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1

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

2

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

3

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

4

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

5

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

6

Cytotoxicity and cell membrane depolarization induced by aluminum oxide nanoparticles in human lung epithelial cells A549  

Microsoft Academic Search

The cytotoxicity of 13 and 22 nm aluminum oxide (Al2O3) nanoparticles was investigated in cultured human bronchoalveolar carcinoma-derived cells (A549) and compared with 20 nm CeO2 and 40 nm TiO2 nanoparticles as positive and negative control, respectively. Exposure to both Al2O3 nanoparticles for 24 h at 10 and 25 µg mL doses significantly decreased cell viability compared with control. However,

Weisheng Lin; Isaac Stayton; Yue-wern Huang; Xiao-Dong Zhou; Yinfa Ma

2008-01-01

7

Nickel oxide nanoparticles exert cytotoxicity via oxidative stress and induce apoptotic response in human liver cells (HepG2).  

PubMed

Increasing use of nickel oxide nanoparticles (NiO NPs) necessitates an improved understanding of their potential impact on human health. Previously, toxic effects of NiO NPs have been investigated, mainly on airway cells. However, information on effect of NiO NPs on human liver cells is largely lacking. In this study, we investigated the reactive oxygen species (ROS) mediated cytotoxicity and induction of apoptotic response in human liver cells (HepG2) due to NiO NPs exposure. Prepared NiO NPs were crystalline and spherical shaped with an average diameter of 44 nm. NiO NPs induced cytotoxicity (cell death) and ROS generation in HepG2 cells in dose-dependent manner. Further, ROS scavenger vitamin C reduced cell death drastically caused by NiO NPs exposure indicating that oxidative stress plays an important role in NiO NPs toxicity. Micronuclei induction, chromatin condensation and DNA damage in HepG2 cells treated with NiO NPs suggest that NiO NPs induced cell death via apoptotic pathway. Quantitative real-time PCR analysis showed that following the exposure of HepG2 cells to NiO NPs, the expression level of mRNA of apoptotic genes (bax and caspase-3) were up-regulated whereas the expression level of anti-apoptotic gene bcl-2 was down-regulated. Moreover, activity of caspase-3 enzyme was also higher in NiO NPs treated cells. To the best of our knowledge this is the first report demonstrating that NiO NPs caused cytotoxicity via ROS and induced apoptosis in HepG2 cells, which is likely to be mediated through bax/bcl-2 pathway. This work warrants careful assessment of Ni NPs before their commercial and industrial applications. PMID:24139157

Ahamed, Maqusood; Ali, Daoud; Alhadlaq, Hisham A; Akhtar, Mohd Javed

2013-11-01

8

Silica nanoparticles-induced cytotoxicity, oxidative stress and apoptosis in cultured A431 and A549 cells.  

PubMed

In medicine, the use of silica nanoparticles (SiO(2) NPs) offers new perspectives in biosensor, drug delivery and cancer therapy. However, questions about potential toxic and deleterious effects of SiO(2) NPs have also been raised. The aim of this study was to investigate the induction of cytotoxicity, oxidative stress and apoptosis by SiO(2) NPs (size 15 nm) in human skin epithelial (A431) and human lung epithelial (A549) cells. SiO(2) NPs (concentration range 25-200 µg/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. SiO(2) NPs were also found to induce oxidative stress in a dose-dependent manner, indicated by depletion of glutathione and induction of reactive oxygen species (ROS) generation and lipid peroxidation. Quantitative real-time polymerase chain reaction analysis showed that following the exposure of cells to SiO(2) NPs, the messenger RNA level of apoptotic genes (caspase-3 and caspase-9) were upregulated in a dose-dependent manner. Moreover, activities of caspase-3 and caspase-9 enzymes were also significantly higher in both kinds of cells exposed to SiO(2) NPs. This study suggested that SiO(2) NPs induce cytotoxicity and apoptosis in A431 and A549 cells, which is likely to be mediated through ROS generation and oxidative stress. PMID:23315277

Ahamed, Maqusood

2013-02-01

9

Silver nanoparticle-induced cytotoxicity in rat brain endothelial cell culture.  

PubMed

Silver nanoparticles (AgNPs) are among the most widely commercialised engineered nanomaterials, because of their antimicrobial properties. They are already commonly used in medical devices, household products and industry. Concerns have been raised about potential adverse health effects due to increasing dispersion of AgNPs in the environment. The present study examined the cytotoxic effects of spherical, citrate-coated AgNPs (10, 50 and 100 nm) in rat brain endothelial (RBE4) cells and investigated whether the observed effects can be explained by the intrinsic toxicity of the particles or the silver ions released from the particles. The results indicated that exposure of RBE4 cells to AgNPs lead to significant reduction in dye uptake as measured with the Neutral red (NR) assay. The effect was found to be related to particle size, surface area, dose and exposure time. In contrast, silver ions increased NR uptake (ca. 10%) in RBE4 cells after 1h, while a reduction in NR uptake was observed after 24h exposure at high concentrations (20-30 ?M). Colony formation, as an indicator of proliferation ability, was completely inhibited by AgNPs at concentrations higher than 1 ?g/ml. Silver ions had less effect on the colony formation of RBE4 cells than AgNPs. PMID:22954533

Grosse, Susann; Evje, Lars; Syversen, Tore

2013-02-01

10

Cytotoxic Potential of Silver Nanoparticles  

PubMed Central

Silver nanoparticles (AgNPs) have been widely used in industrial, household, and healthcare-related products due to their excellent antimicrobial activity. With increased exposure of AgNPs to human beings, the risk of safety has attracted much attention from the public and scientists. In review of recent studies, we discuss the potential impact of AgNPs on individuals at the cell level. In detail, we highlight the main effects mediated by AgNPs on the cell, such as cell uptake and intracellular distribution, cytotoxicity, genotoxicity, and immunological responses, as well as some of the major factors that influence these effects in vivo and in vivo, such as dose, time, size, shape, surface chemistry, and cell type. At the end, we summarize the main influences on the cell and indicate the challenges in this field, which may be helpful for assessing the risk of AgNPs in future.

Zhang, Tianlu; Wang, Liming

2014-01-01

11

Enhanced cytotoxicity and apoptosis-induced anticancer effect of silibinin-loaded nanoparticles in oral carcinoma (KB) cells.  

PubMed

Silibinin (SIL) is a plant derived flavonoid isolated from the fruits and seeds of the milk thistle (Silybum marianum). Silibinin possesses a wide variety of biological applications including anticancer activities but poor aqueous solubility and poor bioavailability limit its potential and efficacy at the tumor sites. In the present study, silibinin was encapsulated in Eudragit® E (EE) nanoparticles in the presence of stabilizing agent polyvinyl alcohol (PVA) and its anticancer efficacy in oral carcinoma (KB) cells was studied. Silibinin loaded nanoparticles (SILNPs) were prepared by nanoprecipitation technique and characterized in terms of size distribution, morphology, surface charge, encapsulation efficiency and in vitro drug release. MTT assay revealed higher cytotoxic efficacy of SILNPs than free SIL in KB cells. Meanwhile, reactive oxygen species (ROS) determination revealed the significantly higher intracellular ROS levels in SILNPs treated cells compared to free SIL treated cells. Therefore, the differential cytotoxicity between SILNPs and SIL may be mediated by the discrepancy of intracellular ROS levels. Moreover, acridine orange (AO) and ethidium bromide (EB) dual staining and reduced mitochondrial membrane potential (MMP) confirmed the induction of apoptosis with nanoparticle treatment. Further, the extent of DNA damage (evaluated by comet assay) was significantly increased in SILNPs than free SIL in KB cells. Taken together, the present study suggests that silibinin-loaded nanoparticles can be used as an effective drug delivery system to produce a better chemopreventive response for the treatment of cancer. PMID:24907761

Gohulkumar, M; Gurushankar, K; Rajendra Prasad, N; Krishnakumar, N

2014-08-01

12

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

Microsoft Academic Search

Background  Some manufactured nanoparticles are metal-based and have a wide variety of applications in electronic, engineering and medicine.\\u000a Until now, many studies have described the potential toxicity of NPs on pulmonary target, while little attention has been\\u000a paid to kidney which is considered to be a secondary target organ. The objective of this study, on human renal culture cells,\\u000a was to

Igor Pujalté; Isabelle Passagne; Brigitte Brouillaud; Mona Tréguer; Etienne Durand; Céline Ohayon-Courtčs; Béatrice L’Azou

2011-01-01

13

Cytotoxicity of nanoparticle-loaded polymer capsules.  

PubMed

Cytotoxic effects of micrometer-sized polymer capsules composed out of alternating layers of polystyrenesulfonate (PSS) and polyallylamine hydrochloride (PAH) on a fibroblast cell line have been investigated with an adhesion assay. For the purpose of visualization with fluorescence nanometer-sized CdTe nanoparticles have been embedded in the walls of the capsules. Similar to free CdTe nanoparticles, toxic Cd-ions are also released from CdTe nanoparticles that have been embedded in capsules. At high capsule concentrations, the capsules start to sediment on top of the cells and thus impair cell viability. PMID:18970193

Kirchner, C; Javier, A Muńoz; Susha, A S; Rogach, A L; Kreft, O; Sukhorukov, G B; Parak, W J

2005-09-15

14

Experimental considerations on the cytotoxicity of nanoparticles  

PubMed Central

Engineered nanoparticles are one of the leading nanomaterials currently under investigation due to their applicability in various fields, including drug and gene delivery, biosensors, cancer treatment and diagnostic tools. Moreover, the number of commercial products containing nanoparticles released on the market is rapidly increasing. Nanoparticles are already widely distributed in air, cosmetics, medicines and even in food. Therefore, the unintended adverse effect of nanoparticle exposure is a growing concern both academically and socially. In this context, the toxicity of nanoparticles has been extensively studied; however, several challenges are encountered due to the lack of standardized protocols. In order to improve the experimental conditions of nanoparticle toxicity studies, serious consideration is critical to obtain reliable and realistic data. The cell type must be selected considering the introduction route and target organ of the nanoparticle. In addition, the nanoparticle dose must reflect the realistic concentration of nanoparticles and must be loaded as a well-dispersed form to observe the accurate size- and shape-dependent effect. In deciding the cytotoxicity assay method, it is important to choose the appropriate method that could measure the toxicity of interest without the false-negative or -positive misinterpretation of the toxicity result.

Kong, Bokyung; Seog, Ji Hyun; Graham, Lauren M; Lee, Sang Bok

2011-01-01

15

Cytotoxicity and genotoxicity of biogenic silver nanoparticles  

NASA Astrophysics Data System (ADS)

Biogenic silver nanoparticles with 40.3 ± 3.5 nm size and negative surface charge (- 40 mV) were prepared with Fusarium oxysporum. The cytotoxicity of 3T3 cell and human lymphocyte were studied by a TaliTM image-based cytometer and the genotoxicity through Allium cepa and comet assay. The results of BioAg-w (washed) and BioAg-nw (unwashed) biogenic silver nanoparticles showed cytotoxicity exceeding 50 ?g/mL with no significant differences of response in 5 and 10 ?g/mL regarding viability. Results of genotoxicity at concentrations 5.0 and 10.0 ug/mL show some response, but at concentrations 0.5 and 1.0 ?g/mL the washed and unwashed silver nanoparticles did not present any effect. This in an important result since in tests with different bacteria species and strains, including resistant, MIC (minimal inhibitory concentration) had good answers at concentrations less than 1.9 ?g/mL. This work concludes that biogenic silver nanoparticles may be a promising option for antimicrobial use in the range where no cyto or genotoxic effect were observed. Furthermore, human cells were found to have a greater resistance to the toxic effects of silver nanoparticles in comparison with other cells.

Lima, R.; Feitosa, L. O.; Ballottin, D.; Marcato, P. D.; Tasic, L.; Durán, N.

2013-04-01

16

In vitro cytotoxicity of fluorescent silica nanoparticles hybridized with aggregation-induced emission luminogens for living cell imaging.  

PubMed

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. PMID:23296280

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

2013-01-01

17

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

18

Cell type-dependent uptake, localization, and cytotoxicity of 1.9 nm gold nanoparticles  

PubMed Central

Background This follow-up study aims to determine the physical parameters which govern the differential radiosensitization capacity of two tumor cell lines and one immortalized normal cell line to 1.9 nm gold nanoparticles. In addition to comparing the uptake potential, localization, and cytotoxicity of 1.9 nm gold nanoparticles, the current study also draws on comparisons between nanoparticle size and total nanoparticle uptake based on previously published data. Methods We quantified gold nanoparticle uptake using atomic emission spectroscopy and imaged intracellular localization by transmission electron microscopy. Cell growth delay and clonogenic assays were used to determine cytotoxicity and radiosensitization potential, respectively. Mechanistic data were obtained by Western blot, flow cytometry, and assays for reactive oxygen species. Results Gold nanoparticle uptake was preferentially observed in tumor cells, resulting in an increased expression of cleaved caspase proteins and an accumulation of cells in sub G1 phase. Despite this, gold nanoparticle cytotoxicity remained low, with immortalized normal cells exhibiting an LD50 concentration approximately 14 times higher than tumor cells. The surviving fraction for gold nanoparticle-treated cells at 3 Gy compared with that of untreated control cells indicated a strong dependence on cell type in respect to radiosensitization potential. Conclusion Gold nanoparticles were most avidly endocytosed and localized within cytoplasmic vesicles during the first 6 hours of exposure. The lack of significant cytotoxicity in the absence of radiation, and the generation of gold nanoparticle-induced reactive oxygen species provide a potential mechanism for previously reported radiosensitization at megavoltage energies.

Coulter, Jonathan A; Jain, Suneil; Butterworth, Karl T; Taggart, Laura E; Dickson, Glenn R; McMahon, Stephen J; Hyland, Wendy B; Muir, Mark F; Trainor, Coleman; Hounsell, Alan R; O'Sullivan, Joe M; Schettino, Giuseppe; Currell, Fred J; Hirst, David G; Prise, Kevin M

2012-01-01

19

In vitro cytotoxicity of transparent yellow iron oxide nanoparticles on human glioma cells.  

PubMed

With rapid development of nanotechnology, concerns about the possible adverse health effects on human beings by using nanomaterials have been raised. Transparent yellow iron oxide (alpha-FeOOH) nanoparticles have been widely used in paints, plastic, rubber, building materials, papermaking, food products and pharmaceutical industry, thus the potential health implications by the exposure should be considered. The purpose of this study is to assess the cytotoxicity of transparent yellow iron oxide nanoparticles on U251 human glioma cells. The alpha-FeOOH nanoparticles are in clubbed shapes with 9 nm in diameter and 43 nm long. The specific surface area is 115.3 m2/g. After physicochemical characterization of the nanoparticles, U251 cells were exposed to a-FeOOH at the doses of 0, 3.75, 15, 60 and 120 microg/mL. The results showed that the alpha-FeOOH nanoparticles reduced the cell viability and induced necrosis and apoptosis in U251 cells. In addition, nanoparticle exposure significantly increased the levels of superoxide anion and nitric oxide in a dose-dependent fashion in the cells. Our results suggest that exposure to alpha-FeOOH nanoparticles induce significant free radical formation and cytotoxic effects. The large surface area that induced high surface reactivity may play an important role in the cytotoxic effect of alpha-FeOOH nanoparticles. PMID:21121365

Wang, Yun; Zhu, Mo-Tao; Wang, Bing; Wang, Meng; Wang, Hua-Jian; OuYang, Hong; Feng, Wei-Yue

2010-12-01

20

In vitro cytotoxicity of silver nanoparticles on osteoblasts and osteoclasts at antibacterial concentrations.  

PubMed

Nanoparticulate silver coatings for orthopaedic implants promise to decrease postoperative infection rates. However, silver-induced cytotoxicity on bone cells has not been investigated in detail. This study investigated the cytotoxic effects of silver nano- and microparticles and Ag(+) on osteoblasts (OBs) and osteoclasts (OCs) and correlated their effects with the antibacterial efficacy on Staphylococcus epidermidis. Silver nanoparticles (50 nm) exhibited strong cytotoxic effects on OBs and OCs. Weak cytotoxic effects were observed for silver microparticles (3 ?m). The cytotoxicity was primarily mediated by a size-dependent release of Ag(+). Antibacterial effects occurred at Ag(+) concentrations that were 2-4 times higher than those inducing cytotoxic effects. Such adverse effects on OB and OC survival may have deleterious effects on the biocompatibility of orthopaedic implants. Our study represents an important step toward the detailed investigation of orthopaedic implant with nanoparticulate silver coatings prior to their widespread clinical usage. PMID:22013878

Albers, Christoph E; Hofstetter, Wilhelm; Siebenrock, Klaus A; Landmann, Regine; Klenke, Frank M

2013-02-01

21

Multifunctional nanoparticles co-delivering Trp2 peptide and CpG adjuvant induce potent cytotoxic T-lymphocyte response against melanoma and its lung metastasis.  

PubMed

Immunotherapy has shown the potential to become an essential component of the successful treatment of various malignancies. In many cases, such as in melanoma, however, induction of a potent and specific T-cell response against the endogenous antigen or self-antigen still remains a major challenge. To induce a potent MHC I-restricted cytotoxic T-lymphocyte (CTL) response, cytosol delivery of an exogenous antigen into dendritic cells is preferred, if not required. Lipid-calcium-phosphate (LCP) nanoparticles represent a new class of intracellular delivery systems for impermeable drugs. We are interested in exploring the potential of LCP NPs for use as a peptide vaccine delivery system for cancer therapy. To increase the encapsulation of Trp2 peptide into the calcium phosphate precipitate core of LCP, two phosphor-serine residues were added to the N-terminal of the peptide (p-Trp2). CpG ODN was also co-encapsulated with p-Trp2 as an adjuvant. The NPs were further modified with mannose to enhance and prolong the cargo deposit into the lymph nodes (LNs), which ensured persistent antigen loading and stimulation. Compared with free Trp2 peptide/CpG, vaccination with LCP encapsulating p-Trp2 and CpG resulted in superior inhibition of tumor growth in both B16F10 subcutaneous and lung metastasis models. An IFN-? production assay and in vivo CTL response study revealed that the improved efficacy was a result of a Trp2-specific immune response. Thus, encapsulation of phospho-peptide antigens into LCP may be a promising strategy for enhancing the immunogenicity of poorly immunogenic self-antigens for cancer therapy. PMID:24004885

Xu, Zhenghong; Ramishetti, Srinivas; Tseng, Yu-Cheng; Guo, Shutao; Wang, Yuhua; Huang, Leaf

2013-11-28

22

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

23

Evaluation of the cytotoxic and inflammatory potential of differentially shaped zinc oxide nanoparticles.  

PubMed

Zinc oxide (ZnO) nanoparticles have wide-ranging applications in a diverse array of industrial and consumer products, from ceramic manufacture and paint formulation to sunscreens and haircare products. Hence, it is imperative to rigorously characterize the health and safety aspects of human exposure to ZnO nanoparticles. This study therefore evaluated the cellular association, cytotoxic and inflammatory potential of spherical and sheet-shaped ZnO nanoparticles (of approximately the same specific surface area ?30 cm˛/g) on mouse and human cell lines (RAW-264.7 and BEAS-2B respectively), as well as with primary cultures of mouse bone marrow-derived dendritic cells (DC). The WST-8 assay demonstrated dose-dependent effects on the cytotoxicity of spherical and sheet-shaped ZnO nanoparticles on both RAW-264.7 and BEAS-2B cells, even though there was no significant effect of shape on the cytotoxicity of ZnO nanoparticles. There was however higher cellular association of spherical versus sheet-shaped ZnO nanoparticles. Measurement of reactive oxygen species (ROS) with the 2',7'-dichlorfluorescein-diacetate (DCFH-DA) assay indicated up to 4-folds increase in ROS level upon exposure to ZnO nanoparticles, but there was again no significant difference between both ZnO nanoparticle shapes. Exposure of primary dendritic cells to ZnO nanoparticles upregulated expression of CD80 and CD86 (well-known markers of DC activation and maturation) and stimulated release of pro-inflammatory cytokines--IL-6 and TNF-?, thus pointing to the potential of ZnO nanoparticles in inducing inflammation. Hence, our study indicated that ZnO nanoparticles can have potential detrimental effects on cells even at dosages where there are little or no observable cytotoxic effects. PMID:21656222

Heng, Boon Chin; Zhao, Xinxin; Tan, Eng Chok; Khamis, Nurulain; Assodani, Aarti; Xiong, Sijing; Ruedl, Christiane; Ng, Kee Woei; Loo, Joachim Say-Chye

2011-12-01

24

Nanoparticle Incorporation of Melittin Reduces Sperm and Vaginal Epithelium Cytotoxicity  

PubMed Central

Melittin is a cytolytic peptide component of bee venom which rapidly integrates into lipid bilayers and forms pores resulting in osmotic lysis. While the therapeutic utility of free melittin is limited by its cytotoxicity, incorporation of melittin into the lipid shell of a perfluorocarbon nanoparticle has been shown to reduce its toxicity in vivo. Our group has previously demonstrated that perfluorocarbon nanoparticles containing melittin at concentrations <10 µM inhibit HIV infectivity in vitro. In the current study, we assessed the impact of blank and melittin-containing perfluorocarbon nanoparticles on sperm motility and the viability of both sperm and vaginal epithelial cells. We found that free melittin was toxic to sperm and vaginal epithelium at concentrations greater than 2 µM (p<0.001). However, melittin nanoparticles were not cytotoxic to sperm (p?=?0.42) or vaginal epithelium (p?=?0.48) at an equivalent melittin concentration of 10 µM. Thus, nanoparticle formulation of melittin reduced melittin cytotoxicity fivefold and prevented melittin toxicity at concentrations previously shown to inhibit HIV infectivity. Melittin nanoparticles were toxic to vaginal epithelium at equivalent melittin concentrations ?20 µM (p<0.001) and were toxic to sperm at equivalent melittin concentrations ?40 µM (p<0.001). Sperm cytotoxicity was enhanced by targeting of the nanoparticles to the sperm surface antigen sperm adhesion molecule 1. While further testing is needed to determine the extent of cytotoxicity in a more physiologically relevant model system, these results suggest that melittin-containing nanoparticles could form the basis of a virucide that is not toxic to sperm and vaginal epithelium. This virucide would be beneficial for HIV serodiscordant couples seeking to achieve natural pregnancy.

Jallouk, Andrew P.; Moley, Kelle H.; Omurtag, Kenan; Hu, Grace; Lanza, Gregory M.; Wickline, Samuel A.; Hood, Joshua L.

2014-01-01

25

Cytotoxicity of selenium nanoparticles in rat dermal fibroblasts  

PubMed Central

Background: Ventilator-associated pneumonia is a deadly nosocomial infection caused by contaminated endotracheal tubes. It has been shown that polyvinyl chloride (PVC, the endotracheal tube substrate) coated with elemental selenium nanoparticles reduces bacterial adherence and proliferation on PVC by over 99%. However, it is not known if selenium nanoparticles elicit a cytotoxic effect in vitro. The purpose of this study was to investigate the cytotoxic effects of PVC coated with selenium nanoparticles on fibroblasts, which are mammalian cells central to endotracheal tube intubation. Methods: Different concentrations of selenium nanoparticles were precipitated onto the PVC surface by reduction of selenium salts using glutathione. Characterization of PVC coated with selenium nanoparticles was done by scanning electron microscopy, energy dispersive x-ray, and contact angle measurements. For the cytotoxicity experiments, fibroblasts were seeded at a density of 5000 cm2 onto PVC coated with three different concentrations of selenium nanoparticles (high, medium, low) and incubated for 4 hours (adhesion) as well as for 24 hours and 72 hours (proliferation). The half-maximal inhibitory concentration (IC50) value was determined after 72 hours using an ultrahigh concentration. MTT assays were used to assess cell viability at the indicated time points. Results: The three concentrations of selenium nanoparticles did not elicit a cytotoxic effect after 72 hours (P < 0.01, n = 3). It was found that the IC50value was at the ultrahigh concentration of selenium nanoparticles. The nanoparticulate elemental selenium concentration previously shown to decrease the function of bacteria was shown not to cause a cytotoxic effect on fibroblasts in vitro. Conclusion: These findings demonstrate great selectivity between bacteria and healthy cells, and are a viable option for coating endotracheal tubes in order to prevent ventilator-associated pneumonia.

Ramos, Joseph F; Webster, Thomas J

2012-01-01

26

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

2013-04-15

27

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

2013-02-01

28

Unraveling the cytotoxic potential of Temozolomide loaded into PLGA nanoparticles  

PubMed Central

Background Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells. Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry. Results PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility. Conclusion PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity.

2014-01-01

29

Differential cytotoxic effects of gold nanoparticles in different mammalian cell lines.  

PubMed

Gold nanoparticles (AuNPs) possess unique properties that have been exploited in several medical applications. However, a more comprehensive understanding of the environmental safety of AuNPs is imperative for use of these nanomaterials. Here, we describe the impacts of AuNPs in various mammalian cell models using an automatic and dye-free method for continuous monitoring of cell growth based on the measurement of cell impedance. Several well-established cytotoxicity assays were also used for comparison. AuNPs induced a concentration-dependent decrease in cell growth. This inhibitory effect was associated with apoptosis induction in Vero cells but not in MRC-5 or NIH3T3 cells. Interestingly, cDNA microarray analyses in MRC-5 cells supported the involvement of DNA damage and repair responses, cell-cycle regulation, and oxidative stress in AuNP-induced cytotoxicity and genotoxicity. Moreover, autophagy appeared to play a role in AuNPs-induced attenuation of cell growth in NIH3T3 cells. In this study, we present a comprehensive overview of AuNP-induced cytotoxicity in a variety of mammalian cell lines, comparing several cytotoxicity assays. Collectively, these assays offer convincing evidence of the cytotoxicity of AuNPs and support the value of a systematic approach for analyzing the toxicology of nanoparticles. PMID:24316248

Chueh, Pin Ju; Liang, Ruei-Yue; Lee, Yi-Hui; Zeng, Zih-Ming; Chuang, Show-Mei

2014-01-15

30

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

31

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

32

Colloidal formulations of etoposide based on poly(butyl cyanoacrylate) nanoparticles: preparation, physicochemical properties and cytotoxicity.  

PubMed

This article describes the preparation, physicochemical characterization and cytotoxicity assessment of novel colloidal formulations of etoposide based on poly(butyl cyanoacrylate) nanoparticles. Nanoparticles were prepared by controlled emulsion polymerization of butyl cyanoacrylate in aqueous medium using two different non-ionic colloidal stabilizers (pluronic F68 and polysorbate 80). The nanoparticles were spherical in shape, with average size ranging from 110-150 nm (empty nanoparticles) to 170-260 nm (drug-loaded nanoparticles), monomodal size distributions, and negative zeta-potentials at pH 7.4. Drug loading efficiency was around 63-68%. More than 80% of the drug was released from the formulations within 6-7h of dialysis experiments. Pluronic-coated nanoparticles possessed lower magnitude of the ?-potentials (around -4 mV) in comparison with the polysorbate-coated ones (around -12 mV). All tested etoposide formulations induced apoptosis in adenocarcinoma human epithelial (A549) cells, as evident from condensation of chromatin and fragmentation of nuclei. It was found that etoposide formulated with poly(butyl cyanoacrylate) nanoparticles and polysorbate 80 exhibited the highest cytotoxicity toward adenocarcinoma cells. PMID:23010022

Yordanov, Georgi; Skrobanska, Ralica; Evangelatov, Alexander

2013-01-01

33

Selective cytotoxicity effect of cerium oxide nanoparticles under UV irradiation.  

