protection against cadmium cytotoxicity in vascular endothelial cells mainly resulted from a decrease in the accumulation of intracellular cadmium, it was likely that bismuth reduces the cytotoxicity of cadmium by the metallothionein-dependent mechanism in the cells. In the present study, the effect of bismuth on the cytotoxicity of cadmium in cultured vascular endothelial cells was investigated. Bismuth alone induces metallothionein but does not protect against cadmium cytotoxicity in the cells. 14 refs., 1 tab.

Kaji, T.; Mishima, A.; Yamamoto, C. [Hokuriku Univ., Kanazawa (Japan)] [and others

1996-04-01

130

Effects of palmitic acid on TNF-?-induced cytotoxicity in SK-Hep-1 cells.  

PubMed

Non-alcoholic steatohepatitis (NASH) is an increasingly common cause of chronic liver disease; however, no specific pharmacologic therapy has been shown to be effective in its treatment. The present study was designed to develop an experimental cell culture model of NASH using four kinds of fatty acids - palmitic acid (PA), stearic acid (SA), linoleic acid (LA), and oleic acid (OA) - and TNF-?, according to the "two-hit" hypothesis. The saturated fatty acids PA and SA are more cytotoxic than the unsaturated fatty acids OA and LA. Cellular lipid accumulation without cytotoxicity was more easily induced with the unsaturated fatty acids than with the saturated fatty acids. PA augmented TNF-?-induced cytotoxicity, while the unsaturated fatty acids attenuated TNF-?-induced cytotoxicity. In a mechanistic study, PA enhanced TNF-?-mediated apoptosis in the absence of oxidative stress, as determined by measuring the cellular glutathione and malondialdehyde levels. Moreover, PA inhibited the TNF-?-induced phosphorylation of AKT, but not c-Jun N-terminal kinase, indicating that inhibition of survival signaling pathways activated by TNF-? may explain the effects of PA on TNF-?-induced cytotoxicity. The in vitro NASH model established in this study may be used to screen drug candidates for suitability for the treatment of NASH. PMID:22683933

Oh, Jung Min; Choi, Jong Min; Lee, Ji Yoon; Oh, Soo Jin; Kim, Hyoung Chin; Kim, Bong Hee; Ma, Jin Yeul; Kim, Sang Kyum

2012-06-07

131

Effect of cell media on polymer coated superparamagnetic iron oxide nanoparticles (SPIONs): colloidal stability, cytotoxicity, and cellular uptake studies.  

PubMed

The influence of the composition of the polymer coated polyvinyl alcohol (PVA), vinyl alcohol/vinyl amine copolymer (A-PVA) and polyethylenimine (PEI) coated superparamagnetic iron oxide nanoparticles (SPIONs) on the colloidal stability, cytotoxicity and cellular uptake of these particles in different cell media is reported in this paper. Although all examined polymer coated SPIONs were stable in water and PBS buffer these colloidal systems had different stabilities in DMEM or RPMI media without and supplemented with fetal calf serum (FCS). We found that A-PVA coating onto the surface of the SPIONs decreased the cytotoxicity of the polymer compared to the same concentration of A-PVA alone. As well, polyplexes of PEI-SPIONs with DNA in concentration used for transfection experiments showed no cytotoxicity compared to PEI and PEI-SPIONs. Our data show that the choice of medium largely influences the uptake of these particles by HeLa cells. The optimal medium is different for the different examined polymer coated SPIONs and it should be determined in each case, individually. PMID:17881203

Petri-Fink, Alke; Steitz, Benedikt; Finka, Andrija; Salaklang, Jatuporn; Hofmann, Heinrich

2007-07-13

132

Effects of cerium oxide nanoparticles to fish and mammalian cell lines: An assessment of cytotoxicity and methodology.  

PubMed

Two cerium oxide nanoparticles (CeO(2) NPs) and one micro-sized CeO(2) particle were thoroughly characterized in their pristine form, in water and in cell culture medium. The particles were tested for cytotoxicity to the H4IIE rat hepatoma cell line or the RTG-2 rainbow trout gonadal cell line by means of four standard cytotoxicity assays. Nominal concentrations were verified by inductively coupled plasma mass spectrometry (ICP-MS) and methods were assessed for their suitability to detect reliably adverse effects due to particle exposure. All three particles showed aggregation in water and media. In the H4IIE cell line, the MTT cytotoxicity test revealed that negative effects could be observed for the CeO(2) NPs after 24h and for all particles after 72h of exposure, making the effects size, concentration and time dependent. No negative effect for the concentrations tested was detected for the remaining three assays and the RTG-2 cell line, making the MTT assay and the H4IIE cell line an appropriate system to assess adverse effects of CeO(2) NPs. A verification of the nominal concentration through ICP-MS revealed that there was a discrepancy between nominal and measured concentration depending on concentration and particle tested. Interferences of particles with assays were found to be present and need to be taken into consideration. PMID:22554435

Rosenkranz, P; Fernández-Cruz, M L; Conde, E; Ramírez-Fernández, M B; Flores, J C; Fernández, M; Navas, J M

2012-04-24

133

Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity.  

PubMed

The latent HIV-1 reservoir remains the major barrier to HIV-1 eradication. Although successful at limiting HIV replication, highly active antiretroviral therapy is unable to cure HIV infection, thus novel therapeutic strategies are needed to eliminate the virus. Magnetic field hyperthermia (MFH) generates thermoablative cytotoxic temperatures in target-cell populations, and has delivered promising outcomes in animal models, as well as in several cancer clinical trials. MFH has been proposed as a strategy to improve the killing of HIV-infected cells and for targeting the HIV latent reservoirs. We wished to determine whether MFH could be used to enhance cytotoxic T-lymphocyte (CTL) targeting of HIV-infected cells in a proof-of-concept study. Here, for the first time, we apply MFH to an infectious disease (HIV-1) using the superparamagnetic iron oxide nanoparticle FeraSpin R. We attempt to improve the cytotoxic potential of T-cell receptor-transfected HIV-specific CTLs using thermotherapy, and assess superparamagnetic iron oxide nanoparticle toxicity, uptake, and effect on cell function using more sensitive methods than previously described. FeraSpin R exhibited only limited toxicity, demonstrated efficient uptake and cell-surface attachment, and only modestly impacted T-cell function. In contrast to the cancer models, insufficient MFH was generated to enhance CTL killing of HIV-infected cells. MFH remains an exciting new technology in the field of cancer therapeutics, which, as technology improves, may have significant potential to enhance CTL function and act as an adjunctive therapy in the eradication of latently infected HIV-positive cells. PMID:23901272

Williams, James P; Southern, Paul; Lissina, Anya; Christian, Helen C; Sewell, Andrew K; Phillips, Rodney; Pankhurst, Quentin; Frater, John

2013-07-23

134

Fabrication of docetaxel surfaced Fe3O4 magnetite nanoparticles and their cytotoxicity on 4 T1 breast cancer cells  

PubMed Central

Background In the recent years, there is an increasing attention to the using of Fe3O4 magnetite nanoparticles (MNPs) as drug delivery systems. Application of this nanoparticles could profit advantages of nanomedicine to enhance biological activity of pharmaceutical ingredients. Methods Fe3O4 MNPs were synthesised by a chemical method and characterized by transmission electron microscopy and energy-dispersive spectroscopy techniques. In the next step, docetaxel-coated Fe3O4 MNPs were prepared, using percipitation method. The surface chemistry of docetaxel-coated Fe3O4 MNPs as well as their thermal decomposition characteristics were examined using fourier transform infrared spectroscopy and thermogravimetric analyzer equipment, respectively. The cytotoxicity assay was conducted on 4?T1 breast cancer carsinoma by MTT assay to evaluate the possible in vitro antiproliferative effects of docetaxel-coated Fe3O4 MNPs. Results During precipitation process, docetaxel molecules were precipitated on the surface of Fe3O4 MNPs by the ratio of 3:100 w/w which indicates that each milligram of coated Fe3O4 MNPs averagely contained 30??g pure docetaxel compound. Docetaxel showed aniproliferative effects against mentioned cell line. The higestest concentartion of docetaxel (80??g/ml) caused about 80% cell death. However, the results demostarted that much lower amounts of docetaxel will be needed in combination of Fe3O4 MNPs to produce the potent antiproliferative effect compared to docetaxel alone. Dose response cytotoxicity assay of docetaxel-coated Fe3O4 MNPs against 4?T1 breast cancer cells showed that lower amount of docetaxel (0.6??g/ml) can exhibit higher cytotoxic effect against this cancer cell line (90% cell death).

2012-01-01

135

Nanoparticle-induced surface reconstruction of phospholipid membranes  

PubMed Central

The nonspecific adsorption of charged nanoparticles onto single-component phospholipid bilayers bearing phosphocholine headgroups is shown, from fluorescence and calorimetry experiments, to cause surface reconstruction at the points where nanoparticles adsorb. Nanoparticles of negative charge induce local gelation in otherwise fluid bilayers; nanoparticles of positive charge induce otherwise gelled membranes to fluidize locally. Through this mechanism, the phase state deviates from the nominal phase transition temperature by tens of degrees. This work generalizes the notions of environmentally induced surface reconstruction, prominent in metals and semiconductors. Bearing in mind that chemical composition in these single-component lipid bilayers is the same everywhere, this offers a mechanism to generate patchy functional properties in phospholipid membranes.

Wang, Bo; Zhang, Liangfang; Bae, Sung Chul; Granick, Steve

2008-01-01

136

Novel route for rapid biosynthesis of copper nanoparticles using aqueous extract of Calotropis procera L. latex and their cytotoxicity on tumor cells.  

PubMed

This paper accounts for novel, low-cost, eco-friendly route for rapid biosynthesis of copper nanoparticles. Cysteine proteases present in the latex of Calotropis procera L. were used to fabricate copper nanoparticles from copper acetate. Copper nanoparticles were initially characterized by transmission electron microscopy (TEM) and X-ray diffraction technique (XRD). Transmission electron microscopy (TEM) was used to estimate the size and shape of nanoparticles. The average size of copper nanoparticles was found to be 15 ± 1.7 nm. Energy dispersive analysis of X-rays (EDAX) showed distinct peaks of copper. Fourier transform infrared spectroscopy (FTIR) was performed to confirm capping behavior of the latex proteins that contributed to long term stability of copper nanoparticles (6 months) in aqueous medium. Copper nanoparticles synthesized by above method were monodisperse type. Cytotoxicity studies of latex stabilized copper nanoparticles were carried out on HeLa, A549 and BHK21 cell lines by MTT dye conversion assay. HeLa, A549 and BHK21 cells showed excellent viability even at 120 ?M concentration of copper nanoparticles. This shows that copper nanoparticles synthesized by above method hold excellent biocompatibility. PMID:22483347

Harne, Shrikant; Sharma, Ashwinikumar; Dhaygude, Mayur; Joglekar, Shreeram; Kodam, Kisan; Hudlikar, Manish

2012-03-20

137

In vitro cytotoxicity of silver nanoparticles in primary rat hepatic stellate cells.  

PubMed

The number of studies concerning silver nanoparticles (AgNPs) has increased, due in part to their potential uses for biomedical applications. These particles have been demonstrated in the elimination of the hepatitis B virus and the inhibition of the proliferation of various cancer cells in vivo and in vitro. Thus, studies on AgNPs may lead to a more efficacious and safer therapeutic approach for chronic liver injury. Hepatic stellate cells (HSCs) are essential interstitial cells in the liver and are the predominant therapeutic target in hepatic fibrosis and liver cirrhosis; however, the intracellular effects of AgNPs on HSCs remain to be elucidated. The aim of the present study was to investigate the effects of AgNPs on the function and metabolism of HSCs. Various concentrations of AgNPs, with a diameter of 10 or 30?50 nm, were incubated with HSCs. Transmission electron microscopy, flow cytometry, enzyme?linked immunosorbent assays, and apoptosis and proliferation detection kits were used to analyze the effects of AgNPs on cell proliferation and metabolism. These studies demonstrated that AgNPs inhibited the proliferation of HSCs and induced their apoptosis in a size- and dose?dependent manner. PMID:24043207

Sun, Xiaojing; Wang, Zhiming; Zhai, Shengyong; Cheng, Yingwen; Liu, Jie; Liu, Binbin

2013-09-13

138

Effect of amorphous silica nanoparticles on in vitro RANKL-induced osteoclast differentiation in murine macrophages  

PubMed Central

Amorphous silica nanoparticles (nSP) have been used as a polishing agent and/or as a remineralization promoter for teeth in the oral care field. The present study investigates the effects of nSP on osteoclast differentiation and the relationship between particle size and these effects. Our results revealed that nSP exerted higher cytotoxicity in macrophage cells compared with submicron-sized silica particles. However, tartrate-resistant acid phosphatase (TRAP) activity and the number of osteoclast cells (TRAP-positive multinucleated cells) were not changed by nSP treatment in the presence of receptor activator of nuclear factor ?B ligand (RANKL) at doses that did not induce cytotoxicity by silica particles. These results indicated that nSP did not cause differentiation of osteoclasts. Collectively, the results suggested that nanosilica exerts no effect on RANKL-induced osteoclast differentiation of RAW264.7 cells, although a detailed mechanistic examination of the nSP70-mediated cytotoxic effect is needed.

2011-01-01

139

Surface induced suppression of magnetization in nanoparticles  

Microsoft Academic Search

A model based on competing exchange interactions is presented for the investigation of nanoparticle magnetization. The ferromagnetic (FM) and antiferromagnetic (AFM) exchange interactions contribute differently at the nanoparticle surface and interior, leading to reduced ferromagnetic order at the surface. This model predicts an unconventional temperature dependence of magnetization and a surface magnetically 'dead layer'. This is confirmed by temperature dependent

C. Westman; S. Jang; C. Kim; S. He; G. Harmon; N. Miller; B. Graves; N. Poudyal; R. Sabirianov; H. Zeng; M. DeMarco; J. P. Liu

2008-01-01

140

Contribution of Ca^{2+} ions influx in Cu (II) or Cr (VI) induced hepatocyte cytotoxicity  

NASA Astrophysics Data System (ADS)

Previously we showed that hepatocyte lysis induced by Cu (II) or Cr (VI) could be partly attributed to membrane lipid peroxidation induced by Cu (II) or Cr (VI) [1, 2]. Changes in Na^+ and Ca^{+2} homeostasis induced when Cu^{+2} or Cr VI were incubated with hepatocytes. Na^+ omission from the media or addition of the Na^+/H^+ exchange inhibitor 5-(N, N-dimethyl)-amiloride markedly increased Cu (II) or Cr (VI) cytotoxicity even though Cu (II) or Cr (VI) did not increase hepatocyte Na^+ when the media contained Na^+. The omission of CI^- from the media or addition of glycine, a CI^- channel blocker also enhanced Cu (II) or Cr (VI) induced cytotoxicity. Intracellular Ca^{+2} levels however were markedly increased when the hepatocytes were incubated with Cu^{+2} or Cr VI in a Na^+ free media and removing media Ca^{+2} with EGTA also prevented Cu (II) or Cr (VI) induced hepatocyte cytotoxicity. This suggests that intracellular Ca^{+2} accumulation contributes to Cu (II) or Cr (VI) induced cytotoxicity and a Na^+_- dependent Ca^{+2} transporter is involved in controlling excessive Ca^{+2} accumulation caused by Cu (II) or Cr (VI).

Pourahmad, J.; O'Brien, P. J.

2003-05-01

141

Changes in Cardiopulmonary Function Induced by Nanoparticles  

PubMed Central

Nanoparticles (NP) are highly applicable in a variety of technological and biomedical fields due to their unique physicochemical properties. The increased development and utilization of NP has amplified human exposure and raised concerns regarding their potential to generate toxicity. The biological impacts of NP exposures have been shown to be dependent on aerodynamic size, chemical composition, and the route of exposure (oral, dermal, intravenous, and inhalation), while recent research has demonstrated the cardiovascular (CV) system as an important site of toxicity. Proposed mechanisms responsible for these effects include inflammation, oxidative stress, autonomic dysregulation, and direct interactions of NP with CV cells. Specifically, NP have been shown to impact vascular endothelial cell (EC) integrity, which may disrupt the dynamic endothelial regulation of vascular tone, possibly altering systemic vascular resistance and impairing the appropriate distribution of blood flow throughout the circulation. Cardiac consequences of NP-induced toxicity include disruption of heart rate and electrical activity via catecholamine release, increased susceptibility to ischemia/reperfusion injury, and modified baroreceptor control of cardiac function. These and other CV outcomes likely contribute to adverse health effects promoting myocardial infarction, hypertension, cardiac arrhythmias, and thrombosis. This review will assess the current knowledge regarding the principle sites of CV toxicity following NP exposure. Furthermore, we will propose mechanisms contributing to altered CV function and hypothesize possible outcomes resulting in decrements in human health.

Mann, Erin E.; Thompson, Leslie C.; Shannahan, Jonathan H.; Wingard, Christopher J.

2012-01-01

142

Trichothecene-induced cytotoxicity on human cell lines  

Microsoft Academic Search

Trichothecene cytotoxicity of type A (T-2 toxin and HT-2 toxin), type B (deoxynivalenol, DON, and nivalenol, NIV), and type\\u000a D (satratoxins G and H) compounds was determined comparatively by using eight permanent human cell lines (Hep-G2, A549, CaCo-2,\\u000a HEp-2, A204, U937, RPMI 8226, and Jurkat). Viability of cells was measured by a water-soluble tetrazolium (WST-1) reagent\\u000a cell proliferation assay assessing

Carina Nielsen; Maximilian Casteel; Andrea Didier; Richard Dietrich; Erwin Märtlbauer

2009-01-01

143

Proteasome inhibition induces apoptosis in primary human natural killer cells and suppresses NKp46-mediated cytotoxicity  

PubMed Central

Background Bortezomib is a selective and potent inhibitor of the proteasome and has prominent effects in vitro and in vivo against tumors. Very recently, cytotoxic effects of bortezomib on immune-competent cells such as T cells and dendritic cells were also revealed. The aim of the study was to investigate the effects of this agent on natural killer cell survival and function. Design and Methods We investigated cytotoxic properties of bortezomib on natural killer cell apoptosis and function. Primary resting natural killer cells were purified from peripheral blood mononuclear cells of healthy donors by negative selection. The apoptotic cells were quantified by dual labeling of recombinant annexin V and propidium iodide. Mitochondrial membrane potential and expression of natural killer cell activating receptors were also quantified by flow cytometry. Natural killer cell cytotoxicity against murine and human tumor cells was tested by chromium 51 release assay. Results Our results demonstrate that bortezomib induces apoptosis in resting natural killer cells in a dose- and time-dependent manner. Glutathione, a reactive oxygen species scavenger, prevented the loss of mitochondrial membrane potential and conferred protection against bortezomib-induced apoptosis in resting natural killer cells, indicating a role for oxidative stress. Additionally, bortezomib significantly decreased expression of the natural killer activating receptor NKp46 in non-apoptotic resting natural killer cells in a dose-dependent manner, and as a result the redirected cytotoxicity mediated via NKp46 activation was diminished. Bay 11-7082, a pharmacological inhibitor of NF-?B activation, also reduced NKp46 expression and suppressed redirected cytotoxicity. Conclusions Bortezomib induces apoptosis in primary resting natural killer cells in a dose- and time-dependent manner, and reduces NKp46 receptor expression as well as natural killer cell cytotoxicity mediated by the NKp46 activation pathway, suggesting that bortezomib may disrupt natural killer cell-mediated immunity through at least two different mechanisms: induction of natural killer cell apoptosis, and suppression of NKp46 receptor-mediated cytotoxicity.

Wang, Xiangling; Ottosson, Astrid; Ji, Chunyan; Feng, Xiaoli; Nordenskjold, Magnus; Henter, Jan-Inge; Fadeel, Bengt; Zheng, Chengyun

2009-01-01

144

Thioglucose bound gold nanoparticles enhance radio-cytotoxic targeting of ovarian cancer  

Microsoft Academic Search

The treatment of ovarian cancer has traditionally been intractable, and required novel approaches to improve therapeutic efficiency. This paper reports that thio-glucose bound gold nanoparticles (Glu-GNPs) can be used as a sensitizer to enhance ovarian cancer radiotherapy. The human ovarian cancer cells, SK-OV-3, were treated by gold nanoparticles (GNPs) alone, irradiation alone, or GNPs in addition to irradiation. Cell uptake

Feng Geng; Kun Song; James Z. Xing; Cunzhong Yuan; Shi Yan; Qifeng Yang; Jie Chen; Beihua Kong

2011-01-01

145

Biocompatible transferrin-conjugated sodium hexametaphosphate-stabilized gold nanoparticles: synthesis, characterization, cytotoxicity and cellular uptake  

Microsoft Academic Search

The feasibility of using gold nanoparticles (AuNPs) for biomedical applications has led to considerable interest in the development of novel synthetic protocols and surface modification strategies for AuNPs to produce biocompatible molecular probes. This investigation is, to our knowledge, the first to elucidate the synthesis and characterization of sodium hexametaphosphate (HMP)-stabilized gold nanoparticles (Au-HMP) in an aqueous medium. The role

Harshala J. Parab; Jing-Hong Huang; Tsung-Ching Lai; Yi-Hua Jan; Ru-Shi Liu; Jui-Ling Wang; Michael Hsiao; Chung-Hsuan Chen; Yeu-Kuang Hwu; Din Ping Tsai; Shih-Yi Chuang; Jong-Hwei S. Pang

2011-01-01

146

Biocompatible transferrin-conjugated sodium hexametaphosphate-stabilized gold nanoparticles: synthesis, characterization, cytotoxicity and cellular uptake  

NASA Astrophysics Data System (ADS)

The feasibility of using gold nanoparticles (AuNPs) for biomedical applications has led to considerable interest in the development of novel synthetic protocols and surface modification strategies for AuNPs to produce biocompatible molecular probes. This investigation is, to our knowledge, the first to elucidate the synthesis and characterization of sodium hexametaphosphate (HMP)-stabilized gold nanoparticles (Au-HMP) in an aqueous medium. The role of HMP, a food additive, as a polymeric stabilizing and protecting agent for AuNPs is elucidated. The surface modification of Au-HMP nanoparticles was carried out using polyethylene glycol and transferrin to produce molecular probes for possible clinical applications. In vitro cell viability studies performed using as-synthesized Au-HMP nanoparticles and their surface-modified counterparts reveal the biocompatibility of the nanoparticles. The transferrin-conjugated nanoparticles have significantly higher cellular uptake in J5 cells (liver cancer cells) than control cells (oral mucosa fibroblast cells), as determined by inductively coupled plasma mass spectrometry. This study demonstrates the possibility of using an inexpensive and non-toxic food additive, HMP, as a stabilizer in the large-scale generation of biocompatible and monodispersed AuNPs, which may have future diagnostic and therapeutic applications.

Parab, Harshala J.; Huang, Jing-Hong; Lai, Tsung-Ching; Jan, Yi-Hua; Liu, Ru-Shi; Wang, Jui-Ling; Hsiao, Michael; Chen, Chung-Hsuan; Hwu, Yeu-Kuang; Tsai, Din Ping; Chuang, Shih-Yi; Pang, Jong-Hwei S.

2011-09-01

147

Protective effect of zinc chloride against cobalt chloride-induced cytotoxicity on vero cells: preliminary results.  

PubMed

The aim of this study was to investigate the possible time- and dose-dependent cytotoxic effects of cobalt chloride on Vero cells. The cultured cells were incubated with different concentrations of cobalt chloride ranging from 0.5 to 1,000 ?M, and cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and resazurin assays. Possible protective effects of vitamin E, coenzyme Q(10), and zinc chloride were also tested in this system. A gradual decrease in cell proliferation was observed at concentrations ~? 200 ?M in incubation periods of 24, 48, 72, and 96 h with MTT assay. Exposure of cells to 500 and 1,000 ?M cobalt chloride caused significant decrease in cell survival. A biphasic survival profile of cells was observed at 1-25 ?M concentration range following 96 h of incubation. With resazurin assay, cytotoxicity profile of CoCl(2) was found comparable to the results of MTT assay, particularly at high concentrations and long incubation periods. Dose-dependent cytotoxicity was noted following exposure of cells to ? 250 ?M of CoCl(2) for 24 h and ? 100 ?M concentrations of CoCl(2) for 48-96 h. Pretreatment of cells with ZnCl(2) for 4 or 24 h provided significant protection against cobalt chloride-induced cytotoxicity when measured with MTT assay. However, vitamin E or coenzyme Q(10) was not protective. CoCl(2) had dose- and time-dependent cytotoxic effects in Vero cells. Preventive effect of ZnCl(2) against CoCl(2)-induced cytotoxicity should be considered in detail to define exact mechanism of toxicity in Vero cells. PMID:22281816

Gürbay, Aylin

2012-01-27

148

Assessment of Cr(VI)-Induced Cytotoxicity and Genotoxicity Using High Content Analysis  

PubMed Central

Oral exposure to high concentrations of hexavalent chromium [Cr(VI)] induces intestinal redox changes, villus cytotoxicity, crypt hyperplasia, and intestinal tumors in mice. To assess the effects of Cr(VI) in a cell model relevant to the intestine, undifferentiated (proliferating) and differentiated (confluent) Caco-2 cells were treated with Cr(VI), hydrogen peroxide or rotenone for 2–24 hours. DNA damage was then assessed by nuclear staining intensity of 8-hydroxydeoxyguanosine (8-OHdG) and phosphorylated histone variant H2AX (?-H2AX) measured by high content analysis methods. In undifferentiated Caco-2, all three chemicals increased 8-OHdG and ?-H2AX staining at cytotoxic concentrations, whereas only 8-OHdG was elevated at non-cytotoxic concentrations at 24 hr. Differentiated Caco-2 were more resistant to cytotoxicity and DNA damage than undifferentiated cells, and there were no changes in apoptotic markers p53 or annexin-V. However, Cr(VI) induced a dose-dependent translocation of the unfolded protein response transcription factor ATF6 into the nucleus. Micronucleus (MN) formation was assessed in CHO-K1 and A549 cell lines. Cr(VI) increased MN frequency in CHO-K1 only at highly cytotoxic concentrations. Relative to the positive control Mitomycin-C, Cr(VI) only slightly increased MN frequency in A549 at mildly cytotoxic concentrations. The results demonstrate that Cr(VI) genotoxicity correlates with cytotoxic concentrations, and that H2AX phosphorylation occurs at higher concentrations than oxidative DNA damage in proliferating Caco-2 cells. The findings suggest that in vitro genotoxicity of Cr(VI) is primarily oxidative in nature at low concentrations. Implications for in vivo intestinal toxicity of Cr(VI) will be discussed.

Thompson, Chad M.; Fedorov, Yuriy; Brown, Daniel D.; Suh, Mina; Proctor, Deborah M.; Kuriakose, Liz; Haws, Laurie C.; Harris, Mark A.

2012-01-01

149

Comparison of intracellular accumulation and cytotoxicity of free mTHPC and mTHPC-loaded PLGA nanoparticles in human colon carcinoma cells  

NASA Astrophysics Data System (ADS)

The second generation photosensitizer mTHPC was approved by the European Medicines Agency (EMA) for the palliative treatment of advanced head and neck cancer in October 2001. It is known that mTHPC possesses a significant phototoxicity against a variety of human cancer cells in vitro but also exhibits dark toxicity and can cause adverse effects (especially skin photosensitization). Due to its poor water solubility, the administration of hydrophobic photosensitizer still presents several difficulties. To overcome the administration problems, the use of nanoparticles as drug carrier systems is much investigated. Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) have been extensively studied as delivery systems into tumours due to their biocompatibility and biodegradability. The goal of this study was the comparison of free mTHPC and mTHPC-loaded PLGA nanoparticles concerning cytotoxicity and intracellular accumulation in human colon carcinoma cells (HT29). The nanoparticles delivered the photosensitizer to the colon carcinoma cells and enabled drug release without losing its activity. The cytotoxicity assays showed a time- and concentration-dependent decrease in cell proliferation and viability after illumination. However, first and foremost mTHPC lost its dark toxic effects using the PLGA nanoparticles as a drug carrier system. Therefore, PLGA nanoparticles are a promising drug carrier system for the hydrophobic photosensitizer mTHPC.

Löw, Karin; Knobloch, Thomas; Wagner, Sylvia; Wiehe, Arno; Engel, Andrea; Langer, Klaus; von Briesen, Hagen

2011-06-01

150

Inducible Costimulator Costimulates Cytotoxic Activity and IFN Production in Activated Murine NK Cells 1  

Microsoft Academic Search

The functions of NK cells are regulated by the balance of activating and inhibitory signals. The inhibitory NK cell receptors are well understood; however, less is known about the activating signaling pathways. To explore whether a costimulatory receptor, inducible costimulator (ICOS), is involved in NK cell function, we assessed the role of ICOS in NK cell-mediated cytotoxicity and cytokine production.

Kouetsu Ogasawara; Steven K. Yoshinaga; Lewis L. Lanier

151

The effect of humic acids on the cytotoxicity of silver nanoparticles to a natural aquatic bacterial assemblage.  

PubMed

The effect of a terrestrial humic acid (HA) and a river HA on the cytotoxicity of silver nanoparticles (AgNPs) to natural aquatic bacterial assemblages (0 ?M, 2.5 ?M and 5 ?M) was measured with spread plate counting. The effect of HA (20 and 40 ppm) on the cytotoxicity of AgNPs ranging in size between 15 and 25 nm was tested in the presence and in the absence of natural sunlight. The experiment was a full factorial, completely randomized design and the results were analyzed using the General Linear Model in SAS. LSMEANS was used to separate the means or combinations of means. Significant main effects of all independent variables, plus interaction effects in all cases except HA/LI and HA/AgNPs/LI were observed. The toxicity of AgNPs to natural aquatic bacterial assemblages appears to be concentration dependent for concentrations between 0 ?M and 5 ?M. The data indicate that the light exposure inhibited viability more than the darkness exposure. The HA treatment groups in the presence of light showed greater reduced viability count compared to darkness exposure groups. The inhibition of bacterial viability counts by AgNPs exposure was less in the light treatment groups containing a terrestrial HA compared to that with a river HA. Difference in the extent of reactive oxygen species formation and adsorption/binding of AgNPs was speculated to account for the observed phenomenon. PMID:20850168

Dasari, Thabitha P; Hwang, Huey-Min

2010-09-17

152

Photo-induced growth of DNA-capped silver nanoparticles  

NASA Astrophysics Data System (ADS)

We report the photo-induced nucleation and growth of silver nanoparticles in aqueous solution in the presence of DNA oligomers. An organic dye (Cy5) was used as a photosensitizer to initiate the nanoparticle growth upon illumination with 647 nm light. The formation of nanoparticles and growth kinetics were observed by extinction spectroscopy, dynamic light scattering, and transmission electron microscopy. Irradiation of the precursor solutions with light at the Cy5 absorption maximum triggered the instantaneous formation of spherical particles with a metallic core ˜15 nm in diameter. Remarkably, the particles feature significantly larger effective hydrodynamic diameters (35 nm) in solution, indicative of a DNA ad-layer on the nanoparticle surface. Centrifugation experiments confirmed that DNA was inseparably associated with the nanoparticles and indicated that DNA oligomers adsorb onto the nanoparticle surface during growth, playing the role of a capping agent. The introduced method is a fast and facile way to prepare DNA-capped silver nanoparticles in a single growth step.

Zon, Vera B.; Burley, Glenn A.; Rant, Ulrich

2012-03-01

153

Preparation, characterization, cytotoxicity and drug release behavior of liposome-enveloped paclitaxel/Fe3O4 nanoparticles.  

PubMed

Phospholipid vesicles encapsulating magnetic nanoparticles (liposome complexes) have been prepared for targeting a drug to a specific organ using a magnetic force, as well as for local hyperthermia therapy. Liposome complexes are also an ideal platform for use as contrast agents of magnetic resonance imaging (MRI). We describe the preparation and characterization of liposomes containing magnetite. These liposomes were obtained by thin film hydration method and Fe3O4 nanoparticles were synthesized by coprecipitation method. They were characterized by an electrophoretic light scattering spectrophotometer, the liposome complexes were subsequently coated using chitosan. We have further investigated the ability of the above formulation for drug delivery and MRI applications. We are specifically interested in evaluating our liposome complexes for drug therapy; hence, we selected paclitaxel for the combination study. The amount of paclitaxel was measured at 227 nm using a UV-Vis spectrophotometer. Cytotoxicity of liposome complexes was treated with the various concentrations of paclitaxel in PC3 cell lines. The structure and properties of liposome complexes were analyzed by FT-IR, XRD and VSM. The particle size was analyzed by TEM and DLS. PMID:21446568

Kim, Min-Jung; Jang, Dae-Hwan; Lee, Young-In; Jung, Hyun Sook; Lee, Hak-Jong; Choa, Yong-Ho

2011-01-01

154

Gangliosides inhibit bee venom melittin cytotoxicity but not phospholipase A(2)-induced degranulation in mast cells.  

PubMed

Sting accident by honeybee causes severe pain, inflammation and allergic reaction through IgE-mediated anaphylaxis. In addition to this hypersensitivity, an anaphylactoid reaction occurs by toxic effects even in a non-allergic person via cytolysis followed by similar clinical manifestations. Auto-injectable epinephrine might be effective for bee stings, but cannot inhibit mast cell lysis and degranulation by venom toxins. We used connective tissue type canine mast cell line (CM-MC) for finding an effective measure that might inhibit bee venom toxicity. We evaluated degranulation and cytotoxicity by measurement of ?-hexosaminidase release and MTT assay. Melittin and crude bee venom induced the degranulation and cytotoxicity, which were strongly inhibited by mono-sialoganglioside (G(M1)), di-sialoganglioside (G(D1a)) and tri-sialoganglioside (G(T1b)). In contrast, honeybee venom-derived phospholipase A(2) induced the net degranulation directly without cytotoxicity, which was not inhibited by G(M1), G(D1a) and G(T1b). For analysis of distribution of G?(q) and G?(i) protein by western blotting, lipid rafts were isolated by using discontinuous sucrose gradient centrifuge. Melittin disrupted the localization of G?(q) and G?(i) at lipid raft, but gangliosides stabilized the rafts. As a result from this cell-based study, bee venom-induced anaphylactoid reaction can be explained with melittin cytotoxicity and phospholipase A(2)-induced degranulation. Taken together, gangliosides inhibit the effect of melittin such as degranulation, cytotoxicity and lipid raft disruption but not phospholipase A(2)-induced degranulation in mast cells. Our study shows a potential of gangliosides as a therapeutic tool for anaphylactoid reaction by honeybee sting. PMID:21334356

Nishikawa, Hirofumi; Kitani, Seiichi

2011-02-18

155

The Variability of oxLDL-induced Cytotoxicity on Different Types of Cell Lines.  

PubMed

The epidemiologic studies indicated an association of obesity with increased incidence of colorectal, breast and ovarian cancer. Further studies found a positive correlation between increased serum oxLDL and an increased risk of the three cancers. In contrast, our previous studies found a negative correlation between the serum oxLDL levels and the risk of leukemia and esophageal cancer. Identification of the variability of cytotoxicity of oxLDL-induced on different types of cell lines is important for understanding the mechanism of oxLDL involved in the tumorigenesis. In the present study, we investigated the effective impacts of oxLDL on the proliferation and apoptosis for the human umbilical vein endothelial cells (HUVEC) and two cancer cell lines (EC-9706 and K562/AO2 with multi-drug resistance). HUVEC, K562/AO2 and EC-9706 cell lines were cultured in the presence of oxLDL, and cell proliferation was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, apoptosis and cell cycle by flow cytometer, mRNA expression by RT-PCR and protein expression by Western blot. OxLDL could inhibit proliferation and apoptosis of the three cell lines; however, there were significant differences of effective action on the viability and apoptosis. The dose of oxLDL-induced cytotoxicity on HUVEC was higher than that on the two tumor cells. The antibody of lectin-like oxLDL receptor-1 (LOX-1-ab) can block oxLDL-induced cytotoxicity. Cells apoptosis is mediated by reducing Bcl-2 and increasing Bax and caspase-3 mRNA and protein expression. This study showed the dose of oxLDL-induced cytotoxicity on HUVEC was higher than that on K562/AO2 and EC-9706 tumor cells. The antibody of LOX-1 receptor can block the oxLDL-induced cytotoxicity. PMID:23479334

Li, Hao; Li, Xin Xiang; Ma, Qing; Cui, Jia

2013-03-12

156

Regulatory T Cells and IL10 Independently Counterregulate Cytotoxic T Lymphocyte Responses Induced by Transcutaneous Immunization  

Microsoft Academic Search

BackgroundThe imidazoquinoline derivate imiquimod induces inflammatory responses and protection against transplanted tumors when applied to the skin in combination with a cognate peptide epitope (transcutaneous immunization, TCI). Here we investigated the role of regulatory T cells (Treg) and the suppressive cytokine IL-10 in restricting TCI-induced cytotoxic T lymphocyte (CTL) responses.Methodology\\/Principal FindingsTCI was performed with an ointment containing the TLR7 agonist

Pamela Stein; Michael Weber; Steve Prüfer; Beate Schmid; Edgar Schmitt; Hans-Christian Probst; Ari Waisman; Peter Langguth; Hansjörg Schild; Markus P. Radsak

2011-01-01

157

Protective effects of heme oxygenase-1 against MPP + -induced cytotoxicity in PC12 cells  

Microsoft Academic Search

Heme oxygenase-1 (HO-1) catalyses the rate-limiting step of heme degradation to biliverdin, which is in turn reduced to bilirubin,\\u000a CO and free iron. HO-1 can be induced by several harmful stimuli including oxidative stress, and it has a protective role\\u000a against the cytotoxicity in different cells. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridinium (MPP+) is a neurotoxic substance that induces the degeneration of dopaminergic neurons. This

Jung-Woo Bae; Mi-Jeong Kim; Choon-Gon Jang; Seok-Yong Lee

2010-01-01

158

The significance of nanoparticles in particle-induced pulmonary fibrosis  

PubMed Central

Exposure to airborne nanoparticles contributes to many chronic pulmonary diseases. Nanoparticles, classified as anthropogenic and natural particles, and fibers of diameters less than 100 nm, have unrestricted access to most areas of the lung due to their size. Size relates to the deposition efficiency of the particle, with particles in the nano-range having the highest efficiencies. The deposition of nanoparticles in the lung can lead to chronic inflammation, epithelial injury, and further to pulmonary fibrosis. Cases of particle-induced pulmonary fibrosis, namely pneumoconiosis, are mostly occupationally influenced, and continue to be documented around the world. The tremendous growth of nanotechnology, however, has spurred fears of increased rates of pulmonary diseases, especially fibrosis. The severity of toxicological consequences warrants further examination of the effects of nanoparticles in humans, possible treatments and increased regulatory measures.

Byrne, James D; Baugh, John A

2008-01-01

159

The significance of nanoparticles in particle-induced pulmonary fibrosis.  

PubMed

Exposure to airborne nanoparticles contributes to many chronic pulmonary diseases. Nanoparticles, classified as anthropogenic and natural particles, and fibers of diameters less than 100 nm, have unrestricted access to most areas of the lung due to their size. Size relates to the deposition efficiency of the particle, with particles in the nano-range having the highest efficiencies. The deposition of nanoparticles in the lung can lead to chronic inflammation, epithelial injury, and further to pulmonary fibrosis. Cases of particle-induced pulmonary fibrosis, namely pneumoconiosis, are mostly occupationally influenced, and continue to be documented around the world. The tremendous growth of nanotechnology, however, has spurred fears of increased rates of pulmonary diseases, especially fibrosis. The severity of toxicological consequences warrants further examination of the effects of nanoparticles in humans, possible treatments and increased regulatory measures. PMID:18523535

Byrne, James D; Baugh, John A

2008-01-01

160

c-Myc induces cellular susceptibility to the cytotoxic action of TNF-alpha.  