PubMed

During photodynamic therapy (PDT) of cancers, there are numerous side effects, accompanied by damage to normal cells/tissues caused by the abnormal elevation of reactive oxygen species (ROS). In this paper, we aim to provide an effective method to reduce the relevant side effects of PDT by using cerium oxide nanoparticles. The well-dispersed poly(vinyl pyrrolidone) stabilized cerium oxide nanoparticles were successfully synthesized by using a one-pot method at 60 degrees C in slightly alkaline environment. The morphological and structural characterizations clearly illustrate the excellent lattice structures of cerium oxide, nanoparticles. The MTT assay indicates that these cerium oxide nanoparticles show no intrinsic cytotoxicity even at a concentration up to 300 micro g/mL. More importantly, the results demonstrate that these nanoparticles can selectively protect human normal cells but not the cancer cells from ROS damage after exposure to UV-radiation, suggesting their potential applications for PDT treatment. The rationale behind the selective protection effect can be attributed to the hindrance of the Ce (III)/Ce (IV) redox reaction cycle on the surface of cerium oxide nanoparticles due to the abnormal intracellular pH in cancer cells. Furthermore, these cerium oxide nanoparticles can be used as effective drug carriers for enhancing drug delivery efficiency to target cancer cells like hepatoma HepG2 cells. This raises the possibility of applying cerium oxide nanoparticles for multifunctional therapeutic applications, i.e., combination of efficient PDT and chemotherapy. PMID:24738336

Zhang, Li; Jiang, Hui; Selke, Matthias; Wang, Xuemei

2014-02-01

34

Microsomal Glutathione Transferase 1 Protects Against Toxicity Induced by Silica Nanoparticles but Not by Zinc Oxide Nanoparticles  

PubMed Central

Microsomal glutathione transferase 1 (MGST1) is an antioxidant enzyme located predominantly in the mitochondrial outer membrane and endoplasmic reticulum and has been shown to protect cells from lipid peroxidation induced by a variety of cytostatic drugs and pro-oxidant stimuli. We hypothesized that MGST1 may also protect against nanomaterial-induced cytotoxicity through a specific effect on lipid peroxidation. We evaluated the induction of cytotoxicity and oxidative stress by TiO2, CeO2, SiO2, and ZnO in the human MCF-7 cell line with or without overexpression of MGST1. SiO2 and ZnO nanoparticles caused dose- and time-dependent toxicity, whereas no obvious cytotoxic effects were induced by nanoparticles of TiO2 and CeO2. We also noted pronounced cytotoxicity for three out of four additional SiO2 nanoparticles tested. Overexpression of MGST1 reversed the cytotoxicity of the main SiO2 nanoparticles tested and for one of the supplementary SiO2 nanoparticles but did not protect cells against ZnO-induced cytotoxic effects. The data point toward a role of lipid peroxidation in SiO2 nanoparticle-induced cell death. For ZnO nanoparticles, rapid dissolution was observed, and the subsequent interaction of Zn2+ with cellular targets is likely to contribute to the cytotoxic effects. A direct inhibition of MGST1 by Zn2+ could provide a possible explanation for the lack of protection against ZnO nanoparticles in this model. Our data also showed that SiO2 nanoparticle-induced cytotoxicity is mitigated in the presence of serum, potentially through masking of reactive surface groups by serum proteins, whereas ZnO nanoparticles were cytotoxic both in the presence and in the absence of serum.

2012-01-01

35

Cytotoxic and genotoxic characterization of titanium dioxide, gadolinium oxide, and poly(lactic-co-glycolic acid) nanoparticles in human fibroblasts.  

PubMed

Engineered nanomaterials have become prevalent in our everyday life. While the popularity of using nanomaterials in consumer products continues to rise, increasing awareness of nanotoxicology has also fuelled efforts to accelerate our understanding of the ill effects that different nanomaterials can bring to biological systems. In this study, we investigated the potential cytotoxicity and genotoxicity of three nanoparticles: titanium dioxide (TiO(2)), terbium-doped gadolinium oxide (Tb-Gd(2)O(3)), and poly(lactic-co-glycolic acid) (PLGA). To evaluate nanoparticle-induced genotoxicity more realistically, a human skin fibroblast cell line (BJ) with less mutated genotype compared with cancer cell line was used. The nanoparticles were first characterized by size, morphology, and surface charge. Cytotoxicity effects of the nanoparticles were then evaluated by monitoring the proliferation of treated BJ cells. Genotoxic influence was ascertained by profiling DNA damage via detection of ?H2AX expression. Our results suggested that both TiO(2) and Tb-Gd(2)O(3) nanoparticles induced cytotoxicity in a dose dependent way on BJ cells. These two nanomaterials also promoted genotoxicity via DNA damage. On the contrary, PLGA nanoparticles did not induce significant cytotoxic or genotoxic effects on BJ cells. PMID:22927021

Setyawati, Magdiel Inggrid; Khoo, Pheng Kian Stella; Eng, Bao Hui; Xiong, Sijing; Zhao, Xinxin; Das, Gautom Kumar; Tan, Timothy Thatt-Yang; Loo, Joachim Say Chye; Leong, David Tai; Ng, Kee Woei

2013-03-01

36

Xanthan gum stabilized gold nanoparticles: Characterization, biocompatibility, stability and cytotoxicity.  

PubMed

Xanthan gum (XG) has been widely used in food, pharmaceutical and cosmetic industries. In the present study, we explored the potential of XG in the synthesis of gold nanoparticle. XG was used as both reducing and stabilizing agent. The effect of various formulation and process variables such as temperature, reaction time, gum concentration, gum volume and gold concentration, in GNP preparation was determined. The XG stabilized, rubey-red XGNP were obtained with 5ml of XG aqueous solution (1.5mg/ml). The optimum temperature was 80°C whereas the reaction time was 3h. The optimized nanoparticles were also investigated as drug delivery carrier for doxorubicin hydrochloride. DOX loaded gold nanoparticles (DXGP) were characterized by dynamic light scattering, TEM, FTIR, and DSC analysis. The synthesized nanoparticle showed mean particle size of 15-20nm and zeta potential -29.1mV. The colloidal stability of DXGP was studied under different conditions of pH, electrolytes and serum. Nanoparticles were found to be stable at pH range between pH 5-9 and NaCl concentration up to 0.5M. In serum, nanoparticles showed significant stability up to 24h. During toxicity studies, nanoparticles were found biocompatible and non-toxic. Compared with free DOX, DXGP displayed 3 times more cytotoxicity in A549 cells. In conclusion, this study provided an insight to synthesize GNP without using harsh chemicals. PMID:24906721

Pooja, Deep; Panyaram, Sravani; Kulhari, Hitesh; Rachamalla, Shyam S; Sistla, Ramakrishna

2014-09-22

37

Synthesis and Cytotoxicity of Y2O3 Nanoparticles of Various Morphologies  

PubMed Central

As the field of nanotechnology continues to grow, evaluating the cytotoxicity of nanoparticles is important in furthering their application within biomedicine. Here, we report the synthesis, characterization, and cytotoxicity of nanoparticles of different morphologies of yttrium oxide, a promising material for biological imaging applications. Nanoparticles of spherical, rod-like, and platelet morphologies were synthesized via solvothermal and hydrothermal methods and characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), light scattering, surface area analysis, thermogravimetric analysis (TGA), and zeta potential measurements. Nanoparticles were then tested for cytotoxicity with human foreskin fibroblast (HFF) cells, with the goal of elucidating nanoparticle characteristics that influence cytotoxicity. Cellular response was different for the different morphologies, with spherical particles exhibiting no cytotoxicity to HFF cells, rod-like particles increasing cell proliferation, and platelet particles markedly cytotoxic. However, due to differences in the nanoparticle chemistry as determined through the characterization techniques, it is difficult to attribute the cytotoxicity responses to the particle morphology. Rather, the cytotoxicity of the platelet sample appears due to the stabilizing ligand, oleylamine, which was present at higher levels in this sample. This study demonstrates the importance of nanoparticle chemistry on in vitro cytotoxicity, and highlights the general importance of thorough nanoparticle characterization as a prerequisite to understanding nanoparticle cytotoxicity.

2010-01-01

38

Cytotoxicity of monodispersed chitosan nanoparticles against the Caco-2 cells  

SciTech Connect

Published toxicology data on chitosan nanoparticles (NP) often lack direct correlation to the in situ size and surface characteristics of the nanoparticles, and the repeated NP assaults as experienced in chronic use. The aim of this paper was to breach these gaps. Chitosan nanoparticles synthesized by spinning disc processing were characterised for size and zeta potential in HBSS and EMEM at pHs 6.0 and 7.4. Cytotoxicity against the Caco-2 cells was evaluated by measuring the changes in intracellular mitochondrial dehydrogenase activity, TEER and sodium fluorescein transport data and cell morphology. Cellular uptake of NP was observed under the confocal microscope. Contrary to established norms, the collective data suggest that the in vitro cytotoxicity of NP against the Caco-2 cells was less influenced by positive surface charges than by the particle size. Particle size was in turn determined by the pH of the medium in which the NP was dispersed, with the mean size ranging from 25 to 333 nm. At exposure concentration of 0.1%, NP of 25 ± 7 nm (zeta potential 5.3 ± 2.8 mV) was internalised by the Caco-2 cells, and the particles were observed to inflict extensive damage to the intracellular organelles. Concurrently, the transport of materials along the paracellular pathway was significantly facilitated. The Caco-2 cells were, however, capable of recovering from such assaults 5 days following NP removal, although a repeat NP exposure was observed to produce similar effects to the 1st exposure, with the cells exhibiting comparable resiliency to the 2nd assault. -- Highlights: ? Chitosan nanoparticles reduced mitochondrial dehydrogenase activity. ? Cellular uptake of chitosan nanoparticles was observed. ? Chitosan nanoparticles inflicted extensive damage to the cell morphology. ? The transport of materials along the paracellular pathway was facilitated.

Loh, Jing Wen [Laboratory for Drug Delivery, Pharmacy, Characterisation and Analysis, University of Western Australia (Australia)] [Laboratory for Drug Delivery, Pharmacy, Characterisation and Analysis, University of Western Australia (Australia); Saunders, Martin [Centre for Microscopy, Characterisation and Analysis, University of Western Australia (Australia)] [Centre for Microscopy, Characterisation and Analysis, University of Western Australia (Australia); Lim, Lee-Yong, E-mail: lee.lim@uwa.edu.au [Laboratory for Drug Delivery, Pharmacy, Characterisation and Analysis, University of Western Australia (Australia) [Laboratory for Drug Delivery, Pharmacy, Characterisation and Analysis, University of Western Australia (Australia); School of Biomedical, Biomolecular and Chemical Sciences, 35 Stirling Hwy, Crawley 6009 (Australia)

2012-08-01

39

Reducing ZnO nanoparticle cytotoxicity by surface modification  

NASA Astrophysics Data System (ADS)

Nanoparticulate zinc oxide (ZnO) is one of the most widely used engineered nanomaterials and its toxicology has gained considerable recent attention. A key aspect for controlling biological interactions at the nanoscale is understanding the relevant nanoparticle surface chemistry. In this study, we have determined the disposition of ZnO nanoparticles within human immune cells by measurement of total Zn, as well as the proportions of extra- and intracellular dissolved Zn as a function of dose and surface coating. From this mass balance, the intracellular soluble Zn levels showed little difference in regard to dose above a certain minimal level or to different surface coatings. PEGylation of ZnO NPs reduced their cytotoxicity as a result of decreased cellular uptake arising from a minimal protein corona. We conclude that the key role of the surface properties of ZnO NPs in controlling cytotoxicity is to regulate cellular nanoparticle uptake rather than altering either intracellular or extracellular Zn dissolution.Nanoparticulate zinc oxide (ZnO) is one of the most widely used engineered nanomaterials and its toxicology has gained considerable recent attention. A key aspect for controlling biological interactions at the nanoscale is understanding the relevant nanoparticle surface chemistry. In this study, we have determined the disposition of ZnO nanoparticles within human immune cells by measurement of total Zn, as well as the proportions of extra- and intracellular dissolved Zn as a function of dose and surface coating. From this mass balance, the intracellular soluble Zn levels showed little difference in regard to dose above a certain minimal level or to different surface coatings. PEGylation of ZnO NPs reduced their cytotoxicity as a result of decreased cellular uptake arising from a minimal protein corona. We conclude that the key role of the surface properties of ZnO NPs in controlling cytotoxicity is to regulate cellular nanoparticle uptake rather than altering either intracellular or extracellular Zn dissolution. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr00458b

Luo, Mingdeng; Shen, Cenchao; Feltis, Bryce N.; Martin, Lisandra L.; Hughes, Anthony E.; Wright, Paul F. A.; Turney, Terence W.

2014-05-01

40

Effect of size and processing method on the cytotoxicity of realgar nanoparticles in cancer cell lines  

PubMed Central

In this study, the effects of the size and Chinese traditional processing (including elutriation, water cleaning, acid cleaning, alkali cleaning) on realgar nanoparticles (RN)-induced antitumor activity in human osteosarcoma cell lines (MG-63) and hepatoma carcinoma cell lines (HepG-2) were investigated. The human normal liver cell line (L-02) was used as control. RN was prepared by high-energy ball milling technology. The results showed that with the assistance of sodium dodecyl sulfate, the size of realgar could be reduced to 127 nm after 12 hours’ ball milling. The surface charge was decreased from 0.83 eV to ?17.85 eV and the content of As2O3 clearly increased. Except for elutriation, the processing methods did not clearly change the size of the RN, but the content of As2O3 was reduced dramatically. In vitro MTT tests indicated that in the two cancer cell lines, RN cytotoxicity was more intense than that of the coarse realgar nanoparticles, and cytotoxicity was typically time- and concentration-dependent. Also, RN cytotoxicities in the HepG-2 and L-02 cells all increased with increasing milling time. Due to the reduction of the As2O3 content, water cleaning, acid cleaning, and alkali cleaning decreased RN cytotoxicity in HepG-2, but RN after elutriation, with the lowest As2O3 (3.5 mg/g) and the smallest size (109.3 nm), showed comparable cytotoxicity in HepG-2 to RN without treatment. Meanwhile, RN-induced cytotoxicity in L-02 cells was clearly reduced. Therefore, it can be concluded that RN may provide a strong antiproliferation effect in the MG-63 and HepG-2 cells. Elutriation processing is a suitable approach to limit the dangerous side-effects of As2O3, while maintaining the effectiveness of RN.

Zhao, Weizhong; Lu, Xun; Yuan, Yuan; Liu, Changsheng; Yang, Baican; Hong, Hua; Wang, Guoying; Zeng, Fanyan

2011-01-01

41

Docetaxel loaded chitosan nanoparticles: Formulation, characterization and cytotoxicity studies.  

PubMed

The primary objective of the present investigation was to explore biodegradable chitosan as a polymeric material for formulating docetaxel nanoparticles (DTX-NPs) to be used as a delivery system for breast cancer treatment. Docetaxel loaded chitosan nanoparticles were formulated by water-in-oil nanoemulsion system and characterized in terms of particle size, zeta potential, polydispersity index, drug entrapment efficiency (EE), loading capacity (LC), scanning electron microscopy (SEM), in vitro release study and drug release kinetics. Further, to evaluate the potential anticancer efficacy of docetaxel loaded chitosan nanoparticulate system, in vitro cytotoxicity studies on human breast cancer cell line (MDA-MB-231) were carried out. The morphological studies revealed the spherical shape of docetaxel loaded chitosan nanoparticles having an average size of 170.1±5.42-227.6±7.87nm, polydispersity index in the range of 0.215±0.041-0.378±0.059 and zeta potential between 28.3 and 31.4mV. Nanoparticles exhibited 65-76% of drug entrapment and 8-12% loading capacity releasing about 68-83% of the drug within 12h following Higuchi's square-root kinetics. An increase of 20% MDA-MB-231 cell line growth inhibition was determined by docetaxel loaded chitosan nanoparticles with respect to the free drug after 72h incubation. PMID:24971551

Jain, Ankit; Thakur, Kanika; Kush, Preeti; Jain, Upendra K

2014-08-01

42

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

43

Reducing ZnO nanoparticle cytotoxicity by surface modification.  

PubMed

Nanoparticulate zinc oxide (ZnO) is one of the most widely used engineered nanomaterials and its toxicology has gained considerable recent attention. A key aspect for controlling biological interactions at the nanoscale is understanding the relevant nanoparticle surface chemistry. In this study, we have determined the disposition of ZnO nanoparticles within human immune cells by measurement of total Zn, as well as the proportions of extra- and intracellular dissolved Zn as a function of dose and surface coating. From this mass balance, the intracellular soluble Zn levels showed little difference in regard to dose above a certain minimal level or to different surface coatings. PEGylation of ZnO NPs reduced their cytotoxicity as a result of decreased cellular uptake arising from a minimal protein corona. We conclude that the key role of the surface properties of ZnO NPs in controlling cytotoxicity is to regulate cellular nanoparticle uptake rather than altering either intracellular or extracellular Zn dissolution. PMID:24740013

Luo, Mingdeng; Shen, Cenchao; Feltis, Bryce N; Martin, Lisandra L; Hughes, Anthony E; Wright, Paul F A; Turney, Terence W

2014-06-01

44

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

45

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

2009-04-01

46

Cytotoxicity of ?-D-glucose coated silver nanoparticles on human lymphocytes  

NASA Astrophysics Data System (ADS)

This study deals with the cytotoxicity of 30 nm sized ?-D-Glucose-coated silver NanoParticles (AgNPs-G) on human lymphocytes isolated from peripheral blood. Human lymphocytes were treated with different amounts (2 or 10×103 NPs/cell) of AgNPs-G for 24hs. AgNPs-G toxicity was assayed with MTT test and morphological observations. Further evaluation included: (i) ROS generation (NBT assay) and (ii) absorption/uptake of AgNPs-G by lymphocytes (GF-AAS). As a general result, AgNPs-G were absorbed/taken up by lymphocytes and cytotoxicity and morphology changes were amount and time-dependent. By incubating cells with the highest NPs amount, only 10% viable lymphocytes were found at the end of experimental time. Parallel to cytotoxicity, morphological modifications and ROS generation were induced, thus supporting the increasing cell deaths. Interestingly, the lower amount of AgNPs-G increased cell viability as the glucose did. Our findings suggest that AgNPs-G-induced cytotoxicity depends on NPs amount and provide evidence of AgNPs-G adsorption/entering by lymphocytes; however, the mechanisms of interaction/internalization needs to be further investigated.

Vergallo, Cristian; Panzarini, Elisa; Izzo, Daniela; Carata, Elisabetta; Mariano, Stefania; Buccolieri, Alessandro; Serra, Antonio; Manno, Daniela; Dini, Luciana

2014-06-01

47

Comparative cytotoxicity studies of carbon-encapsulated iron nanoparticles in murine glioma cells.  

PubMed

Carbon-encapsulated iron nanoparticles (CEINs) have recently emerged as a new class of magnetic nanomaterials with a great potential for an increasing number of biomedical applications. To address the current deficient knowledge of cellular responses due to CEIN exposures, we focused on the investigation of internalization profile and resulting cytotoxic effects of CEINs (0.0001-100 ?g/ml) in murine glioma cells (GL261) in vitro. The studied CEIN samples were characterized (TEM, FT-IR, Zeta potential, Boehm titration) and examined as raw and purified nanomaterials with various surface chemistry composition. Of the four type CEINs (the mean diameter 47-56 nm) studied here, the as-synthesized raw nanoparticles (Fe@C/Fe) exhibited high cytotoxic effects on the plasma cell membrane (LDH, Calcein AM/PI) and mitochondria (MTT, JC-1) causing some pro-apoptotic evens (Annexin V/PI) in glioma cells. The effects of the purified (Fe@C) and surface-modified (Fe@C-COOH and Fe@C-(CH2)2COOH) CEINs were found in quite similar patterns; however, most of these cytotoxic events were slightly diminished compared to those induced by Fe@C/Fe. The study showed that the surface-functionalized CEINs affected the cell cycle progression in both S and G2/M phases to a greater extent compared to that of the rest of nanoparticles studied to data. Taken all together, the present results highlight the importance of the rational design of CEINs as their physicochemical features such as morphology, hydrodynamic size, impurity profiles, and especially surface characteristics are critical determinants of different cytotoxic responses. PMID:24632386

Grudzinski, Ireneusz P; Bystrzejewski, Michal; Cywinska, Monika A; Kosmider, Anita; Poplawska, Magdalena; Cieszanowski, Andrzej; Fijalek, Zbigniew; Ostrowska, Agnieszka

2014-05-01

48

Quercetin-induced cardioprotection against doxorubicin cytotoxicity  

PubMed Central

Background Cancer has continually been the leading cause of death worldwide for decades. Thus, scientists have actively devoted themselves to studying cancer therapeutics. Doxorubicin is an efficient drug used in cancer therapy, but also produces reactive oxygen species (ROS) that induce severe cytotoxicity against heart cells. Quercetin, a plant-derived flavonoid, has been proven to contain potent antioxidant and anti-inflammatory properties. Thus, this in vitro study investigated whether quercetin can decrease doxorubicin-induced cytotoxicity and promote cell repair systems in cardiomyocyte H9C2 cells. Results Proteomic analysis and a cell biology assay were performed to investigate the quercetin-induced responses. Our data demonstrated that quercetin treatment protects the cardiomyocytes in a doxorubicin-induced heart damage model. Quercetin significantly facilitated cell survival by inhibiting cell apoptosis and maintaining cell morphology by rearranging the cytoskeleton. Additionally, 2D-DIGE combined with MALDI-TOF MS analysis indicated that quercetin might stimulate cardiomyocytes to repair damage after treating doxorubicin by modulating metabolic activation, protein folding and cytoskeleton rearrangement. Conclusion Based on a review of the literature, this study is the first to report detailed protective mechanisms for the action of quercetin against doxorubicin-induced cardiomyocyte toxicity based on in-depth cell biology and proteomic analysis.

2013-01-01

49

Relation between the Redox State of Iron-Based Nanoparticles and Their Cytotoxicity toward Escherichia coli  

SciTech Connect

Iron-based nanoparticles have been proposed for an increasing number of biomedical or environmental applications although in vitro toxicity has been observed. The aim of this study was to understand the relationship between the redox state of iron-based nanoparticles and their cytotoxicity toward a Gram-negative bacterium, Escherichia coli. While chemically stable nanoparticles ({gamma}Fe2O3) have no apparent cytotoxicity, nanoparticles containing ferrous and, particularly, zerovalent iron are cytotoxic. The cytotoxic effects appear to be associated principally with an oxidative stress as demonstrated using a mutant strain of E. coli completely devoid of superoxide dismutase activity. This stress can result from the generation of reactive oxygen species with the interplay of oxygen with reduced iron species (FeII and/or Fe0) or from the disturbance of the electronic and/or ionic transport chains due to the strong affinity of the nanoparticles for the cell membrane.

Auffan,M.; Achouak, W.; Rose, J.; Roncato, M.; Chaneac, C.; Waite, D.; Miasion, A.; Woicik, J.; Wiesner, M.; Bottero, J.

2008-01-01

50

Mechanism of ascididemin-induced cytotoxicity.  

PubMed

Some marine animals are rich sources of unique polycyclic aromatic alkaloids that are cytotoxic against tumor cell lines and effective in mouse tumor xenograft models. Ascididemin is a pyridoacridine alkaloid originally derived from a Didemnum sp. tunicate. It has potent cytotoxicity against tumor cells in vitro and in vivo. Preclinical screening at NCI revealed the antineoplastic activities of ascididemin and a synthetic analogue 48. Ascididemin has been reported to inhibit topoisomerase II and induce topoisomerase II-mediated DNA cleavage. This study, however, focuses on the unique ability of ascididemin and two synthetic analogues (48 and 109) to cleave DNA in the absence of topoisomerase I or II. An in vitro assay revealed their concentration-dependent ability to cleave DNA and identified dithiothreitol as the sole requirement for maximal activity. On the basis of shared structural features of the three analogues, a double N-bay region and iminoquinone heterocyclic ring, two possible mechanisms of action were hypothesized: (1) generation of reactive oxygen species facilitated by metal binding to the common phenanthroline bay region, and (2) production of reactive oxygen species by direct reduction of the iminoquinone moiety. Experimental results supported direct iminoquinone reduction and ROS generation as the mechanism of ascididemin cytotoxicity. Antioxidants protected against DNA cleavage in vitro and protected cultured Chinese hamster ovary cells from toxicity. Additionally, it was shown that cells deficient in the ability to repair reactive oxygen species damage to their DNA were more susceptible to ascididemin and analogues than repair competent cells. Ascididemin-treated cells were also shown to induce oxygen-stress related proteins, further implicating the production of reactive oxygen species as the mechanism of cytotoxicity for these molecules. PMID:12588181

Matsumoto, Sandra S; Biggs, Jason; Copp, Brent R; Holden, Joseph A; Barrows, Louis R

2003-02-01

51

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

52

Cytotoxicity evaluation of silica nanoparticles using fish cell lines.  

PubMed

Nanoparticles (NPs) have extensive industrial, biotechnological, and biomedical/pharmaceutical applications, leading to concerns over health risks to humans and biota. Among various types of nanoparticles, silica nanoparticles (SiO2 NPs) have become popular as nanostructuring, drug delivery, and optical imaging agents. SiO2 NPs are highly stable and could bioaccumulate in the environment. Although toxicity studies of SiO2 NPs to human and mammalian cells have been reported, their effects on aquatic biota, especially fish, have not been significantly studied. Twelve adherent fish cell lines derived from six species (rainbow trout, fathead minnow, zebrafish, goldfish, haddock, and American eel) were used to comparatively evaluate viability of cells by measuring metabolic impairment using Alamar Blue. Toxicity of SiO2 NPs appeared to be size-, time-, temperature-, and dose-dependent as well as tissue-specific. However, dosages greater than 100 ?g/mL were needed to achieve 24 h EC50 values (effective concentrations needed to reduce cell viability by 50%). Smaller SiO2 NPs (16 nm) were relatively more toxic than larger sized ones (24 and 44 nm) and external lining epithelial tissue (skin, gills)-derived cells were more sensitive than cells derived from internal tissues (liver, brain, intestine, gonads) or embryos. Higher EC50 values were achieved when toxicity assessment was performed at higher incubation temperatures. These findings are in overall agreement with similar human and mouse cell studies reported to date. Thus, fish cell lines could be valuable for screening emerging contaminants in aquatic environments including NPs through rapid high-throughput cytotoxicity bioassays. PMID:24357037

Vo, Nguyen T K; Bufalino, Mary R; Hartlen, Kurtis D; Kitaev, Vladimir; Lee, Lucy E J

2014-05-01

53

Cytotoxicity and apoptotic effects of tea polyphenol-loaded chitosan nanoparticles on human hepatoma HepG2 cells.  

PubMed

Tea polyphenols have strong antioxidant and antitumor activities. However, these health benefits are limited due to their poor in vivo stability and low bioavailability. Chitosan nanoparticles as delivery systems may provide an alternative approach for enhancing bioavailability of poorly absorbed drugs. In this study, tea polyphenol-loaded chitosan nanoparticles have been prepared using two different chitosan biomaterials, and their antitumor effects were evaluated in HepG2 cells, including cell cytotoxicity comparison, cell morphology analysis, cell apoptosis and cell cycle detection. The results indicated that the tea polyphenol-loaded chitosan nanoparticles showed a branch shape and heterogeneous distribution in prepared suspension. MTT assay suggested that tea polyphenol-loaded chitosan nanoparticles could inhibit the proliferation of HepG2 cells, and the cytotoxicity rates were increased gradually and appeared an obvious dose-dependent relationship. Transmission electron microscope images showed that the HepG2 cells treated with tea polyphenol-loaded chitosan nanoparticles exhibited some typical apoptotic features, such as microvilli disappearance, margination of nuclear chromatin, intracytoplasmic vacuoles and the mitochondrial swelling. In addition, the tea polyphenol-loaded chitosan nanoparticles had relatively weak inhibitory effects on HepG2 cancer cells compared with tea polyphenols. Tea polyphenols not only induced cancer cell apoptosis, but also promoted their necrosis. However, tea polyphenol-loaded chitosan nanoparticles exhibited their antitumor effects mainly through inducing cell apoptosis. Our results revealed that the inhibition effects of tea polyphenol-loaded chitosan nanoparticles on tumor cells probably depended on their controlled drug release and effective cell delivery. The chitosan nanoparticles themselves as the delivery carrier showed limited antitumor effects compared with their encapsulated drugs. PMID:24433880

Liang, Jin; Li, Feng; Fang, Yong; Yang, Wenjian; An, Xinxin; Zhao, Liyan; Xin, Zhihong; Cao, Lin; Hu, Qiuhui

2014-03-01

54

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

2013-06-01

55

Hormesis Effects of Silver Nanoparticles at Non-Cytotoxic Doses to Human Hepatoma Cells  

PubMed Central

Silver nanoparticles (AgNPs) have attracted considerable attentions due to their unique properties and diverse applications. Although it has been reported that AgNPs have acute toxic effects on a variety of cultured mammalian cells and animal models, few studies have been conducted to evaluate the associated risk of AgNPs to human health at non-cytotoxic doses. In this paper, HepG2 cells were exposed to 10 nm and 100 nm AgNPs under non-cytotoxic conditions, and cell viability was assessed. At low doses, AgNPs displayed “hormesis” effects by accelerating cell proliferation. Further studies indicated that the activation states of MAPKs were differentially regulated in this process. Specifically, by increasing the expression of downstream genes, p38 MAPK played a central role in non-cytotoxic AgNP-induced hormesis. Moreover, the treatment of HepG2 cells with silver ions (Ag+) at the same dose levels induced distinct biological effects, suggesting that different intrinsic properties exist for AgNPs and Ag+.

Jiao, Zhi-Hao; Li, Ming; Feng, Yi-Xing; Shi, Jia-Chen; Zhang, Jing; Shao, Bing

2014-01-01

56

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

57

The role of surface functionality in determining nanoparticle cytotoxicity  

PubMed Central

CONSPECTUS Surface properties dictate the behavior of nanomaterials in vitro, in vivo and in the environment. Such properties include surface charge and hydrophobicity. Also key are more complex supramolecular interactions like aromatic stacking and hydrogen bonding, and even surface topology from the structural to the atomic level. Surface functionalization of nanoparticles (NPs) provides an effective way to control the interface between nanomaterials and the biological systems they are designed to interact with. In medicine, for instance, proper control of surface properties can maximize therapeutic or imaging efficacy while minimizing unfavorable side effects. Meanwhile, in environmental science, thoughtful choice of particle coating can minimize the impact of manufactured nanomaterials on the environment. A thorough knowledge of how NP surfaces with various properties effect biological systems is essential for creating NPs with such useful therapeutic and imaging properties as low toxicity, stability, biocompatibility, favorable distribution throughout cells or tissues, and favorable pharmacokinetic profiles--and for reducing the potential environmental impact of manufactured nanomaterials, which are becoming increasingly prominent in the marketplace. In this Account, we discuss our research and that of others into how NP surface properties control interactions with biomolecules and cells at many scales, including the role the particle surface plays in determining in vivo behavior of nanomaterials. These interactions can be benign, beneficial, or lead to dysfunction in proteins, genes and cells, resulting in cytotoxic and genotoxic responses. Understanding these interactions and their consequences helps us to design minimally invasive imaging and delivery agents. We also highlight in this Account how we have fabricated nanoparticles to act as therapeutic agents via tailored interactions with biomacromolecules. These particles offer new therapeutic directions from traditional small molecule therapies, and with potentially greater versatility than is possible with proteins and nucleic acids.

Kim, Sung Tae; Saha, Krishnendu; Kim, Chaekyu; Rotello, Vincent M.

2013-01-01

58

[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

59

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

60

Sequential application of a cytotoxic nanoparticle and a PI3K inhibitor enhances antitumor efficacy.  

PubMed

Nanomedicines that preferentially deploy cytotoxic agents to tumors and molecular targeted therapeutics that inhibit specific aberrant oncogenic drivers are emerging as the new paradigm for the management of cancer. While combination therapies are a mainstay of cancer chemotherapy, few studies have addressed the combination of nanomedicines and molecular targeted therapeutics. Furthermore, limited knowledge exists on the impact of sequencing of such therapeutics and nanomedicines on the antitumor outcome. Here, we engineered a supramolecular cis-platinum nanoparticle, which induced apoptosis in breast cancer cells but also elicited prosurvival signaling via an EGF receptor/phosphoinositide 3-kinase (PI3K) pathway. A combination of mathematical modeling and in vitro and in vivo validation using a pharmacologic inhibitor of PI3K, PI828, demonstrate that administration of PI828 following treatment with the supramolecular cis-platinum nanoparticle results in enhanced antitumor efficacy in breast cancer as compared with when the sequence is reversed or when the two treatments are administered simultaneously. This study addresses, for the first time, the impact of drug sequencing in the case of a combination of a nanomedicine and a targeted therapeutic. Furthermore, our results indicate that a rational combination of cis-platinum nanoparticles and a PI3K-targeted therapeutic can emerge as a potential therapy for breast cancer. PMID:24121494

Pandey, Ambarish; Kulkarni, Ashish; Roy, Bhaskar; Goldman, Aaron; Sarangi, Sasmit; Sengupta, Poulomi; Phipps, Colin; Kopparam, Jawahar; Oh, Michael; Basu, Sudipta; Kohandel, Mohammad; Sengupta, Shiladitya

2014-02-01

61

Secondary cytotoxicity mediated by alveolar macrophages: a contribution to the total efficacy of nanoparticles in lung cancer therapy?  

PubMed

Local treatment of lung cancer using inhalable nanoparticles (NPs) is an emerging and promising treatment option. The aim of this study was to investigate the activation of alveolar macrophages by poly (isobutyl cyanoacrylate) (BIPCA) NPs and the consequences of this activation on H460 lung cancer cells. A methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to determine the primary cytotoxicity, that is, the immediate and direct cytotoxicity of doxorubicin (DOX)-loaded NPs on both cell lines. Macrophages were then treated using EC(50) concentrations of different treatments and co-cultured in a two-compartment system with H460 lung cancer cells. These treatments included DOX solution, blank NPs, and DOX-loaded NPs. The results showed that alveolar macrophages exposed to blank or DOX-loaded NPs showed cytotoxicity against cancer cells after 8 and 24h; this behavior was not expressed by naďve macrophages or macrophages treated with DOX solution. Sample analysis indicated that macrophages have the ability to release back fragments of NPs that were previously phagocytized. Further investigations showed that NPs can induce an increase in the excretion of Th1 cytokines namely, monocytes chemoattractant protein-1 (MCP-1), macrophages inflammatory protein (MIP-1), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). The Th1 cytokines released by the alveolar macrophages might explain the significant secondary cytotoxicity effect on H460 cancer cells. Secondary cytotoxicity mediated by macrophages might compliment the direct cytotoxic effect that NPs have on cancer cells. PMID:20452423

Al-Hallak, Kamal M H D; Azarmi, Shirzad; Anwar-Mohamed, Anwar; Roa, Wilson H; Löbenberg, Raimar

2010-09-01

62

Embedded carbon nanotubes nanoparticles in plasma membrane induce cellular calcium outflow imbalancing.  

PubMed

In this report, embedded single-wall carbon nanotubes (SWCNTs) nanoparticles in plasma membrane inducing cellular calcium outflow imbalancing are disclosed. Compared ssDNA-SWCNTs with polystyrene (PS) nanoparticles, we analyzed the cytotoxicity of these nanoparticles and the effect of these nanoparticles on intracellular Ca2+ ion levels by depletion of Ca2+ from the endoplasmic reticulum (ER) evoked by Thapsigargin (Tg) in SKN-SH cells. The results had shown that ssDNA-SWCNTs and PS nanoparticles have no cytotoxicity on SKN-SH cells. However, contrary to PS nanoparticles, cellular Ca2+ ion outflow imbalancing was investigated in SKN-SH cells after pretreated with ssDNA-SWCNTs induced by Tg, which could be proposed mainly due to the interaction of embedded ssDNA-SWCNTs with cellular membrane. PMID:24738351

Wang, Jingyi; Liu, Ru; Su, Yunming; Li, Wei

2014-06-01

63

Uptake and cytotoxicity of chitosan nanoparticles in human liver cells  

Microsoft Academic Search

Despite extensive research into the biomedical and pharmaceutical applications of nanoparticles, and the liver being the main detoxifying organ in the human body, there are limited studies which delineate the hepatotoxicity of nanoparticles. This paper reports on the biological interactions between liver cells and chitosan nanoparticles, which have been widely recognised as biocompatible. Using the MTT assay, human liver cells

Jing Wen Loh; George Yeoh; Martin Saunders; Lee-Yong Lim

2010-01-01

64

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

2012-08-01

65

Factors influencing the cytotoxicity of zinc oxide nanoparticles: particle size and surface charge  

NASA Astrophysics Data System (ADS)

Zinc oxide (ZnO) nanoparticle is one of the most important materials in diverse applications, since it has UV light absorption, antimicrobial, catalytic, semi-conducting, and magnetic properties. However, there is little information about the toxicological effects of ZnO nanoparticles with respect to physicochemical properties. The aim of this study was, therefore, to evaluate the relationships between cytotoxicity and physicochemical properties of ZnO nanoparticle such as particle size and surface charge in human lung cells. Two different sizes of ZnO nanoparticles (20 and 70 nm) were prepared with positive (+) or negative (-) charge, and then, cytotoxicity of different ZnO nanoparticles was evaluated by measuring cell proliferation in short-term and long-term, membrane integrity, and generation of reactive oxygen species (ROS). The results demonstrated that smaller particles exhibited high cytotoxic effects compared to larger particles in terms of inhibition of cell proliferation, membrane damage, and ROS generation. In addition, positively charged ZnO showed greater ROS production than ZnO with negative charge. These findings suggest that the cytoxicity of ZnO nanoparticles are strongly affected by their particle size and surface charge, highlighting the role of the physicochemical properties of nanoparticles to understand and predict their potential adverse effects on human.

Baek, M.; Kim, M. K.; Cho, H. J.; Lee, J. A.; Yu, J.; Chung, H. E.; Choi, S. J.

2011-07-01

66

An impedance-based high-throughput method for evaluating the cytotoxicity of nanoparticles  

NASA Astrophysics Data System (ADS)

Impedance-based assays can constitute a reliable alternative to the conventional methods used in nanotoxicology due to the important advantages of being label-free and monitoring the cells in real-time. In this study, the suitability of impedance-monitoring for the screening of nanoparticle (NP)-induced cytotoxicity was assessed. The effect of titanium dioxide (TiO2)-NPs on cellular proliferation, viability, spreading, and detachment from substrate was evaluated by continuous impedance-based measurements made with an xCELLigence system. Fibroblasts seeded in microelectrode-embedded E-plates were exposed to spherical anatase nano-TiO2 (5, 10, and 40 nm in diameter) for up to 120 h. An alternative excitation signal (20 mV control voltage amplitude) was applied at 10, 25, and 50 kHz to the microelectrodes in the E-plates. Cells attached to the electrode surfaces act as insulators and lead to an increase in impedance. For validating the impedance-method, Trypan Blue exclusion and ultrahigh resolution imaging (URI) were employed. The general trend observed was a decrease in impedance following exposure to TiO2-NPs. Impedance-based results were in most instances in accordance with those from the Trypan Blue exclusion and URI assays indicating that the impedance-based approach has merit. Further studies are needed to validate it as a high-throughput method for evaluating NPs' cytotoxicity.

Cimpan, M. R.; Mordal, T.; Schölermann, J.; Allouni, Z. E.; Pliquett, U.; Cimpan, E.

2013-04-01

67

Cytotoxicity of hollow silica nanoparticles loaded with photosensitizes on huh-7 cells.  

PubMed

To observe the cytotoxic effect of the photodynamic therapy mediated by the traditional photosensitizer polyhematoporphyrin (C34H38N4NaO5, Photosan-II Photosan-II was loaded into HSNP by one-step wet chemical, PS) and hollow silica nanoparticles (HSNP) loaded PS on Huh-7 cells and compare the cytotoxic effects. -based synthetic route. The cellular viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptotic and necrotic cells were measured by flow cytometry. The suitable drug concentrations of free PS and HSNP loaded PS on Huh-7 cells were 20mg/L and 5mg/L respectively, and the suitable incubation time were 4 h and 2 h respectively. Under the same drug concentration, the survival rates of free PS and HSNP loaded PS were 62.46%±1.93% and 6.54%±1.24% <. Under the same drug concentration and incubation time, the total rates of apoptosis necrosis caused by free PS and HSNP loaded PS mediated PDT were respectively 22.00% ± 2.24% and 87.23% ± 2.1% <. PS-loaded HSNP mediated PDT can inhibit proliferation of cancer cells and induce apoptosis more quickly and effectively. As the loading system of PS, HSNP can make the photosensitizer have stronger solubility and drug concentration efficiency, which can significantly improve the therapeutic effect of PDT. PMID:24816702

Pei, Dongni; Xiong, Li; Lin, Liangwu; Zhong, Dewu

2014-05-01

68

Neuroprotection by pramipexole against dopamine- and levodopa-induced cytotoxicity  

Microsoft Academic Search

Pramipexole, a novel non-ergoline dopamine (DA) agonist, has been applied successfully for treatment of Parkinson's disease (PD). We report here that pramipexole can protect dopaminergic cell line Mes23.5 against dopamine- and levodopa-induced cytotoxicity possibly through a mechanism related to antioxidant activity. In the MES 23.5 cultures, DA and L-DOPA induce a dose- and time-dependent cytotoxicity, as determined by tetrazolium salt

Linglong Zou; Joseph Jankovic; Dominic B. Rowe; Wenjie Xie; Stanley H. Appel; Weidong Le

1999-01-01

69

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

SciTech Connect

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. -- Highlights: ? Role of Nrf2 signaling in silver nanoparticle toxicity. ? Silver nanoparticle toxicity is increased by Nrf2 blockade. ? Nrf2-dependent HO-1 induction protects cells from silver nanoparticle toxicity. ? PI3K and p38MAPK cascades are involved in Nrf2/HO-1 induction.

Kang, Su Jin [Yeungnam University, College of Pharmacy, Gyeongsan-si, Gyeongsangbuk-do 712-749 (Korea, Republic of) [Yeungnam University, College of Pharmacy, Gyeongsan-si, Gyeongsangbuk-do 712-749 (Korea, Republic of); Daegu Haany University, College of Oriental Medicine, Gyeongsan-si, Gyeongsangbuk-do 712-715 (Korea, Republic of); Ryoo, In-geun [Yeungnam University, College of Pharmacy, Gyeongsan-si, Gyeongsangbuk-do 712-749 (Korea, Republic of)] [Yeungnam University, College of Pharmacy, Gyeongsan-si, Gyeongsangbuk-do 712-749 (Korea, Republic of); Lee, Young Joon [Daegu Haany University, College of Oriental Medicine, Gyeongsan-si, Gyeongsangbuk-do 712-715 (Korea, Republic of)] [Daegu Haany University, College of Oriental Medicine, Gyeongsan-si, Gyeongsangbuk-do 712-715 (Korea, Republic of); Kwak, Mi-Kyoung, E-mail: mkwak@catholic.ac.kr [Yeungnam University, College of Pharmacy, Gyeongsan-si, Gyeongsangbuk-do 712-749 (Korea, Republic of) [Yeungnam University, College of Pharmacy, Gyeongsan-si, Gyeongsangbuk-do 712-749 (Korea, Republic of); The Catholic University of Korea, College of Pharmacy, 43-1 Yeokgok 2-dong, Bucheon, Gyeonggi-do 420-743 (Korea, Republic of)

2012-01-01

70

Enhanced Cytotoxicity Suppression of Arsenic Trioxide to Leukemia Cancer Cells by Using Magnetic Nanoparticles  

Microsoft Academic Search

Recently, superparamagnetic nanoparticles of iron oxides have shown great potential in bio-applications, including magnetic resonance imaging contrast enhancement, drug delivery, bio-separation, tissue repair, hyperthermia, and others. In this study, we have explored the enhanced cytotoxicity effect of arsenic trioxide (As2O3) on both sensitive K562 cell line and adriamycin-resistance K562\\/A02 cell line in the absence and presence of Fe3O4 nanoparticles by

Dadong Guo; Wenfeng Song; Xuemei Wang; Baoan Chen

2009-01-01

71

Tailored silica-antibiotic nanoparticles: overcoming bacterial resistance with low cytotoxicity.  

PubMed

New and more aggressive antibiotic resistant bacteria arise at an alarming rate and represent an ever-growing challenge to global health care systems. Consequently, the development of new antimicrobial agents is required to overcome the inefficiency of conventional antibiotics and bypass treatment limitations related to these pathologies. In this study, we present a synthesis protocol, which was able to entrap tetracycline antibiotic into silica nanospheres. Bactericidal efficacy of these structures was tested against bacteria that were susceptible and resistant to antibiotics. For nonresistant bacteria, our composite had bactericidal efficiency comparable to that of free-tetracycline. On the other hand, the synthesized composites were able to avoid bacterial growth of resistant bacteria while free-tetracycline has shown no significant bactericidal effect. Finally, we have investigated the cytotoxicity of these nanoparticles against mammalian cells to check any possible poisoning effect. It was found that these nanospheres are not apoptosis-inducers and only a reduction on the cell replication rate was seen when compared to the control without nanoparticles. PMID:24902085

Capeletti, Larissa Brentano; de Oliveira, Luciane França; Gonçalves, Kaliandra de Almeida; de Oliveira, Jessica Fernanda Affonso; Saito, Angela; Kobarg, Jörg; Santos, Joăo Henrique Zimnoch Dos; Cardoso, Mateus Borba

2014-07-01

72

Cytotoxicity and anti-inflammatory activity of cyclosporine A loaded PLGA nanoparticles for ocular use.  

PubMed

Cyclosporine A loaded poly(lactide-co-glycolide) nanoparticles were prepared using the o/w emulsification solvent evaporation method and the effect of four preparation parameters on particle size and zeta potential was investigated. Release properties of the nanoparticles were examined and in vitro experiments were performed in order to evaluate the cytotoxicity and anti-inflammatory activity of the nanoparticles developed. Particle sizes varied between 191 and 303 nm depending on the different preparation parameters and all nanoparticle dispersions were monodisperse. The nanoparticles showed negative zeta potential values varying between -16 and -35 mV and 57 to 70 % of the amount of loaded cyclosporine A was released after 24 h. None of the nanoparticle formulations showed significant cytotoxicity compared to the negative control using human epithelial cells (HaCaT). Cyclosporine A incorporated in the various nanoparticle formulations retained its anti-inflammatory activity as significant suppression of interleukine-2 secretion in concanavalin A stimulated Jurkat T cells was measured. As the overall influence of the freeze-drying process on the characteristics of nanoparticles was limited, trehalose and carnitine should be preferred as cryoprotectants in ocular formulations for treatment of dry eye disease. PMID:24601220

Hermans, K; Van Den Plas, D; Schreurs, E; Weyenberg, W; Ludwig, A

2014-01-01

73

Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of Etoposide on SK-OV-3 Cells.  

PubMed

The epithelial ovarian carcinoma is one of the most fatal gynecological cancers. Etoposide is used in treating platinum-resistant ovarian cancer. Sodium hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK-OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles (SLNs) of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by MTT assay method. The cellular uptake of the targeted and nontargeted nanoparticles containing sodium fluorescein was also studied. The difference of cell vitality between nontargeted nanoparticles and also targeted nanoparticles with free drug was significant. Targeted nanoparticles also caused more toxicity than nontargeted nanoparticles (P < 0.05). After 4 hours of incubating, the fluorescence was remarkably higher in the cells treated by targeted SLNs rather than nontargeted ones, and there was no observable fluorescence in cells incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a worthwhile potential method for reducing the prescribed dose and systemic side effects of this drug in epithelial ovarian carcinoma. PMID:24868467

Mohammadi Ghalaei, Parviz; Varshosaz, Jaleh; Sadeghi Aliabadi, Hojatollah

2014-01-01

74

Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of Etoposide on SK-OV-3 Cells  

PubMed Central

The epithelial ovarian carcinoma is one of the most fatal gynecological cancers. Etoposide is used in treating platinum-resistant ovarian cancer. Sodium hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK-OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles (SLNs) of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by MTT assay method. The cellular uptake of the targeted and nontargeted nanoparticles containing sodium fluorescein was also studied. The difference of cell vitality between nontargeted nanoparticles and also targeted nanoparticles with free drug was significant. Targeted nanoparticles also caused more toxicity than nontargeted nanoparticles (P < 0.05). After 4 hours of incubating, the fluorescence was remarkably higher in the cells treated by targeted SLNs rather than nontargeted ones, and there was no observable fluorescence in cells incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a worthwhile potential method for reducing the prescribed dose and systemic side effects of this drug in epithelial ovarian carcinoma.

Varshosaz, Jaleh; Sadeghi Aliabadi, Hojatollah

2014-01-01

75

Analysis of the cytotoxicity of differentially sized titanium dioxide nanoparticles in murine MC3T3-E1 preosteoblasts  

Microsoft Academic Search

There is an increased use of nanophase titanium dioxide (TiO2) in bone implants and scaffolds. However, nano-debris is generated at the bone-biomaterial interface. Therefore, TiO2 nanoparticles (NPs) of many sizes were investigated for cytotoxic effects on murine MC3T3-E1 preosteoblasts. These TiO2 NPs induced a time- and dose-dependent decrease in cell viability. There was a significant increase in lactate dehydrogenase\\u000a (LDH)

Yilin Zhang; Weiqiang Yu; Xinquan Jiang; Kaige Lv; Shengjun Sun; Fuqiang Zhang

2011-01-01

76

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

Microsoft Academic Search

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 \\

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

2006-01-01

77

Cytotoxicity of nickel zinc ferrite nanoparticles on cancer cells of epithelial origin  

PubMed Central

In this study, in vitro cytotoxicity of nickel zinc (NiZn) ferrite nanoparticles against human colon cancer HT29, breast cancer MCF7, and liver cancer HepG2 cells was examined. The morphology, homogeneity, and elemental composition of NiZn ferrite nanoparticles were investigated by scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy, respectively. The exposure of cancer cells to NiZn ferrite nanoparticles (15.6–1,000 ?g/mL; 72 hours) has resulted in a dose-dependent inhibition of cell growth determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The quantification of caspase-3 and -9 activities and DNA fragmentation to assess the cell death pathway of the treated cells showed that both were stimulated when exposed to NiZn ferrite nanoparticles. Light microscopy examination of the cells exposed to NiZn ferrite nanoparticles demonstrated significant changes in cellular morphology. The HepG2 cells were most prone to apoptosis among the three cells lines examined, as the result of treatment with NiZn nanoparticles. In conclusion, NiZn ferrite nanoparticles are suggested to have potential cytotoxicity against cancer cells.

Al-Qubaisi, Mothanna Sadiq; Rasedee, Abdullah; Flaifel, Moayad Husein; Ahmad, Sahrim HJ; Hussein-Al-Ali, Samer; Hussein, Mohd Zobir; Eid, Eltayeb EM; Zainal, Zulkarnain; Saeed, Mohd; Ilowefah, Muna; Fakurazi, Sharida; Isa, Norhaszalina Mohd; Zowalaty, Mohamed Ezzat El

2013-01-01

78

The effects of sedimentation and dissolution on the cytotoxicity of Ag nanoparticles.  

PubMed

Nanoparticles (NPs) are being employed for various industrial purposes with increasing frequency, yet the adverse health effects associated with the prolonged exposure of humans and the environment to NPs has not been well-established. Particularly, the effects of the extrinsic (or dynamic) physicochemical properties of NPs in aqueous cell culture media (e.g., hydrodynamic size, aggregation, agglomeration, sedimentation, and dissolution of nanoparticles) on the cytotoxicities of the NPs are barely understood. In this study, to investigate the effects of two important extrinsic properties of Ag NPs, namely the sedimentation and dissolution of Ag NPs, we performed MTT cell viability tests for HeLa cells exposed to Ag NPs with varying extrinsic properties. Ag NPs with different hydrodynamic sizes, sedimentation rates, and dissolution rates were prepared via exposure to NaCl and FBS. Sedimentation of aggregated/agglomerated Ag NPs was found to contribute more significantly to the cytotoxicity of Ag NPs during early periods of exposure, whereas the cytotoxicity was more greatly enhanced later during the exposure period due to the increase in silver ions. Therefore, it is offered that any assessment of NP cytotoxicity should consider the extrinsic properties of NPs, and their time-dependent properties, because the dominant processes affecting NP cytotoxicity may change over time and lead to a misunderstanding or poor prediction of NP cytotoxicity. PMID:24245241

Park, Min Sun; Park, Jonghoon; Jeon, Soo Kyung; Yoon, Tae Hyun

2013-11-01

79

Uptake and cytotoxicity of chitosan nanoparticles in human liver cells  

SciTech Connect

Despite extensive research into the biomedical and pharmaceutical applications of nanoparticles, and the liver being the main detoxifying organ in the human body, there are limited studies which delineate the hepatotoxicity of nanoparticles. This paper reports on the biological interactions between liver cells and chitosan nanoparticles, which have been widely recognised as biocompatible. Using the MTT assay, human liver cells were shown to tolerate up to 4 h of exposure to 0.5% w/v of chitosan nanoparticles (18 {+-} 1 nm, 7.5 {+-} 1.0 mV in culture medium). At nanoparticle concentrations above 0.5% w/v, cell membrane integrity was compromised as evidenced by leakage of alanine transaminase into the extracellular milieu, and there was a dose-dependent increase in CYP3A4 enzyme activity. Uptake of chitosan nanoparticles into the cell nucleus was observed by confocal microscopic analysis after 4 h exposure with 1% w/v of chitosan nanoparticles. Electron micrographs further suggest necrotic or autophagic cell death, possibly caused by cell membrane damage and resultant enzyme leakage.

Loh, Jing Wen [Laboratory for Drug Delivery, Pharmacy, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia); Yeoh, George [School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia); Centre for Medical Research, Western Australian Institute for Medical Research, Nedlands, WA 6009 (Australia); Saunders, Martin [Centre for Microscopy, Characterisation and Analysis, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia); Lim, Lee-Yong, E-mail: limly@cyllene.uwa.edu.a [Laboratory for Drug Delivery, Pharmacy, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia); School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia)

2010-12-01

80

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

PubMed Central

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.

2011-01-01

81

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

82

Effects of internalized gold nanoparticles with respect to cytotoxicity and invasion activity in lung cancer cells.  