PubMed Central

Tumor necrosis factor-alpha (TNF) is a multifunctional cytokine which is cytotoxic for some tumor cells and transformed cells. The molecular mechanisms which render transformed and tumor cells sensitive to the cytotoxic action of TNF are unclear. We show here that an increased expression of the c-Myc oncoprotein strongly increases cellular sensitivity to TNF cytotoxicity. In Rat1A fibroblasts, which are resistant to TNF, the addition of TNF with a concomitant activation of a hormone-inducible c-Myc-estrogen receptor chimera (MycER) resulted in apoptotic cell death. Similarly, c-Myc overexpression enhanced the sensitivity of NIH3T3 fibroblasts to TNF-induced death. The c-Myc and TNF-induced apoptosis was inhibited by ectopic expression of the Bcl2 oncoprotein and by the free oxygen radical scavenging enzyme Mn superoxide dismutase. Furthermore, in highly TNF-sensitive fibrosarcoma cells, antisense c-myc oligodeoxynucleotides caused a specific inhibition of TNF cytotoxicity. Our results suggest that the deregulation of c-Myc, which is common in human tumors and tumor cell lines is one reason why these cells are TNF sensitive. Images

Klefstrom, J; Vastrik, I; Saksela, E; Valle, J; Eilers, M; Alitalo, K

1994-01-01

161

Antibody-dependent and phytohaemagglutinin-induced lymphocyte cytotoxicity in systemic lupus erythematosus.  

PubMed Central

An investigation of cell-mediated cytotoxicity in 22 patients with systemic lupus erythematosus (SLE), using both whole blood and purified peripheral blood mononuclear cells (PBM) to measure antibody-dependent (ADCC) and phytohaemagglutinin (PHA)-induced lymphocyte cytotoxicity for Chang liver cells, has revealed 2 distinct abnormalities in patients with active disease. PHA-induced cytotoxicity was found to be selectively reduced in whole blood assays only (P less than 0.05), whereas ADCC was impaired in both whole blood (P = 0.02) and PBM (P less than 0.05) assays, when comparison was made with 52 normal controls. The addition of patients' sera to corresponding assays utilizing control PBM confirmed that the impaired PHA-induced cytotoxicity resulted from circulating inhibitory serum factors. Surprisingly little effect, however, was exerted on ADCC assays. These findings suggest that there is a reduction in numbers and/or functional capacity of Fc-receptor cells in active SLE, which may have pathogenetic implications.

Wright, J K; Hughes, P; Gelsthorpe, K; Ward, A M; Rowell, N R

1981-01-01

162

Recognition of viral antigens in 6/94 virus-induced T-cell-mediated cytotoxicity.  

PubMed

Distinct events in the virus-stimulated T-cell-mediated cytotoxicity (V-CMC) have been investigated: 1.) The induction of V-CMC is possible by immunizing mice with infectious as well as UV-inactivated virus (parainfluenza type 1 strain 6/94), or with virus-infected cells either compatible or imcompatible with the recipient. 2). Recognition of viral antigens by the effector cells occurs independently of the H2 environment: Fractionation of effector cells on columns loaded with virus-infected cells eliminates virus-specific cytotoxic cells. Effector cells and cells on the column need not share H-2 antigens. The findings are discussed with regard to the H2 restriction of the virus induced T-cells mediated cytotoxicity. PMID:219322

Pickel, K; Solvay, M J

1979-01-24

163

CCL2 is induced by chemotherapy and protects prostate cancer cells from docetaxel - induced cytotoxicity  

PubMed Central

Background Metastatic prostate cancer is either inherently resistant to chemotherapy or rapidly acquires this phenotype after chemotherapy exposure. In this study, we identified a docetaxel-induced resistance mechanism centered on CCL2. Methods we compared the gene expression profiles in individual human prostate cancer specimens before and after exposure to chemotherapy collected from previously untreated patients who participated in a clinical trial of preoperative chemotherapy. Subsequently, we used the gain- and loss- of function approach in vitro to identify a potential mechanism underlying chemotherapy resistance. Results Among the molecular signatures associated with treatment, several genes that regulate the inflammatory response and chemokine activity were upregulated including a significant increase in transcripts encoding the CC chemokine CCL2. Docetaxel increased CCL2 expression in prostate cancer cell lines in vitro. CCL2 specific siRNA inhibited LNCaP and LAPC4 cell proliferation and enhanced the growth inhibitory effect of low-dose docetaxel. In contrast, overexpression of CCL2 or recombinant CCL2 protein stimulated prostate cancer cell proliferation and rescued cells from docetaxel-induced cytotoxicity. This protective effect of CCL2 was associated with activation of the ERK/MAP kinase and PI3K/AKT, inhibition of docetaxel-induced Bcl2 phosphorylation at serine 70, phosphorylation of Bad, and activation of caspase-3. The addition of a PI3K/AKT inhibitor Ly294002 reversed the CCL2 protection, and was additive to docetaxel induced toxicity. Conclusion These results support a mechanism of chemotherapy resistance mediated by cellular stress responses involving the induction of CCL2 expression, and suggest that inhibiting CCL2 activity could enhance therapeutic responses to taxane-based therapy.

Qian, David Z.; Rademacher, Brooks L.S.; Pittsenbarger, Janet; Huang, Chung-Ying; Myrthue, Anne; Higano, Celestia S.; Garzotto, Mark; Nelson, Peter S.; Beer, Tomasz M.

2010-01-01

164

Systematic study of enhanced cytotoxicity effects of gold-based nanoparticles in targeted cancer radiotherapy  

Microsoft Academic Search

Worldwide, cancers are the leading causes of human mortality. To successfully treat advanced-stage cancers, it is important to increase cytotoxicity of targeted tumor cells while reducing side effects on normal cells during radiotherapy. Nanotechnology provides a promising solution to achieve this targeted treatment[1-3]. An ideal strategy is to develop effective nanoscale radio-sensitizers targeting specifically at tumor cells. In this paper,

Kun Song; Peng Xu; Yongde Meng; Jie Chen; Xiaoyan Yang; W. Roa; Beihua Kong; James Xing

2009-01-01

165

Involvement of intracellular Na^+ accumulation in Hg^{+2} or Cd^{+2} induced cytotoxicity  

NASA Astrophysics Data System (ADS)

Previously we showed that hepatocyte lysis induced by Hg^{+2} or Cd^{+2} could be partly attributed to mitochondrial toxicity [1, 2]. Similar changes in Na^+ homeostasis induced when Cd^{+2} or Hg^{+2} was incubated with hepatocytes. Cd^{+2} or Hg^{+2} induced cytotoxicity were prevented by Na^+ omission from the media or by the addition of the Na^+/H^+ exchange inhibitor 5-(N, N-dimethyl)-amiloride. Furthermore the omission of CI^- from the media or 2 addition of glycine, a CI^- channel blocker also prevented Cd^{+2} or Hg^{+2} induced hepatocyte toxicity. A hypotonic media also increased Cd^{+2} or Hg^{+2} induced hepatocyte cytotoxicity. This suggests that Cd^{+2} or Hg^{+2} cytotoxicity could be partly attributed to disruption of cell volume regulation mechanisms. The increased osmotic load caused by the uncontrolled accumulation of intracellular Na^+ in Cd^{+2} or Hg^{+2} treated hepatocytes likely resulted from the activation of Na^+/H^+ exchanger and the Na^+/HCO3^- cotransporter by the acidosis and ATP depletion caused by mitochondrial toxicity.

Pourahmad, J.; O'Brien, P. J.

2003-05-01

166

Magnetic and Cytotoxicity Properties of La 1? x Sr x MnO 3 (0 ?  x  ? 0.5) Nanoparticles Prepared by a Simple Thermal Hydro-Decomposition  

Microsoft Academic Search

This study reports the magnetic and cytotoxicity properties of magnetic nanoparticles of La1?x\\u000a Sr\\u000a x\\u000a MnO3 (LSMO) with x = 0, 0.1, 0.2, 0.3, 0.4, and 0.5 by a simple thermal decomposition method by using acetate salts of La, Sr, and Mn as starting\\u000a materials in aqueous solution. To obtain the LSMO nanoparticles, thermal decomposition of the precursor was carried out at

Sujittra Daengsakul; Chunpen Thomas; Ian Thomas; Charusporn Mongkolkachit; Sineenat Siri; Vittaya Amornkitbamrung; Santi Maensiri

2009-01-01

167

Biocompatibility of magnetic Fe3O4 nanoparticles and their cytotoxic effect on MCF-7 cells  

PubMed Central

Background The objective of this study was to evaluate the synthesis and biocompatibility of Fe3O4 nanoparticles and investigate their therapeutic effects when combined with magnetic fluid hyperthermia on cultured MCF-7 cancer cells. Methods Magnetic Fe3O4 nanoparticles were prepared using a coprecipitation method. The appearance, structure, phase composition, functional groups, surface charge, magnetic susceptibility, and release in vitro were characterized by transmission electron microscopy, x-ray diffraction, scanning electron microscopy-energy dispersive x-ray spectroscopy, and a vibrating sample magnetometer. Blood toxicity, in vitro toxicity, and genotoxicity were investigated. Therapeutic effects were evaluated by MTT [3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide] and flow cytometry assays. Results Transmission electron microscopy revealed that the shapes of the Fe3O4 nanoparticles were approximately spherical, with diameters of about 26.1 ± 5.2 nm. Only the spinel phase was indicated in a comparison of the x-ray diffraction data with Joint Corporation of Powder Diffraction Standards (JCPDS) X-ray powder diffraction files. The O-to-Fe ratio of the Fe3O4 was determined by scanning electron microscopy-energy dispersive x-ray spectroscopy elemental analysis, and approximated pure Fe3O4. The vibrating sample magnetometer hysteresis loop suggested that the Fe3O4 nanoparticles were superparamagnetic at room temperature. MTT experiments showed that the toxicity of the material in mouse fibroblast (L-929) cell lines was between Grade 0 to Grade 1, and that the material lacked hemolysis activity. The acute toxicity (LD50) was 8.39 g/kg. Micronucleus testing showed no genotoxic effects. Pathomorphology and blood biochemistry testing demonstrated that the Fe3O4 nanoparticles had no effect on the main organs and blood biochemistry in a rabbit model. MTT and flow cytometry assays revealed that Fe3O4 nano magnetofluid thermotherapy inhibited MCF-7 cell proliferation, and its inhibitory effect was dose-dependent according to the Fe3O4 nano magnetofluid concentration. Conclusion The Fe3O4 nanoparticles prepared in this study have good biocompatibility and are suitable for further application in tumor hyperthermia.

Chen, Daozhen; Tang, Qiusha; Li, Xiangdong; Zhou, Xiaojin; Zang, Jia; Xue, Wen-qun; Xiang, Jing-ying; Guo, Cai-qin

2012-01-01

168

Cytotoxicity and gene expression changes induced by inorganic and organic trivalent arsenicals in human cells.  

PubMed

Inorganic arsenic (iAs) is a human urinary bladder, skin and lung carcinogen. iAs is metabolized to methylated arsenicals, with trivalent arsenicals more cytotoxic than pentavalent forms in vitro. In this study, cytotoxicity and gene expression changes for arsenite (iAs(III)), monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)) were evaluated in three human cell types, urothelial (1T1), keratinocyte (HEK001) and bronchial epithelial (HBE) cells, corresponding to target organs for iAs-induced cancer. Cells were exposed to arsenicals to determine cytotoxicity and to study gene expression changes. Affymetrix chips were used to determine differentially expressed genes (DEGs) by statistical analysis. Lethal concentrations (LC50) for trivalent arsenicals in all cells ranged from 1.6 to 10?M. MMA(III) and DMA(III) had 4-12-fold greater potency compared to iAs. Increasing concentrations of iAs(III) induced more genes and additional signaling pathways in HBE cells. At equivalent cytotoxic concentrations, greater numbers of DEGs were induced in 1T1 cells compared to the other cells. Each arsenical altered slightly different signaling pathways within and between cell types, but when altered pathways from all three arsenicals were combined, they were similar between cell types. The major signaling pathways altered included NRF2-mediated stress response, interferon, p53, cell cycle regulation and lipid peroxidation. These results show a similar process qualitatively and quantitatively for all three cell types, and support a mode of action involving cytotoxicity and regenerative proliferation. PMID:23876855

Dodmane, Puttappa R; Arnold, Lora L; Kakiuchi-Kiyota, Satoko; Qiu, Fang; Liu, Xiangde; Rennard, Stephen I; Cohen, Samuel M

2013-07-19

169

Amoebicidal activity of phytosynthesized silver nanoparticles and their in vitro cytotoxicity to human cells.  

PubMed

Acanthamoeba causes infections in humans and other animals and it is important to develop treatment therapies. Jatropha curcas, Jatropha gossypifolia and Euphorbia milii plant extracts synthesized stable silver nanoparticles (AgNPs) that were relatively stable. Amoebicidal activity of J. gossypifolia, J. curcas and E. milii leaf extracts showed little effect on viability of Acanthamoeba castellanii trophozoites. Plant-synthesized AgNPs showed higher amoebicidal activity. AgNPs synthesized by J. gossypifolia extract were able to kill 74-27% of the trophozoites at concentrations of 25-1.56 ?g mL(-1) . AgNPs were nontoxic at minimum inhibitory concentration with peripheral blood mononuclear cells. These results suggest biologically synthesized nanoparticles as an alternative candidate for treatment of Acanthamoeba infections. PMID:23746354

Borase, Hemant P; Patil, Chandrashekhar D; Sauter, Ismael P; Rott, Marilise B; Patil, Satish V

2013-07-01

170

Effect of particle size on in vitro cytotoxicity of titania and alumina nanoparticles  

Microsoft Academic Search

Aluminium oxide (Al2O3) and titanium dioxide (TiO2) nanoparticles (NPs) have been widely used in nanotechnology-based products. Recently, researchers and the public have raised concerns about the adverse effects of these NPs in biological systems, particularly in humans. The aim of this study was to investigate the possible adverse effects of these two common metal oxide NPs on human lung epithelium

Zhicheng Wei; Limeng Chen; Deanna M. Thompson; Lupita D. Montoya

2012-01-01

171

Platinum nanoparticles and their cellular uptake and DNA platination at non-cytotoxic concentrations  

Microsoft Academic Search

Three differently sized, highly dispersed platinum nanoparticle (Pt-NP) preparations were generated by supercritical fluid\\u000a reactive deposition (SFRD) and deposited on a ?-cyclodextrin matrix. The average particle size and size distribution were\\u000a steered by the precursor reduction conditions, resulting in particle preparations of 100 nm as characterised\\u000a by TEM and SEM. As reported previously, these Pt-NPs were found to cause DNA strand

Helge GehrkeJoanna; Joanna Pelka; Christian G. Hartinger; Holger Blank; Felix Bleimund; Reinhard Schneider; Dagmar Gerthsen; Stefan Bräse; Marlene Crone; Michael Türk; Doris Marko

2011-01-01

172

Magnetic nanoparticle-induced hyperthermia treatment under magnetic resonance imaging  

Microsoft Academic Search

Super paramagnetic iron oxide Fe3O4 nanoparticles prepared via photochemical reaction in pure form were used for inducing hyperthermia to treat subcutaneous Ehrlich carcinoma implanted in female mice. Our results indicate that the mean temperature profiles at the rectum, periphery of the tumor surface and at the center of the tumor during hyperthermia treatment increased gradually. The maximum temperature achieved in

Alsayed A. M. Elsherbini; Mahmoud Saber; Mohamed Aggag; Ahmed El-Shahawy; Hesham A. A. Shokier

2011-01-01

173

Study on the visible-light-induced photokilling effect of nitrogen-doped TiO2 nanoparticles on cancer cells  

PubMed Central

Nitrogen-doped TiO2 (N-TiO2) nanoparticles were prepared by calcining the anatase TiO2 nanoparticles under ammonia atmosphere. The N-TiO2 showed higher absorbance in the visible region than the pure TiO2. The cytotoxicity and visible-light-induced phototoxicity of the pure- and N-TiO2 were examined for three types of cancer cell lines. No significant cytotoxicity was detected. However, the visible-light-induced photokilling effects on cells were observed. The survival fraction of the cells decreased with the increased incubation concentration of the nanoparticles. The cancer cells incubated with N-TiO2 were killed more effectively than that with the pure TiO2. The reactive oxygen species was found to play an important role on the photokilling effect for cells. Furthermore, the intracellular distributions of N-TiO2 nanoparticles were examined by laser scanning confocal microscopy. The co-localization of N-TiO2 nanoparticles with nuclei or Golgi complexes was observed. The aberrant nuclear morphologies such as micronuclei were detected after the N-TiO2-treated cells were irradiated by the visible light.

2011-01-01

174

Study on the visible-light-induced photokilling effect of nitrogen-doped TiO2 nanoparticles on cancer cells  

NASA Astrophysics Data System (ADS)

Nitrogen-doped TiO2 (N-TiO2) nanoparticles were prepared by calcining the anatase TiO2 nanoparticles under ammonia atmosphere. The N-TiO2 showed higher absorbance in the visible region than the pure TiO2. The cytotoxicity and visible-light-induced phototoxicity of the pure- and N-TiO2 were examined for three types of cancer cell lines. No significant cytotoxicity was detected. However, the visible-light-induced photokilling effects on cells were observed. The survival fraction of the cells decreased with the increased incubation concentration of the nanoparticles. The cancer cells incubated with N-TiO2 were killed more effectively than that with the pure TiO2. The reactive oxygen species was found to play an important role on the photokilling effect for cells. Furthermore, the intracellular distributions of N-TiO2 nanoparticles were examined by laser scanning confocal microscopy. The co-localization of N-TiO2 nanoparticles with nuclei or Golgi complexes was observed. The aberrant nuclear morphologies such as micronuclei were detected after the N-TiO2-treated cells were irradiated by the visible light.

Li, Zheng; Mi, Lan; Wang, Pei-Nan; Chen, Ji-Yao

2011-04-01

175

Cytotoxic effect of Green synthesized silver nanoparticles using Melia azedarach against in vitro HeLa cell lines and lymphoma mice model  

Microsoft Academic Search

This communication explains the biosynthesis of stable silver nanoparticles (AgNPs) from Melia azedarach and its cytotoxicity against in vitro HeLa cells and in vivo Dalton's ascites Lymphoma (DAL) mice model. The AgNPs synthesis was determined by UV- visible spectrum and it was further characterized by Scanning Electron Microscopy (SEM), Dynamic light Scattering (DLS) and X-Ray Diffraction (XRD) analysis. Zeta potential

Raman Sukirtha; Kandula Manasa Priyanka; Jacob Joe Antony; Soundararajan Kamalakkannan; Thangam Ramar; Gunasekaran Palani; Muthukalingan Krishnan; Shanmugam Achiraman

176

Mechanism for alpha-MnO2 nanowire-induced cytotoxicity in Hela cells.  

PubMed

Alpha-Manganese dioxide (alpha-MnO2) nanowires are used as electrode materials to significantly enhance the performance of lithium batteries. In this study, we investigate the nanotoxicity of alpha-MnO2 nanowires toward Hela cells. The alpha-MnO2 nanowires, which were successfully synthesized using the hydrothermal approach, can induce cytotoxicity dose-dependently in Hela cells. The accumulation of reactive oxygen species (ROS) and depletion of glutathione (GSH) are also observed in the nanowire-treated cells. In addition, comet assays and cell nucleus morphology show that both DNA damage and cell apoptosis occur in the nanowires exposure group. Based on these results, a mechanism for alpha-MnO2 nanowire-induced cytotoxicity in Hela cells, which involves the accumulation of ROS, formation of oxidative stress, DNA oxidative damage and cell apoptosis, is proposed. This investigation may provide a fundamental insight to understand the nanotoxicity of wire-shaped nanomaterials. PMID:20352869

Li, Yan; Tian, Xike; Lu, Zhisong; Yang, Chao; Yang, Guangtao; Zhou, Xiaochong; Yao, Hanchao; Zhu, Zhihong; Xi, Zhuge; Yang, Xu

2010-01-01

177

Involvement of mitochondrial pathway in NCTD-induced cytotoxicity in human hepG2 cells  

Microsoft Academic Search

BACKGROUND: Norcantharidin, the demethylated analog of cantharidin derived from a traditional Chinese medicine, Mylabris, has been used in the treatment of anti-cancer effects. However, the detailed mechanisms underlying this process are generally unclear. The aim of this study was to investigate the mechanism of NCTD-induced apoptosis in HepG2 cells. METHODS: The cytotoxicity was measured by MTT assay for cellular viability

Cheng Chang; You-Qing Zhu; Juan-juan Mei; Shi-quan Liu; Jun Luo

2010-01-01

178

The cytotoxic prodigiosin induces phosphorylation of p38MAPK but not of SAPK\\/JNK  

Microsoft Academic Search

Prodigiosin (PG) is a red pigment produced by Serratia marcescens, with cytotoxic and immunosuppressive activity. It induces apoptosis in several cancer cell lines, including Jurkat-T cells. Here we examine the role of two stress-stimulated kinase cascades in this induction. Time course experiments using polyclonal antibodies showed that p38-MAPK phosphorylation began at 15 min and lasted for 3 h, whereas JNK

Beatriz Montaner; Ricardo Pérez-Tomás

2002-01-01

179

Effect of an Iron-Chelator on Ascorbate-Induced Cytotoxicity  

Microsoft Academic Search

We investigated the effect of deferoxamine mesylate (DFO), an iron chelator, to test whether ascorbate-induced cytotoxicity is due to iron-catalyzed oxidation. Exposing human promyelocytic leukemic HL-60 cells to either sodium ascorbate or ascorbic acid for 1 h resulted in the progressive production of apoptotic cells characterized by cell shrinkage, as well as nuclear and internucleosomal DNA fragmentation. The addition of

Hiroshi Sakagami; Kazue Satoh; Kunihiko Fukuchi; Kunihide Gomi; Minoru Takeda

1997-01-01

180

Bowman-Birk protease inhibitor from soybeans enhances cisplatin-induced cytotoxicity in human mesothelioma cells.  

PubMed

Malignant mesothelioma (MM) is an aggressive cancer with no effective treatment options. Enforced expression of the gap junction (GJ) component connexin 43 (Cx43) increases the sensitivity of MM cells to cisplatin. Bowman-Birk protease inhibitor (BBI) induces the restoration of Cx43 in several types of tumor cells. In this study, we examined the capability of BBI to enhance the cytotoxic effect of cisplatin in MM cells via the induction of Cx43. Human MM H28 cells were used. Cell viability was evaluated by a WST-1 assay and proteasomal activity was determined by fluorometric analysis. Protein and mRNA levels were determined by immunoblot analysis and real-time RT-PCR, respectively. GJ function mediated by Cx43 was evaluated using the scrape-loading method. BBI effectively inhibited H28 cell growth in a dose-dependent manner (200-400 ?g/ml). In parallel with the growth inhibition, Cx43 levels (mRNA and protein) and GJ function were elevated by BBI treatment. Knockdown of BBI-induced Cx43 by an antisense nucleotide treatment almost cancelled the growth inhibition. BBI enhanced cisplatin-induced cytotoxicity in H28 cells, and down-regulation of Cx43 by the antisense nucleotide treatment abrogated the enhancing effect of BBI. The induction of Cx43 by BBI contributed to Src inactivation and subsequent induction of Bax. Furthermore, an Src inhibitor (SU6656) also enhanced cisplatin-induced cytotoxicity in H28 cells. These results suggest that BBI improves the cytotoxic efficacy of cisplatin in H28 cells via the inhibition of Src signaling. PMID:22977565

Kashiwagi, Korehito; Virgona, Nantiga; Yamada, Jin; Sato, Ayami; Ota, Masako; Yazawa, Takuya; Yano, Tomohiro

2011-05-12

181

Bowman-Birk protease inhibitor from soybeans enhances cisplatin-induced cytotoxicity in human mesothelioma cells  

PubMed Central

Malignant mesothelioma (MM) is an aggressive cancer with no effective treatment options. Enforced expression of the gap junction (GJ) component connexin 43 (Cx43) increases the sensitivity of MM cells to cisplatin. Bowman-Birk protease inhibitor (BBI) induces the restoration of Cx43 in several types of tumor cells. In this study, we examined the capability of BBI to enhance the cytotoxic effect of cisplatin in MM cells via the induction of Cx43. Human MM H28 cells were used. Cell viability was evaluated by a WST-1 assay and proteasomal activity was determined by fluorometric analysis. Protein and mRNA levels were determined by immunoblot analysis and real-time RT-PCR, respectively. GJ function mediated by Cx43 was evaluated using the scrape-loading method. BBI effectively inhibited H28 cell growth in a dose-dependent manner (200–400 ?g/ml). In parallel with the growth inhibition, Cx43 levels (mRNA and protein) and GJ function were elevated by BBI treatment. Knockdown of BBI-induced Cx43 by an antisense nucleotide treatment almost cancelled the growth inhibition. BBI enhanced cisplatin-induced cytotoxicity in H28 cells, and down-regulation of Cx43 by the antisense nucleotide treatment abrogated the enhancing effect of BBI. The induction of Cx43 by BBI contributed to Src inactivation and subsequent induction of Bax. Furthermore, an Src inhibitor (SU6656) also enhanced cisplatin-induced cytotoxicity in H28 cells. These results suggest that BBI improves the cytotoxic efficacy of cisplatin in H28 cells via the inhibition of Src signaling.

KASHIWAGI, KOREHITO; VIRGONA, NANTIGA; YAMADA, JIN; SATO, AYAMI; OTA, MASAKO; YAZAWA, TAKUYA; YANO, TOMOHIRO

2011-01-01

182

Dicoumarol enhances gemcitabine-induced cytotoxicity in high NQO1-expressing cholangiocarcinoma cells  

Microsoft Academic Search

AIM: To investigate whether dicoumarol, a potent in- hibitor of NAD(P)H quinone oxidoreductase-1 (NQO1), potentiates gemcitabine to induce cytotoxicity in chol- angiocarcinoma cells (CCA) and the role of reactive oxygen generation in sensitizing the cells. METHODS: Four human cell lines with different NQO1 activity were used; the human CCA cell lines, KKU-100, KKU-OCA17, KKU-M214, and Chang liver cells. NQO1 ac-

Benjaporn Buranrat; Auemduan Prawan; Upa Kukongviriyapan; Sarinya Kongpetch; Veerapol Kukongviriyapan

2010-01-01

183

In Situ Observations of Electric-Field Induced Nanoparticle Aggregation  

NASA Astrophysics Data System (ADS)

Nanoparticles have been widely observed to aggregate laterally on electrodes in response to applied electric fields. The mechanism driving this behavior, however, is unclear. Several groups have interpreted the aggregation in terms of electrohydrodynamic or electroosmotic fluid motion, but little corroborating evidence has been presented. Notably, work to date has relied on post situ observations using electron microscopy. Here we present a fluorescence microscopy technique to track the dynamics of nanoparticle aggregation in situ. Fluorescent 20-nm polystyrene nanoparticles are observed to form optically visible aggregates in response to an applied AC field. Although single particle resolution is lost, the existence of aggregates on the electrode surface is marked by growing clusters of increasingly bright intensity. We present a systematic investigation of the effects of applied potential and frequency on the aggregation rate, and we interpret the behavior in terms of a mechanism based on electrically induced convective flow.

Woehl, T. J.; Browning, N. D.; Ristenpart, W. D.

2010-11-01

184

Light-induced binding of metal nanoparticles via surface plasmons  

NASA Astrophysics Data System (ADS)

Recently, nanomachines based on the interaction of nanosize objects with nanostructrued surfaces have attracted much attention. In this work, we study theoretically the light-induced binding forces between a metallic nanosphere and a planar structure, and also between nanoparticles in a diatomic plamonic chain of shelled and unshelled metallic nanoparticles placed alternatively. These forces are calculated by Bergman-Milton spectral representation and multiple image methods within the long wavelength limit. When we tune the incident frequency to the surface plasmon resonant frequency, a stable local minimum in the potential energy is found. It signifies a binding between nanoparticles (nanostructures), which indicates a possible stable structure of the metallic clusters. Such binding is caused by the excitation of collective plasmon modes, which depends on the interparticle distances. This study has potential applications in plasmonic waveguides and colloidal metallic clusters on the nanoscales.

Chan, K. L.; Zheng, M. J.; Yu, K. W.

2010-03-01

185

A simple thermal decomposition synthesis, magnetic properties, and cytotoxicity of La0.7Sr0.3MnO3 nanoparticles  

NASA Astrophysics Data System (ADS)

This study reports the new and simple synthesis of magnetic La0.7Sr0.3MnO3 (LSMO) nanoparticles by thermal decomposition method using acetate salts of La, Sr and Mn as starting materials. To obtain the LSMO nanoparticles, thermal decomposition of the precursor is carried out at the temperatures of 600, 700, 800, 900, and 1000°C for 6 hours. The synthesized LSMO nanoparticles were characterized by XRD, FT-IR, TEM and SEM. Structural characterization shows that the prepared particles consisted of two phases of LaMnO3 (LMO) and LSMO with crystallite sizes ranging from 18 to 55 nm. All the prepared samples have a perovskite structure which changes from cubic to rhombohedral with the increase in the thermal decomposition temperature. Basic magnetic characteristics such as saturation magnetization ( M S) and coercive field ( H C) are evaluated by sample vibrating magnetometry at room temperature (20°C). The samples show soft ferromagnetic behavior with M S values of ˜9-55 emu/g and H C values of ˜8-37 Oe, depending on the crystallite size and thermal decomposition temperature. The relationship between the crystallite size and the magnetic properties is presented and discussed. The cytotoxicity of synthesized LSMO nanoparticles was also evaluated with NIH 3T3 cells and the result showed that the synthesized nanoparticles were not toxic to the cells as determined from cell viability in response to the liquid extraction of LSMO nanoparticles.

Daengsakul, Sujittra; Mongkolkachit, Charusporn; Thomas, Chunpen; Siri, Sineenat; Thomas, Ian; Amornkitbamrung, Vittaya; Maensiri, Santi

2009-08-01

186

Intracellular localisation, geno- and cytotoxic response of polyN-isopropylacrylamide (PNIPAM) nanoparticles to human keratinocyte (HaCaT) and colon cells (SW 480).  

PubMed

PNIPAM nanoparticles, with and without a covalently linked fluorescent label, were prepared by a free radical polymerisation technique. The cyto- and genotoxicity of PNIPAM nanoparticles were analysed in two representative mammalian cell lines, SW480, a colon, and HaCaT, a dermal cell line. Physical characterisation in terms of particle size and zeta potential of the PNIPAM nanoparticles was carried out both in aqueous solution and in the appropriate cell culture media. Uptake and co-localisation of fluorescently labelled PNIPAM nanoparticles was monitored in both cell lines using confocal laser scanning microscope. Genotoxicity analysis using the Comet assay was performed in both cell lines to evaluate any DNA damage. It was observed that the PNIPAM nanoparticles were internalized and localised in lysosomes within 24h. No significant cytotoxic response (pnanoparticles show excellent biocompatibility in vitro. PMID:20600712

Naha, Pratap C; Bhattacharya, Kunal; Tenuta, Tiziana; Dawson, Kenneth A; Lynch, Iseult; Gracia, Amaya; Lyng, Fiona M; Byrne, Hugh J

2010-06-23

187

Reduction of cytotoxicity of natural rubber latex film by coating with PMMA-chitosan nanoparticles.  

PubMed

Poly(methyl methacrylate) (PMMA) latex stabilized by chitosan (CS) oligomer was synthesized via the miniemulsion polymerization. By using 1% CS solution (in 0.1M acetic acid), the spherical PMMA-CS particles with an average size of 380 nm were obtained. The positive zeta potentials at pH 2-7 confirmed the presence of CS as the outermost layer of the latex particles. Therefore, these particles directly interacted with the indigenous non-rubbers at the surface of sulphur prevulcanized natural rubber (SPNR) film. The deposition of PMMA-CS particles caused an increase in surface roughness of the coated SPNR film as a function of latex concentration and immersion time. The simple coating of the rubber substrate with PMMA-CS particles effectively reduced the in vitro cytotoxicity on L-929 cells. This study would be, therefore, helpful for development of latex gloves designed for hypersensitive users. PMID:23769516

Kanjanathaworn, Nuttakun; Polpanich, Duangporn; Jangpatarapongsa, Kulachart; Tangboriboonrat, Pramuan

2013-04-29

188

Molecular dynamics simulations of evaporation-induced nanoparticle assembly  

NASA Astrophysics Data System (ADS)

While evaporating solvent is a widely used technique to assemble nano-sized objects into desired superstructures, there has been limited work on how the assembled structures are affected by the physical aspects of the process. We present large scale molecular dynamics simulations of the evaporation-induced assembly of nanoparticles suspended in a liquid that evaporates in a controlled fashion. The quality of the nanoparticle crystal formed just below the liquid/vapor interface is found to be better at relatively slower evaporation rates, as less defects and grain boundaries appear. This trend is understood as the result of the competition between the accumulation and diffusion times of nanoparticles at the liquid/vapor interface. When the former is smaller, nanoparticles are deposited so fast at the interface that they do not have sufficient time to arrange through diffusion, which leads to the prevalence of defects and grain boundaries. Our results have important implications in understanding assembly of nanoparticles and colloids in non-equilibrium liquid environments.

Cheng, Shengfeng; Grest, Gary S.

2013-02-01

189

Molecular dynamics simulations of evaporation-induced nanoparticle assembly.  

PubMed

While evaporating solvent is a widely used technique to assemble nano-sized objects into desired superstructures, there has been limited work on how the assembled structures are affected by the physical aspects of the process. We present large scale molecular dynamics simulations of the evaporation-induced assembly of nanoparticles suspended in a liquid that evaporates in a controlled fashion. The quality of the nanoparticle crystal formed just below the liquid/vapor interface is found to be better at relatively slower evaporation rates, as less defects and grain boundaries appear. This trend is understood as the result of the competition between the accumulation and diffusion times of nanoparticles at the liquid/vapor interface. When the former is smaller, nanoparticles are deposited so fast at the interface that they do not have sufficient time to arrange through diffusion, which leads to the prevalence of defects and grain boundaries. Our results have important implications in understanding assembly of nanoparticles and colloids in non-equilibrium liquid environments. PMID:23425482

Cheng, Shengfeng; Grest, Gary S

2013-02-14

190

Polar agents with differentiation inducing capacity potentiate tumor necrosis factor-mediated cytotoxicity in human myeloid cell lines  

Microsoft Academic Search

Cotreatment or pretreatment of several hu- man myeloid cell lines (KG!, HL6O, U937, THP1) with the differentiation inducer DMSO was found to potenti- ate the antiproliferative and cytotoxic effects of TNF. In addition, TNF-resistant monocytic cell lines could be sen- sitized to TNF cytotoxicity by DMSO treatment. Other highly polar molecules, known to be potent differentia- tion inducers, showed similar

Stany Depraetere; Bart Vanhaesebroeckt; Walter Fierst; Jean Willems; Marcel Joniau

191

Cytotoxicity, oxidative stress, and genotoxicity in human hepatocyte and embryonic kidney cells exposed to ZnO nanoparticles  

NASA Astrophysics Data System (ADS)

Traces of zinc oxide nanoparticles (ZnO NPs) used may be found in the liver and kidney. The aim of this study is to determine the optimal viability assay for using with ZnO NPs and to assess their toxicity to human hepatocyte (L02) and human embryonic kidney (HEK293) cells. Cellular morphology, mitochondrial function (MTT assay), and oxidative stress markers (malondialdehyde, glutathione (GSH) and superoxide dismutase (SOD)) were assessed under control and exposed to ZnO NPs conditions for 24 h. The results demonstrated that ZnO NPs lead to cellular morphological modifications, mitochondrial dysfunction, and cause reduction of SOD, depletion of GSH, and oxidative DNA damage. The exact mechanism behind ZnO NPs toxicity suggested that oxidative stress and lipid peroxidation played an important role in ZnO NPs-elicited cell membrane disruption, DNA damage, and subsequent cell death. Our preliminary data suggested that oxidative stress might contribute to ZnO NPs cytotoxicity.

Guan, Rongfa; Kang, Tianshu; Lu, Fei; Zhang, Zhiguo; Shen, Haitao; Liu, Mingqi

2012-10-01

192

Attenuation of tumor necrosis factor-induced endothelial cell cytotoxicity and neutrophil chemiluminescence  

SciTech Connect

Our laboratory has previously shown that the administration of tumor necrosis factor (TNF), a cytokine produced by activated mononuclear cells, to guinea pigs produces a syndrome similar to gram-negative sepsis or ARDS. Pentoxifylline (PTX), a methylxanthine, protects against TNF-induced and sepsis-induced acute lung injury in vivo. We now report on in vitro cellular studies of PMN-mediated cellular injury and its attenuation. We studied TNF-induced bovine pulmonary artery endothelial cell (EC) cytotoxicity both with and without PMN. A 51Cr release assay was used to measure EC damage. Further, we investigated PMN function in response to TNF by measuring chemiluminescence. Agents that attenuate EC damage and PMN activation were evaluated in the above assays. Results revealed that TNF causes EC injury (p less than 0.05) and PMN increase TNF-induced EC injury. Furthermore, PTX, aminophylline (AMPH), caffeine, and forskolin attenuate TNF-induced EC cytotoxicity only in the presence of PMN (p less than 0.05). Of interest, dibutyryl cAMP (DBcAMP) protects EC from TNF-induced injury both with and without PMN. Agents that may increase cAMP levels in PMN (PTX, DBcAMP, forskolin, isobutyl methylxanthine, and terbutaline) significantly attenuate TNF-induced PMN chemiluminescence (p less than 0.05). We conclude that TNF causes EC damage and PMN increase this damage. Furthermore, PTX, AMPH, caffeine, and forskolin can attenuate TNF-induced EC injury in the presence of PMN, whereas DBcAMP attenuates TNF-induced EC injury with and without PMN. In addition, agents that may increase intracellular cAMP levels in PMN can attenuate TNF-induced PMN chemiluminescence. Thus, these agents likely attenuate TNF-induced PMN-mediated EC injury through their inhibitory effects on PMN.

Zheng, H.; Crowley, J.J.; Chan, J.C.; Hoffmann, H.; Hatherill, J.R.; Ishizaka, A.; Raffin, T.A. (Stanford Univ. Medical Center, CA (USA))

1990-11-01

193

Can ultrasounds induce cytotoxicity in presence of hematoporphyrin derivative as photodynamic therapy?  

NASA Astrophysics Data System (ADS)

Ultrasounds were described by a few authors as possibly inducing sonodynamic reaction, with singlet oxygen production, as photodynamic therapy. The aim of this project was to evidence this effect and to try to explain its different mechanisms. A specific device was developed with a strict control of temperature to avoid hyperthermia and of acoustical intensity: the characteristics of the US beam and the reproducibility of treatment conditions were strictly evaluated. We studied the frequency of 2.21 MHz using an antiresonance frequency of a transducer. US treatment was applied continuously or in pulsed mode. Human colorectal adenocarcinoma cells (HT-29) were used to test the cytotoxicity using trypan blue exclusion test. Analyses were performed using cell suspensions. Different intensities were studied ranging from 0 to 3.7 W/cm2. Moreover, fluorescence emission spectra of hematoporphyrine derivative (HpD) were recorded before and after US treatment. Results of viability showed a higher cytotoxicity with US alone or with HpD in cell suspensions from 3.7 W/cm2 (20% survival). These results show that cavitation alone can account for the cytotoxic effects of sonotherapy. In fact, cavitation is higher with continuous than with pulsed US treatment. No significant difference was found with or without HpD. HpD fluorescence spectra did not differ before and after US treatment suggesting that no modification of HpD structure was induced by US. Fluorescence spectra showed a very slow and small decrease in fluorescence intensity with time probably caused by the low interfering light used for the experiment. In conclusion, in our experiments, ultrasounds do not seem to induce any chemical reaction with photosensitizers, conversely to what was already reported. However, other photosensitizers, molecules and different cell lines (less resistant) must be studied in order to conclude about the absence of cytotoxicity of this technique.