PubMed

The effect of gold nanoparticles on lung cancer cells is not yet clear. In this study, we investigated the cytotoxicity and cell invasion activity of lung cancer cells after treatment with gold nanoparticles and showed that small gold nanoparticles can be endocytosed by lung cancer cells and that they facilitate cell invasion. The growth of A549 cells was inhibited after treatment with 5-nm gold nanoparticles, but cell invasion increased. Endocytosed gold nanoparticles (size, 10 nm) notably promoted the invasion activity of 95D cells. All these effects of gold nanoparticles were not seen after treatment with larger particles (20 and 40 nm). The enhanced invasion activity may be associated with the increased expression of matrix metalloproteinase 9 and intercellular adhesion molecule-1. In this study, we obtained evidence for the effect of gold nanoparticles on lung cancer cell invasion activity in vitro. Moreover, matrix metalloproteinase 9 and intercellular adhesion molecule-1, key modulators of cell invasion, were found to be regulated by gold nanoparticles. These data also demonstrate that the responses of the A549 and 95D cells to gold nanoparticles have a remarkable relationship with their unique size-dependent physiochemical properties. Therefore, this study provides a new perspective for cell biology research in nanomedicine. PMID:24901215

Liu, Zhengxia; Wu, Yucheng; Guo, Zhirui; Liu, Ying; Shen, Yujie; Zhou, Ping; Lu, Xiang

2014-01-01

83

Effects of Internalized Gold Nanoparticles with Respect to Cytotoxicity and Invasion Activity in Lung Cancer Cells  

PubMed Central

The effect of gold nanoparticles on lung cancer cells is not yet clear. In this study, we investigated the cytotoxicity and cell invasion activity of lung cancer cells after treatment with gold nanoparticles and showed that small gold nanoparticles can be endocytosed by lung cancer cells and that they facilitate cell invasion. The growth of A549 cells was inhibited after treatment with 5-nm gold nanoparticles, but cell invasion increased. Endocytosed gold nanoparticles (size, 10 nm) notably promoted the invasion activity of 95D cells. All these effects of gold nanoparticles were not seen after treatment with larger particles (20 and 40 nm). The enhanced invasion activity may be associated with the increased expression of matrix metalloproteinase 9 and intercellular adhesion molecule-1. In this study, we obtained evidence for the effect of gold nanoparticles on lung cancer cell invasion activity in vitro. Moreover, matrix metalloproteinase 9 and intercellular adhesion molecule-1, key modulators of cell invasion, were found to be regulated by gold nanoparticles. These data also demonstrate that the responses of the A549 and 95D cells to gold nanoparticles have a remarkable relationship with their unique size-dependent physiochemical properties. Therefore, this study provides a new perspective for cell biology research in nanomedicine.

Guo, Zhirui; Liu, Ying; Shen, Yujie; Zhou, Ping; Lu, Xiang

2014-01-01

84

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

2013-06-01

85

Cytotoxicity of Fe3O4/Au composite nanoparticles loaded with doxorubicin combined with magnetic field.  

PubMed

GoldMag (Fe3O4/Au) nanoparticles have the advantages of both magnetic response in an external magnetic field and the immobilization of molecules on their surface in a single step. The cytotoxicities of GoldMag nanoparticles and GoldMag nanoparticles loaded with doxorubicin (Dox-GoldMag) combined with an external magnetic field were tested in vitro on HepG2 malignant tumor cells. The results showed that cell viability remained above 92% when using GoldMag nanoparticles at a concentration as high as 2.0 mg/ml, suggesting the biocompatibility of the nanoparticles. The IC50 (0.731 microg/ml) of the Dox-GoldMag group was higher than that (0.522 microg/ml) of the Dox group (P < 0. 05). However, the Dox-GoldMag group combined with a magnetic field had an obviously increased inhibition rate for the HepG2 cell line and the IC50 was lower than that of the Dox group (0.421 microg/ml). These results indicated that GoldMag nanoparticles loaded with doxorubicin combined with a permanent magnetic field are more cytotoxic and could be a potential targeted drug delivery system. PMID:20662318

Chao, Xu; Shi, Feng; Zhao, Ying-Yong; Li, Ke; Peng, Ming-Li; Chen, Chao; Cui, Ya-Li

2010-07-01

86

Peptide-Tunable Drug Cytotoxicity via One-Step Assembled Polymer Nanoparticles.  

PubMed

A novel class of nanoparticles is developed for the co-delivery of a short cell penetrating peptide and a chemotherapeutic drug to achieve enhanced cytotoxicity. Tunable cytotoxicity is achieved through non-toxic peptide-facilitated gating. The strategy relies on a one-step blending process from polymer building blocks to form monodisperse, PEGylated particles that are sensitive to cellular pH variations. By varying the amount of peptide loading, the chemotherapeutic effects can be enhanced by up to 30-fold. PMID:24375889

Liang, Kang; Richardson, Joseph J; Ejima, Hirotaka; Such, Georgina K; Cui, Jiwei; Caruso, Frank

2014-04-01

87

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

PubMed

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. PMID:22134682

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

2012-01-21

88

Cytotoxicity and Genotoxicity of Ceria Nanoparticles on Different Cell Lines in Vitro  

PubMed Central

Owing to their radical scavenging and UV-filtering properties, ceria nanoparticles (CeO2-NPs) are currently used for various applications, including as catalysts in diesel particulate filters. Because of their ability to filter UV light, CeO2-NPs have garnered significant interest in the medical field and, consequently, are poised for use in various applications. The aim of this work was to investigate the effects of short-term (24 h) and long-term (10 days) CeO2-NP exposure to A549, CaCo2 and HepG2 cell lines. Cytotoxicity assays tested CeO2-NPs over a concentration range of 0.5 ?g/mL to 5000 ?g/mL, whereas genotoxicity assays tested CeO2-NPs over a concentration range of 0.5 ?g/mL to 5000 ?g/mL. In vitro assays showed almost no short-term exposure toxicity on any of the tested cell lines. Conversely, long-term CeO2-NP exposure proved toxic for all tested cell lines. NP genotoxicity was detectable even at 24-h exposure. HepG2 was the most sensitive cell line overall; however, the A549 line was most sensitive to the lowest concentration tested. Moreover, the results confirmed the ceria nanoparticles’ capacity to protect cells when they are exposed to well-known oxidants such as H2O2. A Comet assay was performed in the presence of both H2O2 and CeO2-NPs. When hydrogen peroxide was maintained at 25 ?M, NPs at 0.5 ?g/mL, 50 ?g/mL, and 500 ?g/mL protected the cells from oxidative damage. Thus, the NPs prevented H2O2-induced genotoxic damage.

De Marzi, Laura; Monaco, Antonina; De Lapuente, Joaquin; Ramos, David; Borras, Miquel; Di Gioacchino, Mario; Santucci, Sandro; Poma, Anna

2013-01-01

89

Biosynthesis, Antimicrobial and Cytotoxic Effect of Silver Nanoparticles Using a Novel Nocardiopsis sp. MBRC-1  

PubMed Central

The biosynthesis of nanoparticles has been proposed as a cost effective environmental friendly alternative to chemical and physical methods. Microbial synthesis of nanoparticles is under exploration due to wide biomedical applications, research interest in nanotechnology and microbial biotechnology. In the present study, an ecofriendly process for the synthesis of nanoparticles using a novel Nocardiopsis sp. MBRC-1 has been attempted. We used culture supernatant of Nocardiopsis sp. MBRC-1 for the simple and cost effective green synthesis of silver nanoparticles. The reduction of silver ions occurred when silver nitrate solution was treated with the Nocardiopsis sp. MBRC-1 culture supernatant at room temperature. The nanoparticles were characterized by UV-visible, TEM, FE-SEM, EDX, FTIR, and XRD spectroscopy. The nanoparticles exhibited an absorption peak around 420?nm, a characteristic surface plasmon resonance band of silver nanoparticles. They were spherical in shape with an average particle size of 45 ± 0.15?nm. The EDX analysis showed the presence of elemental silver signal in the synthesized nanoparticles. The FTIR analysis revealed that the protein component in the form of enzyme nitrate reductase produced by the isolate in the culture supernatant may be responsible for reduction and as capping agents. The XRD spectrum showed the characteristic Bragg peaks of 1 2 3, 2 0 4, 0 4 3, 1 4 4, and 3 1 1 facets of the face centered cubic silver nanoparticles and confirms that these nanoparticles are crystalline in nature. The prepared silver nanoparticles exhibited strong antimicrobial activity against bacteria and fungi. Cytotoxicity of biosynthesized AgNPs against in vitro human cervical cancer cell line (HeLa) showed a dose-response activity. IC50 value was found to be 200??g/mL of AgNPs against HeLa cancer cells. Further studies are needed to elucidate the toxicity and the mechanism involved with antimicrobial and anticancer activity of the synthesized AgNPs as nanomedicine.

Manivasagan, Panchanathan; Senthilkumar, Kalimuthu; Sivakumar, Kannan; Kim, Se-Kwon

2013-01-01

90

Neuroprotection by pramipexole against dopamine- and levodopa-induced cytotoxicity.  

PubMed

Pramipexole, a novel non-ergoline dopamine (DA) agonist, has been applied successfully for treatment of Parkinson's disease (PD). We report here that pramipexole can protect dopaminergic cell line Mes23.5 against dopamine- and levodopa-induced cytotoxicity possibly through a mechanism related to antioxidant activity. In the MES 23.5 cultures, DA and L-DOPA induce a dose- and time-dependent cytotoxicity, as determined by tetrazolium salt and trypan blue assays. Furthermore, an in situ terminal deoxynucleotidyl transferase assay demonstrates that DA-induced cell death is apoptotic. Pretreatment with pramipexole in a concentration range (4-100 microM) significantly attenuates DA- or L-DOPA-induced cytotoxicity and apoptosis, an action which is not blocked by D3 antagonist U-99194 A or D2 antagonist raclopride. Pramipexole also protects MES 23.5 cells from hydrogen peroxide-induced cytotoxicity in a dose-dependent manner. In cell-free system, pramipexole can effectively inhibit the formation of melanin, an end product resulting from DA or L-DOPA oxidation. These results indicate that pramipexole exerts its neuroprotective effect possibly through a mechanism, which is independent of DA receptors but related to antioxidation or scavenging of free radicals (e.g. hydrogen peroxide). As a direct DA agonist and potentially neuroprotective agent, pramipexole remains attractive in the treatment of PD. PMID:10227583

Zou, L; Jankovic, J; Rowe, D B; Xie, W; Appel, S H; Le, W

1999-01-01

91

Cytotoxic and proinflammatory effects of PVP-coated silver nanoparticles after intratracheal instillation in rats.  

PubMed

Silver nanoparticles (AgNP) are among the most promising nanomaterials, and their usage in medical applications and consumer products is growing rapidly. To evaluate possible adverse health effects, especially to the lungs, the current study focused on the cytotoxic and proinflammatory effects of AgNP after the intratracheal instillation in rats. Monodisperse, PVP-coated AgNP (70 nm) showing little agglomeration in aqueous suspension were instilled intratracheally. After 24 hours, the lungs were lavaged, and lactate dehydrogenase (LDH), total protein, and cytokine levels as well as total and differential cell counts were measured in the bronchoalveolar lavage fluid (BALF). Instillation of 50 µg PVP-AgNP did not result in elevated LDH, total protein, or cytokine levels in BALF compared to the control, whereas instillation of 250 µg PVP-AgNP caused a significant increase in LDH (1.9-fold) and total protein (1.3-fold) levels as well as in neutrophil numbers (60-fold) of BALF. Furthermore, while there was no change in BALF cytokine levels after the instillation of 50 µg PVP-AgNP, instillation of 250 µg PVP-AgNP resulted in significantly increased levels of seven out of eleven measured cytokines. These finding suggest that exposure to inhaled AgNP can induce moderate pulmonary toxicity, but only at rather high concentrations. PMID:24455451

Haberl, Nadine; Hirn, Stephanie; Wenk, Alexander; Diendorf, Jörg; Epple, Matthias; Johnston, Blair D; Krombach, Fritz; Kreyling, Wolfgang G; Schleh, Carsten

2013-12-19

92

Cytotoxic and proinflammatory effects of PVP-coated silver nanoparticles after intratracheal instillation in rats  

PubMed Central

Summary Silver nanoparticles (AgNP) are among the most promising nanomaterials, and their usage in medical applications and consumer products is growing rapidly. To evaluate possible adverse health effects, especially to the lungs, the current study focused on the cytotoxic and proinflammatory effects of AgNP after the intratracheal instillation in rats. Monodisperse, PVP-coated AgNP (70 nm) showing little agglomeration in aqueous suspension were instilled intratracheally. After 24 hours, the lungs were lavaged, and lactate dehydrogenase (LDH), total protein, and cytokine levels as well as total and differential cell counts were measured in the bronchoalveolar lavage fluid (BALF). Instillation of 50 µg PVP-AgNP did not result in elevated LDH, total protein, or cytokine levels in BALF compared to the control, whereas instillation of 250 µg PVP-AgNP caused a significant increase in LDH (1.9-fold) and total protein (1.3-fold) levels as well as in neutrophil numbers (60-fold) of BALF. Furthermore, while there was no change in BALF cytokine levels after the instillation of 50 µg PVP-AgNP, instillation of 250 µg PVP-AgNP resulted in significantly increased levels of seven out of eleven measured cytokines. These finding suggest that exposure to inhaled AgNP can induce moderate pulmonary toxicity, but only at rather high concentrations.

Hirn, Stephanie; Wenk, Alexander; Diendorf, Jorg; Epple, Matthias; Johnston, Blair D; Krombach, Fritz; Kreyling, Wolfgang G; Schleh, Carsten

2013-01-01

93

In vitro cytotoxicity screening of water-dispersible metal oxide nanoparticles in human cell lines  

Microsoft Academic Search

In this study, we present in vitro cytotoxicity of iron oxide (Fe3O4) and manganese oxide (MnO) using live\\/dead cell assay, lactate dehydrogenase assay, and reactive oxygen species detection\\u000a with variation of the concentration of nanoparticles (5–500 ?g\\/ml), incubation time (18–96 h), and different human cell lines\\u000a (lung adenocarcinoma, breast cancer cells, and glioblastoma cells). The surface of nanoparticles is modified with polyethyleneglycol-derivatized

Jong Young Choi; Su Hee Lee; Hyon Bin Na; Kwangjin An; Taeghwan Hyeon; Tae Seok Seo

2010-01-01

94

Reactive oxygen species mediated DNA damage in human lung alveolar epithelial (A549) cells from exposure to non-cytotoxic MFI-type zeolite nanoparticles.  

PubMed

Increasing utilization of engineered nanoparticles in the field of electronics and biomedical applications demands an assessment of risk associated with deliberate or accidental exposure. Metal based nanoparticles are potentially most important of all the nanoparticles in terms of health risks. Microporous alumino-silicates and pure silicates named as zeolites and zeo-type materials with variety of structures, chemical compositions, particle sizes and morphologies have a significant number of industrial uses such as in catalysis, sorption and ion-exchange processes. In particular, the nanosized particles due to their unique properties are used in hybrid organic-inorganic materials for photography, photonics, electronics, labeling, imaging, and sensing. The aim of the current study is to investigate pure silica MFI-type zeolites nanoparticles with sizes of 50nm and 100nm (samples MFI-50 and MFI-100) under suspended conditions and their toxicological effects on human lung alveolar (A549) cells under in vitro conditions. Live cell imaging showed that the nanoparticles precipitated from the colloidal suspension of cell culture media as large agglomerates, coming in contact with the cell surface through sedimentation. A cellular proliferative capacity test showed the zeolite nanoparticles to exhibit no significant cytotoxicity below a concentration of 100?g/ml. However, both the MFI-50 and MFI-100 nanoparticles induced high intracellular reactive oxygen species (ROS) generation and elevated mitochondrial membrane potential in the A549 cells over the measured time period of 12h and at concentrations up to ?50?g/ml. DNA fragmentation analysis using the comet assay showed that the MFI-50 and MFI-100 nanoparticles cause genotoxicity in a concentration dependent manner. Furthermore, the rate at which maximum genomic damage was caused by MFI-100 nanoparticles in the A549 cells was found to be high as compared to the MFI-50 nanoparticles. However, the damage caused by the MFI-50 nanoparticles was found to accumulate over a longer period of time as compared to MFI-100 nanoparticles. The study therefore points towards the capability of the non-cytotoxic zeolite nanoparticles to induce oxidative stress resulting in short-term altered cellular metabolism up-regulation and genomic instability. Although the damage was found to be short-lived, its persistence over longer durations, or stabilization cannot be neglected. Further studies are in progress to yield a better understanding of the mechanisms for oxidative stress and resulting cascade of events leading to genetic damage in the human lung alveolar epithelial cells following exposure to zeolite nanoparticles of different sizes. PMID:23103338

Bhattacharya, Kunal; Naha, Pratap C; Naydenova, Izabela; Mintova, Svetlana; Byrne, Hugh J

2012-12-17

95

Cytotoxicity Induced by Bismuth Subcitrate in Giardia lamblia Trophozoites  

Microsoft Academic Search

The cytotoxicity of colloidal bismuth subcitrate (CBS) was investigated in cultured Giardia lamblia trophozoites on the basis of cell attachment, morphology and viability studies. The effects on cell membrane integrity were evaluated by the permeability to trypan blue, and the morphological alterations were studied by phase-contrast microscopy and transmission electron microscopy. Our data show that although CBS induced loss of

M. C. Sousa; J. Poiares-da-Silva

1999-01-01

96

Cytotoxicity of liver targeted drug-loaded alginate nanoparticles  

Microsoft Academic Search

In this study, novel liver targeted doxorubicin (DOX) loaded alginate (ALG) nanoparticles were prepared by CaCl2 crosslinking method. Glycyrrhetinic acid (GA, a liver targeted molecule) modified alginate (GA-ALG) was synthesized in a\\u000a heterogeneous system, and the structure of GA-ALG and the substitution degree of GA were analyzed by 1H NMR, FT-IR and elemental analysis. The drug release profile under the

ChuangNian Zhang; Wei Wang; ChunHong Wang; Qin Tian; Wei Huang; Zhi Yuan; XueSi Chen

2009-01-01

97

Glyconanoparticle aided detection of ?-amyloid by magnetic resonance imaging and attenuation of ?-amyloid induced cytotoxicity.  

PubMed

The development of a noninvasive method for the detection of Alzheimer's disease is of high current interest, which can be critical in early diagnosis and in guiding treatment of the disease. The aggregates of ?-amyloid are a pathological hallmark of Alzheimer's disease. Carbohydrates such as gangliosides have been shown to play significant roles in initiation of amyloid aggregation. Herein, we report a biomimetic approach using superparamagnetic iron oxide glyconanoparticles to detect ?-amyloid. The bindings of ?-amyloid by the glyconanoparticles were demonstrated through several techniques including enzyme linked immunosorbent assay, gel electrophoresis, tyrosine fluorescence assay, and transmission electron microscopy. The superparamagnetic nature of the nanoparticles allowed easy detection of ?-amyloid both in vitro and ex vivo by magnetic resonance imaging. Furthermore, the glyconanoparticles not only were nontoxic to SH-SY5Y neuroblastoma cells but also greatly reduced ?-amyloid induced cytotoxicity to cells, highlighting the potential of these nanoparticles for detection and imaging of ?-amyloid. PMID:23590250

Kouyoumdjian, Hovig; Zhu, David C; El-Dakdouki, Mohammad H; Lorenz, Kelly; Chen, Jianjun; Li, Wei; Huang, Xuefei

2013-04-17

98

Cytotoxicity of anticancer drugs incorporated in solid lipid nanoparticles on HT29 colorectal cancer cell line  

Microsoft Academic Search

Solid lipid nanoparticles (SLN) carrying cholesteryl butyrate (chol-but), doxorubicin and paclitaxel had previously been developed, and the antiproliferative effect of SLN formulations versus conventional drug formulations was here evaluated on HT-29 cells. The 50% inhibitory concentration (IC50) values were interpolated from growth curves obtained by trypan blue exclusion assay. In vitro cytotoxicity of SLN carrying chol-but (IC5072h 0.3±0.03 mM vs

L. Serpe; M. G. Catalano; R. Cavalli; E. Ugazio; O. Bosco; R. Canaparo; E. Muntoni; R. Frairia; M. R. Gasco; M. Eandi; G. P. Zara

2004-01-01

99

IgM-induced tumor cell cytotoxicity mediated by normal thymocytes  

PubMed Central

In summary, we have found that IgM, from mice which have undergone regression of primary MSV tumors, will induce cytotoxicity against the appropriate target cells by normal splenocytes and normal thymocytes. The thymocyte-induced cytotoxicity i

1975-01-01

100

Cytotoxicity of iron oxide nanoparticles made from the thermal decomposition of organometallics and aqueous phase transfer with Pluronic F127  

PubMed Central

Magnetic nanoparticles are promising molecular imaging agents due to their relative high relaxivity and the potential to modify surface functionality to tailor biodistribution. In this work we describe the synthesis of magnetic nanoparticles using organic solvents with organometallic precursors. This method results in nanoparticles that are highly crystalline, and have uniform size and shape. The ability to create a monodispersion of particles of the same size and shape results in unique magnetic properties that can be useful for biomedical applications with MR imaging. Before these nanoparticles can be used in biological applications, however, means are needed to make the nanoparticles soluble in aqueous solutions and the toxicity of these nanoparticles needs to be studied. We have developed two methods to surface modify and transfer these nanoparticles to the aqueous phase using the biocompatible co-polymer, Pluronic F127. Cytotoxicity was found to be dependent on the coating procedure used. Nanoparticle effects on a cell-culture model was quantified using concurrent assaying; a LDH assay to determine cytotoxicity and an MTS assay to determine viability for a 24 hour incubation period. Concurrent assaying was done to insure that nanoparticles did not interfere with the colorimetric assay results. This report demonstrates that a monodispersion of nanoparticles of uniform size and shape can be manufactured. Initial cytotoxicity testing of new molecular imaging agents need to be carefully constructed to avoid interference and erroneous results.

Gonzales, Marcela; Mitsumori, Lee M.; Kushleika, John V.; Rosenfeld, Michael E.; Krishnan, Kannan M.

2010-01-01

101

Low cytotoxicity porous Nd2(SiO4)3 nanoparticles with near infrared excitation and emission  

NASA Astrophysics Data System (ADS)

Porous Nd2(SiO4)3 nanoparticles were successfully synthesized by a controlled route. This kind of silicate nanoparticle could be excited by near-infrared (NIR) radiation (808 nm) and triggered a NIR emission (1066 nm) at room temperature. By monitoring the 1066 nm emission, the long-lived luminescent lifetime was determined to be 19.5 µs. These NIR nanoparticles with appropriate diameters (<100 nm) were suitable for cell assays. MTT assays showed that the cytotoxicity of the porous Nd2(SiO4)3 nanoparticles was very low. Therefore, these porous silicate nanoparticles are potential biosafe high-performance NIR biolabeling materials.

Zhang, Xian-Hua; Zeng, Dequan; Zhang, Lei; Zhu, Haomiao; Jin, Guang-Hui; Xie, Zhaoxiong; Chen, Xueyuan; Kang, Junyong; Zheng, Lansun

2011-05-01

102

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

103

Cytotoxic effect and apoptosis induction by silver nanoparticles in HeLa cells  

Microsoft Academic Search

Nanosilver has well-known antibacterial properties, and is widely used in daily life as various medical and general products. In comparison with silver ion, there is serious lacking of information concerning the biological effects of nanoAg. In this study, we observed the cytotoxic effect of nanoAg in HeLa cells. The nanoAg-induced cytotoxicity was lower than that of AgNO3, used as a

Nobuhiko Miura; Yasushi Shinohara

2009-01-01

104

A novel bone cement impregnated with silver-tiopronin nanoparticles: its antimicrobial, cytotoxic, and mechanical properties  

PubMed Central

Post-operatory infections in orthopedic surgeries pose a significant risk. The common approach of using antibiotics, both parenterally or embedded in bone cement (when this is employed during surgery) faces the challenge of the rising population of pathogens exhibiting resistance properties against one or more of these compounds; therefore, novel approaches need to be developed. Silver nanoparticles appear to be an exciting prospect because of their antimicrobial activity and safety at the levels used in medical applications. In this paper, a novel type of silver nanoparticles capped with tiopronin is presented. Two ratios of reagents during synthesis were tested and the effect on the nanoparticles investigated through TEM, TGA, and UV-Vis spectroscopy. Once encapsulated in bone cement, only the nanoparticles with the highest amount of inorganic fraction conferred antimicrobial activity against methicillin resistant Staphylococcus aureus (MRSA) at concentrations as low as 0.1% w/w. No other characteristics of the bone cement, such as cytotoxicity or mechanical properties, were affected by the presence of the nanoparticles. Our work presents a new type of silver nanoparticles and demonstrates that they can be embedded in bone cement to prevent infections once the synthetic conditions are tailored for such applications.

Prokopovich, Polina; Leech, Ralph; Carmalt, Claire J; Parkin, Ivan P; Perni, Stefano

2013-01-01

105

Nanoparticle permeation induces water penetration, ion transport, and lipid flip-flop.  

PubMed

Nanoparticles are generally considered excellent candidates for targeted drug delivery. However, ion leakage and cytotoxicity induced by nanoparticle permeation is a potential problem in such drug delivery schemes because of the toxic effect of many ions. In this study, we have carried out a series of coarse-grained molecular dynamics simulations to investigate the water penetration, ion transport, and lipid molecule flip-flop in a protein-free phospholipid bilayer membrane during nanoparticle permeation. The effect of ion concentration gradient, pressure differential across the membrane, nanoparticle size, and permeation velocity have been examined in this work. Some conclusions from our studies include (1) The number of water molecules in the interior of the membrane during the nanoparticle permeation increases with the nanoparticle size and the pressure differential across the membrane but is unaffected by the nanoparticle permeation velocity or the ion concentration gradient. (2) Ion transport is sensitive to the size of nanoparticle as well as the ion concentration gradient between two sides of the membrane; no anion/cation selectivity is observed for small nanoparticle permeation, while anions are preferentially translocated through the membrane when the size of nanoparticle is large enough. (3) Incidences of lipid molecule flip-flop increases with the size of nanoparticle and ion concentration gradient and decreases with the pressure differential and the nanoparticle permeation velocity. PMID:23171434

Song, Bo; Yuan, Huajun; Pham, Sydney V; Jameson, Cynthia J; Murad, Sohail

2012-12-11

106

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

107

Pearling of lipid vesicles induced by nanoparticles.  

PubMed

We show that cationic nanoparticles encapsulated within vesicles of phosphocholine lipid can induce pearling. The dynamic process occurs as two stages: formation of tubular protrusions followed by pearling instability. The breakup into individual vesicles can be controlled by nanoparticle concentration. PMID:19775107

Yu, Yan; Granick, Steve

2009-10-14

108

Study the cytotoxicity of different kinds of water-soluble nanoparticles in human osteoblast-like MG-63 cells  

SciTech Connect

Highlights: ? Preparation of three kinds of water-soluble QDs: CdTe, CdTe@SiO{sub 2}, Mn:ZnSe. ? Evaluated the cytotoxicity qualitatively and quantitatively. ? Fluorescent staining. ? Detected the total intracellular cadmium in cells. -- Abstract: Quantum nanoparticles have been applied extensively in biological and medical fields, the cytotoxicity of nanoparticles becomes the key point we should concern. In this paper, the cytotoxicity of three kinds of water-soluble nanoparticles: CdTe, CdTe@SiO{sub 2} and Mn:ZnSe was studied. We evaluated the nanoparticles toxicity qualitatively by observing the morphological changes of human osteoblast-like MG-63 cells at different incubation times and colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were carried out to detect the cell viability quantitatively. The results showed that CdTe nanoparticles with high concentrations caused cells to die largely while CdTe@SiO{sub 2} and Mn:ZnSe nanoparticles had no obvious effect. For further study, we studied the relation between the cell viability and the total cadmium concentration in cells and found that the viability of cells treated with CdTe@SiO{sub 2} nanoparticles was higher than that treated with CdTe nanoparticles. We also discovered that the death rate of cells co-incubated with CdTe nanoparticles was proportional to the total intracellular cadmium concentrations.

Niu, Lu [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)] [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China); Li, Yang; Li, Xiaojie [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun 130012 (China)] [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun 130012 (China); Gao, Xue [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)] [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China); Su, Xingguang, E-mail: suxg@jlu.edu.cn [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)] [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)

2012-11-15

109

Preparation, characterization and cytotoxicity of schizophyllan/silver nanoparticle composite.  

PubMed

Silver nanoparticles (Ag-NPs) have been successfully prepared with a simple and "green" chemical reduction method. Triple helical schizophyllan (SPG) was used for the first time as reducing and stabilizing agents. The effect of temperature, silver nitrate/schizophyllan concentrations, pH of the reactions medium and the reaction time were investigated. The obtained schizophyllan/Ag-NP was characterized by UV-vis spectroscopy, TEM, DLS, X-ray diffraction, TGA, and ATR-FTIR. The results revealed that, Ag-NPs attached to SPG through a strong non-covalent interaction, leading to good dispersion of Ag-NPs with a diameter of 6 nm within the biopolymer matrix. By increasing the pH of the reaction medium, the triple helical structure of SPG was partially broken. The SPG/AgNP nanocomposite was non-toxic for mouse fibroblast line (NIH-3T3) and human keratinocyte cell line (HaCaT). PMID:24507278

Abdel-Mohsen, A M; Abdel-Rahman, Rasha M; Fouda, Moustafa M G; Vojtova, L; Uhrova, L; Hassan, A F; Al-Deyab, Salem S; El-Shamy, Ibrahim E; Jancar, J

2014-02-15

110

Role of Free Radicals and Metal Ions in Direct Current-Induced Cytotoxicity  

Microsoft Academic Search

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

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

2006-01-01

111

Chromium(III) oxide nanoparticles induced remarkable oxidative stress and apoptosis on culture cells.  

PubMed

Chromium(III) oxide (Cr(2)O(3)) is used for industrial applications such as catalysts and pigments. In the classical form, namely the fine particle, Cr(2)O(3) is insoluble and chemically stable. It is classified as a low-toxicity chromium compound. Recently, industrial application of nanoparticles (a new form composed of small particles with a diameter of ?100 nm, in at least one dimension) has been increasing. Cellular effects induced by Cr(2)O(3) nanoparticles are not known. To shed light upon this, the release of soluble chromium from Cr(2)O(3) nano- and fine-particles in culture medium was compared. Fine Cr(2)O(3) particles were insoluble in the culture medium; on the contrary, Cr(2)O(3) nanoparticles released soluble hexavalent chromium into the culture medium. Cr(2)O(3) nanoparticles showed severe cytotoxicity. The effect of Cr(2)O(3) nanoparticles on cell viability was higher than that of fine particles. Cr(2)O(3) nanoparticles showed cytotoxicity equal to that of hexavalent chromium (K(2)Cr(2)O(7)). Human lung carcinoma A549 cells and human keratinocyte HaCaT cells showed an increase in intracellular reactive oxygen species (ROS) level and activation of antioxidant defense systems on exposure to Cr(2)O(3) nanoparticles. Exposure of Cr(2)O(3) nanoparticles led to caspase-3 activation, showing that the decrease in cell viability by exposure to Cr(2)O(3) nanoparticles was caused by apoptosis. Cellular responses were stronger in the Cr(2)O(3) nanoparticles-exposed cells than in fine Cr(2)O(3) - and CrCl(3) -exposed cells. Cellular uptake of Cr(2)O(3) particles were observed in nano- and fine-particles. The cellular influence of the extracellular soluble trivalent chromium was lower than that of Cr(2)O(3) nanoparticles. Cr(2)O(3) nanoparticles showed cytotoxicity by hexavalent chromium released at outside and inside of cells. The cellular influences of Cr(2)O(3) nanoparticles matched those of hexavalent chromium. In conclusion, Cr(2)O(3) nanoparticles have a high cytotoxic potential. PMID:21384495

Horie, Masanori; Nishio, Keiko; Endoh, Shigehisa; Kato, Haruhisa; Fujita, Katsuhide; Miyauchi, Arisa; Nakamura, Ayako; Kinugasa, Shinichi; Yamamoto, Kazuhiro; Niki, Etsuo; Yoshida, Yasukazu; Iwahashi, Hitoshi

2013-02-01

112

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

SciTech Connect

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. -- Highlights: ? Ludox CL silica NPs are cytotoxic to WI-38 fibroblasts but not to 3T3-L1 fibroblasts. ? Ludox CL-X silica NPs are cytotoxic to both cell lines. ? In clonogenic assay both silica NPs induce cytotoxicity, higher for CL-X silica. ? Cell cycle analysis shows alterations in both cell lines with both silica NP tested. ? Buthionine sulfoximine enhances cytotoxicity of Ludox CL-X in 3T3-L1 cells.

St?pnik, Maciej, E-mail: mstep@imp.lodz.pl [Nofer Institute of Occupational Medicine, ?ód? (Poland)] [Nofer Institute of Occupational Medicine, ?ód? (Poland); Arkusz, Joanna; Smok-Pieni??ek, Anna [Nofer Institute of Occupational Medicine, ?ód? (Poland)] [Nofer Institute of Occupational Medicine, ?ód? (Poland); Bratek-Skicki, Anna; Salvati, Anna; Lynch, Iseult; Dawson, Kenneth A. [Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4 (Ireland)] [Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4 (Ireland); Gromadzi?ska, Jolanta [Nofer Institute of Occupational Medicine, ?ód? (Poland)] [Nofer Institute of Occupational Medicine, ?ód? (Poland); De Jong, Wim H. [National Institute for Public Health and the Environment, Antonie van Leeuwenhoeklaan 9 NL?3720, Bilthoven (Netherlands)] [National Institute for Public Health and the Environment, Antonie van Leeuwenhoeklaan 9 NL?3720, Bilthoven (Netherlands); Rydzy?ski, Konrad [Nofer Institute of Occupational Medicine, ?ód? (Poland)] [Nofer Institute of Occupational Medicine, ?ód? (Poland)

2012-08-15

113

Biosynthesis of gold nanoparticles using Sargassum swartzii and its cytotoxicity effect on HeLa cells  

NASA Astrophysics Data System (ADS)

In this investigation, biological synthesis of gold nanoparticles (AuNPs) using Sargassum swartzii and its cytotoxicity against human cervical carcinoma (HeLa) cells is reported. The biological synthesis involved the reduction of chloroauric acid led to the formation of AuNPs within 5 min at 60 °C and the formation of AuNPs was confirmed using UV-vis spectrophotometer. The AuNPs were stable; spherical in shape with well-defined dimensions, and the average size of the particle is 35 nm. A zeta potential value of -27.6 mV revealed synthesized AuNPs were highly stable. The synthesized AuNPs exhibited a dose-dependent cytotoxicity against human cervical carcinoma (HeLa) cells. Furthermore, induction of apoptosis was measured by DAPI (4?,6-Diamidino-2-phenylindole dihydrochloride) staining.

Dhas, T. Stalin; Kumar, V. Ganesh; Karthick, V.; Govindaraju, K.; Shankara Narayana, T.

2014-12-01

114

Evaluation on cytotoxicity and genotoxicity of the L-glutamic acid coated iron oxide nanoparticles.  

PubMed

To evaluate the cytotoxicity and genotoxicity of L-glutamic acid (Glu) coated Fe2O3 nanoparticles (hereafter refer as Glu@MNPs) on Chinese Hamster Lung (CHL) cells using Trypan blue dye exclusion assay, Oxidative stress markers, Comet assay and micronucleus (MN) assay. Results showed a low cytotoxicity with an IC50 was 254.739 microg/ml 36 h post incubation period in CHL cells. Furthermore, Cell redox status is slightly disturbed: Glu@MNPs exposure cause reactive oxygen species production, glutathione depletion and inactivation of some antioxidant enzymes: glutathione reductase, superoxide dismutase, but not catalase. Moreover, no significant genotoxic response was observed in CHL cells over concentration ranges from 8 to 128 microg/mL for all exposure time periods. The results suggest that the Glu@MNPs show biocompatibility In Vitro. PMID:22755136

Zhang, Ting; Qian, Li; Tang, Meng; Xue, Yuying; Kong, Lu; Zhang, Shanshan; Pu, Yuepu

2012-03-01

115

Biosynthesis of gold nanoparticles using Sargassum swartzii and its cytotoxicity effect on HeLa cells.  

PubMed

In this investigation, biological synthesis of gold nanoparticles (AuNPs) using Sargassum swartzii and its cytotoxicity against human cervical carcinoma (HeLa) cells is reported. The biological synthesis involved the reduction of chloroauric acid led to the formation of AuNPs within 5min at 60°C and the formation of AuNPs was confirmed using UV-vis spectrophotometer. The AuNPs were stable; spherical in shape with well-defined dimensions, and the average size of the particle is 35nm. A zeta potential value of -27.6mV revealed synthesized AuNPs were highly stable. The synthesized AuNPs exhibited a dose-dependent cytotoxicity against human cervical carcinoma (HeLa) cells. Furthermore, induction of apoptosis was measured by DAPI (4',6-Diamidino-2-phenylindole dihydrochloride) staining. PMID:24934968

Dhas, T Stalin; Kumar, V Ganesh; Karthick, V; Govindaraju, K; Shankara Narayana, T

2014-12-10

116

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

2013-05-15

117

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

118

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

119

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

PubMed

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. PMID:21317892

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

120

In Vitro Cytotoxicity Assessment of an Orthodontic Composite Containing Titanium-dioxide Nano-particles.  

PubMed

Background and aims. Incorporation of nano-particles to orthodontic bonding systems has been considered to prevent enamel demineralization around appliances. This study investigated cytotoxicity of Transbond XT adhesive containing 1 wt% titanium dioxide (TiO2) nano-particles. Materials and methods. Ten composite disks were prepared from each of the conventional and TiO2-containg composites and aged for 1, 3, 5, 7 and 14 days in Dulbecco's Modified Eagle's Medium (DMEM). The extracts were obtained and exposed to culture media of human gingival fibroblasts (HGF) and mouse L929 fibroblasts. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results. Both adhesives were moderately toxic for HGF cells on the first day of the experiment, but the TiO2-containing adhesive produced significantly lower toxicity than the pure adhesive (P<0.05). No significant differences were found in cell viability percentages between the two groups on the other days (P>0.05). There was a significant reduction in cell toxicity with increasing pre-incubation time (P<0.001). L929 cells showed similar toxicity trends, but lower sensitivity to detect cytotoxicity of dental composites. Conclusion. The orthodontic adhesive containing TiO2 nano-particles indicated comparable or even lower toxicity than its nano-particle-free counterpart, indicating that incorporation of 1 wt% TiO2 nano-particles to the composite structure does not result in additional health hazards compared to that occurring with the pure adhesive. PMID:24578816

Heravi, Farzin; Ramezani, Mohammad; Poosti, Maryam; Hosseini, Mohsen; Shajiei, Arezoo; Ahrari, Farzaneh

2013-01-01

121

Iron oxide nanoparticles induce oxidative stress, DNA damage, and caspase activation in the human breast cancer cell line.  

PubMed

Broad applications of iron oxide nanoparticles require an improved understanding of their potential effects on human health. In the present study, we explored the underlying mechanism through which iron oxide nanoparticles induce toxicity in human breast cancer cells (MCF-7). MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) and lactate dehydrogenase assays were used to examine mechanisms of cytotoxicity. Concentration- and time-dependent cytotoxicity was observed in MCF-7 cells. Iron oxide nanoparticles were found to induce oxidative stress evidenced by the elevation of reactive oxygen species generation, lipid peroxidation, and depletion of superoxide dismutase, glutathione, and catalase activities in MCF-7 cells. Nuclear staining was performed using 4', 6-diamidino-2-phenylindole (DAPI), and cells were analyzed with a fluorescence microscope. Iron oxide nanoparticles (60 ?g/ml) induced substantial apoptosis that was identified by morphology, condensation, and fragmentation of the nuclei of the MCF-7 cells. It was also observed that the iron oxide NPs induced caspase-3 activity. DNA strand breakage was detected by comet assay, and it occurred in a concentration- and time-dependent manner. Thus, the data indicate that iron oxide nanoparticles induced cytotoxicity and genotoxicity in MCF-7 cells via oxidative stress. This study warrants more careful assessment of iron oxide nanoparticles before their industrial applications. PMID:24748114

Alarifi, Saud; Ali, Daoud; Alkahtani, Saad; Alhader, M S

2014-06-01

122

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

2013-05-01

123

Magnetic nanoparticles sensitize MCF-7 breast cancer cells to doxorubicin-induced apoptosis  

PubMed Central

Background Resistance of breast cancer cells to the available chemotherapeutics is a major obstacle to successful treatment. Recent studies have shown that magnetic nanoparticles might have significant application in different medical fields including cancer treatment. The goal of this study is to verify the ability of magnetic nanoparticles to sensitize cancer cells to the clinically available chemotherapy. Methods The role of iron oxide nanoparticles, static magnetic field, or a combination in the enhancement of the apoptotic potential of doxorubicin against the resistant breast cancer cells, MCF-7 was evaluated using the MTT assay and the propidium iodide method. Results In the present study, results revealed that pre-incubation of MCF-7 cells with iron oxide nanoparticles before the addition of doxorubicin did not enhance doxorubicin-induced growth inhibition. Pre-incubation of MCF-7 cells with iron oxide nanoparticles followed by a static magnetic field exposure significantly (P?induced cytotoxicity. Sensitization with pre-exposure to the magnetic field was dose-dependent where the highest cytotoxicity was seen at 1 tesla. Further experiments revealed that the anti-proliferative effect of this treatment procedure is due to induction of apoptotic cell death. Conclusions These results might point to the importance of combining magnetic nanoparticles with a static magnetic field in treatment of doxorubicin-refractory breast cancer cells.

2012-01-01

124

Lipid peroxidation and cytotoxicity induced by respirable volcanic ash.  

PubMed

This paper reports that the main component of respirable volcanic ash, allophane, induces lipid peroxidation (LP), the oxidative degradation of lipids in cell membranes, and cytotoxicity in murin monocyle/macrophage cells. Naturally-occurring allophane collected from New Zealand, Japan, and Ecuador was studied. The quantification of LP was conducted using the Thiobarbituric Acid Reactive Substances (TBARS) assay. The cytotoxic effect was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide colorimetric assay. Electron-Paramagnetic Resonance (EPR) determinations of naturally-occurring allophane confirmed the incorporation in the structure and clustering of structural Fe(3+), and nucleation and growth of small-sized Fe (oxyhydr)oxide or gibbsite. LP induced by allophane varied with time, and solid concentration and composition, reaching 6.7±0.2nmolTBARSmgprot(-1). LP was surface controlled but not restricted by structural or surface-bound Fe(3+), because redox processes induced by soluble components other than perferryl iron. The reactivity of Fe(3+) soluble species stemming from surface-bound Fe(3+) or small-sized Fe(3+) refractory minerals in allophane surpassed that of structural Fe(3+) located in tetrahedral or octahedral sites of phyllosilicates or bulk iron oxides. Desferrioxamine B mesylate salt (DFOB) or ethylenediaminetetraacetic acid (EDTA) inhibited LP. EDTA acted as a more effective inhibitor, explained by multiple electron transfer pathways. Registered cell-viability values were as low as 68.5±6.7%. PMID:24793297

Cervini-Silva, Javiera; Antonio-Nieto-Camacho; Gomez-Vidales, Virginia; Ramirez-Apan, María Teresa; Palacios, Eduardo; Montoya, Ascención; Kaufhold, Stephan; Abidin, Zeanal; Theng, Benny K G

2014-06-15

125

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

PubMed Central

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 and oxidative damage in PD cell models. Results Here we show that curcumin can alleviate ?S-induced toxicity, reduce ROS levels and protect cells against apoptosis. We also show that both intracellular overexpression of ?S and extracellular addition of oligomeric ?S increase ROS which induces apoptosis, suggesting that aggregated ?S may induce similar toxic effects whether it is generated intra- or extracellulary. Conclusions Since curcumin is a natural food pigment that can cross the blood brain barrier and has widespread medicinal uses, it has potential therapeutic value for treating PD and other neurodegenerative disorders.

2010-01-01

126

Antioxidant and cytotoxic effect of biologically synthesized selenium nanoparticles in comparison to selenium dioxide.  

PubMed

The present study was designed to evaluate antioxidant and cytotoxic effect of selenium nanoparticles (Se NPs) biosynthesized by a newly isolated marine bacterial strain Bacillus sp. MSh-1. An organic-aqueous partitioning system was applied for purification of the biogenic Se NPs and the purified Se NPs were then investigated for antioxidant activity using DPPH scavenging activity and reducing power assay. Cytotoxic effect of the biogenic Se NPs and selenium dioxide (SeO2) on MCF-7 cell line was assesed by MTT assay. Tranmission electron micrograph (TEM) of the purified Se NPs showed individual and spherical nanostructure in size range of about 80-220nm. The obtained results showed that, at the same concentration of 200?g/mL, Se NPs and SeO2 represented scavenging activity of 23.1±3.4% and 13.2±3.1%, respectively. However, the data obtained from reducing power assay revealed higher electron-donating activity of SeO2 compared to Se NPs. Higher IC50 of the Se NPs (41.5±0.9?g/mL) compared to SeO2 (6.7±0.8?g/mL) confirmed lower cytotoxicity of the biogenic Se NPs on MCF-7 cell line. PMID:24074651

Forootanfar, Hamid; Adeli-Sardou, Mahboubeh; Nikkhoo, Maryam; Mehrabani, Mitra; Amir-Heidari, Bagher; Shahverdi, Ahmad Reza; Shakibaie, Mojtaba

2014-01-01

127

Controllable synthesis of monodispersed silver nanoparticles as standards for quantitative assessment of their cytotoxicity.  

PubMed

Silver nanoparticles (Ag NPs) are appealing due to their excellent antibacterial/antivirus properties. At the meantime, the wide applications of Ag NPs as antibacterial/antivirus agents arise the concern of Ag NPs' toxicity. However, quantitative understanding of the cytotoxicity of Ag NPs is minimum since that the Ag NPs in current studies have wide size distributions, in which the size effect of Ag NPs on cytotoxicity was unable to be accurately evaluated. In this work, unprecedentedly monodispersed Ag NPs with sizes of 25, 35, 45, 60 and 70 nm were obtained, respectively, by using an optimized polyol method with poly(vinyl pyrrolidone) (PVP) as surfactant. It was found that the reaction temperature, reaction time, concentration of the surfactant and reactants are playing important roles in determining the size and size distribution of Ag NPs. With the monodispersed Ag NPs as standard samples, the size- and dose- dependent cytotoxicity of Ag NPs against Human lung fibroblast (HLF) cells was accurately accomplished in terms of cell viability, apoptosis and necrosis, reactive oxygen species, etc. We expect that the monodispersed Ag NPs will act as the standard samples for quantitatively characterizing the toxicity of Ag NPs in vitro and in vivo. PMID:22137123

Li, Lun; Sun, Jie; Li, Xiaoran; Zhang, Yan; Wang, Zhaoxu; Wang, Chunren; Dai, Jianwu; Wang, Qiangbin

2012-02-01

128

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, T P

2013-11-01

129

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

130

Iron(III) and manganese(II) substituted hydroxyapatite nanoparticles: Characterization and cytotoxicity analysis  

NASA Astrophysics Data System (ADS)

Calcium hydroxyapatite (HA) is the main inorganic component of natural bones and can bond to bone directly in vivo. Thus HA is widely used as coating material on bone implants due to its good osteoconductivity and osteoinductivity. Metal ions doped HA have been used as catalyst or absorbents since the ion exchange method has introduced new properties in HA which are inherent to the metal ions. For example, Mn2+ ions have the potential to increase cell adhesion while Fe3+ ions have magnetic properties. Here, Fe(III) substituted hydroxyapatite (Fe-HA) and Mn(II) substituted hydroxyapatite (Mn-HA) were produced by wet chemical method coupled with ion exchange mechanism. Compared with pure HA, the colour of both Fe-HA and Mn-HA nanoparticles changed from white to brown and pink respectively. The intensity of the colours increased with increasing substitution concentrations. XRD patterns showed that all samples were single phased HA while the FTIR spectra revealed all samples possessed the characteristic phosphate and hydroxyl adsorption bands of HA. However, undesired adsorption bands of carbonate substitution (B-type carbonated HA) and H2O were also detected, which was reasonable since the wet chemical method was used in the synthesis of these nanoparticles. FESEM images showed all samples were elongated spheroids with small size distribution and of around 70 nm, regardless of metal ion substitution concentrations. EDX spectra showed the presence of Fe and Mn and ICP-AES results revealed all metal ion substituted HA were non-stoichiometric (Ca/P atomic ratio deviates from 1.67). Fe-HA nanoparticles were paramagnetic and the magnetic susceptibility increased with the increase of Fe content. Based on the extraction assay for cytotoxicity test, both Fe-HA and Mn-HA displayed non-cytotoxicity to osteoblast.

Li, Yan; Teck Nam, Chai; Ooi, Chui Ping

2009-09-01

131

Cytotoxicity of Surface-functionalized Silicon and Germanium Nanoparticles: The Dominant Role of Surface Charges  

PubMed Central

Although it is 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 a target organ for the toxic NPs since a dose-, surface charge- and size-dependent imbalance of the mitochondrial membrane potential was observed. Such 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 in 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.

Bhattacharjee, Sourav; Rietjens, Ivonne MCM; 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 TM; Fink, Mark J; Veinot, Jonathan GC; Kauzlarich, Susan M; Zuilhofa, Han

2013-01-01

132

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

2013-06-01

133

Augmented cytotoxicity of hydroxycamptothecin-loaded nanoparticles in lung and colon cancer cells by chemosensitizing pharmaceutical excipients.  

PubMed

Abstract The aim of this was to investigate and compare the chemosensitizing effect of some pharmaceutical excipients (TPGS, Pluronic P85 and chitosan) by evaluating the cytotoxicity of the chemotherapeutic drug Hydroxy Camptothecin (HCPT) loaded into PLGA nanoparticles. Different nanoparticles formulations were developed and evaluated for size, zeta potential, morphology, loading and encapsulation efficiency as well as in vitro drug release. The cytotoxicity of the nanoparticles was evaluated by MTT assay in A549 (human lung carcinoma cell line) and HT29 (human colon carcinoma cell line) whereas their cellular uptake was determined by confocal laser scanning microscopy and microfluorimetry assay. The results revealed that nanoparticles possessed a desirable nanometric size (revealed by dynamic light scattering measurements and TEM) with appreciable HCPT encapsulation (>48%) and negative surface charge that was switched to positive upon coating with chitosan. The nanoparticles adopted a sustained release phase preceded by initial burst of HCPT that was reduced by chitosan coating. The cytotoxicity of the nanoparticles in A549 and HT29 cells was significantly augmented compared to simple drug solution and basic nanoparticles without excipients. The excipients could be ranked according to their IC50 lowering effect in the following order [TPGS (sixfold lower IC50)?>?Pluronic P85?>?Chitosan]. The augmented cytotoxicity and chemosensitizing effect might be attributed to overcoming drug efflux (in case of TPGS 1000 or Pluronic P85) and/or maximizing internalization by cancer cells (chitosan coating). Acting as chemopotentiators, the studied excipients could have potential in reducing therapeutic HCPT doses and minimizing adverse effects in lung and colon chemotherapy. PMID:24093513

Zaki, Noha M

2014-06-01

134

Physiological changes induced in cardiac myocytes by cytotoxic T lymphocytes  

SciTech Connect

The lethal hit induced by viral specific, sensitized, cytotoxic T lymphocytes (CTL) attacking virus-infected heart cells is important in the pathogenesis of viral myocarditis and reflects the key role of CTL in this immune response. The mechanisms involved are incompletely understood. Studies of the physiological changes induced in mengovirus-infected, cultured, neonatal, rat heart cells by CTL that had been previously sensitized by the same virus are presented. The CTL were obtained from spleens of mengovirus-infected, major histocompatibility complex (MHC) matched adult rats. Cell wall motion was measured by an optical method, action potentials with intracellular microelectrodes, and total exchangeable calcium content by /sup 45/Ca tracer measurements after loading the myocytes with /sup 45/Ca and then exposing them to CTL. After 50 min (mean time) of exposing mengovirus-infected myocytes to the CTL, the mechanical relaxation of the myocyte was slowed, with a subsequent slowing of beating rate and a reduced amplitude of contraction. Impaired relaxation progressed, and prolonged oscillatory contractions lasting up to several seconds appeared, with accompanying oscillations in the prolonged plateau phase of the action potentials. Arrest of the myocyte contractions appeared 98 min (mean time) after exposure to CTL. It is concluded that infection of cultured myocytes with mengovirus predisposes them to attack by mengovirus specific CTL, and that persistent dysfunction of the myocyte is preceded by reversible changes in membrane potential and contraction. This is suggestive of an altered calcium handling by the myocytes possibly resulting in the cytotoxic effect.

Hassin, D.; Fixler, R.; Shimoni, Y.; Rubinstein, E.; Raz, S.; Gotsman, M.S.; Hasin, Y.

1987-01-01

135

Impact of agglomeration and different dispersions of titanium dioxide nanoparticles on the human related in vitro cytotoxicity and genotoxicity.  

PubMed

The published results on nanoparticles cytotoxicity and genotoxicity such as titanium dioxide nanoparticles (TiO(2) NPs) are inconsistent, and often conflicting and insufficient. Since different parameters may have impact on the toxicity results, there is need to lay stress on detailed characterization of NPs and the use of different testing conditions for assessment of NPs toxicity. In order to investigate whether dispersion procedures influence NP cytotoxicity and genotoxicity, we compared two protocols giving TiO(2) NP dispersions with different stability and agglomeration states. Detailed primary and secondary characteristics of both TiO(2) NP dispersions in culture media were carried out before toxicological testing; TK6 human lymphoblast cells, EUE human embryonic epithelial cells and Cos-1 monkey kidney fibroblasts were used to assess cytotoxicity (by trypan blue exclusion, proliferation activity and plating efficiency assays) and genotoxicity (by the comet assay). DNA strand breaks were detected by the alkaline comet assay. DNA oxidation lesions (especially 8-oxo-7,8-dihydroguanine, 8-oxoG) were measured with a modified comet assay including incubation with specific repair enzyme formamidopyrimidine DNA glycosylase (FPG). The TiO(2) NPs dispersion with large agglomerates (3 min sonication and no serum in stock solution) induced DNA damage in all three cell lines, while the TiO(2) NPs dispersed with agglomerates less than 200 nm (foetal serum in stock solution and sonication 15 min) had no effect on genotoxicity. An increased level of DNA oxidation lesions detected in Cos-1 and TK6 cells indicates that the leading mechanism by which TiO(2) NPs trigger genotoxicity is most likely oxidative stress. Our results show that the dispersion method used can influence the results of toxicity studies. Therefore at least two different dispersion procedures should be incorporated into assessment of cyto- and genotoxic effects of NPs. It is important, when assessing the hazard associated with NPs, to establish standard testing procedures and thorough strategies to consider the diverse conditions relevant to possible exposures. PMID:22277962

Magdolenova, Zuzana; Bilani?ová, Dagmar; Pojana, Giulio; Fjellsbř, Lise M; Hudecova, Alexandra; Hasplova, Katarina; Marcomini, Antonio; Dusinska, Maria

2012-02-01

136

A novel quinoline molecular probe and the derived functionalized gold nanoparticles: Sensing properties and cytotoxicity studies in MCF-7 human breast cancer cells.  