Meunier, Anne; Guillemin, Francois H.; Merlin, Jean-Louis; Eikermann, Karine; Schmitt, Sabine; Stoss, Markus; Hopfel, Dieter; Barth, Gerhard; Bolotina, Lina

1996-01-01

194

Magnetic and Cytotoxicity Properties of La1- x Sr x MnO3 (0 ? x ? 0.5) Nanoparticles Prepared by a Simple Thermal Hydro-Decomposition  

NASA Astrophysics Data System (ADS)

This study reports the magnetic and cytotoxicity properties of magnetic nanoparticles of La1- x Sr x MnO3 (LSMO) with x = 0, 0.1, 0.2, 0.3, 0.4, and 0.5 by a simple thermal decomposition method by using acetate salts of La, Sr, and Mn as starting materials in aqueous solution. To obtain the LSMO nanoparticles, thermal decomposition of the precursor was carried out at the temperatures of 600, 700, 800, and 900 °C for 6 h. The synthesized LSMO nanoparticles were characterized by XRD, FT-IR, TEM, and SEM. Structural characterization shows that the prepared particles consist of two phases of LaMnO3 (LMO) and LSMO with crystallite sizes ranging from 20 nm to 87 nm. All the prepared samples have a perovskite structure with transformation from cubic to rhombohedral at thermal decomposition temperature higher than 900 °C in LSMO samples of x ? 0.3. Basic magnetic characteristics such as saturated magnetization ( M S) and coercive field ( H C) were evaluated by vibrating sample magnetometry at room temperature (20 °C). The samples show paramagnetic behavior for all the samples with x = 0 or LMO, and a superparamagnetic behavior for the other samples having M S values of ~20-47 emu/g and the H C values of ~10-40 Oe, depending on the crystallite size and thermal decomposition temperature. Cytotoxicity of the synthesized LSMO nanoparticles was also evaluated with NIH 3T3 cells and the result shows that the synthesized nanoparticles were not toxic to the cells as determined from cell viability in response to the liquid extract of LSMO nanoparticles.

Daengsakul, Sujittra; Thomas, Chunpen; Thomas, Ian; Mongkolkachit, Charusporn; Siri, Sineenat; Amornkitbamrung, Vittaya; Maensiri, Santi

2009-08-01

195

Magnetic and Cytotoxicity Properties of La(1-x)Sr(x)MnO(3) (0 Nanoparticles Prepared by a Simple Thermal Hydro-Decomposition.  

PubMed

This study reports the magnetic and cytotoxicity properties of magnetic nanoparticles of La(1-x)Sr(x)MnO(3) (LSMO) with x = 0, 0.1, 0.2, 0.3, 0.4, and 0.5 by a simple thermal decomposition method by using acetate salts of La, Sr, and Mn as starting materials in aqueous solution. To obtain the LSMO nanoparticles, thermal decomposition of the precursor was carried out at the temperatures of 600, 700, 800, and 900 degrees C for 6 h. The synthesized LSMO nanoparticles were characterized by XRD, FT-IR, TEM, and SEM. Structural characterization shows that the prepared particles consist of two phases of LaMnO(3) (LMO) and LSMO with crystallite sizes ranging from 20 nm to 87 nm. All the prepared samples have a perovskite structure with transformation from cubic to rhombohedral at thermal decomposition temperature higher than 900 degrees C in LSMO samples of x Cytotoxicity of the synthesized LSMO nanoparticles was also evaluated with NIH 3T3 cells and the result shows that the synthesized nanoparticles were not toxic to the cells as determined from cell viability in response to the liquid extract of LSMO nanoparticles. PMID:20596291

Daengsakul, Sujittra; Thomas, Chunpen; Thomas, Ian; Mongkolkachit, Charusporn; Siri, Sineenat; Amornkitbamrung, Vittaya; Maensiri, Santi

2009-05-01

196

Cytotoxicity and anaphase aberrations induced by mineral fibres in cultured human mesothelial cells.  

PubMed

The in vitro cytotoxicity of two amphibole asbestos fibres (amosite and crocidolite), a serpentine asbestos (chrysotile), a non-asbestos fibrous aluminosilicate (erionite) and three different size fractions of both glass wool and rock wool fibres were assessed in an immortalized human mesothelial cell line, MeT-5A. We also investigated the induction of anaphase aberrations by the asbestos and erionite fibres. On a comparison by weight, amosite, crocidolite and chrysotile showed similar toxic effects (2-5 mug/cm(2) of the asbestos fibres caused 50% of cells to die) but erionite was less toxic (10-20 mug/cm(2) was needed for the same effect). When the doses were converted to the number of fibres/cm(2) of culture area, amosite was shown to be about 10 times more cytotoxic than crocidolite and chrysotile. Crocidolite and chrysotile showed similar cytotoxicity, and erionite was again less toxic. Of the man-made mineral fibres (MMMF), thin glass wool was the most cytotoxic (50% cell death for 10-20 mug/cm(2)), followed (in descending order of cytotoxicity) by thin rock wool, coarse glass wool, milled rock wool, milled glass wool and coarse rock wool. In general, the MMMF samples were less toxic than the asbestos and erionite samples. All three asbestos types studied induced anaphase aberrations at high (near toxic) doses. A statistically significant increase in the number of aberrant anaphases was observed in cultures treated with crocidolite or chrysotile at 5 mug/cm(2). The increase was caused by lagging chromatids, chromosomes or chromosome fragments. PMID:20732143

Pelin, K; Husgafvel-Pursiainen, K; Vallas, M; Vanhala, E; Linnainmaa, K

1992-09-01

197

Influenza A Virus Induces an Immediate Cytotoxic Activity in All Major Subsets of Peripheral Blood Mononuclear Cells  

PubMed Central

Background A replication defective influenza A vaccine virus (delNS1 virus) was developed. Its attenuation is due to potent stimulation of the innate immune system by the virus. Since the innate immune system can also target cancer cells, we reasoned that delNS1 virus induced immune-stimulation should also lead to the induction of innate cytotoxic effects towards cancer cells. Methodology/Principal Findings Peripheral blood mononuclear cells (PBMCs), isolated CD56+, CD3+, CD14+ and CD19+ subsets and different combinations of the above subsets were stimulated by delNS1, wild type (wt) virus or heat inactivated virus and co-cultured with tumor cell lines in the presence or absence of antibodies against the interferon system. Stimulation of PBMCs by the delNS1 virus effectively induced cytotoxicity against different cancer cell lines. Surprisingly, virus induced cytotoxicity was exerted by all major subtypes of PBMCs including CD56+, CD3+, CD14+ and CD19+ cells. Virus induced cytotoxicity in CD3+, CD14+ and CD19+ cells was dependent on virus replication, whereas virus induced cytotoxicity in CD56+ cells was only dependent on the binding of the virus. Virus induced cytotoxicity of isolated cell cultures of CD14+, CD19+ or CD56+ cells could be partially blocked by antibodies against type I and type II (IFN) interferon. In contrast, virus induced cytotoxicity in the complete PBMC preparation could not be inhibited by blocking type I or type II IFN, indicating a redundant system of activation in whole blood. Conclusions/Significance Our data suggest that apart from their well known specialized functions all main subsets of peripheral blood cells also initially exert a cytotoxic effect upon virus stimulation. This closely links the innate immune system to the adaptive immune response and renders delNS1 virus a potential therapeutic tool for viro-immunotherapy of cancer.

Baumann, Suzann; Kuznetsova, Irina; Spittler, Andreas; Bergmann, Michael

2009-01-01

198

Protective effects of the citrus flavanones to PC12 cells against cytotoxicity induced by hydrogen peroxide.  

PubMed

Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities. One of the plausible ways to prevent the reactive oxygen species (ROS)-mediated cellular injury is dietary or pharmaceutical augmentation of endogenous antioxidant defense capacity. In this study, we investigated the protective actions of citrus flavanones naringin and nobiletin against the cytotoxicity induced by exposure to hydrogen peroxide (H(2)O(2)) (150?M, 3h) in PC12 cells. The results showed that naringin and nobiletin inhibited the decrease of cell viability (MTT reduction), prevented membrane damage (LDH release), scavenged ROS formation, reduced caspase-3 activity, and attenuated the decrease of mitochondrial membrane potential (MMP), respectively, in H(2)O(2)-induced PC12 cells. Meanwhile, naringin and nobiletin increased superoxide dismutase (SOD) and glutathione (GSH) activity, while decreased malondialdehyde (MDA), the production of lipid peroxidation, in H(2)O(2)-induced PC12 cells. In addition, the percentage of cells undergoing H(2)O(2)-induced apoptosis was decreased in the presence of naringin and nobiletin. These results first demonstrate that naringin and nobiletin, even at physiological concentrations, have neuroprotective effects against H(2)O(2)-induced cytotoxicity in PC12 cells. All the above results suggest that these dietary antioxidants are potential candidates for use in the intervention for neurodegenerative diseases. PMID:20691757

Lu, Yan-Hua; Su, Ming-Yuan; Huang, Hai-Ya; Lin-Li; Yuan, Cai-Gen

2010-08-05

199

Superior neuroprotective effects of cerebrolysin in nanoparticle-induced exacerbation of hyperthermia-induced brain pathology.  

PubMed

In recent years, the incidence of heat stroke and associated brain pathology are increasing Worldwide. More than half of the world's population are living in areas associated with high environmental heat especially during the summer seasons. Thus, new research is needed using novel drug targets to achieve neuroprotection in heat-induced brain pathology. Previous research from our laboratory showed that the pathophysiology of brain injuries following heat stroke are exacerbated by chronic intoxication of engineered nanoparticles of small sizes (50-60 nm) following identical heat exposure in rats. Interestingly, in nanoparticle-intoxicated animals the known neuroprotective agents in standard doses failed to induce effective neuroprotection. This suggests that the dose-response of the drugs either requires modification or new therapeutic agents are needed to provide better neuroprotection in nanoparticle-intoxicated animals after heat stroke. This review is focused on the use of cerebrolysin, a mixture of several neurotrophic factors and active peptide fragments, in relation to other neuroprotective agents normally used to treat ischemic stroke in clinics in nanoparticle-induced exacerbation of brain damage in heat stroke. It appears that cerebrolysin exerts the most superior neuroprotective effects in heat stress as compared to other neuroprotective agents on brain pathology in normal rats. Interestingly, to induce effective neuroprotection in nanoparticle-induced exacerbation of brain pathology a double dose of cerebrolysin is needed. On the other hand, double doses of the other drugs were quite ineffective in reducing brain damage. These observations suggest that the drug type and doses are important factors in attenuating nanoparticle-induced exacerbation of brain pathology in heat stroke. The functional significance and possible mechanisms of drug-induced neuroprotection in nanoparticle-treated, heat-stressed rats are discussed. PMID:22229316

Sharma, Aruna; Muresanu, Dafin Fior; Mössler, Herbert; Sharma, Hari Shanker

2012-02-01

200

Small molecules that protect against ?-amyloid-induced cytotoxicity by inhibiting aggregation of ?-amyloid.  

PubMed

Aggregated ?-amyloid (A?) plays crucial roles in Alzheimer's disease (AD) pathogenesis, therefore blockade of A? aggregation is considered as a potential therapeutic target. We designed and synthesized small molecules to reduce A?-induced cytotoxicity by inhibiting A? aggregation. The small molecules were screened via ThT, MTT, and cell-based cytotoxicity assay (A? burden assay). Selected compounds 1c, 1d, 1e, and 1f were then investigated by evaluating their effects on cognitive impairment of acute AD mice model. Learning and memory dysfunction by injection of A?(1-42) was recovered by administration of these molecules. Especially, 1d showed the best recovery activity in Y-maze task, object recognition task, and passive avoidance task with dose dependent manner. These results suggest that 1d has high potential as a therapeutic agent for AD. PMID:22831802

Lee, Yun Suk; Kim, Hye Yun; Kim, YoungSoo; Seo, Jae Hong; Roh, Eun Joo; Han, Hogyu; Shin, Kye Jung

2012-07-03

201

Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells  

Microsoft Academic Search

Cerium oxide nanoparticles of different sizes (15, 25, 30, 45nm) were prepared by the supercritical synthesis method, and cytotoxicity was evaluated using cultured human lung epithelial cells (BEAS-2B). Exposure of the cultured cells to nanoparticles (5, 10, 20, 40?g\\/ml) led to cell death, ROS increase, GSH decrease, and the inductions of oxidative stress-related genes such as heme oxygenase-1, catalase, glutathione

Eun-Jung Park; Jinhee Choi; Young-Kwon Park

2008-01-01

202

Cytotoxicity, apoptosis and DNA damage induced by Alpinia galanga rhizome extract.  

PubMed

Alpinia galanga, or galangal, has been a popular condiment used in Thai and Asian cuisine for many years. However, relatively little is known of the potential beneficial or adverse health effects of this spice. This study was conducted to analyze the capacity of galangal extract to induce cytotoxicity and DNA damage in six different human cell lines including normal and p53-inactive fibroblasts, normal epithelial and tumour mammary cells and a lung adenocarcinoma cell line. We deliberately focused on treatment with the crude aqueous extract of galangal rhizomes, rather than compounds extracted into an organic solvent, to more closely reflect the mode of dietary consumption of galangal. The cell lines displayed a broad range of cytotoxicity. There was no evidence for preferential cytotoxicity of tumour cells, but there was an indication that p53-active cell lines may be more sensitive than their p53-inactive counterparts. The contribution of apoptosis to total cell killing was only appreciable after exposure to 300 microg/mL of extract. Apoptosis appeared to be independent of p53 expression. Exposure to as little as 100 microg/mL galangal extract generated a significant level of DNA single-strand breaks as judged by the single-cell gel electrophoresis technique (comet assay). The three major UV-absorbing compounds in the aqueous extract were identified by mass spectrometry as 1'-acetoxychavicol acetate and its deacetylated derivatives. However, when tested in A549 human lung adenocarcinoma cells, these compounds were not responsible for the cytotoxicity induced by the complete aqueous extract. PMID:17611930

Muangnoi, P; Lu, M; Lee, J; Thepouyporn, A; Mirzayans, R; Le, X C; Weinfeld, M; Changbumrung, S

2007-07-05

203

Cadmium telluride quantum dot nanoparticle cytotoxicity and effects on model immune responses to Pseudomonas aeruginosa  

PubMed Central

This study examines dose effects of cadmium telluride quantum dots (CdTe-QDs) from two commercial sources on model macrophages (J774A.1) and colonic epithelial cells (HT29). Effects on cellular immune signalling responses were measured following sequential exposure to QDs and Pseudomonas aeruginosa strain PA01. At CdTe-QD concentrations between 10-2 and 10 µg/ml, cells exhibited changes in metabolism and morphology. Confocal imaging revealed QD internalisation and changes in cell–cell contacts, shapes and internal organisations. QD doses below 10-2 µg/ml caused no observed effects. When QD exposures at 10-7 to 10-3 µg/ml preceded PA01 (107 bacteria/ml) challenges, there were elevated cytotoxicity (5–22%, p < 0.05) and reduced levels (two- to fivefold, p < 0.001) of nitric oxide (NO), TNF-?, KC/CXC?1 and IL-8, compared with PA01 exposures alone. These results demonstrate that exposures to sub-toxic levels of CdTe-QDs can depress cell immune-defence functions, which if occurred in vivo would likely interfere with normal neutrophil recruitment for defence against bacteria.

Nguyen, Kathy C; Seligy, Vern L

2013-01-01

204

Cytoprotective Activity of Glycyrrhizae radix Extract Against Arsenite-induced Cytotoxicity  

PubMed Central

Licorice, Glycyrrhizae radix, is one of the herbal medicines in East Asia that has been commonly used for treating various diseases, including stomach disorders. This study investigated the effect of licorice on arsenite (As)-induced cytotoxicity in H4IIE cells, a rat hepatocyte-derived cell line. Cell viability was significantly diminished in As-treated H4IIE cells in a time and concentration-dependent manner. Furthermore, results from flow cytometric assay and DNA laddering in H4IIE cells showed that As treatment induced apoptotic cell death by activating caspase-3. Licorice (0.1 and 1.0?mg?ml?1) treatment significantly inhibited cell death and the activity of caspase-3 in response to As exposure. These results demonstrate that licorice induced a cytoprotective effect against As-induced cell death by inhibition of caspase-3.

Kim, Sang Chan; Park, Sook Jahr; Lee, Jong Rok; Seo, Jung Cheol; Yang, Chae Ha

2008-01-01

205

Emodin enhances gefitinib-induced cytotoxicity via Rad51 downregulation and ERK1/2 inactivation.  

PubMed

Emodin, a tyrosine kinase inhibitor, is a natural anthraquinone derivative found in the roots and rhizomes of numerous plants. It reportedly exhibits an anticancer effect on lung cancer. Gefitinib (Iressa) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for human non-small cell lung cancer (NSCLC). However, the molecular mechanism of how emodin combined with gefitinib decreases NSCLC cell viability is unclear. The recombinase protein Rad51 is essential for homologous recombination repair, and Rad51 overexpression is resistant to DNA double-strand break-inducing cancer therapies. In this study, we found that emodin enhanced the cytotoxicity induced by gefitinib in two NSCLC cells lines, A549 and H1650. Emodin at low doses of 2-10 microM did not affect ERK1/2 activation, mRNA, and Rad51 protein levels; however, it enhanced a gefitinib-induced decrease in phospho-ERK1/2 and Rad51 protein levels by enhancing Rad51 protein instability. Expression of constitutively active MKK1/2 vectors (MKK1/2-CA) significantly rescued the reduced phospho-ERK1/2 and Rad51 protein levels as well as cell viability on gefitinib and emodin cotreatment. Blocking of ERK1/2 activation by U0126 (an MKK1/2 inhibitor) lowered Rad51 protein levels and cell viability in emodin-treated H1650 and A549 cells. Knockdown of Rad51 expression by transfection with si-Rad51 RNA enhanced emodin cytotoxicity. In contrast, Rad51 overexpression protected the cells from the cytotoxic effects induced by emodin and gefitinib. Consequently, emodin-gefitinib cotreatment may serve as the basis for a novel and better therapeutic modality in the management of advanced lung cancer. PMID:19505457

Chen, Ruey-Shyang; Jhan, Jhih-Yuan; Su, Ying-Jhen; Lee, Wei-Ting; Cheng, Chao-Min; Ciou, Shih-Ci; Lin, Szu-Ting; Chuang, Show-Mei; Ko, Jen-Chung; Lin, Yun-Wei

2009-06-06

206

PAHs, PAH-induced carcinogenic potency, and particle-extract-Induced cytotoxicity of traffic-related nano/ultrafine particles.  

PubMed

Polycyclic aromatic hydrocarbons (PAHs) bound in nano/ ultrafine particles from vehicle emissions may cause adverse health effects. However, little is known about the characteristics of the nanoparticle-bound PAHs and the PAH-associated carcinogenic potency/cytotoxicity; therefore, traffic-related nano/ultrafine particles were collected in this study using a microorifice uniform deposition impactor(MOUDI) and a nano-MOUDI. For PM0.056--18, the difference in size-distribution of particulate total-PAHs between non-after-rain and after-rain samples was statistically significant at alpha = 0.05; however, this difference was not significant for PM0.01--0.056. The PAH correlation between PM0.01--0.1 and PM0.1--1.8 was lower for the after-rain samples than forthe non-after-rain samples. The average particulate total-PAHs in five samplings displayed a trimodal distribution with a major peak in the Aitken mode (0.032--0.056 microm). About half of the particulate total-PAHs were in the ultrafine size range. The BaPeq sums of BaP, IND, and DBA (with toxic equivalence factors > or = 0.1) accounted for approximately 90% of the total-BaPeq in the nano/ultrafine particles, although these three compounds contributed little to the mass of the sampled particles. The mean content of the particle-bound total-PAHs/-BaPeqs and the PAH/BaPeq-derived carcinogenic potency followed the order nano > ultrafine > fine > coarse. For a sunny day sample, the cytotoxicity of particle extracts (using 1:1 (v/v) n-hexane/dichloromethane) was significantly higher (p < 0.05) for the nano (particularly the 10-18 nm)/ultrafine particles than for the coarser particles and bleomycin. Therefore, traffic-related nano and ultrafine particles are possibly cytotoxic. PMID:18589992

Lin, Chih-Chung; Chen, Shui-Jen; Huang, Kuo-Lin; Lee, Wen-Jhy; Lin, Wen-Yinn; Tsai, Jen-Hsiung; Chaung, Hso-Chi

2008-06-01

207

d-Amphetamine-induced cytotoxicity and oxidative stress in isolated rat hepatocytes.  

PubMed

Amphetamines (AMP) are potent psychostimulants and commonly used drugs of abuse. Its chronic administration creates tolerance and addiction and also associated with neurotoxicity and hepatocellular damage through oxidative stress. The present study was designed to evaluate the cytotoxic effects as well as the oxidative stress induced by d-amphetamines in isolated rat hepatocytes. Hepatocytes were isolated by collagenase perfusion technique and were exposed to different concentrations of AMP (0.2, 0.4, 0.8 and 1.6mM) in a time-course experiment for up to 2h. AMP exposure induced a significant decrease in cell viability and a significant increase in the leakage of hepatic enzymes {lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and asparate aminotransferase (AST)} in a concentration and time-related manner. In the same experiment, GSH content and thiobarbituric acid reactive substances (TBARS) generation were determined as indices of oxidative stress and lipid peroxidation respectively. AMP exposure results in a significant decrease in cellular GSH content as well as a significant enhancement of TBARS accumulation in a concentration and time-related manners. The obtained results suggested that 2-h exposure of hepatocytes to AMP (0.8mM) was accompanied by submaximal responses. Therefore, a subsequent dose-response experiment was designed to evaluate the role of GSH modulation and oxidative stress in AMP toxicity in hepatocytes at 2h. LDH release and TBARS generation were used as indicators in this experiment. Pretreatment with the GSH-depleting agents, chlorodinitrobenzene (CDNB), buthionine sulfoximine (BSO), or bis(chloroethyl)-nitrosurea (BCNU) enhanced the cytotoxicity of AMP. Conversely, pretreatment with GSH or sulfhydryl compounds such as methionine (MT), cysteine (CYS) or dithiothreitol (DTT) attenuated AMP toxicity. Similarly, co-incubation with enzymatic antioxidants, superoxide dismutase (SOD) or catalase (CAT) or iron chelator, desferroxiamine (DFO) or the hydroxyl radical scavengers, dimethylsulfoxide (DMSO) exhibited significant protection against AMP cytotoxicity. The present results indicate that AMP has a potential cytotoxic effect in isolated rat hepatocytes. AMP cytotoxicity is concentration-dependent. GSH depletion and oxidative stress play an important role in enhancing hepatotoxic potential of AMP in isolated rat hepatocyte. Thiol group-donors, antioxidants, free radical scavengers and iron chelators can play a critical role against AMP-induced cellular damage. PMID:21571509

El-Tawil, Osama S; Abou-Hadeed, Ali H; El-Bab, Mohamed F; Shalaby, Abeir A

2011-05-14

208

Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma.  

PubMed

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in neuroblastoma, a devastating pediatric cancer of the sympathetic nervous system. Germline and somatically acquired ALK aberrations induce increased autophosphorylation, constitutive ALK activation and increased downstream signaling. Thus, ALK is a tractable therapeutic target in neuroblastoma, likely to be susceptible to both small-molecule tyrosine kinase inhibitors and therapeutic antibodies-as has been shown for other receptor tyrosine kinases in malignancies such as breast and lung cancer. Small-molecule inhibitors of ALK are currently being studied in the clinic, but common ALK mutations in neuroblastoma appear to show de novo insensitivity, arguing that complementary therapeutic approaches must be developed. We therefore hypothesized that antibody targeting of ALK may be a relevant strategy for the majority of neuroblastoma patients likely to have ALK-positive tumors. We show here that an antagonistic ALK antibody inhibits cell growth and induces in vitro antibody-dependent cellular cytotoxicity of human neuroblastoma-derived cell lines. Cytotoxicity was induced in cell lines harboring either wild type or mutated forms of ALK. Treatment of neuroblastoma cells with the dual Met/ALK inhibitor crizotinib sensitized cells to antibody-induced growth inhibition by promoting cell surface accumulation of ALK and thus increasing the accessibility of antigen for antibody binding. These data support the concept of ALK-targeted immunotherapy as a highly promising therapeutic strategy for neuroblastomas with mutated or wild-type ALK. PMID:22266870

Carpenter, E L; Haglund, E A; Mace, E M; Deng, D; Martinez, D; Wood, A C; Chow, A K; Weiser, D A; Belcastro, L T; Winter, C; Bresler, S C; Vigny, M; Mazot, P; Asgharzadeh, S; Seeger, R C; Zhao, H; Guo, R; Christensen, J G; Orange, J S; Pawel, B R; Lemmon, M A; Mossé, Y P

2012-01-23

209

Geraniin and amariin, ellagitannins from Phyllanthus amarus, protect liver cells against ethanol induced cytotoxicity.  

PubMed

Ethanol mediated free radical generation plays an important role in the pathogenesis of liver injuries and alcoholic liver diseases. In the present study two ellagitannins namely geraniin and amariin isolated from Phyllanthus amarus were examined for their ability to protect mouse liver slices against ethanol induced toxicity and possible mechanism of its protection. Oxidative stress markers such as, lipid peroxidation, protein carbonyl formation, amount of 8-hydroxy-2-deoxyguanosine and antioxidant enzymes levels were measured using specific biochemical assays. Poly (ADP-ribose) polymerase (PARP), Bax and Bcl2 were checked to assess the induction of apoptosis using western blots. The results showed that geraniin and amariin protected mouse liver slices against ethanol induced cytotoxicity. Both compounds inhibited oxidation of lipid, protein and formation of 8-hydroxy-2-deoxyguanosine, all of which were found to be elevated on exposure to ethanol. These compounds restored the antioxidant enzymes altered on ethanol exposure. Compounds also inhibited the cleavage of PARP and bax and restored Bcl2, induced on exposure to ethanol. In summary, both ellagitannins effectively protected mouse liver slices against ethanol induced cytotoxicity and apoptosis by reducing oxidative damage to biological molecules and modulating Bax/Bcl-2 ratio respectively, thus minimizing liver injury. PMID:22982332

Londhe, Jayant S; Devasagayam, Thomas P A; Foo, L Yeap; Shastry, Padma; Ghaskadbi, Saroj S

2012-09-13

210

The cytotoxic effects of titanium oxide and zinc oxide nanoparticles oh Human Cervical Adenocarcinoma cell membranes  

NASA Astrophysics Data System (ADS)

The importance of titanium dioxide (TiO2) and zinc oxide (ZnO), inorganic metal oxides nanoparticles (NPs) stems from their ubiquitous applications in personal care products, solar cells and food whitening agents. Hence, these NPs come in direct contact with the skin, digestive tracts and are absorbed into human tissues. Currently, TiO2 and ZnO are considered safe commercial ingredients by the material safety data sheets with no reported evidence of carcinogenicity or ecotoxicity, and do not classify either NP as a toxic substance. This study examined the direct effects of TiO2 and ZnO on HeLa cells, a human cervical adenocarcinonma cell line, and their membrane mechanics. The whole cell patch-clamp technique was used in addition to immunohistochemistry staining, TEM and atomic force microscopy (AFM). Additionally, we examined the effects of dexamethasone (DXM), a glucocorticoid steroid known to have an effect on cell membrane mechanics. Overall, TiO2 and ZnO seemed to have an adverse effect on cell membrane mechanics by effecting cell proliferation, altering cellular structure, decreasing cell-cell adhesion, activating existing ion channels, increasing membrane permeability, and possibly disrupting cell signaling.

Mironava, Tatsiana; Applebaum, Ariella; Applebaum, Eliana; Guterman, Shoshana; Applebaum, Kayla; Grossman, Daniel; Gordon, Chris; Brink, Peter; Wang, H. Z.; Rafailovich, Miriam

2013-03-01

211

PEG-chitosan-coated iron oxide nanoparticles with high saturated magnetization as carriers of 10-hydroxycamptothecin: preparation, characterization and cytotoxicity studies.  

PubMed

A magnetic nano-sized carrier for 10-hydroxycamptothecin (HCPT) was prepared by using Fe(3)O(4) nanoparticles as cores and chitosan (CS) as a polymeric shell by a novel reverse ultrasonic emulsification method. Poly(ethylene glycol) (PEG) chains were then coupled onto the magnetic particles (CS-Fe(3)O(4)) to improve their biocompatibility (PEG-CS-Fe(3)O(4)). HCPT was loaded onto PEG-CS-Fe(3)O(4) by a subtle precipitation method. Under optimum conditions, the CS-Fe(3)O(4) was close to spherical in shape with an average size of 174 nm and a high saturated magnetization. After coupling PEG chains, the unspecific adsorption of bovine serum albumin (BSA) on PEG-CS-Fe(3)O(4) decreased significantly. The drug loading content and loading efficiency were 9.8-11.8% and 49-59% for magnetic composite nanoparticles, respectively. HCPT-loaded magnetic composite nanoparticles showed sustained release profiles up to 48 h, and the cumulative release amount of HCPT from nanoparticles at 45°C increased significantly compared to that at 37°C. Cytotoxicity assay suggests that CS-Fe(3)O(4) does not exhibit noteworthy cytotoxicity against HepG2 cells, but the antitumor activities of HCPT-loaded magnetic composite nanoparticles against HepG2 cells increased significantly in comparison with that of pristine HCPT powder. These results reveal the promising potential of PEG-CS-Fe(3)O(4) as a stable magnetic targeting drug carrier in cancer therapy. PMID:23000675

Qu, Jian-Bo; Shao, Hui-Hui; Jing, Guang-Lun; Huang, Fang

2012-08-19

212

Studying the cytotoxicity and oxidative stress induced by two kinds of bentonite particles on human B lymphoblast cells in vitro.  

PubMed

The aim of the present study was to evaluate the cytotoxicity and oxidative stress induced by native and active bentonite particles (BPs) on human B lymphoblast cells using seven assays. Our results showed that the order of cytotoxicity was: active BPs>native BPs>quartz particles (DQ-12)>gypsum, according to the IC50 values in CCK-8 assay and neutral red uptake (NRU) assay. The lactate dehydrogenase (LDH) leakage, the proportions of early apoptotic cells, the reactive oxygen species (ROS) generation, the superoxide dismutase (SOD) inhibition and the malondialdehyde (MDA) release in the native and active BPs groups were significantly higher than those in the gypsum and DQ-12 groups (P<0.05 or P<0.01). Moreover, the cytotoxicity of active BPs with higher adsorption capacity of phenol was higher than that of native BPs with relatively lower adsorption capacity of phenol. The oxidative stress induced by active BPs was significantly higher than that induced by native BPs (P<0.05 or P<0.01). The water-soluble fractions of BPs did not induce the cytotoxicity and ROS generation. These findings indicated that active and native BPs could induce significantly the cytotoxic effects and oxidative stress on human B lymphoblast cells in vitro. The cytotoxic difference between active BPs and native BPs may be associated with the adsorption capacity of BPs and oxidative stress induced by BPs to a certain extent. The insoluble particle fractions may play a main role in the cytotoxic effects and oxidative stress induced by BPs. PMID:19948159

Zhang, Meibian; Lu, Yezhen; Li, Xiaoxue; Chen, Qing; Lu, Longxi; Xing, Mingluan; Zou, Hua; He, Jiliang

2009-12-03

213

Mercuric chloride-induced cytotoxicity and compensatory hypertrophy in rat kidney proximal tubular cells.  

PubMed

Previous work showed that uninephrectomized (NPX) rats are more susceptible to the nephropathy induced by some doses of HgCl2 than sham-operated (SHAM) rats. The aim of the present study was to investigate the cytotoxic effects of HgCl2 in proximal tubular (PT) cells isolated from the kidney(s) of both NPX and SHAM rats. The study was designed to test if isolated PT cells that have undergone compensatory hypertrophy in vivo are more sensitive to the cytotoxic effects of HgCl2 in vitro than PT cells isolated from the kidneys of control animals. PT cells were purified from suspensions of renal cortical cells by Percoll density gradient centrifugation. The cellular content of protein (mg/10(6) cells) was 68% higher and the cellular specific activity (mU/10(6) cells) of lactate dehydrogenase was 56% higher in PT cells isolated from NPX rats than in PT cells isolated from SHAM rats. The cytotoxicity of HgCl2, as assessed by inhibition of lactate dehydrogenase activity, exhibited a steep concentration dependence. In the presence of bovine serum albumin, PT cells from both NPX and SHAM rats displayed no signs of cellular injury at concentrations of HgCl2 less than or equal to 0.1 mM. At concentrations of HgCl2 greater than or equal to 0.25 mM, cellular necrosis occurred rapidly in all PT cells. In the absence of bovine serum albumin, cellular injury and death occurred at concentrations of HgCl2 as low as 0.01 mM. PT cells from NPX rats exhibited signs of cellular injury at lower concentrations of HgCl2 than PT cells from SHAM rats when BSA was absent from the extracellular medium. Preincubation of PT cells from both NPX and SHAM rats with glutathione provided the cells with concentration-dependent protection from the cytotoxic effects of HgCl2. Preincubation of PT cells from both NPX and SHAM rats with the chelating agent 2,3-dimercapto-1-propane sulfonate provided cells with complete protection from the cytotoxic effects of HgCl2 when the concentration of 2,3-dimercapto-1-propane sulfonate was slightly below or higher than the concentration of HgCl2. Results of this study demonstrate the usefulness of freshly isolated PT cells from NPX rats as an in vitro model system to investigate biochemical mechanisms by which compensatory renal growth alters susceptibility to chemical-induced nephrotoxicity. PMID:1578387

Lash, L H; Zalups, R K

1992-05-01

214

Pharmacological ascorbate induces cytotoxicity in prostate cancer cells through ATP depletion and induction of autophagy.  

PubMed

Recent studies have revealed the scientific basis for the use of intravenous (i.v.) vitamin C or ascorbic acid (ascorbate) in treating cancers, and raised the possibility of using i.v. ascorbate as a prooxidant anticancer therapy. Through the production of H2O2, pharmacologic ascorbate can induce some cancer cell death in vitro and inhibit a number of types of tumor growth in animal models. However, the mechanism of cell death triggered by ascorbate is not well understood. In this study, we investigated the cytotoxicity of pharmacological concentrations of ascorbate to human prostate cancer cells and the mechanisms involved. The results showed that ascorbate in the millimolar range induced cytotoxicity in five of the six tested prostate cancer cell lines. The IC50 values in the sensitive prostate cancer cells ranged from 1.9 to 3.5 mmol/l, concentrations clinically achievable with i.v. ascorbate use. All tested androgen-independent cells were sensitive to ascorbate treatment. The ascorbate-insensitive cell line LaPC4 is hormonally dependent. Whereas the reasons for sensitivity/resistance to ascorbate treatment need to be investigated further, cell death in sensitive cells was dependent on H2O2. Ascorbate treatment depleted ATP and induced autophagy in sensitive prostate cancer cells, resulting in cell death. Taken together with previous studies, high-dose ascorbate has the potential to be a novel treatment option to hormone-refractory prostate cancer. PMID:22205155

Chen, Ping; Yu, Jun; Chalmers, Brain; Drisko, Jeanne; Yang, Jun; Li, Benyi; Chen, Qi

2012-04-01

215

Investigating the cytotoxic and apoptosis inducing effects of monoterpenoid stylosin in vitro.  

PubMed

The aim of this study was to investigate the cytotoxic and anticancer activities of stylosin, a monoterpene extracted from an edible plant, Ferula ovina, on 5637 and HFF3 cells using MTT and comet assays and DAPI staining. To assess stylosin effects, cells were cultured in the presence of various concentrations of stylosin during three days; the IC(50) of stylosin on cancerous 5637 cells was less than its value on HFF3 normal cells, indicating that it might have anticancer properties. Investigating the mechanism of stylosin action revealed that it quickly induced DNA lesions and increased the number of apoptotic cells. PMID:21459136

Rassouli, Fatemeh Behnam; Matin, Maryam M; Iranshahi, Mehrdad; Bahrami, Ahmad Reza

2011-03-31

216

Unprecedented inhibition of tubulin polymerization directed by gold nanoparticles inducing cell cycle arrest and apoptosis.  

PubMed

The effect of gold nanoparticles (AuNPs) on the polymerization of tubulin has not been examined till now. We report that interaction of weakly protected AuNPs with microtubules (MTs) could cause inhibition of polymerization and aggregation in the cell free system. We estimate that single citrate capped AuNPs could cause aggregation of ?10(5) tubulin heterodimers. Investigation of the nature of inhibition of polymerization and aggregation by Raman and Fourier transform-infrared (FTIR) spectroscopies indicated partial conformational changes of tubulin and microtubules, thus revealing that AuNP-induced conformational change is the driving force behind the observed phenomenon. Cell culture experiments were carried out to check whether this can happen inside a cell. Dark field microscopy (DFM) combined with hyperspectral imaging (HSI) along with flow cytometric (FC) and confocal laser scanning microscopic (CLSM) analyses suggested that AuNPs entered the cell, caused aggregation of the MTs of A549 cells, leading to cell cycle arrest at the G0/G1 phase and concomitant apoptosis. Further, Western blot analysis indicated the upregulation of mitochondrial apoptosis proteins such as Bax and p53, down regulation of Bcl-2 and cleavage of poly(ADP-ribose) polymerase (PARP) confirming mitochondrial apoptosis. Western blot run after cold-depolymerization revealed an increase in the aggregated insoluble intracellular tubulin while the control and actin did not aggregate, suggesting microtubule damage induced cell cycle arrest and apoptosis. The observed polymerization inhibition and cytotoxic effects were dependent on the size and concentration of the AuNPs used and also on the incubation time. As microtubules are important cellular structures and target for anti-cancer drugs, this first observation of nanoparticles-induced protein's conformational change-based aggregation of the tubulin-MT system is of high importance, and would be useful in the understanding of cancer therapeutics and safety of nanomaterials. PMID:23584723

Choudhury, Diptiman; Xavier, Paulrajpillai Lourdu; Chaudhari, Kamalesh; John, Robin; Dasgupta, Anjan Kumar; Pradeep, Thalappil; Chakrabarti, Gopal

2013-05-21

217

Studying the cytotoxicity and oxidative stress induced by two kinds of bentonite particles on human B lymphoblast cells in vitro  

Microsoft Academic Search

The aim of the present study was to evaluate the cytotoxicity and oxidative stress induced by native and active bentonite particles (BPs) on human B lymphoblast cells using seven assays. Our results showed that the order of cytotoxicity was: active BPs>native BPs>quartz particles (DQ-12)>gypsum, according to the IC50 values in CCK-8 assay and neutral red uptake (NRU) assay. The lactate

Meibian Zhang; Yezhen Lu; Xiaoxue Li; Qing Chen; Longxi Lu; Mingluan Xing; Hua Zou; Jiliang He

2010-01-01

218

Nanoparticles aggravate heat stress induced cognitive deficits, blood–brain barrier disruption, edema formation and brain pathology  

Microsoft Academic Search

Our knowledge regarding the influence of nanoparticles on brain function in vivo during normal or hyperthermic conditions is still lacking. Few reports indicate that when nanoparticles enter into the central nervous system (CNS) they may induce neurotoxicity. On the other hand, nanoparticle-induced drug delivery to the brain enhances neurorepair processes. Thus, it is likely that the inclusion of nanoparticles in

Hari Shanker Sharma; Aruna Sharma

2007-01-01

219

Gold nanoparticles downregulate interleukin-1?-induced pro-inflammatory responses.  