PubMed

A highly selective quinoline-based fluorescent sensor L was designed, prepared and used to monitor zinc ions in Goldfish (Carassius auratus) as model of vertebrate organism. Modified gold nanoparticles having functional quinoline molecules (GNPs@L) were also synthesized and their sensing properties towards different metal ions were also explored in solution, showing high selectively towards the toxic and heavy metal ion mercury. Cell proliferation kit XTT that employs 2,3-bis-(2-methoxy-4-nitro- 5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt (XTT) was used in order to investigate the cytotoxicity of compound L and GNPs@L on the MCF-7 breast cancer cells, showing significant cytotoxicity in comparison with similar reported systems. It was observed that L and GNPs@L compounds induced apoptosis in MCF-7 cancer cells. The cellular uptake of the hybrid system GNPs@L was studied using confocal laser scanning microscopy (CLSM). PMID:24861645

Núńez, Cristina; Oliveira, Elisabete; García-Pardo, Javier; Diniz, Mario; Lorenzo, Julia; Capelo, José Luis; Lodeiro, Carlos

2014-08-01

137

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

PubMed

As titanium dioxide (TiO(2)) 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) TiO(2) 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 TiO(2) 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 TiO(2) 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 TiO(2) nanoparticle-induced L929 cells. These results also suggest that the metabolomic strategy had a great potential in evaluating the cytotoxicity of TiO(2) nanoparticles and thus was very helpful in understanding its underlying molecular mechanisms. PMID:22996321

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

2013-12-01

138

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

2012-08-15

139

Optical forces induced by metal nanoparticle clusters  

NASA Astrophysics Data System (ADS)

The strong field localization generated between closely placed metal particles excited by electromagnetic radiation induces intense forces on small polarizable objects. In this study we investigate the optical forces that can be generated in the vicinity of metal nanoparticle clusters using fully electrodynamic numerical simulations. The influence of the cluster configuration as well as of the excitation parameters is analyzed.

Sancho-Parramon, Jordi; Bosch, Salvador

2014-05-01

140

Natural cell-mediated cytotoxicity against Candida albicans induced by cyclophosphamide: nature of the in vitro cytotoxic effector.  

PubMed Central

We have recently reported the in vivo modulation of resistance to experimental Candida albicans infection by cyclophosphamide (150 mg/kg intraperitoneally) in mice and have shown that increased resistance to the microbial challenge occurs 12 to 21 days after treatment with the drug (Bistoni et al., Infect. Immun. 40: 46-55, 1983). The event is accompanied by the appearance of a highly candidacidal cell population in the spleen and the activation of a subpopulation of natural cytotoxic effectors reactive in vitro against YAC-1 tumor cells. We now provide evidence that these anti-YAC-1 cytotoxic effectors are clearly distinct from the cyclophosphamide-induced candidacidal effectors, which seem to belong to a macrophage-monocyte lineage. The enhanced cytotoxic activity induced by cyclophosphamide was not restricted to C. albicans but was also exerted against a panel of Candida strains.

Baccarini, M; Bistoni, F; Puccetti, P; Garaci, E

1983-01-01

141

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

142

The cellular uptake and cytotoxic effect of silver nanoparticles on chronic myeloid leukemia cells.  

PubMed

Several studies have suggested that silver nanoparticles (AgNPs) have the potential to treat human cancers, including leukemia. However, the detailed cellular mechanisms for AgNPs to inhibit the growth of leukemic cells and their efficacy on clinical isolates of leukemic patients are not elucidated. In this study, the cellular uptake and cytotoxic mechanism of AgNPs in chronic myeloid leukemia (CML) cells were investigated. AgNPs were synthesized with a modified polyol method, which were stable under cell culture conditions with fetal bovine serum (FBS). AgNPs were demonstrated to be able to enter K562 cells (a CML cell line) in a dose-dependent manner and locate in endosomes. Reactive oxygen species (ROS) could be generated upon AgNPs exposure and cause cytotoxicity and apoptosis. It was also found that AgNPs treatment inhibited the viability of cells from CML patients (n = 4). The cell cycle status and several critical regulators were altered upon AgNPs treatment as well. All these cellular and molecular alterations caused by AgNPs exposure could be reversed by the addition of Vitamin C (an antioxidant). These results suggested that proper usage of AgNPs would be of great significance for CML treatment in future. PMID:24734519

Guo, Dawei; Zhao, Yun; Zhang, Yu; Wang, Qing; Huang, Zhihai; Ding, Qi; Guo, Zhirui; Zhou, Xuefeng; Zhu, Lingying; Gu, Ning

2014-04-01

143

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

144

Identifying genetic variants that contribute to chemotherapy-induced cytotoxicity  

PubMed Central

Patients treated with anticancer chemotherapy exhibit variation, both in terms of tumor response and the incidence and severity of adverse effects. The etiology of this variation is multifactorial with genetic factors likely contributing to a significant extent. Pharmacogenetic and genomic studies can be used to identify the genetic variants that contribute to interindividual variation in susceptibility to chemotherapy-induced cytotoxicity. This review will describe candidate and whole-genome approaches, describe the advantages and disadvantages of each, and illustrate how they can be used to obtain clinically relevant information. Specific emphasis is given to recent advances emerging from the International HapMap Project and to the development of genetic signatures, as opposed to expression signatures, to explain drug sensitivity and resistance.

Hartford, Christine M

2009-01-01

145

[Effect of PLGA nanoparticles conjugated with anti-OX40/anti-AFP mAbs on cytotoxicity of CTL cells against hepatocellular carcinoma].  

PubMed

Objective To evaluate the effect of anti-OX40 and anti-AFP antibodies conjugated onto poly(DL-lactide-co-glycolide)-nanoparticles (PLGA-NPs) on the cytotoxic activity of AFP158-166; -specific cytotoxic T lymphocyte (CTL) against hepatocellular carcinoma cells in vitro. Methods PLGA-NPs were prepared by oil-in-water single emulsion solvent evaporation method and covalently conjugated with anti-OX40 and anti-AFP monoclonal antibodies. Scanning electron microscopy (SEM) was utilized for the characterization of the surface morphology and estimation of the size of the PLGA-NPs. The mean diameter and zeta potential of the nanoparticles were measured by dynamic light scattering (DLS) performed in a Zetasiser Nano Series ZEN3600. Antibody conjugation efficiency was determined using bicinchoninic acid (BCA) protein assay. Dendritic cells (DCs) were induced from human peripheral blood mononuclear cells (PBMCs) in the presence of GM-CSF and IL-4, and loaded with AFP158-166; peptide to generate AFP-specific CTL (CTL/AFP158-166;). WST-1, ELISA and lactate dehydrogenase (LDH) methods were respectively used to examine the effects of the anti-OX40/anti-AFP-NPs on CTL/AFP158-166; proliferation, IL-2 and IFN-? production, and cytotoxicity against the tumor cells. Results The obtained nanoparticles were found to be of regular spherical shape and the smooth surface with an average diameter of (300±42) nm and a negative zeta potential of -(25.12±5.34) mV. Approximately 100 ?g antibodies were conjugated to every milligram of the nanoparticles with a conjugation efficiency of about 25% as estimated by BCA protein assay. Proliferation and activation analysis revealed that anti-OX40/anti-AFP mAb-NPs significantly induced CTL proliferation and the secretion of IL-2 and IFN-?. The cytotoxicity assay showed that anti-OX40/anti-AFP-NPs markedly enhanced CTL/AFP158-166; specific killing on HepG2 cells but had no obvious effect on SMMC-7721 cells. Conclusion Anti-OX40 mAb and anti-AFP mAb conjugated to PLGA-NPs could stimulate CTL/AFP158-166; cell proliferation and cytokine production as well as enhancing their specific killing on AFP-positive hepatocellular carcinoma cells. PMID:24721396

Chen, Mingshui; Ouyang, Haichao; Zhou, Shanyong; Li, Jieyu; Ye, Yunbin

2014-04-01

146

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

147

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

148

Cytotoxicity in the age of nano: the role of fourth period transition metal oxide nanoparticle physicochemical properties.  

PubMed

A clear understanding of physicochemical factors governing nanoparticle toxicity is still in its infancy. We used a systematic approach to delineate physicochemical properties of nanoparticles that govern cytotoxicity. The cytotoxicity of fourth period metal oxide nanoparticles (NPs): TiO2, Cr2O3, Mn2O3, Fe2O3, NiO, CuO, and ZnO increases with the atomic number of the transition metal oxide. This trend was not cell-type specific, as observed in non-transformed human lung cells (BEAS-2B) and human bronchoalveolar carcinoma-derived cells (A549). Addition of NPs to the cell culture medium did not significantly alter pH. Physiochemical properties were assessed to discover the determinants of cytotoxicity: (1) point-of-zero charge (PZC) (i.e., isoelectric point) described the surface charge of NPs in cytosolic and lysosomal compartments; (2) relative number of available binding sites on the NP surface quantified by X-ray photoelectron spectroscopy was used to estimate the probability of biomolecular interactions on the particle surface; (3) band-gap energy measurements to predict electron abstraction from NPs which might lead to oxidative stress and subsequent cell death; and (4) ion dissolution. Our results indicate that cytotoxicity is a function of particle surface charge, the relative number of available surface binding sites, and metal ion dissolution from NPs. These findings provide a physicochemical basis for both risk assessment and the design of safer nanomaterials. PMID:24120544

Chusuei, Charles C; Wu, Chi-Heng; Mallavarapu, Shravan; Hou, Fang Yao Stephen; Hsu, Chen-Ming; Winiarz, Jeffrey G; Aronstam, Robert S; Huang, Yue-Wern

2013-11-25

149

Prearmed Effector Cells and the Target Cell Specificity of Lectin Induced Cellular Cytotoxicity.  

National Technical Information Service (NTIS)

Mechanisms were investigated by which plant lectins induce human peripheral blood mononuclear cells to kill red blood cells (RBC) from different species selectively. Cytotoxicity was induced by both mitogenic components of phytohemagglutinin-P (PHA), eryt...

R. P. MacDermott G. S. Nash D. Boldt

1976-01-01

150

Nanoparticle induced self-assembly  

NASA Astrophysics Data System (ADS)

Self-assembly has for the large part focused on the assembly of molecules without guidance or management from an outside source. However, self-assembly is in principle by no means limited to molecules or the nanoscale. A particularly interesting method to the self-assembly of micro- to millimetre sized components is the use of the 'magnetic hole' effect. In this method, nonmagnetic particles can be manipulated by external magnetic fields by immersing them in a dispersion of colloidal, magnetic nanoparticles, denoted ferrofluids. Nonmagnetic particles in magnetized ferrofluids are in many ways ideal model systems to test various forms of particle self-assembly and dynamics. When microspheres are confined to a monolayer between two parallel plates and subjected to static or oscillating magnetic fields they show a variety of dynamical behaviours and assemblages, depending on the frequency and direction of the external fields. A single pair of magnetic holes oscillating in a ferrofluid layer may be used to measure the viscosity of tiny volumes of the fluid. We have also observed ordering of dilute dispersions of macromolecules and nanoparticles in magnetized ferrofluids. The self-assembly at this length scale results from structural correlations between these nanostructures and ferrofluid particles rather than from the macroscopic magnetostatic effect for the magnetic holes.

Helgesen, G.; Svĺsand, E.; Skjeltorp, A. T.

2008-05-01

151

Chitosan/PLA nanoparticles as a novel carrier for the delivery of anthraquinone: synthesis, characterization and in vitro cytotoxicity evaluation.  

PubMed

Designing novel materials for biomedical applications generally require the use of biodegradable materials. This study aims to engineer a biodegradable [chitosan (CS) and poly (lactic acid) (PLA)] as AQ carrier with nanometer dimensions and to evaluate the anticancer potency of the prepared CS/PLA-AQ NPs in human carcinoma (HepG2) cells. CS-PLA complex, which are well dispersed and stable in aqueous solution, was prepared by the precipitation of lactic acid in chitosan solution by dropping method and characterized by SEM, TEM, DLS and FTIR. The results thus displayed that the prepared nanoparticles carried a positive charge and showed the size in the range from 100 to 200 nm. The in vitro (AQ) release study showed that these nanoparticles provided a continuous release of the entrapped AQ for 10 days, and the release behavior was influenced by the pH value of the medium thereby making feasible to develop CS-PLA for enhanced and sustained release of AQ. MTT assay revealed higher cytotoxic efficacy of CS/PLA-AQ NPs than Free AQ in HepG2 cells. Further, the mitochondrial membrane damage indicated by loss of mitochondrial membrane potential and necrotic cell death could be attributed to the increased reactive oxygen species production. Our results also suggest that upon CS/PLA-AQ NPs exposure the cell viability decreased due to apoptosis, as demonstrated by the formation of apoptotic bodies, sub-G1 hypodiploid cells, and DNA fragmentation. Henceforth, CS/PLA-AQ NPs demonstrated a strong antitumor activity in vitro by reducing cell viability, inducing cell necrosis, decreasing the negative surface charge and mitochondrial membrane potential, and fragmenting DNA. PMID:22796782

Jeevitha, D; Amarnath, Kanchana

2013-01-01

152

Evaluation of topically applied copper(II) oxide nanoparticle cytotoxicity in human skin organ culture.  

PubMed

The increasing use of nano-sized materials in our environment, and in many consumer products, dictates new safety concerns. In particular, adequate experimental models are needed to evaluate skin toxicity of metal oxide ions, commonly found in cosmetic and dermatologic preparations. We have addressed the biological effects of topically applied copper oxide (CuO) nanoparticles in human skin organ cultures, using light and electron microscopy, and biochemical tests. Nanoparticles were more toxic than micro-sized particles, and their effects were stronger when supplied in growth medium than in topical application. Still topically applied CuO nanoparticles induced inflammatory cytokine secretion and necrosis, especially in epidermis deprived of its protective cornea. Since nanoparticle penetration was not seen, we propose that they may adhere to skin surface, react with the local acidic environment, and generate soluble ions that make their way to inner sites. This work illustrates the abilities of skin organ culture to evaluate the biological effects of topically-applied materials on skin in vitro. PMID:22954531

Cohen, Dror; Soroka, Yoram; Ma'or, Zeev; Oron, Miriam; Portugal-Cohen, Meital; Brégégčre, François Menahem; Berhanu, Deborah; Valsami-Jones, Eugenia; Hai, Noam; Milner, Yoram

2013-02-01

153

Co-nanoencapsulation of magnetic nanoparticles and selol for breast tumor treatment: in vitro evaluation of cytotoxicity and magnetohyperthermia efficacy  

PubMed Central

Antitumor activities have been described in selol, a hydrophobic mixture of molecules containing selenium in their structure, and also in maghemite magnetic nanoparticles (MNPs). Both selol and MNPs were co-encapsulated within poly(lactic-co-glycolic acid) (PLGA) nanocapsules for therapeutic purposes. The PLGA-nanocapsules loaded with MNPs and selol were labeled MSE-NC and characterized by transmission and scanning electron microscopy, electrophoretic mobility, photon correlation spectroscopy, presenting a monodisperse profile, and positive charge. The antitumor effect of MSE-NC was evaluated using normal (MCF-10A) and neoplastic (4T1 and MCF-7) breast cell lines. Nanocapsules containing only MNPs or selol were used as control. MTT assay showed that the cytotoxicity induced by MSE-NC was dose and time dependent. Normal cells were less affected than tumor cells. Cell death occurred mainly by apoptosis. Further exposure of MSE-NC treated neoplastic breast cells to an alternating magnetic field increased the antitumor effect of MSE-NC. It was concluded that selol-loaded magnetic PLGA-nanocapsules (MSE-NC) represent an effective magnetic material platform to promote magnetohyperthermia and thus a potential system for antitumor therapy.

Estevanato, Luciana LC; Silva, Jaqueline R Da; Falqueiro, Andre M; Mosiniewicz-Szablewska, Ewa; Suchocki, Piotr; Tedesco, Antonio C; Morais, Paulo C; Lacava, Zulmira GM

2012-01-01

154

Cationic Lipid-Coated Gold Nanoparticles as Efficient and Non-Cytotoxic Intracellular siRNA Delivery Vehicles  

Microsoft Academic Search

Purpose  Cationic lipid-coated gold nanoparticles were developed for efficient intracellular delivery of therapeutic siRNA.\\u000a \\u000a \\u000a \\u000a Methods  Particle formation was characterized by UV-visible spectroscopy, atomic force microscopy, and dynamic light scattering analysis.\\u000a Cellular uptake, gene silencing effect, and cytotoxicity were investigated in multiple human cancer cell lines.\\u000a \\u000a \\u000a \\u000a \\u000a Results  Nanoparticles had a spherical nanostructure with highly cationic surface charge and could form stable nanosized polyelectrolyte\\u000a complexes

Won Ho Kong; Ki Hyun Bae; Sung Duk Jo; Jee Seon Kim; Tae Gwan Park

155

Structure-Activity Relationships of Cationic Shell-crosslinked Knedel-like Nanoparticles: Shell Composition and Transfection Efficiency/Cytotoxicity  

PubMed Central

Cationic nanoparticles are a promising class of transfection agents for oligonucleotide and gene delivery, but vary greatly in their effectiveness and cytotoxicity. Recently, we developed a new class of cationic transfection agents based on cationic shell-crosslinked nanoparticles (cSCKs) that efficiently transfect mammalian cells with both oligonucleotides and plasmid DNA. In an effort to further improve transfection efficiency without increasing cytotoxicity, we examined the effects of the composition of primary amine (pa), tertiary amine (ta) and carboxylic acid (ca) groups in the shell of these nanoparticles. A series of discrete complexes of the cSCKs with plasmid DNA (pDNA) or phosphorothioate 2?-OMe oliogonucleotides (ps-MeON) were prepared over a broad range of amine to phosphate ratios (N/P ratio) of 4:1 to 40:1. The sizes of the complexes and the ability of the nanoparticles to completely bind ODNs were found to depend on the cSCK amine to DNA phosphate (N/P) ratio and the cSCK buffering capacity. The cSCKs were then evaluated for their ability to transfect cells with plasmid DNA by monitoring fluorescence from an encoded EGFP, and for delivery of ps-MeON by monitoring luminescence from luciferase resulting from ps-MeON-mediated splicing correction. Whereas the cationic cSCK-pa25-ta75 was found to be best for transfecting plasmid DNA into HeLa cells at an N/P ratio of 20:1, cSCK-pa50-ta50, at an N/P ratio 10:1 was best for ps-MeON delivery. We also found that increasing the proportion of tertiary relative to primary amine reduced the cytotoxicity. These results demonstrate that a dramatic improvement in gene and oligonucleotide delivery efficiency with decreased cytotoxicity in HeLa cells can be achieved by incorporation of tertiary amines into the shells of cSCKs.

Zhang, Ke; Fang, Huafeng; Wang, Zhenghui; Li, Zhou; Taylor, John-Stephen A.; Wooley, Karen L.

2009-01-01

156

Structure-activity relationships of cationic shell-crosslinked knedel-like nanoparticles: shell composition and transfection efficiency/cytotoxicity.  

PubMed

Cationic nanoparticles are a promising class of transfection agents for oligonucleotide and gene delivery, but vary greatly in their effectiveness and cytotoxicity. Recently, we developed a new class of cationic transfection agents based on cationic shell-crosslinked knedel-like nanoparticles (cSCKs) that efficiently transfect mammalian cells with both oligonucleotides and plasmid DNA. In an effort to further improve transfection efficiency without increasing cytotoxicity, we examined the effects of the composition of primary amine (pa), tertiary amine (ta) and carboxylic acid (ca) groups in the shell of these nanoparticles. A series of discrete complexes of the cSCKs with plasmid DNA (pDNA) or phosphorothioate 2'-OMe oliogonucleotides (ps-MeON) were prepared over a broad range of amine to phosphate ratios (N/P ratio) of 4:1-40:1. The sizes of the complexes and the ability of the nanoparticles to completely bind ODNs were found to depend on the cSCK amine to DNA phosphate (N/P) ratio and the cSCK buffering capacity. The cSCKs were then evaluated for their ability to transfect cells with plasmid DNA by monitoring fluorescence from an encoded EGFP, and for delivery of ps-MeON by monitoring luminescence from luciferase resulting from ps-MeON-mediated splicing correction. Whereas the cationic cSCK-pa(25)-ta(75) was found to be best for transfecting plasmid DNA into HeLa cells at an N/P ratio of 20:1, cSCK-pa(50)-ta(50), at an N/P ratio 10:1 was best for ps-MeON delivery. We also found that increasing the proportion of tertiary relative to primary amine reduced the cytotoxicity. These results demonstrate that a dramatic improvement in gene and oligonucleotide delivery efficiency with decreased cytotoxicity in HeLa cells can be achieved by incorporation of tertiary amines into the shells of cSCKs. PMID:19878990

Zhang, Ke; Fang, Huafeng; Wang, Zhenghui; Li, Zhou; Taylor, John-Stephen A; Wooley, Karen L

2010-03-01

157

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

PubMed

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

2013-11-01

158

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.

159

Cytotoxic effect of magnetic iron oxide nanoparticles synthesized via seaweed aqueous extract  

PubMed Central

Magnetic iron oxide nanoparticles (Fe3O4 MNPs) are among the most useful metal nanoparticles for multiple applications across a broad spectrum in the biomedical field, including the diagnosis and treatment of cancer. In previous work, we synthesized and characterized Fe3O4 MNPs using a simple, rapid, safe, efficient, one-step green method involving reduction of ferric chloride solution using brown seaweed (Sargassum muticum) aqueous extract containing hydroxyl, carboxyl, and amino functional groups mainly relevant to polysaccharides, which acts as a potential stabilizer and metal reductant agent. The aim of this study was to evaluate the in vitro cytotoxic activity and cellular effects of these Fe3O4 MNPs. Their in vitro anticancer activity was demonstrated in human cell lines for leukemia (Jurkat cells), breast cancer (MCF-7 cells), cervical cancer (HeLa cells), and liver cancer (HepG2 cells). The cancer cells were treated with different concentrations of Fe3O4 MNPs, and an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to test for cytotoxicity, resulting in an inhibitory concentration 50 (IC50) value of 23.83±1.1 ?g/mL (HepG2), 18.75±2.1 ?g/mL (MCF-7), 12.5±1.7 ?g/mL (HeLa), and 6.4±2.3 ?g/mL (Jurkat) 72 hours after treatment. Therefore, Jurkat cells were selected for further investigation. The representative dot plots from flow cytometric analysis of apoptosis showed that the percentages of cells in early apoptosis and late apoptosis were increased. Cell cycle analysis showed a significant increase in accumulation of Fe3O4 MNP-treated cells at sub-G1 phase, confirming induction of apoptosis by Fe3O4 MNPs. The Fe3O4 MNPs also activated caspase-3 and caspase-9 in a time-response fashion. The nature of the biosynthesis and therapeutic potential of Fe3O4 MNPs could pave the way for further research on the green synthesis of therapeutic agents, particularly in nanomedicine, to assist in the treatment of cancer.

Namvar, Farideh; Rahman, Heshu Sulaiman; Mohamad, Rosfarizan; Baharara, Javad; Mahdavi, Mahnaz; Amini, Elaheh; Chartrand, Max Stanley; Yeap, Swee Keong

2014-01-01

160

Cytotoxic effect of magnetic iron oxide nanoparticles synthesized via seaweed aqueous extract.  

PubMed

Magnetic iron oxide nanoparticles (Fe3O4 MNPs) are among the most useful metal nanoparticles for multiple applications across a broad spectrum in the biomedical field, including the diagnosis and treatment of cancer. In previous work, we synthesized and characterized Fe3O4 MNPs using a simple, rapid, safe, efficient, one-step green method involving reduction of ferric chloride solution using brown seaweed (Sargassum muticum) aqueous extract containing hydroxyl, carboxyl, and amino functional groups mainly relevant to polysaccharides, which acts as a potential stabilizer and metal reductant agent. The aim of this study was to evaluate the in vitro cytotoxic activity and cellular effects of these Fe3O4 MNPs. Their in vitro anticancer activity was demonstrated in human cell lines for leukemia (Jurkat cells), breast cancer (MCF-7 cells), cervical cancer (HeLa cells), and liver cancer (HepG2 cells). The cancer cells were treated with different concentrations of Fe3O4 MNPs, and an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to test for cytotoxicity, resulting in an inhibitory concentration 50 (IC50) value of 23.83±1.1 ?g/mL (HepG2), 18.75±2.1 ?g/mL (MCF-7), 12.5±1.7 ?g/mL (HeLa), and 6.4±2.3 ?g/mL (Jurkat) 72 hours after treatment. Therefore, Jurkat cells were selected for further investigation. The representative dot plots from flow cytometric analysis of apoptosis showed that the percentages of cells in early apoptosis and late apoptosis were increased. Cell cycle analysis showed a significant increase in accumulation of Fe3O4 MNP-treated cells at sub-G1 phase, confirming induction of apoptosis by Fe3O4 MNPs. The Fe3O4 MNPs also activated caspase-3 and caspase-9 in a time-response fashion. The nature of the biosynthesis and therapeutic potential of Fe3O4 MNPs could pave the way for further research on the green synthesis of therapeutic agents, particularly in nanomedicine, to assist in the treatment of cancer. PMID:24899805

Namvar, Farideh; Rahman, Heshu Sulaiman; Mohamad, Rosfarizan; Baharara, Javad; Mahdavi, Mahnaz; Amini, Elaheh; Chartrand, Max Stanley; Yeap, Swee Keong

2014-01-01

161

Biocompatibility of Fe(3)O(4) nanoparticles evaluated by in vitro cytotoxicity assays using normal, glia and breast cancer cells.  

PubMed

In order to reveal the biocompatibility of Fe(3)O(4) nanoparticles and bipolar surfactant tetramethylammonium 11-aminoundecanoate cytotoxicity tests were performed as a function of concentration from low (0.1 microg ml(-1)) to higher concentration (100 microg 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 Fe(3)O(4) nanoparticles in the concentration range of 0.1-10 microg ml(-1), while accountable cytotoxicity can be seen at 100 microg ml(-1). The results of our studies suggest that Fe(3)O(4) 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. PMID:20090199

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

2010-02-19

162

Adriamycin loaded pullulan acetate/sulfonamide conjugate nanoparticles responding to tumor pH: pH-dependent cell interaction, internalization and cytotoxicity in vitro.  

PubMed

The cytotoxicity of adriamycin (ADR)-loaded and pH-sensitive nanoparticles made of pullulan acetate (PA) and sulfonamide (sulfadimethoxine; SDM) (PA/SDM) conjugate to a breast tumor cell line (MCF-7) was investigated to test the feasibility of the nanoparticles in targeting acidic tumor extracellular pH (pH(e)). At pH 6.8, ADR loaded PA/SDM nanoparticles showed cytotoxicity in the cell culture experiment, comparable to that of free ADR at the same ADR concentrations, while the relative cytotoxicity at pH 7.4 was low at the tested concentration range. This pronounced cytotoxicity of the nanoparticles at low pH was attributed to the accelerated release of ADR triggered by pH, enhanced interaction with cells, and internalization. At pH 6.8 and 6.4, the PA/SDM nanoparticles aggressively bounded to MCF-7 cells, probably due to interactions of the cells with hydrophobized nanoparticle surfaces caused by SDM deionization. A confocal laser microscopic study revealed intracellular localization of the drug-loaded nanoparticles. Based on these findings, the pH-sensitive nanoparticles deserve further investigation with an in vivo animal model as a targeted carrier of pH(e). PMID:12618018

Na, Kun; Lee, Eun Seong; Bae, You Han

2003-02-21

163

MECHANISMS OF ASCORBATE-INDUCED CYTOTOXICITY IN PANCREATIC CANCER  

PubMed Central

Purpose Pharmacological concentrations of ascorbate may be effective in cancer therapeutics. We hypothesized that ascorbate concentrations achievable with intravenous dosing would be cytotoxic in pancreatic cancer where the five-year survival is < 3%. Experimental Design Pancreatic cancer cell lines were treated with ascorbate (0, 5, and 10 mM) for one hour, then viability and clonogenic survival were determined. Pancreatic tumor cells were delivered subcutaneously into the flank region of nude mice and allowed to grow at which time they were randomized to receive either ascorbate (4 g/kg) or osmotically equivalent saline (1 M) i.p. for two weeks. Results There was a time and dose-dependent increase in measured H2O2 production with increased concentrations of ascorbate. Ascorbate decreased viability in all pancreatic cancer cell lines, but had no effect on an immortalized pancreatic ductal epithelial cell line. Ascorbate decreased clonogenic survival of the pancreatic cancer cell lines, which was reversed by treatment of cells with scavengers of H2O2. Treatment with ascorbate induced a caspase-independent cell death that was associated with autophagy. In vivo, treatment with ascorbate inhibited tumor growth and prolonged survival. Conclusions These results demonstrate that pharmacological doses of ascorbate, easily achievable in humans, may have potential for therapy in pancreatic cancer.

Du, Juan; Martin, Sean M.; Levine, Mark; Wagner, Brett A.; Buettner, Garry R.; Wang, Sih-han; Taghiyev, Agshin F.; Du, Changbin; Knudson, C. Michael; Cullen, Joseph J.

2009-01-01

164

Photo-induced CdS nanoparticles growth  

NASA Astrophysics Data System (ADS)

A photochemical approach on the size control of CdS nanoparticles is presented. CdS nanoparticles were grown using the photo-induced reaction of sodium thiosulfate with Cadmium sulfate, in the absence of any surfactant. Particles of 5.5-11 nm were obtained by changing the illumination time. The dark growth of nanoparticles was negligible, however we found by optical scattering measurements that a ripening phenomenon occurs and the size of nanoparticles slightly increases with time.

Taghavinia, Nima; Azam Iraji-zad; Mahdavi, S. Mohammad; Reza-esmaili, M.

2005-12-01

165

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

166

Spectroscopic investigations, antimicrobial, and cytotoxic activity of green synthesized gold nanoparticles  

NASA Astrophysics Data System (ADS)

The gold nanoparticles (AuNPs) were synthesized by using naturally available Punica Granatum fruit extract as reducing and stabilizing agent. The biosynthesized AuNPs was characterized by using UV-Vis, fluorescence, high resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) and thermogravimetric (TGA) analysis. The surface plasmon resonance (SPR) band at 585 nm confirmed the reduction of auric chloride to AuNPs. The crystalline nature of the biosynthesized AuNPs was confirmed from the HRTEM images, XRD and selected area electron diffraction (SAED) pattern. The HRTEM images showed the mixture of triangular and spherical-like AuNPs having size between 5 and 20 nm. The weight loss of the AuNPs was measured by TGA as a function of temperature under a controlled atmosphere. The biomolecules are responsible for the reduction of AuCl4- ions and the formation of stable AuNPs which was confirmed by FTIR measurement. The synthesized AuNPs showed an excellent antibacterial activity against Candida albicans (ATCC 90028), Aspergillus flavus (ATCC 10124), Staphylococcus aureus (ATCC 25175), Salmonella typhi (ATCC 14028) and Vibrio cholerae (ATCC 14033). The minimum inhibitory concentration (MIC) of AuNPs was recorded against various microorganisms. Further, the synthesized AuNPs shows an excellent cytotoxic result against HeLa cancer cell lines at different concentrations.

Lokina, S.; Suresh, R.; Giribabu, K.; Stephen, A.; Lakshmi Sundaram, R.; Narayanan, V.

2014-08-01

167

Respiratory epithelial cytotoxicity and membrane damage (holes) caused by amine-modified nanoparticles.  

PubMed

The respiratory epithelium is a significant target of inhaled, nano-sized particles, the biological reactivity of which will depend on its physicochemical properties. Surface-modified, 50 and 100 nm, polystyrene latex nanoparticles (NPs) were used as model particles to examine the effect of particle size and surface chemistry on transformed human alveolar epithelial type 1-like cells (TT1). Live images of TT1 exposed to amine-modified NPs taken by hopping probe ion conductance microscopy revealed severe damage and holes on cell membranes that were not observed with other types of NPs. This paralleled induction of cell detachment, cytotoxicity and apoptotic (caspase-3/7 and caspase-9) cell death, and increased release of CXCL8 (IL-8). In contrast, unmodified, carboxyl-modified 50 nm NPs and the 100 nm NPs did not cause membrane damage, and were less reactive. Thus, the susceptibility and membrane damage to respiratory epithelium following inhalation of NPs will depend on both surface chemistry (e.g., cationic) and nano-size. PMID:21352086

Ruenraroengsak, Pakatip; Novak, Pavel; Berhanu, Deborah; Thorley, Andrew J; Valsami-Jones, Eugenia; Gorelik, Julia; Korchev, Yuri E; Tetley, Teresa D

2012-02-01

168

In vitro cytotoxicity and bioavailability of solid lipid nanoparticles containing tamoxifen citrate.  

PubMed

The objective of this study was to evaluate the influence of solid lipid nanoparticles (SLN) loaded with the poorly water-soluble drug tamoxifen citrate (TC) on the in vitro antitumor activity and bioavailability of the drug. TC-loaded SLN were prepared by solvent injection method using glycerol monostearate (GMS) or stearic acid (SA) as lipid matrix. Poloxamer 188 or tween 80 were used as stabilizers. TC-loaded SLN (F3 and F4) prepared using GMS and stabilized by poloxamer 188 showed highest entrapment efficiency % (86.07?±?1.74 and 90.40?±?1.22%) and reasonable mean particle sizes (130.40?±?9.45 and 243.80?±?12.33 nm), respectively. The in vitro release of TC from F3 and F4 exhibited an initial burst effect followed by a sustained drug release. In vitro cytotoxicity of F3 against human breast cancer cell line MCF-7 showed comparable antitumor activity to free drug. Moreover, the results of bioavailability evaluation of TC-loaded SLN in rats compared to free TC indicated that 160.61% increase in the oral bioavailability of TC. The obtained results suggest that incorporation of the poorly water-soluble drug TC in SLN preserves the in vitro antitumor activity and significantly enhance oral bioavailability of TC in rats. PMID:24032414

Hashem, Fahima M; Nasr, Mohamed; Khairy, Ahmed

2014-11-01

169

An investigation on the antibacterial, cytotoxic, and antibiofilm efficacy of starch-stabilized silver nanoparticles.  

PubMed

The increased emergence of drug resistant microbes creates a major challenge to the scientific community for successful development of effective therapeutics. The antimicrobial activities of silver ions are well known, but limited information is available on the effects of green silver-nanoparticles (AgNPs) on human pathogens. In this article, we evaluated the antibacterial activity of starch-stabilized AgNPs against a panel of human pathogens commonly associated with air, water and food borne infections. The shape and size distribution of AgNPs were characterized by transmission electron microscopy. We showed that AgNPs were more effective against Gram-positive and Gram-negative pathogens as compared with acid-fast bacteria. AgNPs were not cytotoxic to macrophages at the bactericidal concentration and can augment intracellular killing potential of macrophages. Furthermore, we showed that AgNPs disrupt biofilm formation and exhibit better antibacterial activity compared to human cationic antimicrobial peptide LL-37. In summary, our data suggest AgNPs as a promising template for the design of novel antibacterial agents. PMID:22115597

Mohanty, Soumitra; Mishra, Saswati; Jena, Prajna; Jacob, Biju; Sarkar, Biplab; Sonawane, Avinash

2012-08-01

170

Spectroscopic investigations, antimicrobial, and cytotoxic activity of green synthesized gold nanoparticles.  

PubMed

The gold nanoparticles (AuNPs) were synthesized by using naturally available Punica Granatum fruit extract as reducing and stabilizing agent. The biosynthesized AuNPs was characterized by using UV-Vis, fluorescence, high resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) and thermogravimetric (TGA) analysis. The surface plasmon resonance (SPR) band at 585nm confirmed the reduction of auric chloride to AuNPs. The crystalline nature of the biosynthesized AuNPs was confirmed from the HRTEM images, XRD and selected area electron diffraction (SAED) pattern. The HRTEM images showed the mixture of triangular and spherical-like AuNPs having size between 5 and 20nm. The weight loss of the AuNPs was measured by TGA as a function of temperature under a controlled atmosphere. The biomolecules are responsible for the reduction of AuCl4(-) ions and the formation of stable AuNPs which was confirmed by FTIR measurement. The synthesized AuNPs showed an excellent antibacterial activity against Candida albicans (ATCC 90028), Aspergillus flavus (ATCC 10124), Staphylococcus aureus (ATCC 25175), Salmonella typhi (ATCC 14028) and Vibrio cholerae (ATCC 14033). The minimum inhibitory concentration (MIC) of AuNPs was recorded against various microorganisms. Further, the synthesized AuNPs shows an excellent cytotoxic result against HeLa cancer cell lines at different concentrations. PMID:24755638

Lokina, S; Suresh, R; Giribabu, K; Stephen, A; Lakshmi Sundaram, R; Narayanan, V

2014-08-14

171

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

172

Autologous Human Cellular Cytotoxicity Induced by Mitogenic and Nonmitogenic Lectins.  

National Technical Information Service (NTIS)

In this investigation the ability of the mitogenic components of phytohemagglutinin (PHA) and the nonmitogenic lectin, wheat germ agglutinin (WGA), to cause autologous cellular cytotoxicity of human red blood cells (RBC) was compared.

R. P. MacDermott G. S. Nash J. G. Saint E. A. Clark A. G. Zaras

1976-01-01

173

Silica nanoparticles and silver-doped silica nanoparticles induce endoplasmatic reticulum stress response and alter cytochrome P4501A activity.  

PubMed

Engineered silica nanoparticles (SiO(2)-NPs) find widespread application and may lead to exposure of humans and the environment. Here we compare the effects of SiO(2)-NPs and SiO(2)-NPs doped with silver (SiO(2)-Ag-NPs) on survival and cellular function of human liver cells (Huh7) and Pimephales promelas (fathead minnow) fibroblast cells (FMH). In Huh7 cells we investigate effects on the endoplasmatic reticulum (ER), including ER stress, and interactions of nanoparticles (NPs) with metabolizing enzymes and efflux transporters. The NPs formed agglomerates/aggregates in cell culture media as revealed by SEM and TEM. SiO(2) and SiO(2)-1% Ag-NPs were taken up into cells as demonstrated by agglomerates occurring in vesicular-like structures or freely dispersed in the cytosol. Cytotoxicity was more pronounced in Huh7 than in FMH cells, and increased with silver content in silver-doped NPs. Dissolved silver was the most significant factor for cytotoxicity. At toxic and non-cytotoxic concentrations SiO(2)-NPs and SiO(2)-1% Ag-NPs induced perturbations in the function of ER. In Huh7 cells NPs induced the unfolded protein response (UPR), or ER stress response, as demonstrated in induced expression of BiP and splicing of XBP1 mRNA, two selective markers of ER stress. Additionally, SiO(2)-1% Ag-NPs and AgNO(3) induced reactive oxygen species. Pre-treatment of Huh7 cells with SiO(2)-1% Ag-NPs followed by exposure to the inducer benzo(a)pyrene caused a significant reduced induction of CYP1A activity. NPs did not alter the activity of ABC transporters. These data demonstrate for the first time that SiO(2)-NPs and SiO(2)-1% Ag-NPs result in perturbations of the ER leading to the ER stress response. This represents a novel and significant cellular signalling pathway contributing to the cytotoxicity of NPs. PMID:22245057

Christen, Verena; Fent, Karl

2012-04-01

174

Assessment of temporal dose-toxicity relationship of fumed silica nanoparticle in human lung A549 cells by conventional cytotoxicity and ąH-NMR-based extracellular metabonomic assays.  

PubMed

As nanoparticles could form aggregates in biological systems, the dynamics of their dispersity drives the temporal effect of nanoparticles in vitro. To test this hypothesis, the fumed silica nanoparticles (SiNPs) that have primary sizes of 7-14 nm and form aggregates in culture medium were selected for toxicity study in human lung A549 cells. The dispersity of SiNPs was analyzed by dynamic light scattering and transmission of electron microscopy. Cytotoxicity assays including mitochondrial activity, intracellular level of reactive oxygen species (ROS), and membrane damage together with the ąH-NMR-based extracellular metabonomic assay were conducted to determine the temporal dose-effect relationship of SiNPs. In cell culture medium, SiNPs dispersed well initially at 25-100 ?g/ml; however, they sedimented rapidly in a concentration-dependent manner. SiNPs caused a dose-dependent increase of intracellular ROS and cell membrane damage at 4 h and a loss of cell viability after 48 h. SiNPs also induced an elevation of extracellular glucose, lactate, phenylalanine, histidine, and tyrosine levels in a time- and concentration-dependent manner. The dose-effect patterns at 4 h were different from that at 12 and 24 h as assessed by both cytotoxicity and metabonomic assays. Both fitted better with polynomial regression than linear regression, implying multimode action of SiNPs at different concentrations. The early NP-cell interaction and the late sedimentation could be attributable to the temporal effects of SiNPs. The extracellular ąH-NMR-based metabonomics demonstrated a potential as a robust nondestructive tool for monitoring the temporal effect of NPs that tend to aggregate in nature. PMID:24449423

Irfan, Adeel; Cauchi, Michael; Edmands, William; Gooderham, Nigel J; Njuguna, James; Zhu, Huijun

2014-04-01

175

Use of a Rapid Cytotoxicity Screening Approach to Engineer a Safer Zinc Oxide Nanoparticle through Iron Doping  

PubMed Central

The establishment of verifiably safe nanotechnology requires the development of assessment tools to identify hazardous nanomaterial properties that could be modified to improve nanomaterial safety. While there is a lot of debate of what constitutes appropriate safety screening methods, one approach is to use the assessment of cellular injury pathways to collect knowledge about hazardous material properties that could lead to harm to humans and the environment. We demonstrate the use of a multi-parameter cytotoxicity assay that evaluates toxic oxidative stress to compare the effects of titanium dioxide (TiO2), cerium oxide (CeO2) and zinc oxide (ZnO) nanoparticles in bronchial epithelial and macrophage cell lines. The nanoparticles were chosen based on their volume of production and likelihood of spread to the environment. Among the materials, dissolution of ZnO nanoparticles and Zn2+ release were capable of ROS generation and activation of an integrated cytotoxic pathway that includes intracellular calcium flux, mitochondrial depolarization, and plasma membrane leakage. These responses were chosen based on the compatibility of the fluorescent dyes that contemporaneously assess their response characteristics by a semi-automated epifluorescence procedure. Purposeful reduction of ZnO cytotoxicity was achieved by iron doping, which changed the material matrix to slow Zn2+ release. In summary, we demonstrate the utility of a rapid throughput, integrated biological oxidative stress response pathway to perform hazard ranking of a small batch of metal oxide nanoparticles, in addition to showing how this assay can be used to improve nanosafety by decreasing ZnO dissolution through Fe doping.

George, Saji; Pokhrel, Suman; Xia, Tian; Gilbert, Benjamin; Ji, Zhaoxia; Schowalter, Marco; Rosenauer, Andreas; Damoiseaux, Robert; Bradley, Kenneth A; Madler, Lutz; Nel, Andre E

2014-01-01

176

Cytotoxicity, oxidative stress, apoptosis and the autophagic effects of silver nanoparticles in mouse embryonic fibroblasts.  

PubMed

With the advancement of nanotechnology, nanomaterials have been comprehensively applied in our modern society. However, the hazardous impacts of nanoscale particles on organisms have not yet been thoroughly clarified. Currently, there exist numerous approaches to perform toxicity tests, but common and reasonable bio-indicators for toxicity evaluations are lacking. In this study, we investigated the effects of silver nanoparticles (AgNPs) on NIH 3T3 cells to explore the potential application of these nanoparticles in consumer products. Our results demonstrated that AgNPs were taken up by NIH 3T3 cells and localized within the intracellular endosomal compartments. Exposure to AgNPs is a potential source of oxidative stress, which leads to the induction of reactive oxygen species (ROS), the up-regulation of Heme oxygenase 1 (HO-1) expression, apoptosis and autophagy. Interestingly, AgNPs induced morphological and biochemical markers of autophagy in NIH 3T3 cells and induced autophagosome formation, as evidenced by transmission electron microscopic analysis, the formation of microtubule-associated protein-1 light chain-3 (LC3) puncta and the expression of LC3-II protein. Thus, autophagy activation may be a key player in the cellular response against nano-toxicity. PMID:24630838

Lee, Yu-Hsuan; Cheng, Fong-Yu; Chiu, Hui-Wen; Tsai, Jui-Chen; Fang, Chun-Yong; Chen, Chun-Wan; Wang, Ying-Jan

2014-05-01

177

Green synthesis of silver nanoparticles using Ganoderma neo-japonicum Imazeki: a potential cytotoxic agent against breast cancer cells  

PubMed Central

Background Silver nanoparticles (AgNPs) are an important class of nanomaterial for a wide range of industrial and biomedical applications. AgNPs have been used as antimicrobial and disinfectant agents due their detrimental effect on target cells. The aim of our study was to determine the cytotoxic effects of biologically synthesized AgNPs using hot aqueous extracts of the mycelia of Ganoderma neo-japonicum Imazeki on MDA-MB-231 human breast cancer cells. Methods We developed a green method for the synthesis of water-soluble AgNPs by treating silver ions with hot aqueous extract of the mycelia of G. neo-japonicum. The formation of AgNPs was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction, dynamic light scattering, and transmission electron microscopy. Furthermore, the toxicity of synthesized AgNPs was evaluated using a series of assays: such as cell viability, lactate dehydrogenase leakage, reactive oxygen species generation, caspase 3, DNA laddering, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling in human breast cancer cells (MDA-MB-231). Results The ultraviolet-visible absorption spectroscopy results showed a strong resonance centered on the surface of AgNPs at 420 nm. The X-ray diffraction analysis confirmed that the synthesized AgNPs were single-crystalline, corresponding with the result of transmission electron microscopy. Treatment of MDA-MB-231 breast cancer cells with various concentrations of AgNPs (1–10 ?g/mL) for 24 hours revealed that AgNPs could inhibit cell viability and induce membrane leakage in a dose-dependent manner. Cells exposed to AgNPs showed increased reactive oxygen species and hydroxyl radical production. Furthermore, the apoptotic effects of AgNPs were confirmed by activation of caspase 3 and DNA nuclear fragmentation. Conclusion The results indicate that AgNPs possess cytotoxic effects with apoptotic features and suggest that the reactive oxygen species generated by AgNPs have a significant role in apoptosis. The present findings suggest that AgNPs could contribute to the development of a suitable anticancer drug, which may lead to the development of a novel nanomedicine for the treatment of cancers.

Gurunathan, Sangiliyandi; Raman, Jegadeesh; Malek, Sri Nurestri Abd; John, Priscilla A; Vikineswary, Sabaratnam

2013-01-01

178

Preparation and Cytotoxic Evaluation of Magnetite (Fe3O4) Nanoparticles on Breast Cancer Cells and its Combinatory Effects with Doxorubicin used in Hyperthermia  

PubMed Central

Background Magnetic nanoparticles in a variable magnetic field are able to produce heat. This heat (42-45°C) has more selective effect on fast dividing cancer cells than normal tissues. Methods In this work magnetite nanoparticles have been prepared via co-precipitation and phase identification was performed by powder x-ray diffraction (XRD). Magnetic parameters of the prepared nanoparticles were measured by a Vibrating Sample Magnetometer (VSM). A sensitive thermometer has been used to measure the increase of temperature in the presence of an alternating magnetic field. To evaluate the cytotoxicity of nanoparticles, the suspended magnetite nanoparticles in liquid paraffin, doxorubicin and a mixture of both were added to the MDA-MB-468 cells in separate 15 ml tubes and left either in the RT or in the magnetic field for 30 min. Cell survival was measured by trypan blue exclusion assay and flow cytometer. Particle size distribution of the nanoparticles was homogeneous with a mean particles size of 10 nm. A 15°C temperature increase was achieved in presence of an AC magnetic field after 15 min irradiation. Results Biological results showed that magnetite nanoparticles alone were not cytotoxic at RT, while in the alternative magnetic filed more than 50% of cells were dead. Doxorubicin alone was not cytotoxic during 30 min, but in combination with magnetite more than 80% of the cells were killed. Conclusion It could be concluded that doxorubicin and magnetite nanoparticles in an AC magnetic field had combinatory effects against cells.

Sadeghi-Aliabadi, Hojjat; Mozaffari, Morteza; Behdadfar, Behshid; Raesizadeh, Maryam; Zarkesh-Esfahani, Hamid

2013-01-01

179

Cytotoxicity of naphthoquinones and their capacity to generate reactive oxygen species is quenched when conjugated with gold nanoparticles.  

PubMed

Several reports have demonstrated the anticancer activities of plumbagin, a naphthoquinone derivative isolated from plants belonging to Plumbaginaceae family. However, to the best of our knowledge, there are no reports which describe gold nanoconjugation with plumbagin, even though plumbagin is considered to be a promising therapeutic agent. In this report, we demonstrate the fabrication and characterization of gold nanoparticles conjugated with plumbagin (AuPB) that can reduce the toxicity of the latter, and their capacity for cellular localization and generation of reactive oxygen species. The anticancer activity and ability of plumbagin to produce reactive oxygen species was studied and compared with that of bromoderivatives of 1,4 naphthoquinones such as 2-bromo-1,4-naphthoquinone (2-BNQ) and 2,3-dibromo-1, 4-naphthoquinone (2,3-DBNQ) and their gold nanoconjugates. Plumbagin and bromoderivatives of 1,4 naphthoquinones in the form of gold nanoconjugates showed reduced cytotoxicity and apoptosis compared with the pristine compounds, ie, plumbagin, 2-BNQ, and 2,3-DBNQ. Interestingly, we observed that the gold nanoparticles could quench the reactive oxygen species-generating capacity of plumbagin, 2-BNQ, and 2,3-BNQ, which is one of the main mechanisms of action of the naphthoquinones. Therefore, it can be concluded that conjugation with gold nanoparticles can reduce the cytotoxicity of these compounds. PMID:22114475

Srinivas, Priya; Patra, Chitta Ranjan; Bhattacharya, Santanu; Mukhopadhyay, Debabrata

2011-01-01

180

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

181

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

182

Antibacterial and cytotoxic efficacy of extracellular silver nanoparticles biofabricated from chromium reducing novel OS4 strain of Stenotrophomonas maltophilia.  

PubMed

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. PMID:23555625

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

2013-01-01

183

Uptake of gold nanoparticles in murine macrophage cells without cytotoxicity or production of pro-inflammatory mediators.  

PubMed

More information characterizing the biological responses to nanoparticles is needed to allow the U.S. Food and Drug Administration to evaluate the safety and effectiveness of products with nano-scale components. The potential cytotoxicity and inflammatory responses of Au NPs (60 nm, NIST standard reference materials) were investigated in murine macrophages. Cytotoxicity was evaluated by MTT and LDH assays. Cytokines (IL-6, TNF-?), nitric oxide, and ROS were assayed to assess inflammatory responses. Morphological appearance and localization of particles were examined by high resolution illumination microscopy, transmission electron microscopy (TEM), and scanning TEM coupled with EDX spectroscopy. Results showed no cytotoxicity and no elevated production of proinflammatory mediators; however, imaging analyses demonstrated cellular uptake of Au NPs and localization within intracellular vacuoles. These results suggest that 60 nm Au NPs, under the exposure conditions tested, are not cytotoxic, nor elicit pro-inflammatory responses. The localization of Au NPs in intracellular vacuoles suggests endosomal containment and an uptake mechanism involving endocytosis. PMID:20849214

Zhang, Qin; Hitchins, Victoria M; Schrand, Amanda M; Hussain, Saber M; Goering, Peter L

2011-09-01

184

Influence of the surface coating on the cytotoxicity, genotoxicity and uptake of gold nanoparticles in human HepG2 cells.  

PubMed

The toxicological profile of gold nanoparticles (AuNPs) remains controversial. Significant efforts to develop surface coatings to improve biocompatibility have been carried out. In vivo biodistribution studies have shown that the liver is a target for AuNPs accumulation. Therefore, we investigated the effects induced by ~20?nm spherical AuNPs (0-200??M Au) with two surface coatings, citrate (Cit) compared with 11-mercaptoundecanoic acid (11-MUA), in human liver HepG2 cells. Cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release assays after 24 to 72?h of incubation. DNA damage was assessed by the comet assay, 24?h after incubation with the capped AuNPs. Uptake and subcellular distribution of the tested AuNPs was evaluated by quantifying the gold intracellular content by graphite furnace atomic absorption spectrometry (GFAAS) and transmission electron microscopy (TEM), respectively. The obtained results indicate that both differently coated AuNPs did not induce significant cytotoxicity. An inverse concentration-dependent increase in comet tail intensity and tail moment was observed in Cit-AuNPs- but not in MUA-AuNPs-exposed cells. Both AuNPs were internalized in a concentration-dependent manner. However, no differences were found in the extent of the internalization between the two types of NPs. Electron-dense deposits of agglomerates of Cit- and MUA-AuNPs were observed either inside endosomes or in the intercellular spaces. In spite of the absence of cytotoxicity, DNA damage was observed after exposure to the lower concentrations of Cit- but not to MUA-AuNPs. Thus, our data supports the importance of the surface properties to increase the biocompatibility and safety of AuNPs. PMID:23529830

Fraga, Sónia; Faria, Helena; Soares, Maria Elisa; Duarte, José Alberto; Soares, Leonor; Pereira, Eulália; Costa-Pereira, Cristiana; Teixeira, Joăo Paulo; de Lourdes Bastos, Maria; Carmo, Helena

2013-10-01

185

Photo-Induced Cytotoxicity of Water-Soluble Fullerene  

Microsoft Academic Search

The reaction of C60 with poly(ethylene glycol) having a terminal primary amino group or a mixture of ethylene diamine and poly(ethylene glycol) having terminal carboxyl groups resulted in formation of water-soluble C60 conjugates. These conjugates showed strong cytotoxicity to L929 cells upon visible light irradiation as a result of superoxide production.