PubMed

Interleukin 1 beta (IL-1?)-dependent inflammatory disorders, such as rheumatoid arthritis and psoriasis, pose a serious medical burden worldwide, where patients face a lifetime of illness and treatment. Organogold compounds have been used since the 1930s to treat rheumatic and other IL-1?-dependent diseases and, though their mechanisms of action are still unclear, there is evidence that gold interferes with the transmission of inflammatory signalling. Here we show for the first time that citrate-stabilized gold nanoparticles, in a size dependent manner, specifically downregulate cellular responses induced by IL-1? both in vitro and in vivo. Our results indicate that the anti-inflammatory activity of gold nanoparticles is associated with an extracellular interaction with IL-1?, thus opening potentially novel options for further therapeutic applications. PMID:23112137

Sumbayev, Vadim V; Yasinska, Inna M; Garcia, Cesar Pascual; Gilliland, Douglas; Lall, Gurprit S; Gibbs, Bernhard F; Bonsall, David R; Varani, Luca; Rossi, François; Calzolai, Luigi

2012-10-30

220

Methyl jasmonate down-regulates survivin expression and sensitizes colon carcinoma cells towards TRAIL-induced cytotoxicity  

PubMed Central

BACKGROUND AND PURPOSE Methyl jasmonate (MJ) is a plant stress hormone with selective cytotoxic anti-cancer activities. The TNF-related apoptosis-inducing ligand (TRAIL) death pathway is an attractive target for cancer therapy. Although TRAIL receptors are specifically expressed in primary cancer cells and cancer cell lines, many types of cancer cells remain resistant to TRAIL-induced cytotoxicity. Here we have assessed a possible synergy between MJ and TRAIL cytotoxicity in colorectal cancer (CRC) cell lines. EXPERIMENTAL APPROACH CRC cell lines were pre-incubated with sub-cytotoxic concentrations of MJ followed by TRAIL administration. Cell death was determined by XTT assay and microscopy. Cytochrome c release, caspase cleavage, TRAIL-associated factors, X-linked inhibitor of apoptosis (XIAP) and survivin protein levels were detected by immunoblotting. Survivin transcription was examined by RT-PCR. KEY RESULTS Pre-treatment with MJ resulted in increased TRAIL-induced apoptotic cell death, increased cytochrome c release and caspase cleavage. TNFRSF10A, TNFRSF10B, TNFRSF10D, Fas-associated death domain and cellular FLICE-like inhibitory protein remained unchanged during MJ-induced TRAIL sensitization, whereas MJ induced a significant decrease in survivin protein levels. Overexpression of survivin prevented MJ-induced TRAIL cytotoxicity, implying a role for survivin in MJ-induced TRAIL sensitization. MJ decreased survivin mRNA indicating that MJ may affect survivin transcription. In a ?-catenin/transcription factor (TCF)-dependent luciferase activity assay, MJ decreased TCF-dependent transcriptional activity. CONCLUSION AND IMPLICATIONS MJ, at sub-cytotoxic levels, sensitized CRC cells to TRAIL-induced apoptosis. Thus, combinations of MJ and TRAIL, both selective anti-cancer agents, have potential as novel treatments for CRC.

Raviv, Z; Zilberberg, A; Cohen, S; Reischer-Pelech, D; Horrix, C; Berger, MR; Rosin-Arbesfeld, R; Flescher, E

2011-01-01

221

Synthesis of silver nanoparticles using Aegle marmelos plant extract and evaluation of their antimicrobial activities and cytotoxicity  

Microsoft Academic Search

This paper describes a simple and efficient procedure based on the green method for the preparation of silver nanoparticles with a relatively narrow distribution in size. Stable silver nanoparticles have been synthesized by using Aegle marmelos (Vilvam) plant extract as both the reducing and stabilizing agents. The amount of silver nanoparticles synthesized and its qualitative characterization was done by UV-Visible

S. Lokina; V. Narayanan

2011-01-01

222

Multi-walled carbon nanotubes induce cytotoxicity and genotoxicity in human lung epithelial cells.  

PubMed

The increasing use of nanomaterials in consumer products highlights the importance of understanding their potential toxic effects. We evaluated cytotoxic and genotoxic/oxidative effects induced by commercial multi-walled carbon nanotubes (MWCNTs) on human lung epithelial (A549) cells treated with 5, 10, 40 and 100?µg?ml?¹ for different exposure times. Scanning electron microscopy (SEM) analysis, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and lactate dehydrogenase (LDH) assays were performed to evaluate cytotoxicity. Fpg-modified comet assay was used to evaluate direct-oxidative DNA damage. LDH leakage was detected after 2, 4 and 24?h of exposure and viability reduction was revealed after 24?h. SEM analysis, performed after 4 and 24?h exposure, showed cell surface changes such as lower microvilli density, microvilli structure modifications and the presence of holes in plasma membrane. We found an induction of direct DNA damage after each exposure time and at all concentrations, statistically significant at 10 and 40?µg?ml?¹ after 2?h, at 5, 10, 100?µg?ml?¹ after 4?h and at 10?µg?ml?¹ after 24?h exposure. However, oxidative DNA damage was not found. The results showed an induction of early cytotoxic effects such as loss of membrane integrity, surface morphological changes and MWCNT agglomerate entrance at all concentrations. We also demonstrated the ability of MWCNTs to induce early genotoxicity. This study emphasizes the suitability of our approach to evaluating simultaneously the early response of the cell membrane and DNA to different MWCNT concentrations and exposure times in cells of target organ. The findings contribute to elucidation of the mechanism by which MWCNTs cause toxic effects in an in vitro experimental model. PMID:22271384

Cavallo, Delia; Fanizza, Carla; Ursini, Cinzia Lucia; Casciardi, Stefano; Paba, Emilia; Ciervo, Aureliano; Fresegna, Anna Maria; Maiello, Raffaele; Marcelloni, Anna Maria; Buresti, Giuliana; Tombolini, Francesca; Bellucci, Stefano; Iavicoli, Sergio

2012-01-23

223

Protective effects of anethole dithiolethione against oxidative stress-induced cytotoxicity in human Jurkat T cells.  

PubMed

The protective effects of anethole dithiolethione (ADT) against H2O2- or 4-hydroxynonenal (HNE)-induced cytotoxicity in human Jurkat T cells were investigated. Jurkat T cells were pretreated with ADT (10-50 microM) for 18 hr and then challenged with H202 or HNE for up to 4 hr. Cytotoxicity was assessed by measuring: 1) leakage of lactate dehydrogenase from cells to medium; and 2) exclusion of the DNA intercalating fluorescent probe propidium iodide by viable cells. Pretreatment of cells with ADT (10 or 25 microM) for 18 hr significantly protected cells against H202- or HNE-induced cytotoxicity. Treatment of cells with ADT (10-50 microM) for 72 hr significantly increased the activities of catalase and glutathione reductase. The maximum effect of ADT treatment on the activity of these enzymes was observed when cells were treated with 25 microM of ADT for 72 hr. A significant increase in cellular GSH was observed in cells that were treated with ADT for 72 hr. Using monobromobimane as a thiol probe, we consistently observed that cells pretreated for 18 hr with ADT (25 or 50 microM) had also increased total thiol content. Exposure of Jurkat T cells to H202 or HNE resulted in a time-dependent decrease in cellular GSH. ADT (10-50 microM, 18 hr) pretreatment circumvented H202-dependent lowering of cellular GSH. In conclusion, ADT proved to be a potent cytoprotective thiol antioxidant with multifaceted mechanisms of action, suggesting that the drug has a remarkable therapeutic potential. PMID:9698089

Khanna, S; Sen, C K; Roy, S; Christen, M O; Packer, L

1998-07-01

224

2-Deoxy-D-Glucose-induced Cytotoxicity and Radiosensitization in Tumor Cells Is Mediated via Disruptions in Thiol Metabolism1  

Microsoft Academic Search

Exposure to ionizing radiation is believed to cause cell injury via the production of free radicals that are thought to induce oxidative damage. It has been proposed that exposure to agents that enhance oxidative stress- induced injury by disrupting thiol metabolism may sensitize cells to the cytotoxic effects of ionizing radiation. Recently, it has been shown that glucose deprivation selectively

Xiao Lin; Fanjie Zhang; C. Matthew Bradbury; Aradhana Kaushal; Ling Li; Douglas R. Spitz; Rebecca L. Aft; David Gius

225

Cetuximab attenuates its cytotoxic and radiosensitizing potential by inducing fibronectin biosynthesis.  

PubMed

Inherent and acquired resistance to targeted therapeutics continues to emerge as a major clinical obstacle. For example, resistance to EGF receptor targeting occurs commonly, more so than was expected, on the basis of preclinical work. Given emerging evidence that cancer cell-substrate interactions are important determinants of therapeutic sensitivity, we examined the impact of cell-fibronectin interactions on the efficacy of the EGF receptor antibody cetuximab, which is used widely for lung cancer treatment. Our results revealed the potential for cell-fibronectin interactions to induce radioresistance of human non-small cell lung cancer cells. Cell adhesion to fibronectin enhanced tumor cell radioresistance and attenuated the cytotoxic and radiosensitizing effects of cetuximab. Both in vitro and in vivo, we found that cetuximab treatment led to a remarkable induction of fibronectin biosynthesis. Mechanistic analyses revealed the induction was mediated by a p38-MAPK-ATF2 signaling pathway and that RNAi-mediated inhibition of fibronectin could elevate the cytotoxic and radiosensitizing potential of cetuximab. Taken together, our findings show how cell adhesion blunts cetuximab, which, by inducing fibronectin, generates a self-attenuating mechanism of drug resistance. Cancer Res; 73(19); 5869-79. ©2013 AACR. PMID:23950208

Eke, Iris; Storch, Katja; Krause, Mechthild; Cordes, Nils

2013-08-15

226

Semisynthesis of mallotus B from rottlerin: evaluation of cytotoxicity and apoptosis-inducing activity.  

PubMed

Mallotus B (2d) is a prenylated dimeric phloroglucinol compound isolated from Mallotus philippensis. There have been no reports on the synthesis or biological activity of this compound. In the present paper, a semisynthetic preparation of mallotus B is reported via base-mediated intramolecular rearrangement of rottlerin (1), which is one of the major constituents of M. philippensis. The homodimer "rottlerone" was also formed as one of the products of this base-mediated intramolecular reaction. Rottlerin (1), along with rottlerone (2c) and mallotus B (2d), was evaluated for cytotoxicity against a panel of cancer cell lines including HEPG2, Colo205, MIAPaCa-2, PC-3, and HL-60 cells. Mallotus B (2d) displayed cytotoxicity for MIAPaCa-2 and HL-60 cells with IC50 values of 9 and 16 ?M, respectively. Microscopic studies in HL-60 cells indicated that mallotus B (2d) induces cell cycle arrest at the G1 phase and causes defective cell division. It also induces apoptosis, as evidenced by distinct changes in cell morphology. PMID:24041234

Jain, Shreyans K; Pathania, Anup S; Meena, Samdarshi; Sharma, Rajni; Sharma, Ashok; Singh, Baljinder; Gupta, Bishan D; Bhushan, Shashi; Bharate, Sandip B; Vishwakarma, Ram A

2013-09-17

227

Cytotoxicity and genotoxicity induced by photothermal effects of colloidal gold nanorods.  

PubMed

Gold nanorods (Au NRs) that absorb near-infrared (NIR) light have great potential in the field of nanomedicine. Photothermal therapy (PTT), a very attractive cancer therapy in nanomedicine, combines nanomaterials and light. The aim of this study was to elucidate the molecular mechanism involved in Au NR-mediated cytotoxic, genotoxic, and other biological responses, in the presence or absence of NIR irradiation. Specifically, cell death mode, generation of reactive oxygen species, DNA damage, apoptotic gene expression, and cell morphological changes induced by Au NRs under NIR irradiation were evaluated in cancer cells. In human lung adenocarcinoma epithelial cells (A549 cells), mild necrosis via DNA damage was induced by NIR responsive Au NRs. Unlike in the cancer cells, cell viability of normal human lymphocyte was not affected by the combined treatment of Au NRs and NIR irradiation. This study delineates differential cytotoxic and genotoxic susceptibility of cancer and normal cells during photothermal treatment of Au NRs. In conclusion, our results suggest that the photothermal cyto-/genotoxic activity of Au NRs is an effective method for cancer therapy in human lung cancer cells. PMID:23862518

Choi, Young Joo; Kim, Yang Jee; Lee, Joong Won; Lee, Younghyun; Lee, Sunyeong; Lim, Yong-Beom; Chung, Hai Won

2013-06-01

228

Some characteristics of fluoride-induced cell death in rat thymocytes: cytotoxicity of sodium fluoride.  

PubMed

Fluoride is found in the atmosphere, water, soil, coal, food, dental and industrial uses. There were some case reports concerning acute fluoride poisoning in workplaces and laboratories. However, there is limited information concerning the mechanism of fluoride-induced cell death. To study the cytotoxicity of fluoride, the effect of sodium fluoride (NaF) on rat thymocytes has been examined by using a flow cytometer with appropriate fluorescence probes for membrane and cellular parameters. The cytotoxicity of NaF under nominal Ca2+-free condition was significantly lower than that under control condition. NaF also increased intracellular Ca2+ concentration. NaF significantly increased the population of shrunken cells and the cells positive to annexin V. Both are known to be parameters for early stage of apoptosis. However, NaF decreased the population of cells with hypodiploidal DNA, indicating that NaF apparently attenuated spontaneous apoptosis in rat thymocytes. It may be suggested that NaF induces necrosis, associated with some apoptotic characteristics. PMID:17544615

Matsui, Hiroko; Morimoto, Midori; Horimoto, Kanna; Nishimura, Yumiko

2007-04-27

229

Poly(L-lactide)-vitamin E TPGS nanoparticles enhanced the cytotoxicity of doxorubicin in drug-resistant MCF-7 breast cancer cells.  

PubMed

Multiple drug resistance (MDR) seriously reduces the efficacy of many chemotherapeutic agents for cancer. P-Glycoprotein, an efflux pump overexpressed on the cell surface, plays an important role in drug resistance, but several surfactants, such as vitamin E TPGS, can inhibit P-glycoprotein. In this study, a polylactide-surfactant block copolymer poly(l-lactide)-vitamin E TPGS (PLA-TPGS) was synthesized using bidentate sulfonamide zinc ethyl complex as an efficient catalyst, and its self-assembled nanoparticles were used as carriers of doxorubicin. We first found that the activity of P-glycoprotein in drug-resistant breast cancer MCF-7/ADR cells was decreased after incubation with PLA-TPGS nanoparticles. In addition, the nuclear accumulation and cytotoxicity of doxorubicin were significantly increased by encapsulation into the nanoparticles. The enhanced efficacy of the doxorubicin-loaded PLA-TPGS nanoparticles may result from the combination of inhibition of efflux and increased entry of doxorubicin into the nucleus in drug-resistant MCF-7/ADR cells. Therefore, this innovative delivery system has potential to act as a nanomedicine for therapy of both drug-sensitive and drug-resistant cancer. PMID:20722436

Li, Po-Yu; Lai, Ping-Shan; Hung, Wen-Chou; Syu, Wei-Jhe

2010-10-11

230

Enhancement of granulocyte-endothelial cell adherence and granulocyte-induced cytotoxicity by platelet release products.  

PubMed Central

Complement-stimulated granulocytes adhere to and induce significant 51Cr release from endothelial cells in vitro. Platelets were stimulated to undergo release, and these release products significantly enhanced granulocyte-endothelial cell adherence and granulocyte-induced 51Cr release from endothelial cells. Platelet serotonin appeared to mediate these phenomena because serotonin antagonists blocked both the enhanced endothelial adherence and 51Cr release. In addition, added serotonin mimicked the effect seen with the stimulated platelets upon granulocyte--endothelial cell adherence and cytotoxicity completely. This enhancement appeared to be due to serotonin effects upon both the granulocyte and endothelial cells. These data suggest that a released platelet constituent might modulate in vivo granulocyte-endothelial cell interactions in clinical disorders.

Boogaerts, M A; Yamada, O; Jacob, H S; Moldow, C F

1982-01-01

231

The cytotoxic prodigiosin induces phosphorylation of p38-MAPK but not of SAPK/JNK.  

PubMed

Prodigiosin (PG) is a red pigment produced by Serratia marcescens, with cytotoxic and immunosuppressive activity. It induces apoptosis in several cancer cell lines, including Jurkat-T cells. Here we examine the role of two stress-stimulated kinase cascades in this induction. Time course experiments using polyclonal antibodies showed that p38-MAPK phosphorylation began at 15 min and lasted for 3 h, whereas JNK was not phosphorylated, although both proteins were present. SB203580, a selective inhibitor of p38-MAPK, blocked its phosphorylation in PG-treated cells. Taken together, these data suggest that the PG induces phosphorylation of p38-MAPK but not of SAPK/JNK and that it increases the expression of both c-jun and c-fos oncoproteins. PMID:11879978

Montaner, Beatriz; Pérez-Tomás, Ricardo

2002-03-24

232

Opposing roles of glucocorticoid receptor and mineralocorticoid receptor in trimethyltin-induced cytotoxicity in the mouse hippocampus.  

PubMed

The organotin trimethyltin (TMT) is known to cause neuronal degeneration in the murine brain. Earlier studies indicate that TMT-induced neuronal degeneration is enhanced by adrenalectomy and prevented by exogenous glucocorticoid. The aim of this study was to investigate the regulation of TMT neuroxicity by corticosterone receptors including type I (mineralocorticoid receptor, MR) and type II (glucocorticoid receptor, GR) in adult mice. The systemic injection of TMT at the dose of 2.0 or 2.8 mg/kg produced a marked elevation in the level of plasma corticosterone that was both dose and time dependent. The MR agonist aldosterone had the ability to exacerbate TMT cytotoxicity in the dentate granule cell layer, whereas its antagonist spironolactone protected neurons from TMT cytotoxicity there. In contrast, the GR antagonist mifepristone exacerbated the TMT cytotoxicity. Taken together, our data suggest TMT cytotoxicity is oppositely regulated by GR and MR signals, being exacerbated by MR activation in adult mice. PMID:22309794

Ogita, Kiyokazu; Sugiyama, Chie; Acosta, Gabriela Beatriz; Kuramoto, Nobuyuki; Shuto, Makoto; Yoneyama, Masanori; Nakamura, Yukary; Shiba, Tatsuo; Yamaguchi, Taro

2012-01-31

233

Catalase ameliorates polychlorinated biphenyl-induced cytotoxicity in nonmalignant human breast epithelial cells.  

PubMed

Polychlorinated biphenyls (PCBs) are environmental chemical contaminants believed to adversely affect cellular processes. We investigated the hypothesis that PCB-induced changes in the levels of cellular reactive oxygen species (ROS) induce DNA damage resulting in cytotoxicity. Exponentially growing cultures of human nonmalignant breast epithelial cells (MCF10A) were incubated with PCBs for 3 days and assayed for cell number, ROS levels, DNA damage, and cytotoxicity. Exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) or 2-(4-chlorophenyl)benzo-1,4-quinone (4-Cl-BQ), a metabolite of 4-chlorobiphenyl (PCB3), significantly decreased cell number and MTS reduction and increased the percentage of cells with sub-G1 DNA content. Results from electron paramagnetic resonance (EPR) spectroscopy showed a 4-fold increase in the steady-state levels of ROS, which was suppressed in cells pretreated with catalase. EPR measurements in cells treated with 4-Cl-BQ detected the presence of a semiquinone radical, suggesting that the increased levels of ROS could be due to the redox cycling of 4-Cl-BQ. A dose-dependent increase in micronuclei frequency was observed in PCB-treated cells, consistent with an increase in histone 2AX phosphorylation. Treatment of cells with catalase blunted the PCB-induced increase in micronuclei frequency and H2AX phosphorylation that was consistent with an increase in cell survival. Our results demonstrate a PCB-induced increase in cellular levels of ROS causing DNA damage, resulting in cell killing. PMID:18691649

Venkatesha, Venkatasubbaiah A; Venkataraman, Sujatha; Sarsour, Ehab H; Kalen, Amanda L; Buettner, Garry R; Robertson, Larry W; Lehmler, Hans-Joachim; Goswami, Prabhat C

2008-07-22

234

Arsenite induces endothelial cytotoxicity by down-regulation of vascular endothelial nitric oxide synthase  

SciTech Connect

Epidemiological studies have demonstrated a high association of inorganic arsenic exposure with vascular diseases. Recent research has also linked this vascular damage to impairment of endothelial nitric oxide synthase (eNOS) function by arsenic exposure. However, the role of eNOS in regulating the arsenite-induced vascular dysfunction still remains to be clarified. In our present study, we investigated the effect of arsenite on Akt1 and eNOS and its involvement in cytotoxicity of vascular endothelial cells. Our study demonstrated that arsenite decreased the protein levels of both Akt1 and eNOS accompanied with increased levels of ubiquitination of total cell lysates. We found that inhibition of the ubiquitin-proteasome pathway by MG-132 could partially protect Akt1 and eNOS from degradation by arsenite together with a proportional protection from the arsenite-induced cytoxicity. Moreover, up-regulation of eNOS protein expression significantly attenuated the arsenite-induced cytotoxicity and eNOS activity could be significantly inhibited after incubation with arsenite for 24 h in a cell-free system. Our study indicated that endothelial eNOS activity could be attenuated by arsenite via the ubiquitin-proteasome-mediated degradation of Akt1/eNOS as well as via direct inhibition of eNOS activity. Our study also demonstrated that eNOS actually played a protective role in arsenite-induced cytoxicity. These observations supported the hypothesis that the impairment of eNOS function by arsenite is one of the mechanisms leading to vascular changes and diseases.

Tsou, T.-C. [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 100 Shih-Chuan 1st Road, Kaohsiung 807 (China)]. E-mail: tctsou@nhri.org.tw; Tsai, F.-Y. [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 100 Shih-Chuan 1st Road, Kaohsiung 807 (China); Hsieh, Y.-W. [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 100 Shih-Chuan 1st Road, Kaohsiung 807 (China); Li, L.-A. [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 100 Shih-Chuan 1st Road, Kaohsiung 807 (China); Yeh, S.C [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 100 Shih-Chuan 1st Road, Kaohsiung 807 (China); Chang, L.W. [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 100 Shih-Chuan 1st Road, Kaohsiung 807 (China)

2005-11-01

235

Mechanistic insights into the cytotoxicity and genotoxicity induced by glycidamide in human mammary cells.  

PubMed

Acrylamide (AA) is a well-known industrial chemical classified as a probable human carcinogen. Benign and malignant tumours at different sites, including the mammary gland, have been reported in rodents exposed to AA. This xenobiotic is also formed in many carbohydrate-rich foods prepared at high temperatures. For this reason, AA is an issue of concern in terms of human cancer risk. The epoxide glycidamide (GA) is thought to be the ultimate genotoxic AA metabolite. Despite extensive experimental and epidemiological data focused on AA-induced breast cancer, there is still lack of information on the deleterious effects induced by GA in mammary cells. The work reported here addresses the characterisation and modulation of cytotoxicity, generation of reactive oxygen species, formation of micronuclei (MN) and quantification of specific GA-DNA adducts in human MCF10A epithelial cells exposed to GA. The results show that GA significantly induces MN, impairs cell proliferation kinetics and decreases cell viability at high concentrations by mechanisms not involving oxidative stress. KU55933, an inhibitor of ataxia telangiectasia mutated kinase, enhanced the cytotoxicity of GA (P < 0.05), supporting a role of this enzyme in regulating the repair of GA-induced DNA lesions. Moreover, even at low GA levels, N7-GA-Gua adducts were generated in a linear dose-response manner in MCF10A cells. These results confirm that human mammary cells are susceptible to GA toxicity and reinforce the need for additional studies to clarify the potential correlation between dietary AA exposure and breast cancer risk in human populations. PMID:24150595

Bandarra, Susana; Fernandes, Ana S; Magro, Inês; Guerreiro, Patrícia S; Pingarilho, Marta; Churchwell, Mona I; Gil, Octávia Monteiro; Batinic-Haberle, Ines; Gonçalves, Sandrina; Rueff, José; Miranda, Joana P; Marques, M Matilde; Beland, Frederick A; Castro, Matilde; Gaspar, Jorge F; Oliveira, Nuno G

2013-11-01

236

Two-dimensional nanoparticle self-assembly using plasma-induced Ostwald ripening.  

PubMed

In this work, a novel Ag nanoparticle self-assembly process based on plasma-induced two-dimensional Ostwald ripening is demonstrated. Ag nanoparticles are deposited on p-doped Si substrates using a DC magnetron sputtering process. With the assistance of O(2)/Ar plasma treatment, different sizes and patterns of Ag nanoparticles are formed, due to the Ostwald ripening. The evolution of plasma-induced nanoparticle ripening is studied and a clear increase in particle size and a decrease in particle density are observed with increasing plasma treatment. From the experiments, it is concluded that the initial nanoparticle density and the plasma gas mixture (Ar/O(2) ratio) are important factors that affect the ripening process. The proposed plasma-directed Ag nanoparticle self-assembly provides a rapid method of tailoring the nanoparticle distribution on substrates, with potential applications in the fields of solar cells, biosensors, and catalysis. PMID:21483049

Tang, J; Photopoulos, P; Tserepi, A; Tsoukalas, D

2011-04-11

237

Two-dimensional nanoparticle self-assembly using plasma-induced Ostwald ripening  

NASA Astrophysics Data System (ADS)

In this work, a novel Ag nanoparticle self-assembly process based on plasma-induced two-dimensional Ostwald ripening is demonstrated. Ag nanoparticles are deposited on p-doped Si substrates using a DC magnetron sputtering process. With the assistance of O2/Ar plasma treatment, different sizes and patterns of Ag nanoparticles are formed, due to the Ostwald ripening. The evolution of plasma-induced nanoparticle ripening is studied and a clear increase in particle size and a decrease in particle density are observed with increasing plasma treatment. From the experiments, it is concluded that the initial nanoparticle density and the plasma gas mixture (Ar/O2 ratio) are important factors that affect the ripening process. The proposed plasma-directed Ag nanoparticle self-assembly provides a rapid method of tailoring the nanoparticle distribution on substrates, with potential applications in the fields of solar cells, biosensors, and catalysis.

Tang, J.; Photopoulos, P.; Tserepi, A.; Tsoukalas, D.

2011-06-01

238

Titanium dioxide nanoparticles inhibit proliferation and induce morphological changes and apoptosis in glial cells.  

PubMed

Titanium dioxide nanoparticles (TiO(2) NPs) are widely used in the chemical, electrical and electronic industries. TiO(2) NPs can enter directly into the brain through the olfactory bulb and be deposited in the hippocampus region. We determined the effect of TiO(2) NPs on rat and human glial cells, C6 and U373, respectively. We evaluated proliferation by crystal violet staining, internalization of TiO(2) NPs, and cellular morphology by TEM analysis, as well as F-actin distribution by immunostaining and cell death by detecting active caspase-3 and DNA fragmentation. TiO(2) NPs inhibited proliferation and induced morphological changes that were related with a decrease in immuno-location of F-actin fibers. TiO(2) NPs were internalized and formation of vesicles was observed. TiO(2) NPs induced apoptosis after 96h of treatment. Hence, TiO(2) NPs had a cytotoxic effect on glial cells, suggesting that exposure to TiO(2) NPs could cause brain injury and be hazardous to health. PMID:23044362

Márquez-Ramírez, Sandra Gissela; Delgado-Buenrostro, Norma Laura; Chirino, Yolanda Irasema; Iglesias, Gisela Gutiérrez; López-Marure, Rebeca

2012-10-05

239

Cerium oxide nanoparticle-induced pulmonary inflammation and alveolar macrophage functional change in rats.  

PubMed

The use of cerium compounds as diesel fuel catalyst results in the emission of cerium oxide nanoparticles (CeO2) in the exhaust. This study characterized the potential effects of CeO2 exposure on lung toxicity. Male Sprague Dawley rats were exposed to CeO2 by a single intratracheal instillation at 0.15, 0.5, 1, 3.5 or 7 mg/kg body weight. At 1 day after exposure, CeO2 significantly reduced NO production, but increased IL-12 production, by alveolar macrophages (AM) in response to ex vivo lipopolysacchride (LPS) challenge, and caused AM apoptosis, through activation of caspases 9 and 3. CeO2 exposure markedly increased suppressor of cytokine signaling-1 at 1-day and elevated arginase-1 at 28-day post exposure in lung cells, while osteopontin was significantly elevated in lung tissue at both time points. CeO2 induced inflammation, cytotoxicity, air/blood barrier damage, and phospholipidosis with enlarged AM. Thus, CeO2 induced lung inflammation and injury in lungs which may lead to fibrosis. PMID:20925443

Ma, Jane Y; Zhao, Hongwen; Mercer, Robert R; Barger, Mark; Rao, Murali; Meighan, Terence; Schwegler-Berry, Diane; Castranova, Vincent; Ma, Joseph K

2010-10-06

240

Gold Nanoparticle Sensor for Homocysteine Thiolactone-Induced Protein Modification  

PubMed Central

Homocysteine thiolactone-induced protein modification (HTPM) is a unique post-translational protein modification that is recognized as an emergent biomarker for cardiovascular disease. HTPM involves the site-specific acylation of proteins at lysine residues by homocysteine thiolactone (HTL) to produce protein homocystamide, which has been found at elevated levels in patients with coronary heart disease. Herein, we report the development of a novel gold nanoparticle (GNP) biochemical sensor for detection of protein homocystamide in an in vitro serum protein-based model system. Human serum albumin (HSA) and human sera were subjected to HTPM in vitro to produce HSA-homocystamide or serum protein homocystamide, respectively, which was subsequently treated with citrate-capped GNPs. This GNP sensor typically provided instantaneous visual confirmation of HTPM in the protein model systems. Transmission electron microscopy images of the GNPs in the presence of HSA-homocystamide suggest that modification-directed nanoparticle assembly is the mechanism by which the biochemical sensor produces a colorimetric signal. The resultant nanoparticle-protein assembly exhibited excellent thermal and dilutional stability, which is expected for a system stabilized by chemisorption and intermolecular disulfide bonding. The sensor typically provided a linear response for modified human sera concentrations greater than ~5 mg/mL. The calculated limit of detection and calibration sensitivity for the method in human sera were 5.2 mg/mL and 13.6 AU · (?g/mL)?1, respectively.

Gates, Arther T.; Fakayode, Sayo O.; Lowry, Mark; Ganea, Gabriela M.; Murugeshu, Abitha; Robinson, James W.; Strongin, Robert M.; Warner, Isiah M.

2009-01-01

241

A Vault Nanoparticle Vaccine Induces Protective Mucosal Immunity  

PubMed Central

Background Generation of robust cell-mediated immune responses at mucosal surfaces while reducing overall inflammation is a primary goal for vaccination. Here we report the use of a recombinant nanoparticle as a vaccine delivery platform against mucosal infections requiring T cell-mediated immunity for eradication. Methodology/Principal Findings We encapsulated an immunogenic protein, the major outer membrane protein (MOMP) of Chlamydia muridarum, within hollow, vault nanocapsules (MOMP-vaults) that were engineered to bind IgG for enhanced immunity. Intranasal immunization (i.n) with MOMP-vaults induced anti-chlamydial immunity plus significantly attenuated bacterial burden following challenge infection. Vault immunization induced anti-chlamydial immune responses and inflammasome formation but did not activate toll-like receptors. Moreover, MOMP-vault immunization enhanced microbial eradication without the inflammation usually associated with adjuvants. Conclusions/Significance Vault nanoparticles containing immunogenic proteins delivered to the respiratory tract by the i.n. route can act as “smart adjuvants” for inducing protective immunity at distant mucosal surfaces while avoiding destructive inflammation.

Champion, Cheryl I.; Kickhoefer, Valerie A.; Liu, Guangchao; Moniz, Raymond J.; Freed, Amanda S.; Bergmann, Liisa L.; Vaccari, Dana; Raval-Fernandes, Sujna; Chan, Ann M.; Rome, Leonard H.; Kelly, Kathleen A.

2009-01-01

242

Iron Oxide Nanoparticle-induced Oxidative Stress and Genotoxicity in Human Skin Epithelial and Lung Epithelial Cell Lines.  

PubMed

Iron oxide (Fe3O4) nanoparticles (IONPs) have received much attention for their utility in biomedical applications such as magnetic resonance imaging, drug delivery and hyperthermia. Recent studies reported that IONPs induced cytotoxicity in mammalian cells. However, little is known about the genotoxicity of IONPs following exposure to human cells. In this study, we investigated the cytotoxicity, oxidative stress and genotoxicity of IONPs in two human cell lines; skin epithelial A431 and lung epithelial A549. Prepared IONPs were polygonal in shape with a smooth surface and had an average diameter of 25 nm. IONPs (25-100 ?g/ml) induced dose-dependent cytotoxicity in both types of cells, which was demonstrated by cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) and lactate dehydrogenase leakage assays. IONPs were also found to induce oxidative stress in a dose-dependent manner, evident by depletion of glutathione and induction of reactive oxygen species (ROS) and lipid peroxidation. Comet assay revealed that level of DNA damage was higher with concentration of IONPs in both types of cells. Quantitative real-time PCR analysis showed that following the exposure of cells to IONPs, the expression levels of mRNA of caspase-3 and caspase-9 genes were higher. We also observed the higher activity of caspase-3 and caspase-9 enzymes in IONPs treated cells. Moreover, western blot analysis showed that protein expression level of cleaved caspase-3 was up-regulated by IONPs in both types of cells. Taken together, our data demonstrates that IONPs have potential to induce genotoxicity in A431 and A549 cells, which is likely to be mediated through ROS generation and oxidative stress. This study suggests that genotoxic effects of IONPs should be further investigated at in vivo level. PMID:23621530

Ahamed, Maqusood; Alhadlaq, Hisham A; Alam, Javed; Khan, M A Majeed; Ali, Daoud; Alarafi, Saud

2013-01-01

243

Immunomodulatory Drug Lenalidomide (CC5013, IMiD3) Augments Anti-CD40 SGN-40Induced Cytotoxicity in Human Multiple Myeloma: Clinical Implications  

Microsoft Academic Search

SGN-40, a humanized immoglobulin G1 (IgG1) anti-CD40 monoclonal antibody, mediates cytotoxicity against human multiple myeloma (MM) cells via suppression of interleukin (IL)-6-inducedproliferativeandantiapoptoticeffectsaswellas antibody-dependent cell-mediated cytotoxicity (ADCC). Here, we studied the clinical significance of an immunomodulatory drug lenalidomide on SGN-40-induced cytotoxicity against CD138+CD40+ MM lines and patient MM cells. Pretreatment with lenalidomide sensitized MM cells to SGN-40-induced cell death. Combined lenalidomide

Yu-Tzu Tai; Xian-Feng Li; Laurence Catley; Rory Coffey; Iris Breitkreutz; Jooeun Bae; Weihua Song; Klaus Podar; Teru Hideshima; Dharminder Chauhan; Robert Schlossman; Paul Richardson; Steven P. Treon; Iqbal S. Grewal; Nikhil C. Munshi; Kenneth C. Anderson

244

Arecoline induced cell cycle arrest, apoptosis, and cytotoxicity to human endothelial cells.  

PubMed

Betel quid (BQ) chewing is a common oral habit in South Asia and Taiwan. BQ consumption may increase the risk of oral squamous cell carcinoma (OSCC), oral submucous fibrosis (OSF), and periodontitis as well as systemic diseases (atherosclerosis, hypertension, etc.). However, little is known about the toxic effect of BQ components on endothelial cells that play important roles for angiogenesis, carcinogenesis, tissue fibrosis, and cardiovascular diseases. EAhy 926 (EAHY) endothelial cells were exposed to arecoline, a major BQ alkaloid, for various time periods. Cytotoxicity was estimated by 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay. The cell cycle distribution of EAHY cells residing in sub-G0/G1, G0/G1, S-, and G2/M phases was analyzed by propidium iodide staining of cellular DNA content and flow cytometry. Some EAHY cells retracted, became round-shaped in appearance, and even detached from the culture plate after exposure to higher concentrations of arecoline (> 0.4 mM). At concentrations of 0.4 and 0.8 mM, arecoline induced significant cytotoxicity to EAHY cells. At similar concentrations, arecoline induced G2/M cell cycle arrest and increased sub-G0/G1 population, a hallmark of apoptosis. Interestingly, prolonged exposure to arecoline (0.1 mM) for 12 and 21 days significantly suppressed the proliferation of EAHY cells, whereas EAHY cells showed adaptation and survived when exposed to 0.05 mM arecoline. These results suggest that BQ components may contribute to the pathogenesis of OSF and BQ chewing-related cardiovascular diseases via toxicity to oral or systemic endothelial cells, leading to impairment of vascular function. During BQ chewing, endothelial damage may be induced by areca nut components and associate with the pathogenesis of OSF, periodontitis, and cardiovascular diseases. PMID:21847594

Tseng, Shuei-Kuen; Chang, Mei-Chi; Su, Cheng-Yao; Chi, Lin-Yang; Chang, Jenny Zwei-Ching; Tseng, Wan-Yu; Yeung, Sin-Yuet; Hsu, Ming-Lun; Jeng, Jiiang-Huei

2011-08-17

245

Lentinula edodes (Shiitake) mushroom extract protects against hydrogen peroxide induced cytotoxicity in peripheral blood mononuclear cells.  

PubMed

Lentinula edodes (Berk) Pegler, commonly known as Shiitake mushroom has been used as medicinal food in Asian countries, especially in China and Japan and is believed to possess strong immunomodulatory property. In the present study, the methanolic extract of the fruit bodies of L. edodes was investigated for cytoprotective effect against H2O2-induced cytotoxicity in human peripheral blood mononuclear cells (PBMCs) by measuring the activities of xanthine oxidase (XO) and glutathione peroxidase (GPx) . H2O2 at a concentration of 5 microM caused 50% inhibition of PBMCs viability. The extract improved the PBMC viability and exerted a dose-dependent protection against H2O2-induced cytotoxicity. At 100 microg/ml of extract concentration, the cell viability increased by 60% compared with the PBMCs incubated with H2O2 alone. The extract also inhibited XO activity in PBMC, while showing moderate stimulatory effect on GPx. However, in the presence of H2O2 alone, both the enzyme activities were increased significantly. The GPx activity increased, possibly in response to the increased availability of H2O2 in the cell. When the cells were pretreated with the extract and washed (to remove the extract) prior to the addition of H2O2, the GPx and XO activities as well as the cell viability were comparable to those when incubated with the extract alone. Thus, it is suggested that one of the possible mechanisms via which L. edodes methanolic extract confers protection against H2O2-induced oxidative stress in PBMC is by inhibiting the superoxide-producing XO and increasing GPx activity which could rapidly inactivate H2O2. PMID:19517993

Kuppusamy, U R; Chong, Y L; Mahmood, A A; Indran, M; Abdullah, Noorlidah; Vikineswary, S

2009-04-01

246

Chemoprevention and cytotoxic effect of Bauhinia variegata against N-nitrosodiethylamine induced liver tumors and human cancer cell lines  

Microsoft Academic Search

The chemopreventive and cytotoxic effect of ethanol extract of Bauhinia variegata (EBV) was evaluated in N-nitrosodiethylamine (DEN, 200mg\\/kg) induced experimental liver tumor in rats and human cancer cell lines. Oral administration of ethanol extract of Bauhinia variegata (250mg\\/kg) effectively suppressed liver tumor induced by DEN as revealed by decrease in DEN induced elevated levels of serum glutamate pyruvate transaminase (SGPT),

B. Rajkapoor; B. Jayakar; N. Murugesh; D. Sakthisekaran

2006-01-01

247

Ameliorative effects of taurine against methimazole-induced cytotoxicity in isolated rat hepatocytes.  

PubMed

Methimazole is used as an antithyroid drug to control the symptoms of hyperthyroidism and maintain patients in a euthyroid state. Administration of this drug is associated with agranulocytosis and hepatotoxicity, which are the two most significant adverse effects. The present investigation was conducted to study the protective role of taurine against cytotoxicity induced by methimazole and its proposed reactive intermediary metabolite, N-methylthiourea, in an in vitro model of isolated rat hepatocytes.At different points in time, markers such as cell viability, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential, and hepatocyte glutathione content were evaluated.Treating hepatocytes with methimazole resulted in cytotoxicity characterized by the reduction in cell viability, an increase in ROS formation and lipid peroxidation, mitochondrial membrane potential collapse, and a reduction in cellular glutathione content. Furthermore, a significant amount of oxidized glutathione (GSSG) was formed when rat hepatocytes were treated with methimazole. N-methylthiourea toxicity was accompanied by a reduction in cellular GSH content, but no significant changes in lipid peroxidation, ROS formation, GSSG production, or changes in mitochondrial membrane potential were detected. Administration of taurine (200 ?M) effectively reduced the toxic effects of methimazole or its metabolite in isolated rat hepatocytes. PMID:23264945

Heidari, Reza; Babaei, Hossein; Eghbal, Mohammad Ali

2012-08-06

248

Cytotoxicity and apoptosis-inducing effect of steroidal saponins from Dioscorea zingiberensis Wright against cancer cells.  

PubMed

Steroidal saponins from Dioscorea zingiberensis Wright (DZW) have shown cytotoxic activity in cancer cells. In this study, we isolated and identified seven steroidal saponins from the rhizomes of DZW: diosgenin, trillin, diosgenin diglucoside, deltonin, zingiberensis saponin (ZS), protodeltonin and parvifloside. Our results showed that these seven compounds inhibited the proliferation of a panel of established human and murine cancer cell lines in vitro. ZS had more cytotoxic effect than the other saponins, even close to doxorubicin on the murine colon carcinoma cell line C26. The proliferation inhibitory effect of ZS was associated with its apoptosis-inducing effect by activation of caspase-3 and caspase-9 and specific proteolytic cleavage of poly (ADP-ribose) polymerase. Exposure of C26 to ZS also resulted in Bax upregulation and Bcl-2 downregulation. In conclusion, the findings of this study demonstrated that ZS is an effective natural agent for cancer therapy, which may be mediated, in part, by induction of apoptosis, and DZW's potential as an anticancer agent is worth being further investigated. PMID:22575181

Tong, Qing-Yi; He, Yang; Zhao, Qing-Bing; Qing, Yong; Huang, Wen; Wu, Xiao-Hua

2012-05-07

249

UVA-induced oxidative damage and cytotoxicity depend on the mode of exposure.  

PubMed

The reciprocity rule (Bunsen-Roscoe law) states that a photochemical reaction is directly proportional to the total energy dose, irrespective of the dose distribution. In photomedicine the validity of this law is usually taken for granted, although the influence of radiation intensity and dose distribution are largely unknown. We have examined in a tissue culture model the effects of fractionated versus single dose exposure to UV from a metal halide source on survival, DNA synthesis, glutathione, and oxidative membrane damage. Exposure to fractionated UVA was followed by an increased rate of cell death compared to single dose exposure, when intervals between fractions where short (10-120 min). Longer intervals had the opposite effect. Corresponding results were obtained for DNA synthesis (BrdU incorporation). The increased cytotoxicity of dose fractionation with short intervals could not be abrogated by non-enzymatic antioxidants (astaxanthin, ascorbic acid, alpha-tocopherol). Fractionated irradiation with short intervals led to higher degree of depletion of glutathione (GSH) and to enhanced formation of thiobarbituric acid reactive substances (TBARS) in comparison to an identical single dose. Long intervals between fractions induced opposite effects. Taken together, these data indicate that immediately after UVA exposure cells are more sensitive to a further oxidative attack making repeated exposure with short intervals more cytotoxic than continuous single dose UVA. This might have implications also for responses to UVA in vivo and further studies will have to extend these findings to the situation in healthy and diseased human skin. PMID:15896646

Merwald, Helga; Klosner, Gabriele; Kokesch, Claudia; Der-Petrossian, Manon; Hönigsmann, Herbert; Trautinger, Franz

2005-06-01

250

Ameliorative Effects of Taurine Against Methimazole-Induced Cytotoxicity in Isolated Rat Hepatocytes  

PubMed Central

Methimazole is used as an antithyroid drug to control the symptoms of hyperthyroidism and maintain patients in a euthyroid state. Administration of this drug is associated with agranulocytosis and hepatotoxicity, which are the two most significant adverse effects. The present investigation was conducted to study the protective role of taurine against cytotoxicity induced by methimazole and its proposed reactive intermediary metabolite, N-methylthiourea, in an in vitro model of isolated rat hepatocytes. At different points in time, markers such as cell viability, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential, and hepatocyte glutathione content were evaluated. Treating hepatocytes with methimazole resulted in cytotoxicity characterized by the reduction in cell viability, an increase in ROS formation and lipid peroxidation, mitochondrial membrane potential collapse, and a reduction in cellular glutathione content. Furthermore, a significant amount of oxidized glutathione (GSSG) was formed when rat hepatocytes were treated with methimazole. N-methylthiourea toxicity was accompanied by a reduction in cellular GSH content, but no significant changes in lipid peroxidation, ROS formation, GSSG production, or changes in mitochondrial membrane potential were detected. Administration of taurine (200 ?M) effectively reduced the toxic effects of methimazole or its metabolite in isolated rat hepatocytes.

Heidari, Reza; Babaei, Hossein; Eghbal, Mohammad Ali

2012-01-01

251

Hydrogen peroxide degradation and selective carbidopa-induced cytotoxicity against human tumor lines.  

PubMed

The carcinoid tumor, an uncommon neuroendocrine neoplasm, is associated with serotonin overproduction as is more common small cell lung carcinoma (SCLC). alpha-Methyl-dopahydrazine (carbidopa), an inhibitor of the serotonin synthetic enzyme aromatic-L-amino acid decarboxylase, proved lethal to NCI-H727 lung carcinoid cells as well as NCI-H146 and NCI-H209 SCLC cells, but not to five other human tumor cell lines of differing origins [Gilbert JA, Frederick LM, Ames MM. The aromatic-L-amino acid decarboxylase inhibitor carbidopa is selectively cytotoxic to human pulmonary carcinoid and small cell lung carcinoma cells. Clin. Cancer Res. 2000;6:4365-72]. The mechanism of carbidopa cytotoxicity remained an unanswered question. We present data here that incubation of the catechol carbidopa (100 microM) in RPMI and DMEM culture media yielded molar equivalents of hydrogen peroxide (H2O2) within 2-4 h. Alkaline elution studies revealed carbidopa-dependent single-strand DNA breaks in sensitive carcinoid cells comparable to those induced by similar concentrations of H2O2. Neither compound induced significant DNA damage in carbidopa-resistant NCI-H460 large cell lung carcinoma cells. Furthermore, when carbidopa was incubated with a variety of tumor cell types, not only were decreased media H2O2 concentrations detected in the presence of cells, but cell lines least sensitive to carbidopa degraded exogenous H2O2 more rapidly than did sensitive cells. Implicated in these studies, pyruvate degraded H2O2 in RPMI in a dose- and time-dependent manner and reversed carbidopa-induced cytotoxicity to carcinoid cells. Extracellular pyruvate levels produced per h by resistant large cell lung carcinoma cells averaged four-fold that of sensitive carcinoid cells plated at equal density (24 h time course). Finally, carbidopa exposure (100 microM, 24 h) depleted extracellular pyruvate from sensitive carcinoid cells, but reduced pyruvate levels from resistant NCI-H460 cells less than 17%. PMID:15794936

Gilbert, Judith A; Frederick, Linda M; Pobst, Lori J; Ames, Matthew M

2005-04-15

252

Differential effects of radical scavengers on X-ray-induced mutation and cytotoxicity in human cells  

SciTech Connect

The cytotoxic and mutagenic effects of X irradiation on a human lymphoblast cell line were examined in the presence of two radioprotective agents which modulate damage to DNA. The cells were treated with X rays alone or in the presence of either dimethyl sulfoxide or cysteamine. Surviving fraction and mutation to trifluorothymidine resistance (tk locus) and to 6-thioguanine resistance (hgprt locus) were measured. Survival was enhanced when the cells were irradiated in the presence of dimethyl sulfoxide; the D0 rose from 58 to 107 rad. However, at both genetic loci the induced mutant fractions were identical in the presence or absence of dimethyl sulfoxide. Survival was enhanced to a greater degree when the cells were irradiated in the presence of cysteamine; the D0 rose from 58 to 200 rad. Cysteamine also protected the cells from X-ray-induced mutation; the frequencies of X-ray-induced mutation at both the tk and hgprt loci were reduced by 50-75%. No protective effects were observed unless dimethyl sulfoxide or cysteamine was present during irradiation. These findings are discussed in terms of the hypothesis that, unlike for cell killing, radiation-induced mutagenesis in human lymphoblast cells is not mediated by the actions of aqueous free radicals, but rather by the direct effects of ionizing radiation.

Corn, B.W.; Liber, H.L.; Little, J.B.

1987-01-01

253

Investigation of T-2 Mycotoxin-Induced Cytotoxicity in Vitro and Protective Effects of Flavonoid Compounds.  

National Technical Information Service (NTIS)

Aspects of the in vitro cytotoxic effects of T-2 mycotoxin on murine thymocytes were investigated. Cytotoxicity was found to be consistent when tested bi-weekly for a four month period. Cytotoxicity reached maximal values over a narrow range of doses and ...

R. J. F. Markham V. L. DiNinno N. P. Erhardt D. Penman A. R. Bhatti

1986-01-01

254

Saturated Fatty Acid-Induced Cytotoxicity in Liver Cells Does Not Involve Phosphatase and Tensin Homologue Deleted on Chromosome 10  

PubMed Central

Liver specific deletion of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) induces steatosis and hypersensitivity to insulin. Saturated fatty acids, which induce endoplasmic reticulum stress and cell death, appear to increase PTEN, whereas unsaturated fatty acids which do not induce endoplasmic reticulum stress or cell death reduce this protein. In the present study, the role of PTEN in saturated fatty acid-induced cytotoxicity was examined in H4IIE and HepG2 liver cells. Palmitate and stearate increased the expression of PTEN, whereas the unsaturated fatty acids, oleate and linoleate, reduced PTEN expression in both cell types. SiRNA-mediated knockdown of PTEN did not increase liver cell triglyceride stores or reduce palmitate- or stearate-mediated ER stress or apoptosis. These results suggest that PTEN does not play a significant role in saturated fatty acid-induced cytotoxicity in these liver cell models and in the absence of insulin.

Wang, Dong; Wei, Yuren; Gentile, Christopher L.; Pagliassotti, Michael J.

2013-01-01

255

Targeting Activation Induced Cytidine Deaminase Overcome Tumor Evasion of Immunotherapy by Cytotoxic T Lymphocytes  

PubMed Central

Activation induced cytidine deaminase (AID) is an enzyme essential for the generation of antibody diversity in B cells and is considered to be a general gene mutator. In addition, AID expression was also implicated in the pathogenesis of human B cell malignancies and associated with poor prognosis. Here we report that siRNA silencing of AID in plasmacytoma dramatically increased its susceptibility to immunotherapy by cytotoxic T lymphocytes. AID silencing did not decrease the mutation frequencies of tumor antigen gene P1A. Gene-array analysis showed dramatically altered expression of a number of genes in AID-silenced plasmacytoma cells and upregulation of CD200 was shown to be in favor of tumor eradication by CTL. Taken together, we demonstrate a novel function of AID in tumor evasion of CTL therapy and that targeting AID should be beneficial in the immunotherapy of AID positive tumors.

Liu, Jin-Qing; Joshi, Pramod S.; Wang, Chuansong; El-Omrani, Hani Y.; Xiao, Yi; Liu, Xiuping; Hagan, John P.; Liu, Chang-Gong; Wu, Lai-Chu; Bai, Xue-Feng

2010-01-01

256

Tribuli fructus constituents protect against tacrine-induced cytotoxicity in HepG2 cells.  

PubMed

A new phenolic amide, tribulusimide D (4-hydroxy-N-[3-(4-hydroxy-3-methoxyphenyl)-1-oxo-2-propen-1-yl]-3-methoxybenzamide) (1), together with a known phenolic amide, terrestriamide ((E)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxyphenyl)-2-oxoethyl]-prop-2-enamide) (2) and a flavonol glycoside, quercetin-3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (3) were isolated from the H2O extract of Tribuli Fructus. Compounds 1 and 3 showed significant hepatoprotective activities, with EC50 values of 13.46 +/- 0.2 and 7.06 +/- 0.7 microM, respectively, against tacrine-induced cytotoxicity in HepG2 cells. PMID:20191345

Byun, Erisa; Jeong, Gil-Saeng; An, Ren-Bo; Min, Tae Sun; Kim, Youn-Chul

2010-02-27

257

Ion beam induced effects on the ferromagnetism in Pd nanoparticles  

SciTech Connect

Present study demonstrates the role of metal-insulator interface and ion irradiation induced defects on the ferromagnetic properties of the non-magnetic materials. Magnetic properties of the Pd nanoparticles(NPs) embedded in the a-silica matrix synthesized using atom beam sputtering technique, were determined using SQUID magnetometry measurements which showed that ferromagnetic response of Pd increased by 3.5 times on swift heavy ion(SHI) irradiation. The ferromagnetic behavior of the as-deposited Pd NPs is due to strain induced by the surrounding matrix and modification in the electronic structure at the Pd-silica interface as revealed by insitu XRD and XPS investigations, respectively. The defects created by the SHI bombardment are responsible for enhancement of the magnetization in the Pd NPs.

Kulriya, P. K.; Mehta, B. R.; Agarwal, D. C.; Agarwal, Kanika; Kumar, Praveen; Shivaprasad, S. M.; Avasthi, D. K. [Materials Science Group, Inter University Accelerator Centre, New Delhi, Delhi (India); Department of Physics, Indian Institute of Technology, Delhi, Delhi (India); Materials Science Group, Inter University Accelerator Centre, New Delhi, Delhi (India); Department of Physics, Indian Institute of Technology, Delhi, Delhi (India); CPMU, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, Karnatka (India); Materials Science Group, Inter University Accelerator Centre, New Delhi, Delhi (India)

2012-06-05

258

PEG2000-DPSE-coated quercetin nanoparticles remarkably enhanced anticancer effects through induced programed cell death on C6 glioma cells.  

PubMed

In this study, PEGylated nanoparticles quercetin drug delivery vehicles were investigated as carriers for anticancer drugs induced programed cell death (PCD). PEG2000-DPSE-coated quercetin nanoparticles were prepared and tumor cell killing efficacy was studied on glioma C6 cells and assayed for cell survival, apoptosis, or necrosis. The levels of ROS production and mitochondrial membrane potential (??m) were determined. Western blot assayed p53, p-p53, cytochrome C, and caspase proteins expression were also studied. Results indicate that PEG2000-DPSE-QUE-NPS showed dose-dependent cytotoxicity to C6 glioma cells and enhanced ROS accumulation induced upregulation of p53 protein, which was accompanied with an increase in cytochrome c and caspase-3 protein levels. These results support the hypothesis that quercetin nanoparticles-coated PEG2000-DPSE remarkably enhanced anticancer effect of induced programed cell death on C6 glioma cells. Overall, PEG2000-DPSE-coated quercetin nanoparticles showed promising potential as a drug carrier for cancer therapy. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3076-3085, 2013. PMID:23529952

Wang, Gang; Wang, Junjie; Luo, Jie; Wang, Lei; Chen, Xuanli; Zhang, Liping; Jiang, Shanqing

2013-03-25

259

Tuning the cellular uptake and cytotoxicity properties of oligonucleotide intercalator-functionalized mesoporous silica nanoparticles with human cervical cancer cells HeLa.  

PubMed

A series of organically functionalized, MCM-41 type mesoporous silica nanoparticle materials (PAP-LP-MSN and AP-PAP-MSN) with different pore sizes (5.7 nm and 2.5 nm, respectively) were synthesized and characterized. We selectively decorated the exterior particle surface of PAP-LP-MSN and the interior pore surface of AP-PAP-MSN with an oligonucleotide intercalating phenanthridinium functionality. While phenanthridinium itself is a cell membrane impermeable molecule, we demonstrated that both phenanthridinium-immobilized PAP-LP-MSN and AP-PAP-MSN materials could indeed be internalized by live human cervical cancer cells (HeLa). We discovered that the PAP-LP-MSN nanoparticles with the phenanthridium groups located on the exterior surface were able to bind to cytoplasmic oligonucleotides, such as messenger RNAs, of HeLa cells resulting in severe cell growth inhibition. In contrast, the cytotoxicity of AP-PAP-MSN, where the same oligonucleotide intercalating molecules were anchored inside the pores, was significantly lowered upon the endocytosis by HeLa cells. We envision that this approach of combining the selective functionalization of the two different surfaces (exterior particle and interior pore surfaces) with morphology control of mesoporous silica nanoparticles would lead to a new generation of nanodevices with tunable biocompatibility and cell membrane trafficking properties for many biomedical applications. PMID:19932923

Vivero-Escoto, Juan L; Slowing, Igor I; Lin, Victor S-Y

2009-11-24

260

Benthic cyanobacteria from the Baltic Sea contain cytotoxic Anabaena, Nodularia, and Nostoc strains and an apoptosis-inducing Phormidium strain.  

PubMed

Benthic cyanobacteria from aquatic environments have been reported to produce biologically active metabolites. However, the toxicity and other biological activities of benthic cyanobacteria from the Baltic Sea are not well known. We determined the biological activities of 21 Anabaena, Calothrix, Nodularia, Nostoc, and Phormidium strains isolated from benthic littoral habitats of the Baltic Sea. We studied whether benthic cyanobacterial extracts caused cytotoxicity by necrosis or induced apoptosis in two mammalian cell lines, a human leukemia cell line (HL-60) and a mouse fibroblast cell line (3T3 Swiss), and examined potential hepatotoxin (microcystin and nodularin) production. Five of the six benthic Anabaena strains, one of the two Nostoc strains, and two of the three Nodularia strains were highly cytotoxic to human leukemia cells. The Calothrix and Phormidium strains did not cause LDH leakage, but the extract of Phormidium strain BECID15 induced apoptosis in the HL-60 cells. Neither the microcystin synthetase E (mcyE) nor the nodularin synthetase F (ndaF) gene was amplified by PCR, and no microcystins or nodularins were detected by the protein phosphatase inhibition assay from the cyanobacterial strains included in this study. This indicates that benthic Baltic cyanobacteria contain potentially harmful cytotoxic compounds even though they do not produce microcystins or nodularins. These cytotoxic compounds remain to be characterized, and the mechanisms of cytotoxicity need to be studied further. PMID:15892066

Surakka, Anu; Sihvonen, Leila M; Lehtimäki, Jaana M; Wahlsten, Matti; Vuorela, Pia; Sivonen, Kaarina

2005-06-01

261

Increased metallothionein gene expression in 5-aza-2'-deoxycytidine-induced resistance to cadmium cytotoxicity.  

PubMed

The pyrimidine analog, 5-azacytidine (AZA-CR), has been shown to increase the expression of the metallothionein (MT) gene and to induce tolerance to cadmium toxicity. Since incorporation into DNA of AZA-CR appears to be required for this effect, the deoxynucleoside of AZA-CR should also be effective. Therefore, this study was undertaken to assess the effect of 5-aza-2'-deoxycytidine (AZA-CdR) pretreatment on cadmium-induced cytotoxicity and MT expression in cultured cells. TRL 1215 cells in log phase of growth were exposed to AZA-CdR (0.4, 0.8, 4.0, 8.0 microM) followed 48 h later by the addition of cadmium (10 microM). MT concentrations were measured 24 h after the addition of cadmium. AZA-CdR alone caused modest, dose-related increases in MT levels (2.3-fold maximum), while cadmium alone resulted in a 9.5-fold increase. Pretreatment with AZA-CdR in combination with cadmium caused a 19--24-fold increase in cellular MT at all doses of AZA-CdR. Addition of the DNA synthesis inhibitor, hydroxyurea (HU), to the incubation medium during AZA-CdR exposure prevented the enhancing effect of the analog on cadmium induction of MT accumulation. Time course studies revealed that AZA-CdR pretreatment reduced the time required for cadmium to induce MT levels from 4--8 h to 0--2 h. AZA-CdR pretreated cells placed in suspension with cadmium (125 microM) showed a marked reduction in cadmium-induced cytotoxicity as reflected by reduced glutamic-oxaloacetic transaminase (GOT) loss. Uptake studies showed that AZA-CdR pretreatment had no effect on cadmium transport during the initial phases of exposure, indicating that an alteration in the toxicokinetics of the metal did not account for the reduction in toxicity. AZA-CdR did, however, cause hypomethylation of the MT-I gene. These results suggest that AZA-CdR pretreatment induces tolerance to cadmium toxicity by increasing the genetic expression of MT possibly through hypomethylation of the MT gene. PMID:2456160

Waalkes, M P; Miller, M S; Wilson, M J; Bare, R M; McDowell, A E

1988-01-01

262

Autophagy Plays a Critical Role in ChLym-1-Induced Cytotoxicity of Non-Hodgkin's Lymphoma Cells  

PubMed Central

Autophagy is a critical mechanism in both cancer therapy resistance and tumor suppression. Monoclonal antibodies have been documented to kill tumor cells via apoptosis, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In this study, we report for the first time that chLym-1, a chimeric anti-human HLA-DR monoclonal antibody, induces autophagy in Raji Non-Hodgkin’s Lymphoma (NHL) cells. Interestingly, inhibition of autophagy by pharmacological inhibitors (3-methyladenine and NH4Cl) or genetic approaches (siRNA targeting Atg5) suppresses chLym-1-induced growth inhibition, apoptosis, ADCC and CDC in Raji cells, while induction of autophagy could accelerate cytotoxic effects of chLym-1 on Raji cells. Furthermore, chLym-1-induced autophagy can mediate apoptosis through Caspase 9 activation, demonstrating the tumor-suppressing role of autophagy in antilymphoma effects of chLym-1. Moreover, chLym-1 can activate several upstream signaling pathways of autophagy including Akt/mTOR and extracellular signal-regulated kinase 1/2 (Erk1/2). These results elucidate the critical role of autophagy in cytotoxicity of chLym-1 antibody and suggest a potential therapeutic strategy of NHL therapy by monoclonal antibody chLym-1 in combination with autophagy inducer.

Li, Yubin; Wang, Shaofei; Wang, Ziyu; Sun, Yun; Gao, Hongjian; Zhang, Guoping; Feng, Meiqing; Ju, Dianwen

2013-01-01

263

Efficacy of cerebroprotective substances in the management of functional disorders induced by the cytotoxic brain oedema-producing substance hexachlorophene  

Microsoft Academic Search

The hexachlorophene-induced cytotoxic brain oedema is used as experimental model of brain damage, suitable for testing cerebroprotective substances. It has clinical importance since many brain injuries are accompanied by an oedema. The primary target of the neurotoxin, hexachlorophene, is the neuronal cell membrane, but it also causes secondary effects including a disruption of myelin lamellae, increases in water and sodium

K. Andreas

1993-01-01

264

Soluble Proteins Delivered to Dendritic Cells Via pH-sensitive Liposomes Induce Primary Cytotoxic T Lymphocyte Responses In Vitro  

Microsoft Academic Search

Summary Effective immunity to many infectious agents, particularly viruses, requires a CD8 + cytotoxic T lymphocyte (CTL) response. Understanding how to achieve CTL induction with soluble proteins is important for vaccine development since such antigens are usually not processed appropriately to induce CTL. In the present report, we have demonstrated that a potent primary CTL response against a soluble protein

Smita Nair; Fan Zhou; Kamani Reddy; S Leaf Huang; Barry T. Rouse

1992-01-01

265

Novel Plant Virus-Based Vaccine Induces Protective Cytotoxic T-Lymphocyte-Mediated Antiviral Immunity through Dendritic Cell Maturation  

Microsoft Academic Search

Currently used vaccines protect mainly through the production of neutralizing antibodies. However, anti- bodies confer little or no protection for a majority of chronic viral infections that require active involvement of cytotoxic T lymphocytes (CTLs). Virus-like particles (VLPs) have been shown to be efficient inducers of cell-mediated immune responses, but administration of an adjuvant is generally required. We recently reported

Patrick Lacasse; Jerome Denis; R. Lapointe; D. Leclerc; A. Lamarre

2008-01-01

266

Cytotoxicity studies of Dynasan 114 solid lipid nanoparticles (SLN) on RAW 264.7 macrophages-impact of phagocytosis on viability and cytokine production.  

PubMed

Solid lipid nanoparticles (SLN) based on Dynasan 114 (D114) were tested using RAW 264.7 cells. The influence of different surfactants on the cytotoxicity of this type of SLN was examined, expressed as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) viability and the production of cytokines such as interleukin 6 (IL-6), IL-12 and tumour necrosis factor-alpha (TNF-alpha). Results were compared with previously obtained data when peritoneal mouse macrophages were used. SLN produced with stabilizers/surfactants such as poloxamer 188, sodium cholate, Lipoid S75, Tween 80, Poloxamine 908 and sodium dodecylsulfate were shown to be nontoxic towards RAW 264.7 cells. Cytokine production was reduced and stimulation, expressed in elevated cytokine levels, could not be found. Using cetylpyridinium chloride (CPC) as stabilizing surfactant, SLN became cytotoxic in a concentration-dependent manner. Not only were the viabilities reduced but also cytokine production. Cytotoxic effects of CPC stabilized SLN could be antagonized using cytochalasin B to block phagocytosis. D114-SLN produced with pharmaceutically accepted surfactants for intravenous injection (poloxamer 188, Lipoid S75, sodium cholate, Tween 80) were very well tolerated by the cells. Even sodium dodecylsulfate-stabilized D114-SLN did not exert toxic effects. Comparison of the RAW 264.7 data with previously obtained data from toxicity studies of D114-SLN towards peritoneal mouse macrophages showed similar results. This offers the possibility of using the RAW 264.7 cell line for cytotoxicity studies of colloidal drug carrier systems, rather than using laboratory animals as source of macrophages for these kinds of studies. PMID:15233867

Olbrich, Carsten; Schöler, Nadja; Tabatt, Kerstin; Kayser, Oliver; Müller, Rainer Helmut

2004-07-01

267

Mechanisms of nanoparticle-induced oxidative stress and toxicity.  

PubMed

The rapidly emerging field of nanotechnology has offered innovative discoveries in the medical, industrial, and consumer sectors. The unique physicochemical and electrical properties of engineered nanoparticles (NP) make them highly desirable in a variety of applications. However, these novel properties of NP are fraught with concerns for environmental and occupational exposure. Changes in structural and physicochemical properties of NP can lead to changes in biological activities including ROS generation, one of the most frequently reported NP-associated toxicities. Oxidative stress induced by engineered NP is due to acellular factors such as particle surface, size, composition, and presence of metals, while cellular responses such as mitochondrial respiration, NP-cell interaction, and immune cell activation are responsible for ROS-mediated damage. NP-induced oxidative stress responses are torch bearers for further pathophysiological effects including genotoxicity, inflammation, and fibrosis as demonstrated by activation of associated cell signaling pathways. Since oxidative stress is a key determinant of NP-induced injury, it is necessary to characterize the ROS response resulting from NP. Through physicochemical characterization and understanding of the multiple signaling cascades activated by NP-induced ROS, a systemic toxicity screen with oxidative stress as a predictive model for NP-induced injury can be developed. PMID:24027766

Manke, Amruta; Wang, Liying; Rojanasakul, Yon

2013-08-20

268

Protective effect of taurine on triorthocresyl phosphate (TOCP)-induced cytotoxicity in C6 glioma cells.  

PubMed

Triorthocresyl phosphate (TOCP) an organophosphorus ester can cause neurotoxicity via oxidative stress pathway. Taurine is an antioxidant. The objective of this study was to investigate the protective effect of taurine on TOCP-induced cytotoxicity in C6 glioma cell. The C6 glioma cells were pretreated with 0, 1, 3, and 9 mM of taurine for 30 min prior to 1 mM TOCP treatment. After 48 h, cell survival was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release. The content of glutathione (GSH) and the activity of glutathione peroxidase (GPx) were also analyzed by kits. Our results showed that survival of the glioma cells decreased in the group treated with TOCP alone and increased significantly in the groups pretreated with taurine in a concentration-dependent manner. TOCP induced decrease in the activity of GPx and the content of GSH. However, taurine prevented these decreases. Our results suggested that taurine has protective effect on TOCP-induced toxicity to glioma cells via elevating antioxidant capacity. PMID:23392886

Li, Yachen; Piao, Fengyuan; Liu, Xiaohui

2013-01-01

269

Effect of magnetic nanoparticles on apoptosis and cell cycle induced by wogonin in Raji cells  

PubMed Central

Traditional Chinese medicine is gradually becoming a new source of anticancer drugs. One such example is wogonin, which is cytotoxic to various cancer cell lines in vitro. However, due to its low water solubility, wogonin is restricted to clinical administration. Recently, the application of drug-coated magnetic nanoparticles (MNPs) to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention. In this study, wogonin was conjugated with the drug delivery system of MNPs by mechanical absorption polymerization to fabricate wogonin-loaded MNPs. It was demonstrated that MNPs could strengthen wogonin-induced cell inhibition, apoptosis, and cell cycle arrest in Raji cells by methylthiazol tetrazolium assay, flow cytometer assay, and nuclear 4?,6-diamidino-2-phenylindole staining. Furthermore, the molecular mechanisms of these phenomena were explored by western blot, in which the protein levels of caspase 8 and caspase 3 were increased significantly while those of survivin and cyclin E were decreased significantly in wogonin-MNPs group. These findings suggest that the combination of wogonin and MNPs provides a promising strategy for lymphoma therapy.

Wang, Lei; Zhang, Haijun; Chen, Baoan; Xia, Guohua; Wang, Shuai; Cheng, Jian; Shao, Zeye; Gao, Chong; Bao, Wen; Tian, Liang; Ren, Yanyan; Xu, Peipei; Cai, Xiaohui; Liu, Ran; Wang, Xuemei

2012-01-01

270

Kupffer cell-mediated hepatic injury induced by silica nanoparticles in vitro and in vivo  

PubMed Central

Silica nanoparticles (SiO2 NPs) have been shown to exert cytotoxic effects in hepato-cytes and to cause liver injury. In the liver, Kupffer cells (KCs), as the resident macrophages, play an important role in the normal physiology and homeostasis of the liver. Nevertheless, few studies have attempted to clarify the role of KCs in hepatic injury induced by SiO2 NPs. In this study, we treated Buffalo rat liver (BRL) cells with the supernatants of SiO2 NP-stimulated KCs to determine KC-mediated hepatotoxicity and its underlying preliminary mechanism. We also examined the response of KCs and liver injury in vivo after the administration of SiO2 NPs. The results showed that KCs stimulated by SiO2 NPs release large amounts of reactive oxygen species, tumor necrosis factor-? and nitric oxide. After BRL cells were cultured with the supernatants of SiO2 NP-stimulated KCs, the viability of BRL cells was reduced, and increases in aspartate aminotransferase and lactate dehydrogenase leakage were observed. Exposure to SiO2 NPs in vivo caused KC hyperplasia, hepatic inflammation, and oxidative stress, which led to changes in the biochemical composition of the liver. These data suggest that SiO2 NPs activate KCs to mediate hepatic injury and that the preliminary mechanism involves the release of bioactive substances from KCs.

Chen, Qingqing; Xue, Yang; Sun, Jiao

2013-01-01

271

Hypoxia-induced cytotoxic drug resistance in osteosarcoma is independent of HIF-1Alpha.  

PubMed

Survival rates from childhood cancer have improved dramatically in the last 40 years, such that over 80% of children are now cured. However in certain subgroups, including metastatic osteosarcoma, survival has remained stubbornly poor, despite dose intensive multi-agent chemotherapy regimens, and new therapeutic approaches are needed. Hypoxia is common in adult solid tumours and is associated with treatment resistance and poorer outcome. Hypoxia induces chemotherapy resistance in paediatric tumours including neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma, in vitro, and this drug resistance is dependent on the oxygen-regulated transcription factor hypoxia inducible factor-1 (HIF-1). In this study the effects of hypoxia on the response of the osteosarcoma cell lines 791T, HOS and U2OS to the clinically relevant cytotoxics cisplatin, doxorubicin and etoposide were evaluated. Significant hypoxia-induced resistance to all three agents was seen in all three cell lines and hypoxia significantly reduced drug-induced apoptosis. Hypoxia also attenuated drug-induced activation of p53 in the p53 wild-type U2OS osteosarcoma cells. Drug resistance was not induced by HIF-1? stabilisation in normoxia by cobalt chloride nor reversed by the suppression of HIF-1? in hypoxia by shRNAi, siRNA, dominant negative HIF or inhibition with the small molecule NSC-134754, strongly suggesting that hypoxia-induced drug resistance in osteosarcoma cells is independent of HIF-1?. Inhibition of the phosphoinositide 3-kinase (PI3K) pathway using the inhibitor PI-103 did not reverse hypoxia-induced drug resistance, suggesting the hypoxic activation of Akt in osteosarcoma cells does not play a significant role in hypoxia-induced drug resistance. Targeting hypoxia is an exciting prospect to improve current anti-cancer therapy and combat drug resistance. Significant hypoxia-induced drug resistance in osteosarcoma cells highlights the potential importance of hypoxia as a target to reverse drug resistance in paediatric osteosarcoma. The novel finding of HIF-1? independent drug resistance suggests however other hypoxia related targets may be more relevant in paediatric osteosarcoma. PMID:23785417

Adamski, Jennifer; Price, Andrew; Dive, Caroline; Makin, Guy

2013-06-13

272

Cytoprotective and antioxidant activity of seabuckthorn (Hippophae rhamnoides L.) flavones against tert-butyl hydroperoxide-induced cytotoxicity in lymphocytes.  

PubMed

This study was designed to determine the cytoprotective activity of flavones of seabuckthorn (Hippophae rhamnoides L.) against tert-butyl hydroperoxide (tert-BOOH), used as an oxidant to induce oxidative damage, with lymphocytes as the model system. Addition of tert-BOOH (250 microM) to the cells resulted in enhanced cytotoxicity and free radical production. The intracellular calcium levels, caspase activity, and apoptosis were significantly increased following tert-BOOH treatment. Seabuckthorn flavones at the concentration of 100 microg/mL significantly inhibited tert-BOOH-induced cytotoxicity and free radical production and also restored the antioxidant status to that of control cells. Seabuckthorn flavones also significantly restricted tert-BOOH-induced apoptosis by decreasing intracellular calcium levels and caspase activity. The extract also decreased tert-BOOH-induced formation of DNA breaks by 30%. These observations suggest that the flavones of seabuckthorn have marked cytoprotective properties, which could be attributed to the antioxidant activity. PMID:19298209

Geetha, S; Ram, M Sai; Sharma, S K; Ilavazhagan, G; Banerjee, P K; Sawhney, R C

2009-02-01

273

Synthesis of Magnetic Nanoparticles (Fe and FePt) by Plasma-Induced Cathodic Discharge Electrolysis  

Microsoft Academic Search

Magnetic nanoparticles of Fe and FePt intermetallic compound were synthesized in molten LiCl-KCl-CsCl electrolyte under 1 atm of Ar atmosphere using plasma-induced cathodic discharge electrolysis. First, a synthesis of fine and uniform Fe nanoparticles was successfully conducted at various Fe(II) ion concentrations. Fe nanoparticles less than 50 nm with a narrow distribution width were obtained at low Fe(II) ion concentration

Manabu Tokushige; Takashi Yamanaka; Akira Matsuura; Tokujiro Nishikiori; Yasuhiko Ito

2009-01-01

274

Numerical investigation of nanoparticle-assisted laser-induced interstitial thermotherapy toward tumor and cancer treatments  

Microsoft Academic Search

In this work, we numerically investigated nanoparticle-assisted laser-induced interstitial thermotherapy for tumor\\/cancer\\u000a treatments. The goal of the study was to investigate the therapeutic effects of treatment conditions including laser wavelength,\\u000a power, exposure time, concentrations of tailored nanoparticles, and optical\\/thermal properties of the tissue that is under\\u000a treatment. It was found that using absorbing preferential nanoparticles as the photothermal agent weakens

Xiao Xu; Andrew Meade; Yildiz Bayazitoglu

2011-01-01

275

Inorganic salt-induced phase control and optical characterization of cadmium sulfide nanoparticles  

Microsoft Academic Search

Phase-controlled synthesis of CdS nanoparticles from zinc-blende to wurtzite has been successfully realized by an inorganic salt-induced process with no use of surfactants or other ligands in an ultrasound-assisted microwave synthesis system. Pure zinc-blende CdS nanoparticles were produced without adding NaCl, while mixed zinc-blende and wurtzite nanoparticles were obtained by adding NaCl\\/Cd2 + molar ratios below 1, and pure wurtzite

Guo’an Tai; Jianxin Zhou; Wanlin Guo

2010-01-01

276

Carbon-encapsulated Fe nanoparticles from detonation-induced pyrolysis of ferrocene  

Microsoft Academic Search

Carbon-encapsulated Fe nanoparticles with size between 5 and 20nm were synthesized via a picric acid-detonation-induced pyrolysis of ferrocene, which is characterized by a self-heating and extremely fast process. The nanoparticles exhibit well-constructed core–shell structures, with bcc-Fe cores and graphitic shells. The graphitic shells can protect effectively the cores against the attack of HNO3 solution. The formation of the core–shell nanoparticles

Yi Lu; Zhenping Zhu; Zhenyu Liu

2005-01-01

277

Shear-induced 1-D alignment of alumina nanoparticles in coatings  

Microsoft Academic Search

Atomic Force Microscopy and Scanning Electron Microscopy were used to study shear-induced alignment of alumina and silica\\u000a nanoparticles in two-component polyurethane clear coatings. 1-D strings of nanoparticles, formed in an extended pearl-necklace\\u000a fashion were observed near the surfaces of cured films at nanoparticle volume fractions less than 0.05. This alignment is\\u000a affected by the shear conditions of the application method.

Lucas J. Brickweg; Bryce R. Floryancic; Erik D. Sapper; Raymond H. Fernando

2007-01-01

278

Gangliosides inhibit bee venom melittin cytotoxicity but not phospholipase A{sub 2}-induced degranulation in mast cells  

SciTech Connect

Sting accident by honeybee causes severe pain, inflammation and allergic reaction through IgE-mediated anaphylaxis. In addition to this hypersensitivity, an anaphylactoid reaction occurs by toxic effects even in a non-allergic person via cytolysis followed by similar clinical manifestations. Auto-injectable epinephrine might be effective for bee stings, but cannot inhibit mast cell lysis and degranulation by venom toxins. We used connective tissue type canine mast cell line (CM-MC) for finding an effective measure that might inhibit bee venom toxicity. We evaluated degranulation and cytotoxicity by measurement of {beta}-hexosaminidase release and MTT assay. Melittin and crude bee venom induced the degranulation and cytotoxicity, which were strongly inhibited by mono-sialoganglioside (G{sub M1}), di-sialoganglioside (G{sub D1a}) and tri-sialoganglioside (G{sub T1b}). In contrast, honeybee venom-derived phospholipase A{sub 2} induced the net degranulation directly without cytotoxicity, which was not inhibited by G{sub M1}, G{sub D1a} and G{sub T1b}. For analysis of distribution of G{alpha}{sub q} and G{alpha}{sub i} protein by western blotting, lipid rafts were isolated by using discontinuous sucrose gradient centrifuge. Melittin disrupted the localization of G{alpha}{sub q} and G{alpha}{sub i} at lipid raft, but gangliosides stabilized the rafts. As a result from this cell-based study, bee venom-induced anaphylactoid reaction can be explained with melittin cytotoxicity and phospholipase A{sub 2}-induced degranulation. Taken together, gangliosides inhibit the effect of melittin such as degranulation, cytotoxicity and lipid raft disruption but not phospholipase A{sub 2}-induced degranulation in mast cells. Our study shows a potential of gangliosides as a therapeutic tool for anaphylactoid reaction by honeybee sting.

Nishikawa, Hirofumi; Kitani, Seiichi, E-mail: drkitani@kaiyodai.ac.jp

2011-05-01

279

Herpes Simplex Virus Type 1 Renders Infected Cells Resistant to Cytotoxic T-Lymphocyte-Induced Apoptosis  

PubMed Central

Many viruses interfere with apoptosis of infected cells, presumably preventing cellular apoptosis as a direct response to viral infection. Since cytotoxic T lymphocytes (CTL) induce apoptosis of infected cells as part of the “lethal hit,” inhibition of apoptosis could represent an effective immune evasion strategy. We report here herpes simplex virus type 1 (HSV-1) interference with CTL-induced apoptosis of infected cells and show that HSV-1 inhibits the nuclear manifestations of apoptosis but not the membrane changes. The HL-60 cell line (human promyelocytic leukemia) undergoes apoptosis in response to many stimuli, including incubation with ethanol. After HSV-1 infection (strains E115 and 17+), ethanol-treated cells did not produce oligonucleosomal DNA fragments characteristic of apoptosis, as assayed by gel electrophoresis and enzyme-linked immunosorbent assay. Inhibition was detected 2 h after infection and increased over time. Importantly, HSV-1-infected cells were resistant to apoptosis induced by antigen-specific CD4+ CTL, despite the fact that CTL recognition and degranulation in response to infected targets remained intact. Unlike HSV-1, HSV-2 (strains 333 and HG52) did not inhibit DNA fragmentation. In contrast to the inhibition of DNA fragmentation by HSV-1, none of the HSV-1 or -2 strains interfered with the ethanol-induced exposure of surface phosphatidylserine characteristic of apoptosis, as determined by annexin V binding. These results demonstrate that genes of HSV-1 inhibit the nuclear manifestations of apoptosis but not the membrane manifestations, suggesting that these may be mediated via separate pathways. They also suggest that HSV-1 inhibition of CTL-induced apoptosis may be an important mechanism of immune evasion.

Jerome, Keith R.; Tait, Jonathan F.; Koelle, David M.; Corey, Lawrence

1998-01-01

280

Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species  

PubMed Central

Background Zinc oxide nanoparticles (ZnO NPs) have received much attention for their implications in cancer therapy. It has been reported that ZnO NPs induce selective killing of cancer cells. However, the underlying molecular mechanisms behind the anticancer response of ZnO NPs remain unclear. Methods and results We investigated the cytotoxicity of ZnO NPs against three types of cancer cells (human hepatocellular carcinoma HepG2, human lung adenocarcinoma A549, and human bronchial epithelial BEAS-2B) and two primary rat cells (astrocytes and hepatocytes). Results showed that ZnO NPs exert distinct effects on mammalian cell viability via killing of all three types of cancer cells while posing no impact on normal rat astrocytes and hepatocytes. The toxicity mechanisms of ZnO NPs were further investigated using human liver cancer HepG2 cells. Both the mRNA and protein levels of tumor suppressor gene p53 and apoptotic gene bax were upregulated while the antiapoptotic gene bcl-2 was downregulated in ZnO NP-treated HepG2 cells. ZnO NPs were also found to induce activity of caspase-3 enzyme, DNA fragmentation, reactive oxygen species generation, and oxidative stress in HepG2 cells. Conclusion Overall, our data demonstrated that ZnO NPs selectively induce apoptosis in cancer cells, which is likely to be mediated by reactive oxygen species via p53 pathway, through which most of the anticancer drugs trigger apoptosis. This study provides preliminary guidance for the development of liver cancer therapy using ZnO NPs.

Akhtar, Mohd Javed; Ahamed, Maqusood; Kumar, Sudhir; Khan, MA Majeed; Ahmad, Javed; Alrokayan, Salman A

2012-01-01

281

BET Inhibition Silences Expression of MYCN and BCL2 and Induces Cytotoxicity in Neuroblastoma Tumor Models  

PubMed Central

BET family proteins are epigenetic regulators known to control expression of genes involved in cell growth and oncogenesis. Selective inhibitors of BET proteins exhibit potent anti-proliferative activity in a number of hematologic cancer models, in part through suppression of the MYC oncogene and downstream Myc-driven pathways. However, little is currently known about the activity of BET inhibitors in solid tumor models, and whether down-regulation of MYC family genes contributes to sensitivity. Here we provide evidence for potent BET inhibitor activity in neuroblastoma, a pediatric solid tumor associated with a high frequency of MYCN amplifications. We treated a panel of neuroblastoma cell lines with a novel small molecule inhibitor of BET proteins, GSK1324726A (I-BET726), and observed potent growth inhibition and cytotoxicity in most cell lines irrespective of MYCN copy number or expression level. Gene expression analyses in neuroblastoma cell lines suggest a role of BET inhibition in apoptosis, signaling, and N-Myc-driven pathways, including the direct suppression of BCL2 and MYCN. Reversal of MYCN or BCL2 suppression reduces the potency of I-BET726-induced cytotoxicity in a cell line-specific manner; however, neither factor fully accounts for I-BET726 sensitivity. Oral administration of I-BET726 to mouse xenograft models of human neuroblastoma results in tumor growth inhibition and down-regulation MYCN and BCL2 expression, suggesting a potential role for these genes in tumor growth. Taken together, our data highlight the potential of BET inhibitors as novel therapeutics for neuroblastoma, and suggest that sensitivity is driven by pleiotropic effects on cell growth and apoptotic pathways in a context-specific manner.

Wyce, Anastasia; Ganji, Gopinath; Smitheman, Kimberly N.; Chung, Chun-wa; Korenchuk, Susan; Bai, Yuchen; Barbash, Olena; Le, BaoChau; Craggs, Peter D.; McCabe, Michael T.; Kennedy-Wilson, Karen M.; Sanchez, Lydia V.; Gosmini, Romain L.; Parr, Nigel; McHugh, Charles F.; Dhanak, Dashyant; Prinjha, Rab K.; Auger, Kurt R.; Tummino, Peter J.

2013-01-01

282

BET inhibition silences expression of MYCN and BCL2 and induces cytotoxicity in neuroblastoma tumor models.  

PubMed

BET family proteins are epigenetic regulators known to control expression of genes involved in cell growth and oncogenesis. Selective inhibitors of BET proteins exhibit potent anti-proliferative activity in a number of hematologic cancer models, in part through suppression of the MYC oncogene and downstream Myc-driven pathways. However, little is currently known about the activity of BET inhibitors in solid tumor models, and whether down-regulation of MYC family genes contributes to sensitivity. Here we provide evidence for potent BET inhibitor activity in neuroblastoma, a pediatric solid tumor associated with a high frequency of MYCN amplifications. We treated a panel of neuroblastoma cell lines with a novel small molecule inhibitor of BET proteins, GSK1324726A (I-BET726), and observed potent growth inhibition and cytotoxicity in most cell lines irrespective of MYCN copy number or expression level. Gene expression analyses in neuroblastoma cell lines suggest a role of BET inhibition in apoptosis, signaling, and N-Myc-driven pathways, including the direct suppression of BCL2 and MYCN. Reversal of MYCN or BCL2 suppression reduces the potency of I-BET726-induced cytotoxicity in a cell line-specific manner; however, neither factor fully accounts for I-BET726 sensitivity. Oral administration of I-BET726 to mouse xenograft models of human neuroblastoma results in tumor growth inhibition and down-regulation MYCN and BCL2 expression, suggesting a potential role for these genes in tumor growth. Taken together, our data highlight the potential of BET inhibitors as novel therapeutics for neuroblastoma, and suggest that sensitivity is driven by pleiotropic effects on cell growth and apoptotic pathways in a context-specific manner. PMID:24009722

Wyce, Anastasia; Ganji, Gopinath; Smitheman, Kimberly N; Chung, Chun-Wa; Korenchuk, Susan; Bai, Yuchen; Barbash, Olena; Le, BaoChau; Craggs, Peter D; McCabe, Michael T; Kennedy-Wilson, Karen M; Sanchez, Lydia V; Gosmini, Romain L; Parr, Nigel; McHugh, Charles F; Dhanak, Dashyant; Prinjha, Rab K; Auger, Kurt R; Tummino, Peter J

2013-08-23

283

The Cdk inhibitor flavopiridol enhances temozolomide-induced cytotoxicity in human glioma cells.  

PubMed

The recent progress in chemotherapy for malignant gliomas is attributable to the introduction of the DNA-methylating agent temozolomide (TMZ); however, drug resistance remains a major issue. Previous studies have shown that TMZ induces prolonged arrest of human glioma cells in the G2/M phase of the cell cycle followed by a senescence-like phenomenon or mitotic catastrophe. These findings suggest that the G2 checkpoint is linked to DNA repair mechanisms. We investigated the effect of a cyclin-dependent kinase (Cdk) inhibitor flavopiridol (FP) that inhibits the action of Cdc2, a key protein in the G2 checkpoint pathway, on TMZ-treated glioma cells. Colony formation efficiency revealed that FP potentiated the cytotoxicity of TMZ in glioma cells in a p53-independent manner. This effect was clearly associated with the suppression of key proteins at the G2-M transition, accumulation of the cells exclusively at the G2 phase, and increase in a double-stranded DNA break marker (seen on performing immunoblotting). TMZ-resistant clones showed activation of the G2 checkpoint in response to TMZ, while FP treatment resensitized these clones to TMZ. FP also enhanced the cytotoxicity of TMZ in U87MG-AktER cells. Moreover, administration of TMZ and/or FP to nude mice with xenografted U87MG cells revealed that FP sensitized xenografted U87MG cells to TMZ in these mice. Our findings suggest that TMZ resistance could be promoted by enhanced DNA repair activity in the G2-M transition and that a Cdk inhibitor could suppress this activity, leading to potentiation of TMZ action on glioma cells. PMID:23943501

Hayashi, Takuro; Adachi, Kazuhide; Ohba, Shigeo; Hirose, Yuichi

2013-08-13

284

PI-103 sensitizes acute myeloid leukemia stem cells to daunorubicin-induced cytotoxicity.  

PubMed

To date, acute myeloid leukemia (AML) shows very poor outcome for conventional chemotherapy. Leukemia stem cells (LSCs) are insensitive to conventional chemotherapeutic drugs and play a central role in the pathogenesis of AML. Failure to effectively ablate these cells may lead to AML relapse following chemotherapy. Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway is constructively activated in LSCs. This pathway can be inhibited by PI-103, a novel synthesized molecule of the pyridofuropyrimidine class, resulting in the apoptosis of LSCs. Therefore, we investigate the influences of PI-103 in combination with daunorubicin (DNR) on the LSCs. Our data indicate that PI-103 synergistically sensitizes LSCs to DNR-induced cytotoxicity. In addition, the PI-103/DNR co-treatment can induce significant apoptosis in LSCs, but sparing hematopoietic stem cells. The synergistic effect and the LSCs-specific apoptosis mechanism may be associated with the inhibition of PI3K/Akt/mTOR signaling pathway. Our results suggest that PI-103 in combination with DNR may be a potent and less toxic therapy for targeting LSCs and deserve further preclinical and clinical studies in the treatment of AML. PMID:23335068

Ding, Qian; Gu, Ran; Liang, Jiayi; Zhang, Xiangzhong; Chen, Yunxian

2013-01-19

285

Lymphocytes with cytotoxic activity induce rapid microtubule axonal destabilization independently and before signs of neuronal death.  

PubMed

MS (multiple sclerosis) is the most prevalent autoimmune disease of the CNS (central nervous system) historically characterized as an inflammatory and demyelinating disease. More recently, extensive neuronal pathology has lead to its classification as a neurodegenerative disease as well. While the immune system initiates the autoimmune response it remains unclear how it orchestrates neuronal damage. In our previous studies, using in vitro cultured embryonic neurons, we demonstrated that MBP (myelin basic protein)-specific encephalitogenic CD4 T-cells induce early neuronal damage. In an extension of those studies, here we show that polarized CD4 Th1 and Th17 cells as wells as CD8 T-cells and NK (natural killer) cells induce microtubule destabilization within neurites in a contact-independent manner. Owing to the cytotoxic potential of these immune cells, we isolated the luminal components of lytic granules and determined that they were sufficient to drive microtubule destabilization. Since lytic granules contain cytolytic proteins, we determined that the induction of microtubule destabilization occurred prior to signs of apoptosis. Furthermore, we determined that microtubule destabilization was largely restricted to axons, sparing dendrites. This study demonstrated that lymphocytes with cytolytic activity have the capacity to directly drive MAD (microtubule axonal destabilization) in a bystander manner that is independent of neuronal death. PMID:23289514

Miller, Nichole M; Shriver, Leah P; Bodiga, Vijaya L; Ray, Avijit; Basu, Sreemanti; Ahuja, Rajiv; Jana, Arundhati; Pahan, Kalipada; Dittel, Bonnie N

2013-02-06

286

Regulatory T Cells and IL-10 Independently Counterregulate Cytotoxic T Lymphocyte Responses Induced by Transcutaneous Immunization  

PubMed Central

Background The imidazoquinoline derivate imiquimod induces inflammatory responses and protection against transplanted tumors when applied to the skin in combination with a cognate peptide epitope (transcutaneous immunization, TCI). Here we investigated the role of regulatory T cells (Treg) and the suppressive cytokine IL-10 in restricting TCI-induced cytotoxic T lymphocyte (CTL) responses. Methodology/Principal Findings TCI was performed with an ointment containing the TLR7 agonist imiquimod and a CTL epitope was applied to the depilated back skin of C57BL/6 mice. Using specific antibodies and FoxP3-diphteria toxin receptor transgenic (DEREG) mice, we interrogated inhibiting factors after TCI: by depleting FoxP3+ regulatory T cells we found that specific CTL-responses were greatly enhanced. Beyond this, in IL-10 deficient (IL-10-/-) mice or after blocking of IL-10 signalling with an IL-10 receptor specific antibody, the TCI induced CTL response is greatly enhanced indicating an important role for this cytokine in TCI. However, by transfer of Treg in IL-10-/- mice and the use of B cell deficient JHT-/- mice, we can exclude Treg and B cells as source of IL-10 in the setting of TCI. Conclusion/Significance We identify Treg and IL-10 as two important and independently acting suppressors of CTL-responses induced by transcutaneous immunization. Advanced vaccination strategies inhibiting Treg function and IL-10 release may lead the development of effective vaccination protocols aiming at the induction of T cell responses suitable for the prophylaxis or treatment of persistent infections or tumors.

Stein, Pamela; Weber, Michael; Prufer, Steve; Schmid, Beate; Schmitt, Edgar; Probst, Hans-Christian; Waisman, Ari; Langguth, Peter; Schild, Hansjorg; Radsak, Markus P.

2011-01-01

287

Surfactant-induced postsynthetic modulation of Pd nanoparticle crystallinity.  

SciTech Connect

Modulation of Pd nanoparticle (NP) crystallinity is achieved by switching the surfactants of different binding strengths. Pd NPs synthesized in the presence of weak binding surfactants such as oleylamine possess polyhedral shapes and a polycrystalline nature. When oleylamine is substituted by trioctylphosphine, a much stronger binding surfactant, the particles become spherical and their crystallinity decreases significantly. Moreover, the Pd NPs reconvert their polycrystalline structure when the surfactant is switched back to oleylamine. Through control experiments and molecular dynamics simulation, we propose that this unusual nanocrystallinity transition induced by surfactant exchange was resulted from a counterbalance between the surfactant binding energy and the nanocrystal adhesive energy. The findings represent a novel postsynthetic approach to tailoring the structure and corresponding functional performance of nanomaterials.

Liu, Y.; Wang, C.; Wei, Y.; Zhu, L.; Li, D.; Jiang, J. S.; Markovic, N. M.; Stamenkovic, V. R.; Sun, S. (Materials Science Division); (Brown Univ.); (Chinese Academy of Sciences)

2011-02-01

288

Influence of laser parameters on nanoparticle-induced membrane permeabilization  

NASA Astrophysics Data System (ADS)

Light-absorbing nanoparticles that are heated by short laser pulses can transiently increase membrane permeability. We evaluate the membrane permeability by flow cytometry assaying of propidium iodide and fluorescein isothiocyanate dextran (FITC-D) using different laser sources. The dependence of the transfection efficiency on laser parameters such as pulse duration, irradiant exposure, and irradiation mode is investigated. For nano- and also picosecond irradiation, we show a parameter range where a reliable membrane permeabilization is achieved for 10-kDa FITC-D. Fluorescent labeled antibodies are able to penetrate living cells that are permeabilized using these parameters. More than 50% of the cells are stained positive for a 150-kDa IgG antibody. These results suggest that the laser-induced permeabilization approach constitutes a promising tool for targeted delivery of larger exogenous molecules into living cells.

Yao, Cuiping; Qu, Xiaochao; Zhang, Zhenxi; Hüttmann, Gereon; Rahmanzadeh, Ramtin

2009-09-01

289

Nanoparticle injection to single animal cells using femtosecond laser-induced impulsive force  

NASA Astrophysics Data System (ADS)

An impulsive force, which was generated by focusing tightly a femtosecond laser into a cell culture medium, was applied to inject nanoparticles into local areas of a single mouse fibroblast NIH3T3 cell. When the impulsive force was induced near the cell, the nanoparticles adhering on the cell membrane were introduced, which was directly confirmed by confocal fluorescence microscopy.

Yamaguchi, Atsushi; Hosokawa, Yoichiroh; Louit, Guillaume; Asahi, Tsuyoshi; Shukunami, Chisa; Hiraki, Yuji; Masuhara, Hiroshi

2008-10-01

290

Implications of silver nanoparticle induced cell apoptosis for in vitro gene therapy  

NASA Astrophysics Data System (ADS)

The impact of manufactured nanomaterials on human health and the environment is a major concern for commercial use of nanotechnology based products. A judicious choice of selective usage, lower nanomaterial concentration and use in combination with conventional therapeutic materials may provide the best solution. For example, silver nanoparticles (Ag NPs) are known to be bactericidal and also cytotoxic to mammalian cells. Herein, we investigate the molecular mechanism of Ag NP mediated cytotoxicity in both cancer and non-cancer cells and find that optimum particle concentration leads to programmed cell death in vitro. Also, the benefit of the cytotoxic effects of Ag NPs was tested for therapeutic use in conjunction with conventional gene therapy. The synergistic effect of Ag NPs on the uracil phosphoribosyltransferase expression system sensitized the cells more towards treatment with the drug 5-fluorouracil. Induction of the apoptotic pathway makes Ag NPs a representative of a new chemosensitization strategy for future application in gene therapy.

Gopinath, P.; Gogoi, Sonit Kumar; Chattopadhyay, Arun; Sankar Ghosh, Siddhartha

2008-02-01

291

Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides.  

PubMed

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. PMID:18654167

Chen, Junping; Patil, Swanand; Seal, Sudipta; McGinnis, James F

2006-10-29

292

Lactobacillus casei HY7213 ameliorates cyclophosphamide-induced immunosuppression in mice by activating NK, cytotoxic T cells and macrophages.  

PubMed

Lactic acid bacteria (LAB) have recently attracted considerable attention as treatment options for immune diseases, the incidence of which has been increasing worldwide. The ability of tumor necrosis factor-? producing LAB isolated from cheese to inhibit NF-?B activation in lipopolysaccharide (LPS)-stimulated peritoneal macrophages was investigated. Among the tested LAB, Lactobacillus casei HY7213 inhibited NF-?B activation most potently. Therefore, we measured its immunopotentiating effect in cyclophosphamide (CP)-immunosuppressed mice. When HY7213 was orally administered for 5 or 15 d, it reversed the CP immunosuppressant effect by increasing body and spleen weights, blood red and white blood cells levels, and splenocyte and bone marrow cells counts. Treatment with CP in mice markedly reduced concanavalin A (ConA)-induced T cell proliferation to 54% compared to the normal group. Oral administration of HY7213 in CP-immunosuppressed mice reversed that value to 95% of the normal group on day 15. Furthermore, oral administration of HY7213 to CP-treated mice significantly enhanced the expression of IL-2 and IFN-? in ConA-induced splenic cytotoxic T cells, restored the CP-impaired phagocytosis of macrophage, and increased the cytotoxicity of natural killer (NK) and cytotoxic T cells derived from spleen and bone marrow against YAC-1. Based on these findings, we suggest that HY7213 may promote the recovery of immunosuppression caused by chemotherapeutic agents, such as CP, by activating NK cells, cytotoxic T cells and macrophages. PMID:23672525

Jang, Se-Eun; Joh, Eun-Ha; Ahn, Young-Tae; Huh, Chul-Sung; Han, Myung Joo; Kim, Dong-Hyun

2013-06-01

293

The determination and prevention of cytotoxic effects induced in human lymphocytes by the alkylating agent 2,2'-dichlorodiethyl sulfide (sulfur mustard, HD).  

PubMed

2,2'-Dichlorodiethyl sulfide (sulfur mustard, HD, 1,1'-thio-bis[2-chloroethane]) is a potent vesicant which can cause severe lesions to skin, lung, and eyes. There is no convenient in vitro or in vivo method(s) to objectively measure the damage induced by HD; therefore, a simple in vitro method was developed using human peripheral lymphocytes to study HD-induced cytotoxicity. The cytotoxicity of HD was measured using dye exclusion as an indicator of human lymphocyte viability. Exposure to HD resulted in both a time- and a concentration-dependent cytotoxic effect on human lymphocytes. Using this in vitro assay, the effectiveness of various therapeutics (niacin, niacinamide, and 3-aminobenzamide) in preventing HD-induced cytotoxicity was studied. Niacinamide and 3-aminobenzamide prevented the cytotoxic effects of HD for up to 2 days. PMID:1532867

Meier, H L; Johnson, J B

1992-04-01

294

Determination and prevention of cytotoxic effects induced in human lymphocytes by the alkylating agent 2,2`-dichlorodiethyl sulfide (sulfur mustard, HD). (Reannouncement with new availability information)  

SciTech Connect

2,2`-Dichlorodiethyl sulfide (sulfur mustard), HD, 1,1`thiobis(2-chloroethane) is a potent vesicant which can cause severe lesions to skin, lung, and eyes. There is no convenient in vitro or in vivo method(s) to objectively measure the damage induced by HD; therefore, a simple in vitro method was developed using human peripheral lymphocytes to study HD-induced cytotoxicity. The cytotoxicity of HD was measured using dye exclusion as an indicator of human lymphocyte viability. Exposure to HD resulted in both a time- and a concentration-dependent cytotoxic effect on human lymphocytes. Using this in vitro assay, the effectiveness of various therapeutics (niacin, niacinamide, and 3-aminobenzamide) in preventing HD-induced cytotoxicity was studied. Niacinamide and 3-aminobenzamide prevented the cytotoxic effects of HD for up to 2 days.

Meier, H.L.; Johnson, J.B.

1992-12-31

295

Inhibition of sulfur mustard-induced cytotoxicity and inflammation by the macrolide antibiotic roxithromycin in human respiratory epithelial cells  

PubMed Central

Background Sulfur mustard (SM) is a potent chemical vesicant warfare agent that remains a significant military and civilian threat. Inhalation of SM gas causes airway inflammation and injury. In recent years, there has been increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE) cells and bronchial/tracheal epithelial (BTE) cells. Cell viability, expression of proinflammatory cytokines including interleukin (IL)-1?, IL-6, IL-8 and tumor necrosis factor (TNF), and expression of inducible nitric oxide synthase (iNOS) were examined, since these proinflammatory cytokines/mediators are import indicators of tissue inflammatory responses. We suggest that the influence of roxithromycin on SM-induced inflammatory reaction could play an important therapeutic role in the cytotoxicity exerted by this toxicant. Results MTS assay and Calcein AM/ethidium homodimer (EthD-1) fluorescence staining showed that roxithromycin decreased SM cytotoxicity in both SAE and BTE cells. Also, roxithromycin inhibited the SM-stimulated overproduction of the proinflammatory cytokines IL-1?, IL-6, IL-8 and TNF at both the protein level and the mRNA level, as measured by either enzyme-linked immunosorbent assay (ELISA) or real-time RT-PCR. In addition, roxithromycin inhibited the SM-induced overexpression of iNOS, as revealed by immunocytochemical analysis using quantum dots as the fluorophore. Conclusion The present study demonstrates that roxithromycin has inhibitory effects on the cytotoxicity and inflammation provoked by SM in human respiratory epithelial cells. The decreased cytotoxicity in roxithromycin-treated cells likely depends on the ability of the macrolide to down-regulate the production of proinflammatory cytokines and/or mediators. The results obtained in this study suggest that macrolide antibiotics may serve as potential vesicant respiratory therapeutics through mechanisms independent of their antibacterial activity.

Gao, Xiugong; Ray, Radharaman; Xiao, Yan; Barker, Peter E; Ray, Prabhati

2007-01-01

296

The synthesis and characterization of poly(?-glutamic acid)-coated magnetite nanoparticles and their effects on antibacterial activity and cytotoxicity  

NASA Astrophysics Data System (ADS)

Magnetite nanoparticles (MNPs) modified with sodium and calcium salts of poly(?-glutamic acid) (NaPGA and CaPGA) were synthesized by the coprecipitation method, followed by characterization and evaluation of their antibacterial and cytotoxic effects. Superparamagnetic MNPs are particularly attractive for magnetic driving as well as bacterial biofilm and cell targeting in in vivo applications. Characterization of synthesized MNPs by the Fourier transform infrared spectra and magnetization curves confirmed the PGA coating on MNPs. The mean diameter of NaPGA- and CaPGA-coated MNPs as determined by transmission electron microscopy was 11.8 and 14 nm, respectively, while the x-ray diffraction pattern revealed the as-synthesized MNPs to be pure magnetite. Based on agar dilution assay, both NaPGA- and CaPGA-coated MNPs showed a lower minimum inhibitory concentration in Salmonella enteritidis SE 01 than the commercial antibiotics linezolid and cefaclor, but the former was effective against Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 10832, whereas the latter was effective against Escherichia coli O157:H7 TWC 01. An in vitro cytotoxicity study in human skin fibroblast cells as measured by MTT assay implied the as-synthesized MNPs to be nontoxic. This outcome demonstrated that both ?-PGA-modified MNPs are cytocompatible and possess antibacterial activity in vitro, and thereby should be useful in in vivo studies for biomedical applications.

Inbaraj, B. Stephen; Kao, T. H.; Tsai, T. Y.; Chiu, C. P.; Kumar, R.; Chen, B. H.

2011-02-01

297

Nonsolvents-induced swelling of poly(methyl methacrylate) nanoparticles.  

PubMed

Polymer nanoparticles have been used in a wide variety of applications. In most of these applications, they are generally dispersed in a non-solvent. However, the effect of the non-solvent on the structure, physical properties and function of the nanoparticles has not yet ever taken into account. In this study, monodispersed poly(methyl methacrylate) (PMMA) nanoparticles were prepared by a surfactant-free emulsion polymerization. The PMMA nanoparticles were dispersed in water and in methanol, both typical non-solvents for PMMA, so that we could discuss the effect of the non-solvent on the nanoparticles. Dynamic light scattering measurements revealed that the hydrodynamic radius of the PMMA nanoparticles in methanol was larger than the same PMMA dispersed in water. Their DLS values were also larger than the radius of the nanoparticles measured by atomic force microscopy. When pyrene was dispersed in methanol with the PMMA nanoparticles, it was incorporated into the nanoparticles. These results clearly indicate that non-solvent molecules can be sorbed into polymer nanoparticles because the area of the interface, where polymer segments might be dissolved into liquid phases, as the total volume is quite larger for such nanoparticles. Therefore, based on our findings, it can be arguably established that the present assumption for a polymer not to be swollen in its non-solvent is not necessarily true. PMID:23955567

Shundo, Atsuomi; Hori, Koichiro; Penaloza, David P; Yoshihiro, Kazuki; Annaka, Masahiko; Tanaka, Keiji

2013-08-16

298

Cytotoxic Activities of Silver Nanoparticles and Silver Ions in Parent and Tamoxifen-Resistant T47D Human Breast Cancer Cells and Their Combination Effects with Tamoxifen against Resistant Cells  

PubMed Central

Studies on biomedical applications of nanoparticles are growing with a rapid pace. In medicine, nanoparticles may be the solution for multi-drug-resistance which is still a major drawback in chemotherapy of cancer. In the present study, we investigated the potential cytotoxic effect of silver nanoparticles (Ag NPs) and silver ions (Ag+) in both parent and tamoxifen-resistant T47D cells in presence and absence of tamoxifen. Ag NPs were synthesized (< 28 nm) and MTT assay was carried out. The associated IC50 values were found to be: 6.31 µg/ml for Ag NPs/parent cells, 37.06 µg/ml for Ag NPs/tamoxifen-resistant cells, 33.06 µg/ml for Ag+/parent cells and 10.10 µg/ml for Ag+/resistant cells. As a separate experiment, the effect of subinhibitory concentrations of Ag NPs and Ag+ on the proliferation of tamoxifen-resistant cells was evaluated at non-toxic concentrations of tamoxifen. Our results suggested that in non-cytotoxic concentrations of silver nanomaterials and tamoxifen, the combinations of Ag+-tamoxifen and Ag NPs-tamoxifen are still cytotoxic. This finding may be of great potential benefit in chemotherapy of breast cancer; since much lower doses of tamoxifen may be needed to produce the same cytotoxic effect and side effects will be reduced.

Ostad, Seyed Naser; Dehnad, Shahrzad; Nazari, Zeinab Esmail; Fini, Shohreh Tavajohi; Mokhtari, Narges; Shakibaie, Mojtaba; Shahverdi, Ahmad Reza

2010-01-01

299

Dissociation of the vacuolar and macroautophagic cytopathology from the cytotoxicity induced by the lipophilic local anesthetic bupivacaine.  

PubMed

Local anesthetics, like many other cationic drugs, induce a vacuolar and macroautophagic cytopathology that has been observed in vivo and in various cell types; some also induce cytotoxicity of mitochondrial origin (apoptosis and necrosis) and it is not known whether the 2 types of toxicity overlap or interact. We compared bupivacaine with a more hydrophilic agent, lidocaine, for morphological, functional, and toxicological responses in a previously exploited nonneuronal system, primary smooth muscle cells. Bupivacaine induced little vacuolization (?2.5 mmol/L, 4 h), but elicited autophagic accumulation (?0.5 mmol/L, 4 h) and was massively cytotoxic at 2.5-5 mmol/L (4-24 h), the latter effect being unabated by the V-ATPase inhibitor bafilomycin A1. Lidocaine exerted little cytotoxicity at and below 5 mmol/L for 24 h, but intensely induced the V-ATPase-dependent vacuolar and autophagic cytopathology. Bupivacaine was more potent than lidocaine in disrupting mitochondrial potential, as judged by Mitotracker staining (significant proportions of cells affected in the 1-5 and 5-10 mmol/L concentration ranges, respectively). The addition of mitochondrial-inactivating toxins antimycin A and oligomycin to lidocaine (2.5 mmol/L) reproduced the profile of bupivacaine action (low intensity of vacuolization and retained autophagic accumulation). The high potency of bupivacaine as a mitochondrial toxicant eclipses the benign vacuolar and autophagic response seen with more hydrophilic local anesthetics. PMID:21812528

Morissette, Guillaume; Bawolak, Marie-Thérèse; Marceau, François

2011-07-01

300

Silver nanoparticle induced blood-brain barrier inflammation and increased permeability in primary rat brain microvessel endothelial cells.  

PubMed

The current report examines the interactions of silver nanoparticles (Ag-NPs) with the cerebral microvasculature to identify the involvement of proinflammatory mediators that can increase blood-brain barrier (BBB) permeability. Primary rat brain microvessel endothelial cells (rBMEC) were isolated from adult Sprague-Dawley rats for an in vitro BBB model. The Ag-NPs were characterized by transmission electron microscopy (TEM), dynamic light scattering, and laser Doppler velocimetry. The cellular accumulation, cytotoxicity (6.25-50 ?g/cm(3)) and potential proinflammatory mediators (interleukin [IL]-1?, IL-2, tumor necrosis factor [TNF] ?, and prostaglandin E(2) [PGE(2)]) of Ag-NPs (25, 40, or 80 nm) were determined spectrophotometrically, cell proliferation assay (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide) and ELISA. The results show Ag-NPs-induced cytotoxic responses at lower concentrations for 25 and 40 nm when compared with 80-nm Ag-NPs. The proinflammatory responses in this study demonstrate both Ag-NPs size and time-dependent profiles, with IL-1B preceding both TNF and PGE(2) for 25 nm. However, larger Ag-NPs (40 and 80 nm) induced significant TNF responses at 4 and 8 h, with no observable PGE(2) response. The increased fluorescein transport observed in this study clearly indicates size-dependent increases in BBB permeability correlated with the severity of immunotoxicity. Together, these data clearly demonstrate that larger Ag-NPs (80 nm) had significantly less effect on rBMEC, whereas the smaller particles induced significant effects on all the end points at lower concentrations and/or shorter times. Further, this study suggests that Ag-NPs may interact with the cerebral microvasculature producing a proinflammatory cascade, if left unchecked; these events may further induce brain inflammation and neurotoxicity. PMID:20713472

Trickler, William J; Lantz, Susan M; Murdock, Richard C; Schrand, Amanda M; Robinson, Bonnie L; Newport, Glenn D; Schlager, John J; Oldenburg, Steven J; Paule, Merle G; Slikker, William; Hussain, Saber M; Ali, Syed F

2010-08-16

301

Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide.  

PubMed

Endothelial cells, macrophages, neutrophils, and neuronal cells generate superoxide (O2-) and nitric oxide (.NO) which can combine to form peroxynitrite anion (ONOO-). Peroxynitrite, known to oxidize sulfhydryls and to yield products indicative of hydroxyl radical (.OH) reaction with deoxyribose and dimethyl sulfoxide, is shown herein to induce membrane lipid peroxidation. Peroxynitrite addition to soybean phosphatidylcholine liposomes resulted in malondialdehyde and conjugated diene formation, as well as oxygen consumption. Lipid peroxidation was greater at acidic and neutral pH, with no significant lipid peroxidation occurring above pH 9.5. Addition of ferrous (Fe+2) or ferric (Fe+3) iron did not enhance lipid peroxide formation over that attributable to peroxynitrite alone. Diethylenetetraminepentacetic acid (DTPA) or iron removal from solutions by ion-exchange chromatography decreased conjugated diene formation by 25-50%. Iron did not play an essential role in initiating lipid peroxidation, since DTPA and iron depletion of reaction systems were only partially inhibitory. In contrast, desferrioxamine had an even greater concentration-dependent inhibitory effect, completely abolishing lipid peroxidation at 200 microM. The strong inhibitory effect of desferrioxamine on lipid peroxidation was due to direct reaction with peroxynitrous acid in addition to iron chelation. We conclude that the conjugate acid of peroxynitrite, peroxynitrous acid (ONOOH), and/or its decomposition products, i.e., .OH and nitrogen dioxide (.NO2), initiate lipid peroxidation without the requirement of iron. These observations demonstrate a potential mechanism contributing to O2-(-)and .NO-mediated cytotoxicity. PMID:1654835

Radi, R; Beckman, J S; Bush, K M; Freeman, B A

1991-08-01

302

Exogenous hydrogen sulfide induces functional inhibition and cell death of cytotoxic lymphocytes subsets.  

PubMed

The toxic effects of exogenous hydrogen sulfide on peripheral blood lymphocytes have been investigated in detail. Hydrogen sulfide is now considered as a gasotransmitter with specific functional roles in different cell types, like neurons and vascular smooth muscle. Here we show that exogenous hydrogen sulfide induces a caspase-independent cell death of peripheral blood lymphocytes that depends on their intracellular glutathione levels, with a physiologically relevant subset specificity for CD8+ T cells and NK cells. Although lymphocyte activation does not modify their sensitivity to HS-, after 24 h exposure to hydrogen sulfide surviving lymphocyte subsets show a dramatically decreased proliferation in response to mitogens and a reduced IL-2 production. Overall, our data demonstrate that HS- reduces the cellular cytotoxic response of peripheral blood lymphocytes as well as their production of IL-2, therefore de-activating the major players of local inflammatory responses, adding new basic knowledge to the clinically well known anti-inflammatory effects of sulfur compounds. PMID:17516567

Mirandola, Prisco; Gobbi, Giuliana; Sponzilli, Ivonne; Pambianco, Maurizia; Malinverno, Chiara; Cacchioli, Antonio; De Panfilis, Giuseppe; Vitale, Marco

2007-12-01

303

Antibody-dependent cell lysis by NK cells is preserved after sarcoma-induced inhibition of NK cell cytotoxicity.  

PubMed

Osteosarcoma and Ewing's sarcoma tumor cells are susceptible to IL15-induced or antibody-mediated cytolytic activity of NK cells in short-term cytotoxicity assays. When encountering the tumor environment in vivo, NK cells may be in contact with tumor cells for a prolonged time period. We explored whether a prolonged interaction with sarcoma cells can modulate the activation and cytotoxic activity of NK cells. The 40 h coculture of NK cells with sarcoma cells reversibly interfered with the IL15-induced expression of NKG2D, DNAM-1 and NKp30 and inhibited the cytolytic activity of NK cells. The inhibitory effects on receptor expression required physical contact between NK cells and sarcoma cells and were independent of TGF-?. Five days pre-incubation of NK cells with IL15 prevented the down-regulation of NKG2D and cytolytic activity in subsequent cocultures with sarcoma cells. NK cell Fc?RIIIa/CD16 receptor expression and antibody-mediated cytotoxicity were not affected after the coculture. Inhibition of NK cell cytotoxicity was directly linked to the down-regulation of the respective NK cell-activating receptors. Our data demonstrate that the inhibitory effects of sarcoma cells on the cytolytic activity of NK cells do not affect the antibody-dependent cytotoxicity and can be prevented by pre-activation of NK cells with IL15. Thus, the combination of cytokine-activated NK cells and monoclonal antibody therapy may be required to improve tumor targeting and NK cell functionality in the tumor environment. PMID:23624801

Pahl, Jens H W; Ruslan, S Eriaty N; Kwappenberg, Kitty M C; van Ostaijen-Ten Dam, Monique M; van Tol, Maarten J D; Lankester, Arjan C; Schilham, Marco W

2013-04-27

304

Kinetics of cytotoxicity induced by immunotoxins. Enhancement by lysosomotropic amines and carboxylic ionophores.  

PubMed

The kinetics of cytotoxicity induced by ricin and a series of immunotoxins consisting of ricin A-chain coupled to antibodies against cell-surface antigens has been studied. The inhibition of protein synthesis in cells treated with immunotoxins or ricin occurs after a lag period. The rate of protein synthesis decreases according to a mono-exponential function, indicating a first-order process. With increasing concentration of immunotoxin, a maximal rate of inhibition is reached. The inactivation rate induced by immunotoxins was much slower than that achieved with ricin, even when products were compared on a basis of an identical number of molecules bound per cell, demonstrating the real higher efficacy of ricin. The time required to reduce protein synthesis by 90%, denoted T10, was 1.4-1.6 h with ricin, 60 h with anti-T65 immunotoxin on CEM human T leukemia cells (T65 positive), 65 h with anti-p97 immunotoxin on SK-MEL 28 human melanoma cells (p97 positive), and 20 h with an IgM anti-Thy 1.2 immunotoxin on WEHI-7 mouse T leukemia cells (Thy 1.2 positive). In this latter case, when the IgM antibody was replaced by an IgG anti-Thy 1.2, a 5-fold increase in the inactivation rate was obtained, demonstrating the importance of the binding moiety for the immunotoxins. Lysosomotropic amines such as ammonium chloride, chloroquine, and methylamine and carboxylic ionophores such as monensin, which are known to interfere with the uptake of certain macromolecules, strongly increased the rate of protein synthesis inhibition by all immunotoxins tested and increased 4-50,000-fold the sensitivity of cells to the immunotoxin. Enhancement in the inactivation rate was as much as 7-10-fold when either of these compounds was added, generating T10 values comparable to those of ricin. PMID:6746651

Casellas, P; Bourrie, B J; Gros, P; Jansen, F K

1984-08-10

305

TRPC1 protects human SH-SY5Y cells against salsolinol-induced cytotoxicity by inhibiting apoptosis  

Microsoft Academic Search

Salsolinol, an endogenous neurotoxin, may be involved in the pathogenesis of Parkinson's disease. In this study, we sought to determine whether salsolinol-induced cytotoxicity in SH-SY5Y human neuroblastoma cells, a cloned cell line which expresses dopaminergic activity, could be prevented by overexpressing a Ca2+ channel, transient receptor potential (TRPC1) protein. Exposure of SH-SY5Y cells to 500 ?M salsolinol for 12 h resulted in

Sunitha Bollimuntha; Manuchair Ebadi; Brij B. Singh

2006-01-01

306

Triptolide induced cytotoxic effects on human promyelocytic leukemia, T cell lymphoma and human hepatocellular carcinoma cell lines  

Microsoft Academic Search

Triptolide, a traditional Chinese medicine, has been reported to be effective in the treatment of auto-immune diseases, and it can also induce anti-neoplastic activity on several human tumor cell lines. This study investigates the cytotoxic function and the functional mechanism of triptolide on tumor cells. Promyelocytic leukemia, (HL-60), T cell lymphoma (Jurkat), and human hepatocelluar carcinoma (SMMC-7721) cells were subjected

Ella Wai-Ching Chan; Samuel Chak-Sum Cheng; Fion Wan-Yee Sin; Yong Xie

2001-01-01

307

Cytotoxic and apoptosis-inducing ent-kaurane-type diterpenoids from the Japanese liverwort Jungermannia truncata NEES.  

PubMed

Five new ent-kaurane-type diterpenoids and a new gymnomitrane (=barbatane)-type sesquiterpenoid have been isolated from the Japanese liverwort Jungermannia truncata NEES, together with twelve previously known ent-kaurane-type diterpenoids. The structures of the new compounds were elucidated by two-dimensional (2D) NMR experiments and chemical reaction. Some of the isolated compounds showed cytotoxicity against human leukemia cell lines and induced apoptosis. PMID:12045336

Nagashima, Fumihiro; Kondoh, Masuo; Uematsu, Toshinari; Nishiyama, Akiko; Saito, Sayaka; Sato, Masao; Asakawa, Yoshinori

2002-06-01

308

Reactive oxygen species-mediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells  

Microsoft Academic Search

BACKGROUND: Saikosaponin-a and -d, two naturally occurring compounds derived from Bupleurum radix, have been shown to exert anti-cancer activity in several cancer cell lines. However, the effect of combination of saikosaponins with chemotherapeutic drugs has never been addressed. Thus, we investigated whether these two saikosaponins have chemosensitization effect on cisplatin-induced cancer cell cytotoxicity. METHODS: Two cervical cancer cell lines, HeLa

Qiong Wang; Xue-lian Zheng; Lan Yang; Fang Shi; Lin-bo Gao; Ying-jia Zhong; Hong Sun; Fan He; Yong Lin; Xia Wang

2010-01-01

309

Inflammatory and cytotoxic responses of an alveolar-capillary coculture model to silica nanoparticles: Comparison with conventional monocultures  

Microsoft Academic Search

BACKGROUND: To date silica nanoparticles (SNPs) play an important role in modern technology and nanomedicine. SNPs are present in various materials (tyres, electrical and thermal insulation material, photovoltaic facilities). They are also used in products that are directly exposed to humans such as cosmetics or toothpaste. For that reason it is of great concern to evaluate the possible hazards of

Jennifer Kasper; Maria I Hermanns; Christoph Bantz; Michael Maskos; Roland Stauber; Christine Pohl; Ronald E Unger; James C Kirkpatrick

2011-01-01

310

Outer membrane vesicles of Vibrio vulnificus deliver cytolysin-hemolysin VvhA into epithelial cells to induce cytotoxicity.  

PubMed

The Gram-negative bacterium Vibrio vulnificus produces cytotoxins that induce the acute death of host cells. However, the secretory mechanisms of such cytotoxins have not been extensively studied. Previously, we reported that substantial amounts of V. vulnificus cytolysin-hemolysin (VvhA) are produced in vivo during the bacterial infection in mice and that this cytotoxin, in conjunction with RtxA1, mediates cytotoxicity. In this study, we investigated whether V. vulnificus cells release outer membrane vesicles (OMVs), which are used by some Gram-negative bacteria to deliver virulence factors into host cells. We found that V. vulnificus produce OMVs and that these vesicles can induce host cell death. This process appears to be mediated by VvhA, as evidenced by the finding that OMVs isolated from VvhA-null mutants do not induce cytotoxicity. In addition, cholesterol sequestration in the host cells prevents OMV-mediated VvhA delivery, indicating that VvhA-bearing OMVs interact with cholesterol on the host cell surface. Furthermore, intracellular expression experiments revealed that VvhA-mediated cytotoxicity is driven by its N-terminal leukocidin domain. PMID:20682286

Kim, Young Ran; Kim, Bang Ul; Kim, Soo Young; Kim, Choon Mee; Na, Hee Sam; Koh, Jeong Tae; Choy, Hyon E; Rhee, Joon Haeng; Lee, Shee Eun

2010-08-01

311

Tumor Induced Inactivation of Natural Killer Cell Cytotoxic Function; Implication in Growth, Expansion and Differentiation of Cancer Stem Cells  

PubMed Central

Accumulated evidence indicates that cytotoxic function of immune effectors is largely suppressed in the tumor microenvironment by a number of distinct effectors and their secreted factors. The aims of this review are to provide a rationale and a potential mechanism for immunosuppression in cancer and to demonstrate the significance of such immunosuppression in cellular differentiation and progression of cancer. To that end, we have recently shown that NK cells mediate significant cytotoxicity against primary oral squamous carcinoma stem cells (OSCSCs) as compared to their more differentiated oral squamous carcinoma cells (OSCCs). In addition, human embryonic stem cells (hESCs), Mesenchymal Stem Cells (hMSCs), dental pulp stem cells (hDPSCs) and induced pluripotent stem cells (hiPSCs) were all significantly more susceptible to NK cell mediated cytotoxicity than their differentiated counterparts or parental cells from which they were derived. We have also reported that inhibition of differentiation or reversion of cells to a less-differentiated phenotype by blocking NF?B or targeted knock down of COX2 in primary monocytes in vivo significantly augmented NK cell function. Total population of monocytes and those depleted of CD16(+) subsets were able to substantially prevent NK cell mediated lysis of OSCSCs, MSCs and DPSCs. Taken together, our results suggest that stem cells are significant targets of the NK cell cytotoxicity. The concept of split anergy in NK cells and its contribution to tissue repair and regeneration and in tumor resistance and progression will be discussed in this review.

Jewett, Anahid; Tseng, Han-Ching

2011-01-01

312

Microbially induced synthesis of cubic and hexagonal selenium nanoparticles.  

PubMed

Nanobiotechnology represents an economic alternative for chemical and physical methods of nanoparticles formation. The objectives of this study were to synthesize selenium nanoparticles by microbial processes using anaerobic metal-reducing bacteria as well as to characterize mineralogical properties of the nanoparticles. The selenium nanoparticles were about 200 nm in size and ball shaped. Microbial processes for elemental selenium synthesis may be useful for recovery of natural selenate in the natural environments and immobilization of selenium isotope in the high level nuclear waste disposal sites. PMID:23755605

Park, Bitna; Kang, Serku; Moon, Wonjin; Roh, Yul

2013-03-01

313

Determination and prevention of cytotoxic effects induced in human lymphocytes by the alkylating agent 2,2`-dichlorodiethyl sulfide (sulfur mustard, HD). (Reannouncement with new availability information)  

Microsoft Academic Search

2,2`-Dichlorodiethyl sulfide (sulfur mustard), HD, 1,1`thiobis(2-chloroethane) is a potent vesicant which can cause severe lesions to skin, lung, and eyes. There is no convenient in vitro or in vivo method(s) to objectively measure the damage induced by HD; therefore, a simple in vitro method was developed using human peripheral lymphocytes to study HD-induced cytotoxicity. The cytotoxicity of HD was measured

H. L. Meier; J. B. Johnson

1992-01-01

314

Cellular cytotoxic response induced by highly purified multi-wall carbon nanotube in human lung cells  

Microsoft Academic Search

Carbon nanotubes, a promising nanomaterial with unique characteristics, have applications in a variety of fields. The cytotoxic\\u000a effects of carbon nanotubes are partially due to the induction of oxidative stress; however, the detailed mechanisms of nanotube\\u000a cytotoxicity and their interaction with cells remain unclear. In this study, the authors focus on the acute toxicity of vapor-grown\\u000a carbon fiber, HTT2800, which

Tamotsu Tsukahara; Hisao Haniu

2011-01-01

315

Temperature induced phase separation of luminescent silica nanoparticles in Triton X-100 solutions.  

PubMed

The aggregation and cloud point behavior of Tb(III)-doped silica nanoparticles has been studied in Triton X-100 (TX-100) solutions at various concentration conditions by fluorimetry, dynamic light scattering, electrophoresis and transmission electron microscopy methods. The temperature responsive behavior of nanoparticles is observed at definite concentration of TX-100, where the aggregation of TX-100 at the silica/water interface is evident from the increased size of the silica nanoparticles. The reversible dehydration of TX-100 aggregates at the silica/water interface should be assumed as the main reason of the temperature induced phase separation of silica nanoparticles. The distribution of nanoparticles between aqueous and surfactant rich phases at the phase separation conditions can be modified by the effect of additives. PMID:21163490

Mustafina, Asiya R; Elistratova, Julia G; Bochkova, Olga D; Burilov, Vladimir A; Fedorenko, Svetlana V; Konovalov, Alexander I; Soloveva, Svetlana Ye

2010-11-23

316

Functionalization-induced improvement in magnetic properties of Fe3O4 nanoparticles for biomedical applications  

NASA Astrophysics Data System (ADS)

Fe3O4 were synthesized nanoparticles by thermal decomposition method with oleic acid as the surfactant, and to make them suitable for aqueous environments, dopamine ligand exchange was carried out on the particles. The nanoparticle size and phase was quantified by transmission electron microscopy (TEM) and x-ray diffraction (XRD), respectively. Superconducting quantum interference device magnetometry confirmed superparamagnetic behavior in both nanoparticles. A surprising and significant increase in the remanence MR, saturation magnetization MS, and blocking temperature TB of the particles was found after dopamine functionalization, even though TEM and XRD studies revealed no change in the particles' size and/or structure. The results are consistent with an increase in the magnetic size of the nanoparticle core induced by the dopamine ligand exchange process. These effects are tentatively attributed to surface bonding effects that alter the canted magnetic state of the Fe3O4 nanoparticles.

Nagesha, Dattatri K.; Plouffe, Brian D.; Phan, Minh; Lewis, Laura H.; Sridhar, Srinivas; Murthy, Shashi K.

2009-04-01

317

Optically induced Zn/ZnO nanoparticles selective deposition on singlemode fiber optic end  

NASA Astrophysics Data System (ADS)

A study of optically induced Zn/ZnO nanoparticles selective deposition using a coherent light source on single-mode fiber optic end is presented. In the numerical studies, Zn/ZnO spherical nanoparticles are considered dissolved in isopropyl alcohol with different diameters under the influence of a Gaussian beam with fundamental mode and linear polarization. The results of this study show that the gradient force is not sufficient to move Zn nanoparticles toward optical fiber end face, but it is sufficient to move ZnO nanoparticles of a certain diameter. In the experimental studies, Zn/ZnO nanoparticles were mixed with isopropyl alcohol and subsequently deposited on the fiber end face using an infrared laser. The results obtained by atomic force and optical microscopy show a good uniform distribution of nanostructures deposited on the core of the fiber end face.

Ortega-Mendoza, J. G.; Chávez, F.; Zaca-Moran, P.; Ramos-Garcia, R.; Felipe, C.; Pérez-Sánzhez, G. F.; Gutiérrez, Jaime G.; Goiz, O.

2011-09-01

318

Thermal accommodation coefficients for laser-induced incandescence sizing of metal nanoparticles in monatomic gases  

NASA Astrophysics Data System (ADS)

The capabilities of time-resolved laser-induced incandescence (TiRe-LII), a combustion diagnostic used almost exclusively to measure soot primary particles, could potentially be extended to size aerosolized metal nanoparticles. In order to do this, however, it is necessary to characterize the thermal accommodation coefficient, ?, which specifies the heat conduction rate between the laser-energized nanoparticles and the surrounding gas. This paper extends a molecular dynamics (MD) methodology to calculate ? for Fe/He, Fe/Ar, Mo/He, and Mo/Ar systems. A comparative analysis of the results shows that ? is most strongly influenced by the potential well between the gas molecule and nanoparticle surface. Finally, the MD-derived value for ? is used to recover the nanoparticle size distribution for TiRe-LII measurements made on molybdenum nanoparticles in argon.

Daun, K. J.; Sipkens, T. A.; Titantah, J. T.; Karttunen, M.

2013-09-01

319

Nonviral cell labeling and differentiation agent for induced pluripotent stem cells based on mesoporous silica nanoparticles.  

PubMed

The generation of induced pluripotent stem cells (iPSCs) is an innovative personalized-regenerative technology, which can transform own-self somatic cells into embryonic stem (ES)-like cells, which have the potential to differentiate into all cell types of three dermal lineages. However, how to quickly, efficiently, and safely produce specific-lineage differentiation from pluripotent-state cells and iPSCs is still an open question. The objective of the present study was to develop a platform of a nonviral gene delivery system of mesoporous silica nanoparticles (MSNs) to rapidly generate iPSC-derived definitive-lineage cells, including endodermal-differentiated cells. We also evaluated the feasibility and efficiency of FITC-conjugated MSNs (FMSNs) for labeling of iPSCs and utilized the multifunctional properties of FMSNs for a suitable carrier for biomolecule delivery. We showed that FMSNs of various surface charges could be efficiently internalized by iPSCs without causing cytotoxicity. The levels of reactive oxygen species and pluripotent status, including in vitro stemness signatures and in vivo teratoma formation, remained unaltered. Notably, positive-charged FMSN enhanced cellular uptake efficiency and retention time. Moreover, when using positive-charged FMSN to deliver hepatocyte nuclear factor 3? (HNF3?) plasmid DNA (pDNA), the treated iPSCs exhibited significantly improved definitive endoderm formation and further quickly differentiated into hepatocyte-like cells with mature functions (low-density lipoprotein uptake and glycogen storage) within 2 weeks in vitro. Double delivery of pHNF3? further improved mRNA expression levels of liver-specific genes. These findings reveal the multiple advantages of FMSNs to serve as ideal vectors not only for stem cell labeling but also for safe gene delivery to promote the production of hepatocyte-like cells from iPSCs. PMID:24063246

Chen, Wei; Tsai, Ping-Hsing; Hung, Yann; Chiou, Shih-Hwa; Mou, Chung-Yuan

2013-09-30

320

Biological effects induced by BSA-stabilized silica nanoparticles in mammalian cell lines.  

PubMed

Much of the concerns regarding engineered nanoparticle (NP) toxicity are based on knowledge from previous studies on particles in ambient air or occupational situations. E.g., the effects of exposure to silica dust particles have been studied intensely due to the carcinogenicity of crystalline silica. However, the increasing usage of engineered amorphous silica NPs has emphasized the need for further mechanistic insight to predict the consequences of exposure to the amorphous type of silica NPs. The present study focused on the in vitro biological effects following exposure to well-dispersed, BSA-stabilized, amorphous silica NPs whereas unmodified silica NPs where included for reasons of comparison. The cytotoxicity of the silica NPs was investigated in six different cell lines (A549, THP-1, CaCo-2, ASB-XIV, J-774A.1, and Colon-26) selected to explore the significance of organ and species sensitivity in vitro. Viability data demonstrated that macrophages were most sensitive to silica NP and interestingly, murine cell lines were generally found to be more sensitive than comparable human cell lines. Further studies were conducted in the human epithelial lung cell line, A549, to explore the molecular mechanism of silica toxicity. Generation of reactive oxygen species, one of the proposed toxicological mechanisms of NPs, was investigated in A549 cells by the dichlorofluorescin (DCF) assay to be significantly induced at NP concentrations above 113 ?g/mL. However, induction of oxidative stress related pathways was not found after silica NP exposure for 24 h in gene array studies conducted in A549 cells at a relatively low NP concentration (EC20). Up-regulated genes (more than 2-fold) were primarily related to lipid metabolism and biosynthesis whereas down-regulated genes included several processes such as transcription, cell junction, extra cellular matrix (ECM)-receptor interaction and others. Thus, gene expression data proposes that several cellular processes other than oxidative stress could be affected by exposure to silica NPs. PMID:23623845

Foldbjerg, Rasmus; Wang, Jing; Beer, Christiane; Thorsen, Kasper; Sutherland, Duncan S; Autrup, Herman

2013-04-25

321

Cerium dioxide nanoparticles induce apoptosis and autophagy in human peripheral blood monocytes.  

PubMed

Cerium dioxide nanoparticles (CeO(2) NPs) have diversified industrial uses, and novel therapeutic applications are actively being pursued. There is a lack of mechanistic data concerning the effects of CeO(2) NPs on primary human cells. We aimed at characterizing the cytotoxic effects of CeO(2) NPs in human peripheral blood monocytes. CeO(2) NPs and their suspensions were thoroughly characterized, including using transmission electron microscopy (TEM), dynamic light scattering, and zeta potential analysis. Blood from healthy human volunteers was drawn through phlebotomy, and CD14+ cells were isolated. Cells were exposed to CeO(2) NPs (0.5-10 ?g/mL) for 20 or 40 h, and mechanisms of cell injury were studied. TEM revealed that CeO(2) NPs are internalized by monocytes and are found either in vesicles or free in the cytoplasm. CeO(2) NP exposure leads to decrease in cell viability, and treated cells exhibit characteristic hallmarks of apoptosis (activation of Bax, loss of mitochondrial membrane potential, DNA fragmentation). CeO(2) NP toxicity is caused by mitochondrial damage and overexpression of apoptosis inducing factor, but is not due to caspase activation or reactive oxygen species production. Moreover, CeO(2) NP exposure leads to autophagy, which is further increased after pharmacological inhibition of tumor suppressor protein p53. Inhibition of autophagy partially reverses cell death by CeO(2) NPs. It is concluded that CeO(2) NPs are toxic to primary human monocytes at relatively low doses. PMID:22717232

Hussain, Salik; Al-Nsour, Faris; Rice, Annette B; Marshburn, Jamie; Yingling, Brenda; Ji, Zhaoxia; Zink, Jeffrey I; Walker, Nigel J; Garantziotis, Stavros

2012-06-27

322

Ion-induced photon emission under nanoparticle fabrication  

NASA Astrophysics Data System (ADS)

Metal-ion implantation is well established as a suitable technique for fabrication of nanoparticles embedded in insulators. Photon emission induced by 60 keV Cu- incident ion was in situ measured over a wavelength range from 200 to 900 nm. Special attention was paid to the behavior of the Cu I atomic line emission related to the mass transport of implants. Based on comparison of experimental results for the wide band gap materials (SiO2 and MgAl2O4) with those for metals (W, Mo, Al), it is concluded that, at the beginning of ion bombardment, the radiation is mostly emitted by backscattered atoms. The causes of this are different for the different groups of materials: the high backscattering yield in the case of metals and the high survival probability of the excited backscattered atoms in the case of insulators, when the excitation levels lie below the conduction band edge and the radiative decay is only the available channel for deexcitation. Significant contribution in the Cu I line intensity was observed with increasing dose due to sputtered Cu atoms.

Bandourko, V. V.; Umeda, N.; Zhdanov, S. K.; Kishimoto, N.

2002-06-01

323

Polychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated by antioxidants after exposure.  

PubMed

PCBs and PCB metabolites have been suggested to cause cytotoxicity by inducing oxidative stress, but the effectiveness of antioxidant intervention after exposure has not been established. Exponentially growing MCF-10A human breast and RWPE-1 human prostate epithelial cells continuously exposed for 5 days to 3 microM PCBs [Aroclor 1254 (Aroclor), PCB153, and the 2-(4-chlorophenyl)-1,4-benzoquinone metabolite of PCB3 (4ClBQ)] were found to exhibit growth inhibition and clonogenic cell killing, with 4ClBQ having the most pronounced effects. These PCBs were also found to increase steady-state levels of intracellular O(2)(*-) and H(2)O(2) (as determined by dihydroethidium, MitoSOX red, and 5-(and 6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate oxidation). These PCBs also caused 1.5- to 5.0-fold increases in MnSOD activity in MCF-10A cells and 2.5- to 5-fold increases in CuZnSOD activity in RWPE-1 cells. Measurement of MitoSOX red oxidation with confocal microscopy coupled with colocalization of MitoTracker green in MCF-10A and RWPE-1 cells supported the hypothesis that PCBs caused increased steady-state levels of O(2)(*-) in mitochondria. Finally, treatment with either N-acetylcysteine (NAC) or the combination of polyethylene glycol (PEG)-conjugated CuZnSOD and PEG-catalase added 1 h after PCBs significantly protected these cells from PCB toxicity. These results support the hypothesis that exposure of exponentially growing human breast and prostate epithelial cells to PCBs causes increased steady-state levels of intracellular O(2)(*-) and H(2)O(2), induction of MnSOD or CuZnSOD activity, and clonogenic cell killing that could be inhibited by a clinically relevant thiol antioxidant, NAC, as well as by catalase and superoxide dismutase after PCB exposure. PMID:19796678

Zhu, Yueming; Kalen, Amanda L; Li, Ling; Lehmler, Hans-J; Robertson, Larry W; Goswami, Prabhat C; Spitz, Douglas R; Aykin-Burns, Nukhet

2009-09-28

324

Thermotherapy enhances oxaliplatin-induced cytotoxicity in human colon carcinoma cells  

PubMed Central

AIM: To observe the synergistic effects of hyperthermia in oxaliplatin-induced cytotoxicity in human colon adenocarcinoma Lovo cells. METHODS: The human colon adenocarcinoma cell line Lovo was obtained from Sun Yat-Sen University. Cells were sealed with parafilm and placed in a circulating water bath, and was maintained within 0.01??°C of the desired temperature (37??°C, 39??°C, 41??°C, 43??°C and 45??°C). Thermal therapy was given alone to the negative control group while oxaliplatin was administered to the treatment group at doses of 12.5 ?g/mL and 50 ?g/mL. Identification of morphological changes, 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and Western blotting were used to investigate the effect of thermochemotherapy on human colon adenocarcinoma Lovo cells, including changes in the signal pathway related to apoptosis. RESULTS: A temperature-dependent inhibition of cell growth was observed after oxaliplatin exposure, while a synergistic interaction was detected preferentially with sequential combination. Thermochemotherapy changed the morphology of Lovo cells, increased the inhibition rate of the Lovo cells (P < 0.05) and enhanced cellular population in the G0/G1 phase (16.7% ± 4.8 % in phase S plus 3.7% ± 2.4 % in phase G2/M, P < 0.05). Thermochemotherapy increased apoptosis through upregulating p53, Bax and downregulating Bcl-2. Protein levels were elevated in p53, Bax/Bcl-2 in thermochemotherapy group as compared with the control group (P < 0.05). CONCLUSION: Thermochemotherapy may play an important role in apoptosis via the activation of p53, Bax and the repression of Bcl-2 in Lovo cells.

Zhang, Xiang-Liang; Hu, An-Bin; Cui, Shu-Zhong; Wei, Hong-Bo

2012-01-01

325

Occupational Styrene Exposure Induces Stress-Responsive Genes Involved in Cytoprotective and Cytotoxic Activities  

PubMed Central

Objective The aim of this study was to evaluate the expression of a panel of genes involved in toxicology in response to styrene exposure at levels below the occupational standard setting. Methods Workers in a fiber glass boat industry were evaluated for a panel of stress- and toxicity-related genes and associated with biochemical parameters related to hepatic injury. Urinary styrene metabolites (MA+PGA) of subjects and environmental sampling data collected for air at workplace were used to estimate styrene exposure. Results Expression array analysis revealed massive upregulation of genes encoding stress-responsive proteins (HSPA1L, EGR1, IL-6, IL-1?, TNSF10 and TNF?) in the styrene-exposed group; the levels of cytokines released were further confirmed in serum. The exposed workers were then stratified by styrene exposure levels. EGR1 gene upregulation paralleled the expression and transcriptional protein levels of IL-6, TNSF10 and TNF? in styrene exposed workers, even at low level. The activation of the EGR1 pathway observed at low-styrene exposure was associated with a slight increase of hepatic markers found in highly exposed subjects, even though they were within normal range. The ALT and AST levels were not affected by alcohol consumption, and positively correlated with urinary styrene metabolites as evaluated by multiple regression analysis. Conclusion The pro-inflammatory cytokines IL-6 and TNF? are the primary mediators of processes involved in the hepatic injury response and regeneration. Here, we show that styrene induced stress responsive genes involved in cytoprotection and cytotoxicity at low-exposure, that proceed to a mild subclinical hepatic toxicity at high-styrene exposure.

Strafella, Elisabetta; Bracci, Massimo; Staffolani, Sara; Manzella, Nicola; Giantomasi, Daniele; Valentino, Matteo; Amati, Monica; Tomasetti, Marco; Santarelli, Lory

2013-01-01

326

Effect of adjuvants on immunization with dengue virus-induced cytotoxic factor.  

PubMed Central

Specific active immunization with dengue type 2 virus (DV)-induced cytokine, cytotoxic factor (CF), prevents CF-mediated pathology in mice. The present study was undertaken to determine the optimum dose of CF and the effect of different adjuvants on the immune response as assessed by the study of anti-CF antibody titre by ELISA and protection against increase in capillary permeability to challenging dose of 3 micrograms CF. The maximum protection of 94 +/- 4% against increase in capillary permeability was observed at week 4 after immunization with 5 micrograms dose of CF mixed with Freund's incomplete adjuvant (FIA), which gradually decreased to 21 +/- 10% on week 24. With a dose of 10 micrograms the protection obtained was 79 +/- 5%, but persisted for a longer time at a higher level. The response was poor with 1 microgram dose of CF. The mean anti-CF antibody titres gradually decreased after reaching the peak at week 4 after immunization. Mice immunized with different adjuvants emulsified with 5 micrograms CF were challenged at different intervals with 3 micrograms CF. Maximum protection observed with CF + tetanus toxoid (TT) and 84/246 was about 93 +/- 2% and 97 +/- 2%, while that with alhydrogel was 33 +/- 12% and with bacille Calmette-Guérin (BCG) was 67 +/- 4%. At week 24 after immunization, however, the best response was obtained with 10 micrograms of adjuvant 84/246. Intracerebral challenge with 10 or 100 LD50 dose of dengue type 2 virus showed significantly prolonged mean survival time and delayed onset of signs of sickness in immunized mice compared with normal mice. The maximum survival time was with adjuvant 84/246 even at week 24. The findings thus show that the optimum dose of CF is 5 micrograms and the adjuvant of choice is 84/246.

Mukerjee, R; Chaturvedi, U C

1995-01-01

327

Aging Induced Ag Nanoparticle Rearrangement under Ambient Atmosphere and Consequences for Nanoparticle-Enhanced DNA Biosensing  

PubMed Central

Localized surface plasmons of metallic nanoparticles can strongly amplify the magnitude of the surrounding electric field. This in turn enhances fluorescence from nearby fluorophores. However, little is known regarding how time-dependent changes in nanoparticle structure due to exposure to the ambient environment affect their behavior in plasmonic devices. Here, we report the interesting finding that the aging of a nanostructured Ag substrate in ambient atmosphere markedly improves the fluorescence signal of a plasmonic-based DNA detection system. The effect can be observed with an exposure time as short as two days, and a nearly 17-fold signal enhancement can be achieved with 30 days of aging. Analysis of substrate surface topography by atomic force microscopy (AFM) reveals a substantial change in nanoparticle morphology as the substrates age despite being covalently attached to a solid dry substrate. Nanoparticle morphological changes also manifest in extinction spectra. This process can be further accelerated by light. Together, our findings address the important question of Ag nanoparticle stability over time and its potential ramifications for plasmon-enabled sensors. They also imply that nanoparticle aging may be used strategically to tune nanoparticle size and geometry and plasmon spectrum, which may be beneficial for studies on plasmonics as well as sensor optimization.

Peng, Hsin-I; Krauss, Todd D.; Miller, Benjamin L.

2010-01-01

328

Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish.  

PubMed

Silver nanoparticles (AgNPs) find increasing applications, and therefore humans and the environment are increasingly exposed to them. However, potential toxicological implications are not sufficiently known. Here we investigate effects of AgNPs (average size 120nm) on zebrafish in vitro and in vivo, and compare them to human hepatoma cells (Huh7). AgNPs are incorporated in zebrafish liver cells (ZFL) and Huh7, and in zebrafish embryos. In ZFL cells AgNPs lead to induction of reactive oxygen species (ROS), endoplasmatic reticulum (ER) stress response, and TNF-?. Transcriptional alterations also occur in pro-apoptotic genes p53 and Bax. The transcriptional profile differed in ZFL and Huh7 cells. In ZFL cells, the ER stress marker BiP is induced, concomitant with the ER stress marker ATF-6 and spliced XBP-1 after 6h and 24h exposure to 0.5g/L and 0.05g/L AgNPs, respectively. This indicates the induction of different pathways of the ER stress response. Moreover, AgNPs induce TNF-?. In zebrafish embryos exposed to 0.01, 0.1, 1 and 5mg/L AgNPs hatching was affected and morphological defects occurred at high concentrations. ER stress related gene transcripts BiP and Synv are significantly up-regulated after 24h at 0.1 and 5mg/L AgNPs. Furthermore, transcriptional alterations occurred in the pro-apoptotic genes Noxa and p21. The ER stress response was strong in ZFL cells and occurred in zebrafish embryos as well. Our data demonstrate for the first time that AgNPs lead to induction of ER stress in zebrafish. The induction of ER stress can have several consequences including the activation of apoptotic and inflammatory pathways. PMID:23800688

Christen, Verena; Capelle, Martinus; Fent, Karl

2013-06-22

329

Citrate-capped silver nanoparticles showing good bactericidal effect against both planktonic and sessile bacteria and a low cytotoxicity to osteoblastic cells.  

PubMed

A common problem with implants is that bacteria can form biofilms on their surfaces, which can lead to infection and, eventually, to implant rejection. An interesting strategy to inhibit bacterial colonization is the immobilization of silver (Ag) species on the surface of the devices. The aim of this paper is to investigate the action of citrate-capped silver nanoparticles (AgNPs) on clinically relevant Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria in two different situations: (i) dispersed AgNPs (to assess the effect of AgNPs against planktonic bacteria) and (ii) adsorbed AgNPs on titanium (Ti) substrates, a material widely used for implants (to test their effect against sessile bacteria). In both cases, the number of surviving cells was quantified. The small amount of Ag on the surface of Ti has an antimicrobial effect similar to that of pure Ag surfaces. We have also investigated the capability of AgNPs to kill planktonic bacteria and their cytotoxic effect on UMR-106 osteoblastic cells. The minimum bactericidal concentration found for both strains is much lower than the AgNP concentration that leads to cytotoxicity to osteoblasts. Planktonic P. aeruginosa show a higher susceptibility to Ag than S. aureus, which can be caused by the different wall structures, while for sessile bacteria, similar results are obtained for both strains. This can be explained by the presence of extracellular polymeric substances in the early stages of P. aeruginosa biofilm formation. Our findings can be important to improving the performance of Ti-based implants because a good bactericidal action is obtained with very small quantities of Ag, which are not detrimental to the cells involved in the osseointegration process. PMID:23534883

Flores, Constanza Y; Miñán, Alejandro G; Grillo, Claudia A; Salvarezza, Roberto C; Vericat, Carolina; Schilardi, Patricia L

2013-04-12

330

Cytotoxicity assessment of some carbon nanotubes and related carbon nanoparticle aggregates and the implications for anthropogenic carbon nanotube aggregates in the environment.  

PubMed

Nanotechnology and nanomaterials have become the new frontier world-wide over the past few years and prospects for the production and novel uses of large quantities of carbon nanotubes in particular are becoming an increasing reality. Correspondingly, the potential health risks for these and other nanoparticulate materials have been of considerable concern. Toxicological studies, while sparse, have been concerned with virtually uncharacterized, single wall carbon nanotubes, and the conclusions have been conflicting and uncertain. In this research we performed viability assays on a murine lung macrophage cell line to assess the comparative cytotoxicity of commercial, single wall carbon nanotubes (ropes) and two different multiwall carbon nanotube samples; utilizing chrysotile asbestos nanotubes and black carbon nanoaggregates as toxicity standards. These nanotube materials were completely characterized by transmission electron microscopy and observed to be aggregates ranging from 1 to 2 microm in mean diameter, with closed ends. The cytotoxicity data indicated a strong concentration relationship and toxicity for all the carbon nanotube materials relative to the asbestos nanotubes and black carbon. A commercial multiwall carbon nanotube aggregate exhibiting this significant cell response was observed to be identical in structure to multiwall carbon nanotube aggregates demonstrated to be ubiquitous in the environment, and especially in indoor environments, where natural gas or propane cooking stoves exist. Correspondingly, preliminary epidemiological data, although sparse, indicate a correlation between asthma incidence or classification, and exposure to gas stoves. These results suggest a number of novel epidemiological and etiological avenues for asthma triggers and related respiratory or other environmental health effects, especially since indoor number concentrations for multiwall carbon nanotube aggregates is at least 10 times the outdoor concentration, and virtually all gas combustion processes are variously effective sources. These results also raise concerns for manufactured carbon nanotube aggregates, and related fullerene nanoparticles. PMID:16705799

Murr, L E; Garza, K M; Soto, K F; Carrasco, A; Powell, T G; Ramirez, D A; Guerrero, P A; Lopez, D A; Venzor, J

2005-04-01

331

Swift heavy-ion irradiation-induced shape and structural transformation in cobalt nanoparticles  

SciTech Connect

The shape and structural evolution of Co nanoparticles embedded in SiO{sub 2} and subjected to swift heavy-ion irradiation have been investigated over a wide energy and fluence range. Modifications of the nanoparticle size and shape were characterized with transmission electron microscopy and small-angle x-ray scattering. Nanoparticles below a threshold diameter remained spherical in shape and progressively decreased in size under irradiation due to dissolution. Nanoparticles above the threshold diameter transformed into nanorods with their major dimension parallel to the incident ion direction. Modifications of the atomic-scale structure of the Co nanoparticles were identified with x-ray absorption spectroscopy. Analysis of the x-ray absorption near-edge spectra showed that prior to irradiation all Co atoms were in a metallic state, while after irradiation Co atoms were in both oxidized and metallic environments, the former consistent with dissolution. The evolution of the nanoparticle short-range order was determined from extended x-ray absorption fine structure spectroscopy. Structural changes in the Co nanoparticles as a function of ion fluence included an increase in disorder and asymmetric deviation from a Gaussian interatomic distance distribution coupled with a decrease in bondlength. Such changes resulted from the irradiation-induced decrease in nanoparticle size and subsequent dissolution.

Sprouster, D.J.; Giulian, R.; Araujo, L.L.; Kluth, P.; Johannessen, B.; Cookson, D.J.; Ridgway, M.C. (Aust. Synch.); (ANU)

2012-02-07

332

Analysis and optimization of silver nanoparticles laser synthesis with emission spectroscopy of induced plasma.  

PubMed

Emission spectroscopy of the laser induced plasma is used to characterize the laser synthesis of silver nanoparticles in water via attributing the thermodynamic parameters of the plasma plume to qualitative features of the synthesized nanoparticles. In this approach, effects of the pulse energy and frequency of a pulsedNd:YAGlaser on nanoparticles synthesis yield and size distribution is studied by an analysis on the behavior of electron temperature and total density of the plasma dominant species (neutral Ag atoms; AgI). Variation of these thermodynamic parameters obtained from the time-integrated emission spectroscopy of the induced plasma was found to be in a closed correlation with the mentioned characteristics of the synthesized nanoparticles. Assessment of the qualitative features of nanoparticles was performed by evaluating the particles concentration in liquid, optical absorption spectroscopy and transmission electron microscopy. Finally, the optimum operating conditions for the synthesis of silver nanoparticles in pure water is determined by summarizing the results of emission spectroscopy observations attributed to the mentioned characteristics of synthesized nanoparticles. PMID:22849073

Dadras, Siamak; Torkamany, Mohammad Javad; Jafarkhani, Parvaneh

2012-04-01

333

pH-Induced aggregation of gold nanoparticles for photothermal cancer therapy.  

PubMed

We report a "smart" gold nanoparticle that is designed to aggregate in mild acidic intracellular environments by its hydrolysis-susceptible citraconic amide surface. With a relatively small size of 10 nm, the "smart" gold nanoparticles can be efficiently internalized into cancerous cells. Triggered by pH change, the nanoparticle surfaces are engineered to have both positive and negative charges. Electrostatic attractions between the nanoparticles can rapidly form aggregates inside the cells, and the aggregates accumulate as the exocytosis is blocked by the increased size. Endocytosis of gold nanoparticles and the aggregation are monitored real-time by dark field optical microscopy. The pH-induced formation of aggregates shifts the absorption to far-red and near-infrared. The absorption shift to longer wavelength is used for photothermal cancer therapy as it guarantees maximal tissue penetration for potential therapeutic applications. The gold nanoparticles show selective and efficient destruction of cancerous cells with an intensity threshold of 5 W/cm(2) to induce the thermal destruction. In the intensity range 5-13 W/cm(2), the circular area of damaged cells increases linearly with the irradiation power density. This shows a new proof-of-concept for photothermal cancer therapy that exploits collective plasmon modes of metal nanoparticles. PMID:19772360

Nam, Jutaek; Won, Nayoun; Jin, Ho; Chung, Hyokyun; Kim, Sungjee

2009-09-30

334

Controllable aggregates of silver nanoparticle induced by methanol for surface-enhanced Raman scattering  

NASA Astrophysics Data System (ADS)

In this work, a series of highly sensitive surface-enhanced Raman scattering substrates have been achieved based on the controllable aggregation of silver nanoparticles. In such system, hexadecylamine-capped silver nanoparticles were ink-jet printed on glass substrates and subsequently dipped into methanol solution. An aggregation was induced due to preferential dissolution of hexadecylamine into methanol and partial removal of the protective layers on silver nanoparticle surfaces, which exhibited stable and controllable Raman enhancement effect. This strategy could be further extended to construct various chemical and biological functional sensors.

Zhang, Zhiliang; Wen, Yongqiang

2012-10-01

335

Magnetic nanoparticle density mapping from the magnetically induced displacement data: a simulation study  

PubMed Central

Background Magnetic nanoparticles are gaining great roles in biomedical applications as targeted drug delivery agents or targeted imaging contrast agents. In the magnetic nanoparticle applications, quantification of the nanoparticle density deposited in a specified region is of great importance for evaluating the delivery of the drugs or the contrast agents to the targeted tissues. We introduce a method for estimating the nanoparticle density from the displacement of tissues caused by the external magnetic field. Methods We can exert magnetic force to the magnetic nanoparticles residing in a living subject by applying magnetic gradient field to them. The nanoparticles under the external magnetic field then exert force to the nearby tissues causing displacement of the tissues. The displacement field induced by the nanoparticles under the external magnetic field is governed by the Navier's equation. We use an approximation method to get the inverse solution of the Navier's equation which represents the magnetic nanoparticle density map when the magnetic nanoparticles are mechanically coupled with the surrounding tissues. To produce the external magnetic field inside a living subject, we propose a coil configuration, the Helmholtz and Maxwell coil pair, that is capable of generating uniform magnetic gradient field. We have estimated the coil currents that can induce measurable displacement in soft tissues through finite element method (FEM) analysis. Results From the displacement data obtained from FEM analysis of a soft-tissue-mimicking phantom, we have calculated nanoparticle density maps. We obtained the magnetic nanoparticle density maps by approximating the Navier's equation to the Laplacian of the displacement field. The calculated density maps match well to the original density maps, but with some halo artifacts around the high density area. To induce measurable displacement in the living tissues with the proposed coil configuration, we need to apply the coil currents as big as 104A. Conclusions We can obtain magnetic nanoparticle maps from the magnetically induced displacement data by approximating the Navier's equation under the assumption of uniform-gradient of the external magnetic field. However, developing a coil driving system with the capacity of up to 104A should be a great technical challenge.

2012-01-01

336

Fabrication of fluorescent silica nanoparticles with aggregation-induced emission luminogens for cell imaging.  

PubMed

Fluorescence-based techniques have found wide applications in life science. Among various luminogenic materials, fluorescent nanoparticles have attracted much attention due to their fabulous emission properties and potential applications as sensors. Here, we describe the fabrication of fluorescent silica nanoparticles (FSNPs) containing aggregation-induced emission (AIE) luminogens. By employing surfactant-free sol-gel reaction, FSNPs with uniform size and high surface charge and colloidal stability are generated. The FSNPs emit strong light upon photoexcitation, due to the AIE characteristic of the silole -aggregates in the hybrid nanoparticles. The FSNPs are cytocompatible and can be utilized as fluorescent visualizer for intracellular imaging for HeLa cells. PMID:23546668

Chen, Sijie; Lam, Jacky W Y; Tang, Ben Zhong

2013-01-01

337

Electric-field-induced alignment of block copolymer/nanoparticle blends.  

PubMed

External electric fields readily align birefringent block-copolymer mesophases. In this study the effect of gold nanoparticles on the electric-field-induced alignment of a lamellae-forming polystyrene-block-poly(2-vinylpyridine) copolymer is assessed. Nanoparticles are homogeneously dispersed in the styrenic phase and promote the quantitative alignment of lamellar domains by substantially lowering the critical field strength above which alignment proceeds. The results suggest that the electric-field-assisted alignment of nanostructured block copolymer/nanoparticle composites may offer a simple way to greatly mitigate structural and orientational defects of such films under benign experimental conditions. PMID:23495246

Liedel, Clemens; Schindler, Kerstin A; Pavan, Mariela J; Lewin, Christian; Pester, Christian W; Ruppel, Markus; Urban, Volker S; Shenhar, Roy; Böker, Alexander

2013-03-13

338

Nanoparticle-induced negative differential resistance and memory effect in polymer bistable light-emitting device  

NASA Astrophysics Data System (ADS)

Recently, electrical bistability was demonstrated in polymer thin films incorporated with metal nanoparticles [J. Ouyang, C. W. Chu, C. R. Szmanda, L. P. Ma, and Y. Yang, Nat. Mater. 3, 918 (2004)]. In this letter, we show the evidence that electrons are the dominant charge carriers in these bistable devices. Direct integration of bistable polymer layer with a light-emitting polymer layer shows a unique light-emitting property modulated by the electrical bistability. A unique negative differential resistance induced by the charged gold nanoparticles is observed due to the charge trapping effect from the nanoparticles when interfaced with the light-emitting layer.

Tseng, Ricky J.; Ouyang, Jianyong; Chu, Chih-Wei; Huang, Jinsong; Yang, Yang

2006-03-01

339

Titanium dioxide nanoparticles induce emphysema-like lung injury in mice  

Microsoft Academic Search

Titanium dioxide nanoparticles (nano- TiO2) have been widely used as a photocatalyst in air and water cleaning. However, these nanoparticles inha- lation can induce pulmonary toxicity and its mechanism is not fully understood. In this study we investigated the pulmonary toxicity of nanoTiO2 and its molecular pathogenesis. The adult male ICR mice were exposed to intratracheal single dose of 0.1

Huei-Wen Chen; Sheng-Fang Su; Chiang-Ting Chien; Wei-Hsiang Lin; Sung-Liang Yu; Cheng-Chung Chou; Jeremy J. W. Chen; Pan-Chyr Yang

2006-01-01

340

Increasing the cisplatin cytotoxicity and cisplatin-induced DNA damage by conferone in 5637 cells.  

PubMed

Despite widespread application of cisplatin in treatment of transitional cell carcinomas, its efficiency is far from satisfactory due to acquired drug resistance. The present study was carried out to estimate the effects of conferone, a sesquiterpene-coumarin isolated from Ferula badrakema, on increasing cisplatin cytotoxicity in 5637 cells. In order to determine conferone effects, 5637 cells were cultured in the presence of different concentrations of conferone and cisplatin in combination. The cytotoxicity and DNA damaging effects were then studied using MTT and comet assays, respectively. The results revealed that 24?h after the combination of 1?µg?mL?¹ cisplatin with 32?µg?mL?¹ conferone, the cytotoxicity of cisplatin was increased by 36.76%, and comet assay analyses showed that conferone could enhance the DNA damaging effects of cisplatin by 41%. PMID:21988674

Neshati, Vajiheh; Matin, Maryam M; Bahrami, Ahmad Reza; Iranshahi, Mehrdad; Rassouli, Fatemeh B; Saeinasab, Morvarid

2011-10-11

341

The p53-reactivating small-molecule RITA enhances cisplatin-induced cytotoxicity and apoptosis in head and neck cancer.  

PubMed

We evaluated whether the restoration of p53 function by the p53-reactivating small molecule RITA (reactivation of p53 and induction of tumor cell apoptosis enhances cisplatin-induced cytotoxicity and apoptosis in head-and-neck cancer (HNC). RITA induced prominent accumulation and reactivation of p53 in a wild-type TP53-bearing HNC cell line. RITA showed maximal growth suppression in tumor cells showing MDM2-dependent p53 degradation. RITA promoted apoptosis in association with upregulation of p21, BAX, and cleaved caspase-3; notably, the apoptotic response was blocked by pifithrin-?, demonstrating its p53 dependence. With increasing concentrations, RITA strongly induced apoptosis rather than G2-phase arrest. In combination therapy, RITA enhanced cisplatin-induced growth inhibition and apoptosis of HNC cells invitro and in vivo. Our data suggest that the restoration of p53 tumor-suppressive function by RITA enhances the cytotoxicity and apoptosis of cisplatin, an action that may offer an attractive strategy for treating HNC. PMID:22634494

Roh, Jong-Lyel; Ko, Jung Ho; Moon, Soo Jin; Ryu, Chang Hwan; Choi, Jun Young; Koch, Wayne M

2012-05-22

342

A cell-based, multiparametric sensor approach characterises drug-induced cytotoxicity in human liver HepG2 cells.  

PubMed

Drug-induced toxicity is of considerable concern in drug discovery and development, placing emphasis on the need for predictive in vitro technologies that identify potential cytotoxic side effects of drugs. A label-free, real-time, multiparametric cytosensor system has therefore been established for in vitro assessment of drug-induced toxicity. The system is based on monitoring cellular oxygen consumption, acidification and impedance of human hepatocarcinoma-derived HepG2 cells. The read-out derived from the multiparametric cytosensor system has been optimised and permits sensitive, reliable, and simultaneous recording of cell physiological signals, such as metabolic activity, cellular respiration and morphological changes and cell adhesion upon exposure to a drug. Analysis of eight prototypic reference drugs revealed distinct patterns of drug-induced physiological signals. Effects proved to be rigidly concentration-dependent. Based on signal patterns and reversibility of the observed effects, compounds could be classified based as triggering mechanisms of respiratory or metabolic stress or conditions leading to cell death (necrosis-like and apoptosis-like). A test-flag-risk mitigation strategy is proposed to address potential risks for drug-induced cytotoxicity. PMID:23416262

Seeland, Swen; Török, Michael; Kettiger, Helene; Treiber, Alexander; Hafner, Mathias; Huwyler, Jörg

2013-02-14

343

Visible laser induced fusion and fragmentation of thionicotinamide-capped gold nanoparticles  

Microsoft Academic Search

Thionicotinamide-capped gold nanoparticles undergo fusion as well as fragmentation upon laser pulse excitation (532 nm). The aggregation effect which is induced by thionicotinamide also disappears following laser pulse excitation. The morphological changes induced by thermal and photochemical effects were found to influence the optical properties of these particles.

Hiroaki Fujiwara; Shozo Yanagida; Prashant V. Kamat

1999-01-01

344

Factors affecting T cell responses induced by fully synthetic glyco-gold-nanoparticles  

NASA Astrophysics Data System (ADS)

We have synthesized and characterized nearly monodisperse and highly pure gold nanoparticles (2 and 5 nm) coated with non-immunoactive mono- and disaccharides, modelled after the capsular polysaccharide of serogroup A of the Neisseria meningitidis bacterium. We have used them to test their ability to induce immune cell responses as a consequence of their multivalency. The results indicate that they are indeed immunoactive and that immunoactivity is strongly dependent on size, and larger, 5 nm nanoparticles perform far better than smaller, 2 nm ones. Immune response (activation of macrophages) initiates with the whole nanoparticle recognition by the surface of antigen-presenting cells, independent of the saccharide oligomerization (or charge) on the nanoparticle surface. The induction of T cell proliferation and the increase of IL-2 levels, a consequence of the expression of MHC II involved in antigen presentation, require the presence of a disaccharide on the nanoparticle, not just a monosaccharide. A possible explanation is that, at this stage, the saccharides are detached from the gold surface. These results may provide leads for designing new saccharide-based, nanoparticle-conjugate vaccines.We have synthesized and characterized nearly monodisperse and highly pure gold nanoparticles (2 and 5 nm) coated with non-immunoactive mono- and disaccharides, modelled after the capsular polysaccharide of serogroup A of the Neisseria meningitidis bacterium. We have used them to test their ability to induce immune cell responses as a consequence of their multivalency. The results indicate that they are indeed immunoactive and that immunoactivity is strongly dependent on size, and larger, 5 nm nanoparticles perform far better than smaller, 2 nm ones. Immune response (activation of macrophages) initiates with the whole nanoparticle recognition by the surface of antigen-presenting cells, independent of the saccharide oligomerization (or charge) on the nanoparticle surface. The induction of T cell proliferation and the increase of IL-2 levels, a consequence of the expression of MHC II involved in antigen presentation, require the presence of a disaccharide on the nanoparticle, not just a monosaccharide. A possible explanation is that, at this stage, the saccharides are detached from the gold surface. These results may provide leads for designing new saccharide-based, nanoparticle-conjugate vaccines. Electronic supplementary information (ESI) available: Fig. S1-S10 mentioned in the text related to the syntheses of nanosystems, nanoparticle characterization, and biological tests. See DOI: 10.1039/c2nr32338a

Fallarini, Silvia; Paoletti, Tiziana; Battaglini, Carolina Orsi; Ronchi, Paolo; Lay, Luigi; Bonomi, Renato; Jha, Satadru; Mancin, Fabrizio; Scrimin, Paolo; Lombardi, Grazia

2012-12-01

345

Histologic and apoptotic changes induced by titanium dioxide nanoparticles in the livers of rats  

PubMed Central

Titanium dioxide (TiO2) nanoparticles are among the top five nanoparticles used in consumer products, paints, and pharmaceutical preparations. Given that exposure to such nanoparticles is mainly via the skin and inhalation, the present study was conducted in male Wistar albino rats (Rattus norvegicus). Our aim was to investigate the effect of TiO2 nanoparticles on hepatic tissue in an attempt to understand their toxicity and the potential effect of their therapeutic and diagnostic use. To investigate the effects of TiO2 nanoparticles on liver tissue, 30 healthy male Wistar albino rats were exposed to TiO2 nanoparticles at doses of 63 mg, 126 mg, and 252 mg per animal for 24 and 48 hours. Serum glutamate oxaloacetate transaminase and alkaline phosphatase activity was altered. Changes in hepatocytes can be summarized as hydropic degeneration, cloudy swelling, fatty degeneration, portal and lobular infiltration by chronic inflammatory cells, and congested dilated central veins. The histologic alterations observed might be an indication of hepatocyte injury due to the toxicity of TiO2 nanoparticles, resulting in an inability to deal with accumulated residues from the metabolic and structural disturbances caused by these nanoparticles. The appearance of cytoplasmic degeneration and destruction of nuclei in hepatocytes suggests that TiO2 nanoparticles interact with proteins and enzymes in hepatic tissue, interfering with antioxidant defense mechanisms and leading to generation of reactive oxygen species which, in turn, may induce stress in hepatocytes, promoting atrophy, apoptosis, and necrosis. More immunohistochemical and ultrastructural investigations are needed in relation to TiO2 nanoparticles and their potential effects when used as therapeutic and diagnostic tools.

Alarifi, Saud; Ali, Daoud; Al-Doaiss, Amin A; Ali, Bahy A; Ahmed, Mukhtar; Al-Khedhairy, Abdulaziz A

2013-01-01

346

Nanocontact-induced catalytic activation in palladium nanoparticles  

Microsoft Academic Search

We report the synthesis and catalytic studies of novel palladium nanostructures assembled from small nanoparticles by a surfactant-templated method. These one-dimensional nanomaterials comprise high-density nanocontacts of ~1 nm in contact length at the particle-particle interface. In contrast to dispersed Pd nanoparticles (~5 nm), the polycrystalline palladium nanowires exhibit enhanced (~200 times) catalytic reactivity towards carbon-carbon cross-couplings under mild conditions. Theoretical

Changlong Jiang; Sadananda Ranjit; Zhongyu Duan; Yu Lin Zhong; Kian Ping Loh; Chun Zhang; Xiaogang Liu

2009-01-01

347

Coverage induced regulation of Au nanoparticles during pulsed laser deposition  

NASA Astrophysics Data System (ADS)

The effects induced during the covering/embedding of metal nanoparticles (NPs) produced by pulsed laser deposition (PLD) and their impact on the structural and optical properties have been studied by producing pairs of samples containing Au NPs that are either uncovered (i.e., at the surface) or covered (i.e., embedded in an amorphous a-Al2O3 host). The main result is that covering species can sputter up to 100% of the Au atoms, the smaller the NPs the higher the sputtered fraction. This fraction has been simulated using standard models for ion bombardment and taking into account the kinetic energy distribution of arriving species and the cohesive energy dependence on NPs dimensions. Although all models well predict the order of magnitude of the sputtering yield, the calculated values are generally smaller than the experimental ones and do not account for the experimental dependence on NPs dimensions. This disagreement is discussed in terms of the limitations of standard models that do not take into account the lower adhesion of small NPs to the substrate, the high flux of species involved in PLD and, possibly to lesser extent, the use of some bulk material parameters. The metal sputtering during the coverage regulates the NPs morphology, through a reduction of dimensions and dimension dispersion. Most changes of structural features and optical spectra when covering the NPs are directly related to the variation in the amount of metal with the exception of a strong blueshift of the surface plasmon resonance when NPs are covered. This shift could be consistent with mixing of covering layer species and metal at the surface of the NPs.

Resta, V.; Gonzalo, J.; Afonso, C. N.; Piscopiello, E.; García López, J.

2011-05-01

348

Potassium Dichromate Induced Cytotoxicity, Genotoxicity and Oxidative Stress in Human Liver Carcinoma (HepG2) Cells  

PubMed Central

Chromium is a widespread industrial waste. The soluble hexavalent chromium Cr (VI) is an environmental contaminant widely recognized to act as a carcinogen, mutagen and teratogen towards humans and animals. The fate of chromium in the environment is dependent on its oxidation state. Hexavalent chromium primarily enters the cells and undergoes metabolic reduction to trivalent chromium, resulting in the formation of reactive oxygen species together with oxidative tissue damage and a cascade of cellular events. However, the results from in vitro studies are often conflicting. The aim of this study was to develop a model to establish relationships between cytotoxicity, genotoxicity and oxidative stress, in human liver carcinoma [HepG2] cells exposed to potassium dichromate. HepG2 cells were cultured following standard protocols and exposed to various concentrations [0–50 ?M] of potassium dichromate [K2Cr2O7]. Following exposure to the toxic metal, the MTT assay was performed to assess the cytotoxicity, the thiobarbituric acid test to evaluate the degree of lipid peroxidation as an indicator of oxidative stress and the alkaline comet assay was used to assess DNA damage to study genotoxicity. The results of the study indicated that potassium dichromate was cytotoxic to HepG2 cells. The LD50 values of 8.83 ± 0.89 ?g/ml, 6.76 ± 0.99 ?g/ml, respectively, for cell mortality at 24 and 48 hrs were observed, indicating a dose- and time-dependent response with regard to the cytotoxic effects of potassium dichromate. A statistically significant increase in the concentration of malondialdehyde [MDA], an indicator of lipid peroxidation, was recorded in exposed cells [15.9 – 69.9 ?M] compared to control [13 ?M]. Similarly, a strong dose-response relationship (p<0.05) was also obtained with respect to potassium dichromate induced DNA damage (comet assay) in HepG2 cells exposed [3.16 ± 0.70 – 24.84 ± 1.86 microns – mean comet tail length]; [12.4 ± 1.45% – 76 ± 1.49% – % tail DNA] to potassium dichromate than control [3.07 ± 0.26 microns – mean comet tail length]; [2.69 + 0.19% – % Tail DNA], respectively. The results demonstrated that potassium dichromate was highly cytotoxic to HepG2 cells, and its cytotoxicity seems to be mediated by oxidative stress and DNA damage.

Patlolla, Anita K.; Barnes, Constance; Hackett, Diahanna; Tchounwou, Paul B.

2009-01-01

349

Methyl tert-butyl ether (MTBE) induced Ca(2+)-dependent cytotoxicity in isolated rabbit tracheal epithelial cells.  

PubMed

As a volatile synthetic organic chemical, methyl tert-butyl ether (MTBE) was the most common gasoline additive. The increasing use of MTBE raised concern over its health safety. Inhalation was the principle route of exposure for the general population. This study used a model of rabbit tracheal epithelial cells (RTEs) in primary culture to investigate the cytotoxic effects induced by MTBE and the potential mechanism. RTEs were incubated with medium alone (control), 0.5, 50, 5000ppm MTBE respectively. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo liumbromide) assay, staining with fluorescein diacetate, propidium iodide and lactate dehydrogenase leakage ratio were used to assess MTBE cytotoxicity on cells. We also observed a significant elevation in cytosolic Ca2+ by fluorescence probe Fluo-3AM at 3, 6 and 12h following exposure to MTBE. Loss of mitochondrial membrane potential (MMP) was detected following 12 and 24h treatment of NP and assessment by rhodamine 123 (Rh123) staining. Activity changes of the Ca(2+)-ATPase, Ca(2+)-Mg(2+)-ATPase following MTBE treatment displayed a similar trend, suggesting an initial elevation before 6h and subsequent dramatic decrease at 12h. Our results demonstrated that induction of cell injury, associated with mitochondrial dysfunction, and alterations in cytosolic Ca2+ in RTEs represent key mechanisms by which MTBE exerts its cytotoxic effects. PMID:18715547

Wang, Yajing; Chen, Chang; Wu, Tao; Xu, Jing; Han, Xiaodong

2008-07-31

350

Evaluation of cytotoxic, oxidative stress, proinflammatory and genotoxic responses of micro- and nano-particles of dolomite on human lung epithelial cells A(549).  

PubMed

Dolomite is a natural mineral of great industrial importance and used worldwide, thus millions of workers are at risk of occupational exposure. Its toxicity is however, meagerly documented. In the present investigation, a dolomite powder obtained from its milling unit was analyzed by some standard methods namely, optical microscopy, transmission electron microscopy and dynamic light scattering. Results showed that dolomite powder contained particles of different shapes and size both microparticles (MPs) and nanoparticles (NPs), suggesting potential occupational exposure of these particles. An attempt was therefore, made to investigate dolomite toxicity in a particle size-dependent manner in human lung epithelial cells A(549). The comparative toxicity evaluation of MPs and NPs was carried out by assessing their effects on cell viability, membrane damage, glutathione, reactive oxygen species (ROS), lipid peroxidation (LPO), micronucleus (MN) and proinflammatory cytokines, namely tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?) and interleukin-6 (IL-6). These markers of cytotoxicity, genotoxicity and inflammation were assayed in cells exposed to MPs and NPs in a dose-and time-dependent manner. Invariably, their toxic effects were dose-and time-dependent while NPs in general were significantly more toxic. Notably, NPs caused oxidative stress, genotoxicity and inflammatory responses, as seen by significant induction of ROS, LPO, MN, TNF-?, IL-1? and IL-6. Thus, the study tends to suggest that separate health safety standards would be required for micrometer and nanometer scale particles of dolomite. PMID:22785077

Patil, Govil; Khan, Mohd Imran; Patel, Devendra Kumar; Sultana, Sarwat; Prasad, Rajendra; Ahmad, Iqbal

2012-06-08

351

Dexamethasone-loaded block copolymer nanoparticles induce leukemia cell death and enhance therapeutic efficacy: a novel application in pediatric nanomedicine.  

PubMed

Nanotechnology approaches have tremendous potential for enhancing treatment efficacy with lower doses of chemotherapeutics. Nanoparticle (NP)-based drug delivery approaches are poorly developed for childhood leukemia. Dexamethasone (Dex) is one of the most common chemotherapeutic drugs used in the treatment of childhood leukemia. In this study, we encapsulated Dex in polymeric NPs and validated their antileukemic potential in vitro and in vivo. NPs with an average diameter of 110 nm were assembled from an amphiphilic block copolymer of poly(ethylene glycol) (PEG) and poly(?-caprolactone) (PCL) bearing pendant cyclic ketals (ECT2). The blank NPs were nontoxic to cultured cells in vitro and to mice in vivo. Encapsulation of Dex into the NPs (Dex-NP) did not compromise the bioactivity of the drug. Dex-NPs induced glucocorticoid phosphorylation and showed cytotoxicity similar to the free Dex in leukemic cells. Studies using NPs labeled with fluorescent dyes revealed leukemic cell surface binding and internalization. In vivo biodistribution studies showed NP accumulation in the liver and spleen with subsequent clearance of the particles with time. In a preclinical model of leukemia, Dex-NPs significantly improved the quality of life and survival of mice as compared to the free drug. To our knowledge, this is the first report showing the efficacy of polymeric NPs to deliver Dex to potentially treat childhood leukemia and reveals that low doses of Dex should be sufficient for inducing cell death and improving survival. PMID:23194373

Krishnan, Vinu; Xu, Xian; Barwe, Sonali P; Yang, Xiaowei; Czymmek, Kirk; Waldman, Scott A; Mason, Robert W; Jia, Xinqiao; Rajasekaran, Ayyappan K

2012-11-29

352

Cytotoxicity in human skin fibroblasts induced by photoactivated polycyclic aromatic hydrocarbons  

Microsoft Academic Search

Polycyclic aromatic hydrocarbons (PAH) require chemical modification in order to exert their mutagenic\\/carcinogenic activity on biological systems. The mode of activation which has been most extensively studied involves enzyme-catalyzed oxidation reactions but PAH can also be modified into oxidized and radical intermediates upon exposure to various radiations. The resulting products have been shown to be cytotoxic, mutagenic and carcinogenic in

G. F. Strniste; R. J. Brake

1980-01-01

353

Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats  

PubMed Central

Purpose Celastrol, a traditional Chinese medicine, is widely used in anti-inflammation and anti-angiogenesis research. However, the poor water solubility of celastrol restricts its further application. This paper aims to study the effect of celastrol nanoparticles (CNPs) on corneal neovascularization (CNV) and determine the possible mechanism. Methods To improve the hydrophilicity of celastrol, celastrol-loaded poly(ethylene glycol)-block-poly(?-caprolactone) nanopolymeric micelles were developed. The characterization of CNPs was measured by dynamic light scattering and transmission electron microscopy analysis. Celastrol loading content and release were assessed by ultraviolet-visible analysis and high performance liquid chromatography, respectively. In vitro, human umbilical vein endothelial cell proliferation and capillary-like tube formation were assayed. In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats. Immunohistochemistry for CD68 assessed the macrophage infiltration of the cornea on day 6 after surgery. Real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to evaluate the messenger ribonucleic acid and protein levels, respectively, of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea. Results The mean diameter of CNPs with spherical shape was 48 nm. The celastrol loading content was 7.36%. The release behavior of CNPs in buffered solution (pH 7.4) showed a typical two-phase release profile. CNPs inhibited the proliferation of human umbilical vein endothelial cells in a dose-independent manner and suppressed the capillary structure formation. After treatment with CNPs, the length and area of CNV reduced from 1.16 ± 0.18 mm to 0.49 ± 0.12 mm and from 7.71 ± 0.94 mm2 to 2.29 ± 0.61 mm2, respectively. Macrophage infiltration decreased significantly in the CNP-treated corneas. CNPs reduced the expression of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea on day 6 after suturing. Conclusion CNPs significantly inhibited suture-induced CNV by suppressing macrophage infiltration and the expression of vascular endothelial growth factor and matrix metalloproteinase 9 in the rat cornea.

Li, Zhanrong; Yao, Lin; Li, Jingguo; Zhang, Wenxin; Wu, Xianghua; Liu, Yi; Lin, Miaoli; Su, Wenru; Li, Yongping; Liang, Dan

2012-01-01

354

Cytotoxic Activity and Apoptosis-Inducing Potential of Di-spiropyrrolidino and Di-spiropyrrolizidino Oxindole Andrographolide Derivatives  

PubMed Central

Anticancer role of andrographolide is well documented. To find novel potent derivatives with improved cytotoxicity than andrographolide on cancer cells, two series of di-spiropyrrolidino- and di-spiropyrrolizidino oxindole andrographolide derivatives prepared by cyclo-addition of azomethine ylide along with sarcosine or proline (viz. sarcosine and proline series respectively) and substitution of different functional groups (-CH3, -OCH3 and halogens) were examined for their cytotoxic effect on a panel of six human cancer cell lines (colorectal carcinoma HCT116 cells, pancreatic carcinoma MiaPaCa-2 cells, hepatocarcinoma HepG2 cells, cervical carcinoma HeLa cells, lung carcinoma A549 and melanoma A375 cells). Except halogen substituted derivatives of proline series (viz. CY2, CY14 and CY15 for Br, Cl and I substitution respectively), none of the other derivatives showed improved cytotoxicity than andrographolide in the cancer cell lines examined. Order of cytotoxicity of the potent compounds is CY2>CY14>CY15>andrographolide. Higher toxicity was observed in HCT116, MiaPaCa-2 and HepG2 cells. CY2, induced death of HCT116 (GI50 10.5), MiaPaCa-2 (GI50 11.2) and HepG2 (GI50 16.6) cells were associated with cell rounding, nuclear fragmentation and increased percentage of apoptotic cells, cell cycle arrest at G1 phase, ROS generation, and involvement of mitochondrial pathway. Upregulation of Bax, Bad, p53, caspases-3,-9 and cleaved PARP; downregulation of Bcl-2, cytosolic NF-?B p65, PI3K and p-Akt; translocation of P53/P21, NF-?B p65 were seen in CY2 treated HCT116 cells. Thus, three halogenated di-spiropyrrolizidino oxindole derivatives of andrographolide are found to be more cytotoxic than andrographolide in some cancer cells. The most potent derivative, CY2 induced death of the cancer cells involves ROS dependent mitochondrial pathway like andrographolide.

Hazra, Abhijit; Naskar, Subhendu; Nandy, Abhishek; Munda, Rudra Narayan; Das, Subhadip; Chatterjee, Nabanita; Mondal, Nirup Bikash; Banerjee, Sukdeb; Saha, Krishna Das

2013-01-01

355

Biocompatibility of crystalline opal nanoparticles  

PubMed Central

Background Silica nanoparticles are being developed as a host of biomedical and biotechnological applications. For this reason, there are more studies about biocompatibility of silica with amorphous and crystalline structure. Except hydrated silica (opal), despite is presents directly and indirectly in humans. Two sizes of crystalline opal nanoparticles were investigated in this work under criteria of toxicology. Methods In particular, cytotoxic and genotoxic effects caused by opal nanoparticles (80 and 120 nm) were evaluated in cultured mouse cells via a set of bioassays, methylthiazolyldiphenyl-tetrazolium-bromide (MTT) and 5-bromo-2?-deoxyuridine (BrdU). Results 3T3-NIH cells were incubated for 24 and 72 h in contact with nanocrystalline opal particles, not presented significant statistically difference in the results of cytotoxicity. Genotoxicity tests of crystalline opal nanoparticles were performed by the BrdU assay on the same cultured cells for 24 h incubation. The reduction of BrdU-incorporated cells indicates that nanocrystalline opal exposure did not caused unrepairable damage DNA. Conclusions There is no relationship between that particles size and MTT reduction, as well as BrdU incorporation, such that the opal particles did not induce cytotoxic effect and genotoxicity in cultured mouse cells.

2012-01-01

356

Cytotoxic effects induced by unmodified and organically modified nanoclays in the human hepatic HepG2 cell line.  

PubMed

The term 'nanoclay' generically refers to the natural clay mineral, montmorillonite, with silica and alumina as the dominant constituents. The incorporation of nanoclays into polymeric systems dramatically enhances their barrier properties as well as their thermal and mechanical resistance. Consequently, nanoclays are employed in a wide range of industrial applications with recent studies reporting potential use in the modulation of drug release. With the increase in manufacturing of nanoclay-containing products, information on the toxicological and health effects of nanoclay exposure is warranted. Thus, the objective of the present study was to evaluate the cytotoxicity of two different nanoclays: the unmodified nanoclay, Cloisite Na+ ®, and the organically modified nanoclay, Cloisite 93A®, in human hepatoma HepG2 cells. Following 24?h exposure the nanoclays significantly decreased cell viability. Cloisite Na+ induced intracellular reactive oxygen species (ROS) formation which coincided with increased cell membrane damage, whilst ROS generation did not play a role in Cloisite 93A-induced cell death. Neither of the nanoclays induced caspase-3/7 activation. Moreover, in the cell culture medium the nanoclays aggregated differently and this appeared to have an effect on their mechanisms of toxicity. Taken together, our data demonstrate that nanoclays are highly cytotoxic and as a result pose a possible risk to human health. PMID:20677180

Lordan, Sinéad; Kennedy, James E; Higginbotham, Clement L

2011-01-01

357

Kava extract, an herbal alternative for anxiety relief, potentiates acetaminophen-induced cytotoxicity in rat hepatic cells.  

PubMed

The widely used over-the-counter analgesic acetaminophen (APAP) is the leading cause of acute liver failure in the United States and due to this high incidence, a recent FDA Advisory Board recommended lowering the maximum dose of APAP. Kava herbal dietary supplements have been implicated in several human liver failure cases leading to the ban of kava-containing products in several Western countries. In the US, the FDA has issued warnings about the potential adverse effects of kava, but kava dietary supplements are still available to consumers. In this study, we tested the potential of kava extract to potentiate APAP-induced hepatocyte cytotoxicity. In rat primary hepatocytes, co-treatment with kava and APAP caused 100% loss of cell viability, while the treatment of kava or APAP alone caused ?50% and ?30% loss of cell viability, respectively. APAP-induced glutathione (GSH) depletion was also potentiated by kava. Co-exposure to kava decreased cellular ATP concentrations, increased the formation of reactive oxygen species, and caused mitochondrial damage as indicated by a decrease in mitochondrial membrane potential. In addition, similar findings were obtained from a cultured rat liver cell line, clone-9. These observations indicate that kava potentiates APAP-induced cytotoxicity by increasing the magnitude of GSH depletion, resulting in oxidative stress and mitochondrial dysfunction, ultimately leading to cell death. These results highlight the potential for drug-dietary supplement interactions even with widely used over-the-counter drugs. PMID:21397479

Yang, Xi; Salminen, William F

2011-03-11

358

Protective cytotoxic T lymphocyte responses against paramyxoviruses induced by epitope-based DNA vaccines: involvement of IFN-gamma.  

PubMed

Plasmid DNA vectors have been constructed with minigenes encoding a single cytotoxic T lymphocyte (CTL) epitope from either the M2 protein of respiratory syncytial virus (RSV) or from the nucleoprotein of measles virus (MV) with or without a signal sequence (also called secretory or leader sequence). Following intradermal immunization, plasmids in which the CTL epitopes were expressed in-frame with the signal sequence were more effective at inducing peptide- and virus-specific CTL responses than plasmids expressing CTL epitopes without the signal sequence. This immunization resulted in protection against MV-induced encephalitis and a significant reduction in viral load following RSV challenge. The reduction of viral load following RSV challenge was abrogated by prior injection with anti-IFN-gamma antibodies. These results highlight the ability of epitope-based DNA immunization to induce protective immune responses to well-defined epitopes and indicate the potential of this approach for the development of vaccines against infectious diseases. PMID:9796910

Hsu, S C; Obeid, O E; Collins, M; Iqbal, M; Chargelegue, D; Steward, M W

1998-10-01

359

Gliotoxin-Induced Cytotoxicity Proceeds via Apoptosis and Is Mediated by Caspases and Reactive Oxygen Species in LLC-PK1 Cells  

Microsoft Academic Search

Renal failure associated with aspergillosis is caused by patho- genic fungi. Gliotoxin is a toxic epipolythiodioxopiperazine me- tabolite produced by the pathogens. The present study investi- gated the cytotoxicity and underlying mechanisms induced by gliotoxin in LLC-PK1 cells, a porcine renal proximal tubular cell line. Gliotoxin at 100 ng\\/ml did not show a cytotoxic effect, but unmasked a dose-dependent cell

Xiaoming Zhou; Aiping Zhao; Gertrud Goping; Przemyslaw Hirszel

2000-01-01

360

Visible laser induced positive ion emissions from NaCl nanoparticles prepared by droplet rapid drying  

NASA Astrophysics Data System (ADS)

A novel convenient way for the formation of sodium chloride (NaCl) nanoparticles on silicon wafer is proposed by using a droplet rapid drying method. The laser induced positive ion emissions from NaCl nanoparticles with and without water treatment is demonstrated by using a laser desorption/ionization time-of-flight mass spectrometer, with laser intensity well below the plasma formation threshold. It is found that the positive ion emissions from NaCl nanoparticles are obviously higher than that from microsize NaCl particles under soft 532 nm laser irradiations, and water adsorption can efficiently enhance the ion emissions from NaCl nanoparticles. The initial kinetic energies of the emitted ions are estimated as 16-17 eV. The synergy of the ultra-thermal effect in nanomaterials, the defect-mediated multiphoton processes, and the existence of intermediate states in NaCl-water interfaces are suggested as the mechanisms.

Sun, Mao-Xu; Guo, Deng-Zhu; Xing, Ying-Jie; Zhang, Geng-Min

2012-09-01

361

Photo-induced electric polarizability of Fe3O4 nanoparticles in weak optical fields.  

PubMed

Using a developed co-precipitation method, we synthesized spherical Fe3O4 nanoparticles with a wide nonlinear absorption band of visible radiation. Optical properties of the synthesized nanoparticles dispersed in an optically transparent copolymer of methyl methacrylate with styrene were studied by optical spectroscopy and z-scan techniques. We found that the electric polarizability of Fe3O4 nanoparticles is altered by low-intensity visible radiation (I ? 0.2 kW/cm2; ? = 442 and 561 nm) and reaches a value of 107 Å3. The change in polarizability is induced by the intraband phototransition of charge carriers. This optical effect may be employed to improve the drug uptake properties of Fe3O4 nanoparticles. PACS: 33.15.Kr78.67.Bf42.70.Nq. PMID:23837726

Milichko, Valentin A; Nechaev, Anton I; Valtsifer, Viktor A; Strelnikov, Vladimir N; Kulchin, Yurii N; Dzyuba, Vladimir P

2013-07-09

362

Photo-induced electric polarizability of Fe3O4 nanoparticles in weak optical fields  

PubMed Central

Using a developed co-precipitation method, we synthesized spherical Fe3O4 nanoparticles with a wide nonlinear absorption band of visible radiation. Optical properties of the synthesized nanoparticles dispersed in an optically transparent copolymer of methyl methacrylate with styrene were studied by optical spectroscopy and z-scan techniques. We found that the electric polarizability of Fe3O4 nanoparticles is altered by low-intensity visible radiation (I ? 0.2 kW/cm2; ? = 442 and 561 nm) and reaches a value of 107 Å3. The change in polarizability is induced by the intraband phototransition of charge carriers. This optical effect may be employed to improve the drug uptake properties of Fe3O4 nanoparticles. PACS 33.15.Kr 78.67.Bf 42.70.Nq

2013-01-01

363

Skin dendritic cell targeting via microneedle arrays laden with antigen-encapsulated poly-D,L-lactide-co-glycolide nanoparticles induces efficient antitumor and antiviral immune responses.  

PubMed

The efficacious delivery of antigens to antigen-presenting cells (APCs), in particular, to dendritic cells (DCs), and their subsequent activation remains a significant challenge in the development of effective vaccines. This study highlights the potential of dissolving microneedle (MN) arrays laden with nanoencapsulated antigen to increase vaccine immunogenicity by targeting antigen specifically to contiguous DC networks within the skin. Following in situ uptake, skin-resident DCs were able to deliver antigen-encapsulated poly-d,l-lactide-co-glycolide (PGLA) nanoparticles to cutaneous draining lymph nodes where they subsequently induced significant expansion of antigen-specific T cells. Moreover, we show that antigen-encapsulated nanoparticle vaccination via microneedles generated robust antigen-specific cellular immune responses in mice. This approach provided complete protection in vivo against both the development of antigen-expressing B16 melanoma tumors and a murine model of para-influenza, through the activation of antigen-specific cytotoxic CD8(+) T cells that resulted in efficient clearance of tumors and virus, respectively. In addition, we show promising findings that nanoencapsulation facilitates antigen retention into skin layers and provides antigen stability in microneedles. Therefore, the use of biodegradable polymeric nanoparticles for selective targeting of antigen to skin DC subsets through dissolvable MNs provides a promising technology for improved vaccination efficacy, compliance, and coverage. PMID:23373658

Zaric, Marija; Lyubomska, Oksana; Touzelet, Olivier; Poux, Candice; Al-Zahrani, Sharifah; Fay, Francois; Wallace, Leah; Terhorst, Dorothea; Malissen, Bernard; Henri, Sandrine; Power, Ultan F; Scott, Christopher J; Donnelly, Ryan F; Kissenpfennig, Adrien

2013-02-15

364

HIV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state.  

PubMed

This study demonstrates that human immunodeficiency virus type 1 (HIV-1) Tat protein amplifies the activity of tumor necrosis factor (TNF), a cytokine that stimulates HIV-1 replication through activation of NF-kappa B. In HeLa cells stably transfected with the HIV-1 tat gene (HeLa-tat cells), expression of the Tat protein enhanced both TNF-induced activation of NF-kappa B and TNF-mediated cytotoxicity. A similar potentiation of TNF effects was observed in Jurkat T cells and HeLa cells treated with soluble Tat protein. TNF-mediated activation of NF-kappa B and cytotoxicity involves the intracellular formation of reactive oxygen intermediates. Therefore, Tat-mediated effects on the cellular redox state were analyzed. In both T cells and HeLa cells HIV-1 Tat suppressed the expression of Mn-dependent superoxide dismutase (Mn-SOD), a mitochondrial enzyme that is part of the cellular defense system against oxidative stress. Thus, Mn-SOD RNA protein levels and activity were markedly reduced in the presence of Tat. Decreased Mn-SOD expression was associated with decreased levels of glutathione and a lower ratio of reduced:oxidized glutathione. A truncated Tat protein (Tat1-72), known to transactivate the HIV-1 long terminal repeat (LTR), no longer affected Mn-SOD expression, the cellular redox state or TNF-mediated cytotoxicity. Thus, our experiments demonstrate that the C-terminal region of HIV-1 Tat is required to suppress Mn-SOD expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione (GSH) and the GSH:oxidized GSH (GSSG) ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7859743

Westendorp, M O; Shatrov, V A; Schulze-Osthoff, K; Frank, R; Kraft, M; Los, M; Krammer, P H; Dröge, W; Lehmann, V

1995-02-01

365