N. Nakajima; C. Nishi; F. M. Li; Y. Ikada

1996-01-01

186

Nitric Oxide Donor Doxorubicins Accumulate into Doxorubicin-Resistant Human Colon Cancer Cells Inducing Cytotoxicity  

PubMed Central

Products 4 and 5, obtained by conjugation of doxorubicin with nitric oxide (NO) donor nitrooxy and phenylsulfonyl furoxan moieties, respectively, accumulate in doxorubicin-resistant human colon cancer cells (HT29-dx), inducing high cytotoxicity. This behavior parallels the ability of the compounds to generate NO, detected as nitrite, in these cells. Preliminary immunoblotting studies suggest that the mechanism that underlies the cytotoxic effect could involve inhibition of cellular drug efflux due to nitration of tyrosine residues of the MRP3 protein pump.

2011-01-01

187

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

Microsoft Academic Search

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

Ajay Kumar Gupta; Stephen Wells

2004-01-01

188

Comparative study of the cytotoxic and genotoxic effects of titanium oxide and aluminium oxide nanoparticles in Chinese hamster ovary (CHO-K1) cells  

Microsoft Academic Search

The aim of this study was to analyze the cytotoxicity and genotoxicity of titanium oxide (TiO2) and aluminium oxide (Al2O3) nanoparticles (NPs) on Chinese hamster ovary (CHO-K1) cells using neutral red (NR), mitochondrial activity (by MTT assay), sister chromatid exchange (SCE), micronucleus (MN) formation, and cell cycle kinetics techniques. Results showed a dose-related cytotoxic effect evidenced after 24h by changes

A. L. Di Virgilio; M. Reigosa; P. M. Arnal; M. Fernández Lorenzo de Mele

2010-01-01

189

INHIBITORS OF HYDROPEROXIDE METABOLISM ENHANCE ASCORBATE-INDUCED CYTOTOXICITY  

PubMed Central

Pharmacological ascorbate, via its oxidation, has been proposed as a pro-drug for the delivery of H2O2 to tumors. Pharmacological ascorbate decreases clonogenic survival of pancreatic cancer cells, which can be reversed by treatment with scavengers of H2O2. The goal of this study was to determine if inhibitors of intracellular hydroperoxide detoxification could enhance the cytotoxic effects of ascorbate. Human pancreatic cancer cells were treated with ascorbate alone or in combination with inhibitors of hydroperoxide removal including the glutathione disulfide reductase inhibitor 1,3 bis (2-chloroethyl)-1-nitrosurea (BCNU), siRNA targeted to glutathione disulfide reductase (siGR), and 2-deoxy-D-glucose (2DG), which inhibits glucose metabolism. Changes in the intracellular concentration of H2O2 were determined by analysis of the rate of aminotriazole-mediated inactivation of endogenous catalase activity. Pharmacological ascorbate increased intracellular H2O2 and depleted intracellular glutathione. When inhibitors of H2O2 metabolism were combined with pharmacological ascorbate the increase in intracellular H2O2 was amplified and cytotoxicity was enhanced. We conclude that inclusion of agents that inhibit cellular peroxide removal produced by pharmacological ascorbate leads to changes in the intracellular redox state resulting in enhanced cytotoxicity.

Olney, Kristen E.; Du, Juan; van 't Erve, Thomas J.; Witmer, Jordan R.; Sibenaller, Zita A.; Wagner, Brett A.; Buettner, Garry R.; Cullen, Joseph J.

2013-01-01

190

The challenge to relate the physicochemical properties of colloidal nanoparticles to their cytotoxicity.  

PubMed

Nanomaterials offer opportunities to construct novel compounds for many different fields. Applications include devices for energy, including solar cells, batteries, and fuel cells, and for health, including contrast agents and mediators for photodynamic therapy and hyperthermia. Despite these promising applications, any new class of materials also bears a potential risk for human health and the environment. The advantages and innovations of these materials must be thoroughly compared against risks to evaluate each new nanomaterial. Although nanomaterials are often used intentionally, they can also be released unintentionally either inside the human body, through wearing of a prosthesis or the inhalation of fumes, or into the environment, through mechanical wear or chemical powder waste. This possibility adds to the importance of understanding potential risks from these materials. Because of fundamental differences in nanomaterials, sound risk assessment currently requires that researchers perform toxicology studies on each new nanomaterial. However, if toxicity could be correlated to the basic physicochemical properties of nanomaterials, those relationships could allow researchers to predict potential risks and design nanomaterials with minimum toxicity. In this Account we describe the physicochemical properties of nanoparticles (NPs) and how they can be determined and discuss their general importance for cytotoxicity. For simplicity, we focus primarily on in vitro toxicology that examines the interaction of living cells with engineered colloidal NPs with an inorganic core. Serious risk assessment of NPs will require additional in vivo studies. Basic physicochemical properties of nanoparticulate materials include colloidal stability, purity, inertness, size, shape, charge, and their ability to adsorb environmental compounds such as proteins. Unfortunately, the correlation of these properties with toxicity is not straightforward. First, for NPs released either unintentionally or intentionally, it can be difficult to pinpoint these properties in the materials. Therefore, researchers typically use NP models with better defined properties, which don't include the full complexity of most industrially relevant materials. In addition, many of these properties are strongly mutually connected. Therefore, it can be difficult to vary individual properties in NP models while keeping the others constant. PMID:22786674

Rivera-Gil, Pilar; Jimenez de Aberasturi, Dorleta; Wulf, Verena; Pelaz, Beatriz; del Pino, Pablo; Zhao, Yuanyuan; de la Fuente, Jesus M; Ruiz de Larramendi, Idoia; Rojo, Teófilo; Liang, Xing-Jie; Parak, Wolfgang J

2013-03-19

191

Dephosphorylation of ribosomal protein P0 in response to troglitazone-induced cytotoxicity.  

PubMed

Troglitazone (TRO)-induced cytotoxicity was investigated in HepG2 cells. The cells were exposed to TRO as well as rosiglitazone (RSG) at concentrations of 0, 25, 50 and 75 microM for 48 h. Total proteins were separated by two-dimensional electrophoresis and visualized by silver staining. We focused on a protein spot at an approximate molecular weight of 35 kDa and isoelectric point (pI) of 5.7, which appeared only with the cytotoxic concentrations (50 and 75 microM) of TRO, but not with the low concentration (25 microM) of TRO or any concentrations of RSG. This protein spot was subjected to amino acid sequence analysis and identified as ribosomal protein P0 (P0). Interestingly, without any significant induction of its protein and mRNA, P0 was dephosphorylated depending on the concentration- and time-dependent manner of TRO-induced cytotoxicity. Pretreatment with a general caspase inhibitor, Z-VAD.fmk, prevented cleavage of caspase-3 but demonstrated a slight improvement of cytotoxicity induced by TRO. Thus, these effects could not prevent the dephosphorylation of P0. Our results strongly suggest that a post-translational modification, dephosphorylation, of P0 is associated with TRO-induced cytotoxicity. PMID:16893617

Maniratanachote, Rawiwan; Minami, Keiichi; Katoh, Miki; Nakajima, Miki; Yokoi, Tsuyoshi

2006-10-25

192

The molecular mechanisms of diallyl disulfide and diallyl sulfide induced hepatocyte cytotoxicity.  

PubMed

Diallyl disulfide (DADS) and diallyl sulfide (DAS) are the major metabolites found in garlic oil and have been reported to lower cholesterol and prevent cancer. The molecular cytotoxic mechanisms of DADS and DAS have not been determined. The cytotoxic effectiveness of hydrogen versus allyl sulfides towards hepatocytes was found to be as follows: NaHS>DADS>DAS. Hepatocyte mitochondrial membrane potential was decreased and reactive oxygen species (ROS) and TBARS formation was increased by all three allyl sulfides. (1) DADS induced cytotoxicity was prevented by the H(2)S scavenger hydroxocobalamin, which also prevented cytochrome oxidase dependent mitochondrial respiration suggesting that H(2)S inhibition of cytochrome oxidase contributed to DADS hepatocyte cytotoxicity. (2) DAS cytotoxicity on the other hand was prevented by hydralazine, an acrolein trap. Hydralazine also prevented DAS induced GSH depletion, decreased mitochondrial membrane potential and increased ROS and TBARS formation. Chloral hydrate, the aldehyde dehydrogenase 2 inhibitor, however had the opposite effects, which could suggest that acrolein contributed to DAS hepatocyte cytotoxicity. PMID:19428347

Truong, D; Hindmarsh, W; O'Brien, P J

2009-06-15

193

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

194

Plasma-induced crystallization of silicon nanoparticles  

NASA Astrophysics Data System (ADS)

While the formation of nanoparticles in nonthermal plasmas is well known, the heating mechanism leading to their crystallization is poorly understood. In this study, we investigate the crystallization of amorphous silicon nanoparticles in nonthermal plasmas using a tandem plasma configuration. Amorphous silicon nanoparticles with diameters of 3, 4 or 5 nm are formed in a low-power nonthermal upstream plasma, and injected directly into a second separate downstream plasma. Crystallization of the amorphous silicon nanoparticles is investigated as a function of the power used to maintain the second plasma. This approach allows for the decoupling of nanoparticle synthesis and heating. The nanoparticle properties and plasma conditions are examined to obtain a comprehensive understanding of nanoparticle heating and crystallization. The particle crystallinity was studied using x-ray diffraction, Raman spectroscopy, and transmission electron microscopy. We discovered a threshold power for complete crystallization of the particles. A combination of comprehensive plasma characterization with a nanoparticle heating model reveals the underlying plasma physics leading to crystallization. Here we found that the nanoparticles reach temperatures as high as 750-850 K in the secondary plasma, which is well above the gas temperature and sufficient for complete nanoparticle crystallization. While we demonstrate this method of predicting nanoparticle temperature using silicon, the approach can be applied broadly to other plasma-synthesized nanomaterials.

Kramer, N. J.; Anthony, R. J.; Mamunuru, M.; Aydil, E. S.; Kortshagen, U. R.

2014-02-01

195

Effect of PEG molecular weight on stability, T2 contrast, cytotoxicity, and cellular uptake of superparamagnetic iron oxide nanoparticles (SPIONs).  

PubMed

Superparamagnetic iron oxide nanoparticles (SPIONs) are currently unavailable as MRI contrast agents for detecting atherosclerosis in the clinical setting because of either low signal enhancement or safety concerns. Therefore, a new generation of SPIONs with increased circulation time, enhanced image contrast, and less cytotoxicity is essential. In this study, monodisperse SPIONs were synthesized and coated with polyethylene glycol (PEG) of varying molecular weights. The resulting PEGylated SPIONs were characterized, and their interactions with vascular smooth muscle cells (VSMCs) were examined. SPIONs were tested at different concentrations (100 and 500ppm Fe) for stability, T2 contrast, cytotoxicity, and cellular uptake to determine an optimal formulation for in vivo use. We found that at 100ppm Fe, the PEG 2K SPIONs showed adequate stability and magnetic contrast, and exhibited the least cytotoxicity and nonspecific cellular uptake. An increase in cell viability was observed when the SPION-treated cells were washed with PBS after 1h incubation compared to 5 and 24h incubation without washing. Our investigation provides insight into the potential safe application of SPIONs in the clinic. PMID:24877593

Park, Yoonjee C; Smith, Jared B; Pham, Tuan; Whitaker, Ragnhild D; Sucato, Christopher A; Hamilton, James A; Bartolak-Suki, Elizabeth; Wong, Joyce Y

2014-07-01

196

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

197

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

198

Deficient spontaneous cell-mediated cytotoxicity and lectin-induced cellular cytotoxicity by peripheral blood mononuclear cells from Thai adults naturally infected with malaria.  

PubMed

To assess general cytotoxic effector cell capabilities by peripheral blood mononuclear cells from patients with active malaria infections, we examined antibody-dependent cellular cytotoxicity, spontaneous cell-mediated cytotoxicity, and lectin-induced cellular cytotoxicity by using human and chicken erythrocyte, Chang cell line, and K562 cell line targets. By using human erythrocyte and Change cell line targets, we found that Thai adults naturally infected with malaria had significantly impaired lectin-induced cellular cytotoxicity. In addition, spontaneous cell-mediated cytotoxicity was deficient with K562 but not with Chang cell line targets. Finally, no change in antibody-dependent cellular cytotoxicity was observed when chicken erythrocyte or Chang cell line targets were used. These observations, coupled with our previous observations of a physical loss of peripheral blood T cells, the presence of lymphocytotoxic serum antibodies, and defective T suppressor cell generation in patients with malaria, indicate that major alterations in the cellular immune system occur in patients with active malaria infections. PMID:6339549

Gilbreath, M J; Pavanand, K; MacDermott, R P; Phisphumvithi, P; Permpanich, B; Wimonwattrawatee, T

1983-02-01

199

Cytotoxicity and drug release behavior of PNIPAM grafted on silica-coated iron oxide nanoparticles  

Microsoft Academic Search

The nanoparticles containing thermosensitive and magnetic properties were investigated for their potential use as a novel\\u000a drug carrier for targeted and controlled release drug delivery system. These thermosensitive and magnetic nanoparticles were\\u000a prepared by grafting thermosensitive poly (N-isopropylacrylamide) (PNIPAM) on the surface of silica (SiO2)-coated Fe3O4 nanoparticles with the particle size of 18.8 ± 1.6 nm. Adsorption and desorption behavior of bovine serum

Yi-Hsin Lien; Tzong-Ming Wu; Jhao-Huei Wu; Jiunn-Wang Liao

200

Synthesis and cytotoxicity assessment of superparamagnetic iron–gold core–shell nanoparticles coated with polyglycerol  

Microsoft Academic Search

Core–shell iron–gold (Fe@Au) nanoparticles were synthesized by a facile reverse micelle procedure and the effect of water to surfactant molar ratio (w) on the size, size distribution and magnetic properties of the nanoparticles was studied. MTT assay was utilized to evaluate the cell toxicity of the nanoparticles. To functionalize the particles for MRI imaging and targeted drug delivery, the particles

T. Jafari; A. Simchi; N. Khakpash

2010-01-01

201

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

2013-04-01

202

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

203

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

204

Schisandra fructus extract ameliorates doxorubicin-induce cytotoxicity in cardiomyocytes: altered gene expression for detoxification enzymes  

Microsoft Academic Search

The effect of Schisandra fructus extract (SFE) on doxorubicin (Dox)-induced cardiotoxicity was investigated in H9c2 cardiomyocytes. Dox, which is an antineoplastic\\u000a drug known to induce cardiomyopathy possibly through production of reactive oxygen species, induced significant cytotoxicity,\\u000a intracellular reactive oxygen species (ROS), and lipid peroxidation. SFE treatment significantly increased cell survival up\\u000a to 25%, inhibited intracellular ROS production in a time-

Eun Hye Choi; Nari Lee; Hyun Jung Kim; Mi Kyung Kim; Sung-Gil Chi; Dae Young Kwon; Hyang Sook Chun

2008-01-01

205

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

NASA Astrophysics Data System (ADS)

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.

Nabeshi, Hiromi; Yoshikawa, Tomoaki; Akase, Takanori; Yoshida, Tokuyuki; Tochigi, Saeko; Hirai, Toshiro; Uji, Miyuki; Ichihashi, Ko-Ichi; Yamashita, Takuya; Higashisaka, Kazuma; Morishita, Yuki; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-Ichi; Itoh, Norio; Yoshioka, Yasuo; Tsutsumi, Yasuo

2011-07-01

206

Serine protease HtrA1 modulates chemotherapy-induced cytotoxicity.  

PubMed

Resistance to chemotherapy presents a serious challenge in the successful treatment of various cancers and is mainly responsible for mortality associated with disseminated cancers. Here we show that expression of HtrA1, which is frequently downregulated in ovarian cancer, influences tumor response to chemotherapy by modulating chemotherapy-induced cytotoxicity. Downregulation of HtrA1 attenuated cisplatin- and paclitaxel-induced cytotoxicity, while forced expression of HtrA1 enhanced cisplatin- and paclitaxel-induced cytotoxicity. HtrA1 expression was upregulated by both cisplatin and paclitaxel treatment. This upregulation resulted in limited autoproteolysis and activation of HtrA1. Active HtrA1 induces cell death in a serine protease-dependent manner. The potential role of HtrA1 as a predictive factor of clinical response to chemotherapy was assessed in both ovarian and gastric cancer patients receiving cisplatin-based regimens. Patients with ovarian or gastric tumors expressing higher levels of HtrA1 showed a higher response rate compared with those with lower levels of HtrA1 expression. These findings uncover what we believe to be a novel pathway by which serine protease HtrA1 mediates paclitaxel- and cisplatin-induced cytotoxicity and suggest that loss of HtrA1 in ovarian and gastric cancers may contribute to in vivo chemoresistance. PMID:16767218

Chien, Jeremy; Aletti, Giovanni; Baldi, Alfonso; Catalano, Vincenzo; Muretto, Pietro; Keeney, Gary L; Kalli, Kimberly R; Staub, Julie; Ehrmann, Michael; Cliby, William A; Lee, Yean Kit; Bible, Keith C; Hartmann, Lynn C; Kaufmann, Scott H; Shridhar, Viji

2006-07-01

207

Evaluation of pulsed laser ablation in liquids generated gold nanoparticles as novel transfection tools: efficiency and cytotoxicity  

NASA Astrophysics Data System (ADS)

Varying transfection efficiencies and cytotoxicity are crucial aspects in cell manipulation. The utilization of gold nanoparticles (AuNP) has lately attracted special interest to enhance transfection efficiency. Conventional AuNP are usually generated by chemical reactions or gas pyrolysis requiring often cell-toxic stabilizers or coatings to conserve their characteristics. Alternatively, stabilizer- and coating-free, highly pure, colloidal AuNP can be generated by pulsed laser ablation in liquids (PLAL). Mammalian cells were transfected efficiently by addition of PLAL-AuNP, but data systematically evaluating the cell-toxic potential are lacking. Herein, the transfection efficiency and cytotoxicity of PLAL AuNP was evaluated by transfection of a mammalian cell line with a recombinant HMGB1/GFP DNA expression vector. Different methods were compared using two sizes of PLAL-AuNP, commercialized AuNP, two magnetic NP-based protocols and a conventional transfection reagent (FuGENE HD; FHD). PLAL-AuNP were generated using a Spitfire Pro femtosecond laser system delivering 120 fs laser pulses at a wavelength of 800 nm focusing the fs-laser beam on a 99.99% pure gold target placed in ddH2O. Transfection efficiencies were analyzed after 24h using fluorescence microscopy and flow cytometry. Toxicity was assessed measuring cell proliferation and percentage of necrotic, propidium iodide positive cells (PI %). The addition of PLAL-AuNP significantly enhanced transfection efficiencies (FHD: 31 %; PLAL-AuNP size-1: 46 %; size-2: 50 %) with increased PI% but no reduced cell proliferation. Commercial AuNP-transfection showed significantly lower efficiency (23 %), slightly increased PI % and reduced cell proliferation. Magnetic NP based methods were less effective but showing also lowest cytotoxicity. In conclusion, addition of PLAL-AuNP provides a novel tool for transfection efficiency enhancement with acceptable cytotoxic side-effects.

Willenbrock, Saskia; Durán, María. Carolina; Barchanski, Annette; Barcikowski, Stephan; Feige, Karsten; Nolte, Ingo; Murua Escobar, Hugo

2014-03-01

208

Mucin secretion induced by titanium dioxide nanoparticles.  

PubMed

Nanoparticle (NP) exposure has been closely associated with the exacerbation and pathophysiology of many respiratory diseases such as Chronic Obstructive Pulmonary Disease (COPD) and asthma. Mucus hypersecretion and accumulation in the airway are major clinical manifestations commonly found in these diseases. Among a broad spectrum of NPs, titanium dioxide (TiO(2)), one of the PM10 components, is widely utilized in the nanoindustry for manufacturing and processing of various commercial products. Although TiO(2) NPs have been shown to induce cellular nanotoxicity and emphysema-like symptoms, whether TiO(2) NPs can directly induce mucus secretion from airway cells is currently unknown. Herein, we showed that TiO(2) NPs (<75 nm) can directly stimulate mucin secretion from human bronchial ChaGo-K1 epithelial cells via a Ca(2+) signaling mediated pathway. The amount of mucin secreted was quantified with enzyme-linked lectin assay (ELLA). The corresponding changes in cytosolic Ca(2+) concentration were monitored with Rhod-2, a fluorescent Ca(2+) dye. We found that TiO(2) NP-evoked mucin secretion was a function of increasing intracellular Ca(2+) concentration resulting from an extracellular Ca(2+) influx via membrane Ca(2+) channels and cytosolic ER Ca(2+) release. The calcium-induced calcium release (CICR) mechanism played a major role in further amplifying the intracellular Ca(2+) signal and in sustaining a cytosolic Ca(2+) increase. This study provides a potential mechanistic link between airborne NPs and the pathoetiology of pulmonary diseases involving mucus hypersecretion. PMID:21283816

Chen, Eric Y T; Garnica, Maria; Wang, Yung-Chen; Chen, Chi-Shuo; Chin, Wei-Chun

2011-01-01

209

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

2012-06-15

210

Role of surface charge and oxidative stress in cytotoxicity of organic monolayer-coated silicon nanoparticles towards macrophage NR8383 cells  

Microsoft Academic Search

BACKGROUND: Surface charge and oxidative stress are often hypothesized to be important factors in cytotoxicity of nanoparticles. However, the role of these factors is not well understood. Hence, the aim of this study was to systematically investigate the role of surface charge, oxidative stress and possible involvement of mitochondria in the production of intracellular reactive oxygen species (ROS) upon exposure

Sourav Bhattacharjee; Laura HJ de Haan; Nynke M Evers; Xue Jiang; Antonius TM Marcelis; Han Zuilhof; Ivonne MCM Rietjens; Gerrit M Alink

2010-01-01

211

Cytotoxic and apoptosis-inducing activities of limonoids from the seeds of Azadirachta indica (neem).  

PubMed

Thirty-five limonoids, including 15 of the azadiradione type (1-15), five of the gedunin type (16-20), four of the azadirachtin type (21-24), nine of the nimbin type (25-33), and two degraded limonoids (34, 35), isolated from Azadirachta indica seed extracts, were evaluated for their cytotoxic activities against five human cancer cell lines. Seven compounds (3, 6, 7, 16, 18, 28, and 29) exhibited cytotoxic activity against one or more cell lines. Among these compounds, 7-deacetyl-7-benzoylepoxyazadiradione (7), 7-deacetyl-7-benzoylgeduin (18), and 28-deoxonimbolide (28) exhibited potent cytotoxic activity against HL60 leukemia cells with IC(50) values in the range 2.7-3.1 ?M. Compounds 7, 18, and 28 induced early apoptosis in HL60 cells, observed by flow cytometry. Western blot analysis showed that compounds 7, 18, and 28 activated caspases-3, -8, and -9 in HL60 cells. This suggested that compounds 7, 18, and 28 induced apoptotic cell death in HL60 cells via both the mitochondrial- and the death receptor-mediated pathways. Futhermore, compound 7 was shown to possess high selective cytotoxicity for leukemia cells since it exhibited only weak cytotoxicity against a normal lymphocyte cell line (RPMI 1788). PMID:21381696

Kikuchi, Takashi; Ishii, Koichi; Noto, Taisuke; Takahashi, Akitomo; Tabata, Keiichi; Suzuki, Takashi; Akihisa, Toshihiro

2011-04-25

212

Parameters of Reserpine Analogs That Induce MSH2/MSH6-Dependent Cytotoxic Response  

PubMed Central

Mismatch repair proteins modulate the cytotoxicity of several chemotherapeutic agents. We have recently proposed a “death conformation” of the MutS homologous proteins that is distinguishable from their “repair conformation.” This conformation can be induced by a small molecule, reserpine, leading to DNA-independent cell death. We investigated the parameters for a small reserpine-like molecule that are required to interact with MSH2/MSH6 to induce MSH2/MSH6-dependent cytotoxic response. A multidisciplinary approach involving structural modeling, chemical synthesis, and cell biology analyzed reserpine analogs and modifications. We demonstrate that the parameters controlling the induction of MSH2/MSH6-dependent cytotoxicity for reserpine-analogous molecules reside in the specific requirements for methoxy groups, the size of the molecule, and the orientation of molecules within the protein-binding pocket. Reserpine analog rescinnamine showed improved MSH2-dependent cytotoxicity. These results have important implications for the identification of compounds that require functional MMR proteins to exhibit their full cytotoxicity, which will avoid resistance in MMR-deficient cells.

Vasilyeva, Aksana; Clodfelter, Jill E.; Gorczynski, Michael J.; Gerardi, Anthony R.; King, S. Bruce; Salsbury, Freddie; Scarpinato, Karin D.

2010-01-01

213

Parameters of Reserpine Analogs That Induce MSH2/MSH6-Dependent Cytotoxic Response.  

PubMed

Mismatch repair proteins modulate the cytotoxicity of several chemotherapeutic agents. We have recently proposed a "death conformation" of the MutS homologous proteins that is distinguishable from their "repair conformation." This conformation can be induced by a small molecule, reserpine, leading to DNA-independent cell death. We investigated the parameters for a small reserpine-like molecule that are required to interact with MSH2/MSH6 to induce MSH2/MSH6-dependent cytotoxic response. A multidisciplinary approach involving structural modeling, chemical synthesis, and cell biology analyzed reserpine analogs and modifications. We demonstrate that the parameters controlling the induction of MSH2/MSH6-dependent cytotoxicity for reserpine-analogous molecules reside in the specific requirements for methoxy groups, the size of the molecule, and the orientation of molecules within the protein-binding pocket. Reserpine analog rescinnamine showed improved MSH2-dependent cytotoxicity. These results have important implications for the identification of compounds that require functional MMR proteins to exhibit their full cytotoxicity, which will avoid resistance in MMR-deficient cells. PMID:20936178

Vasilyeva, Aksana; Clodfelter, Jill E; Gorczynski, Michael J; Gerardi, Anthony R; King, S Bruce; Salsbury, Freddie; Scarpinato, Karin D

2010-01-01

214

Role of Bim in diallyl trisulfide-induced cytotoxicity in human cancer cells  

PubMed Central

The aim of this study was to investigate the effect of garlic constituent diallyl trisulfide (DATS) on the cell death signaling pathway in a human breast cell line (MDA-MB-231). We observed that DATS (10–100 ?M) treatment resulted in a dose- and time-dependent cytotoxicity. Treatment of MDA-MB-231 cells with a cytotoxicity inducing concentration of DATS (50–80 ?M) resulted in an increase in the intracellular level of reactive oxygen species (ROS). Data from assay with MitoSOX™ Red reagent suggest that mitochondria are the main source of ROS generation during DATS treatment. DATS-induced oxidative stress was detected through glutaredoxin (GRX), a redox-sensing molecule, and subsequently GRX was dissociated from apoptosis signal-regulating kinase 1 (ASK1). Dissociation of GRX from ASK1 resulted in the activation of ASK1. ASK1 activated a downstream signal transduction JNK (C-Jun N-terminal kinase)-Bim pathway. SP600125, a JNK inhibitor, inhibited DATS-induced Bim phosphorylation and protected cells from DATS-induced cytotoxicity. Our results indicate that the cytotoxicity caused by DATS is mediated by the generation of ROS and subsequent activation of the ASK1-JNK-Bim signal transduction pathway in human breast carcinoma MDA-MB-231 cells.

Lee, Byeong-Chel; Park, Bae-Hang; Kim, Seog-Young; Lee, Yong J.

2010-01-01

215

Comparison of the cytotoxicity induced by different exposure to sodium arsenite in two fish cell lines  

Microsoft Academic Search

Arsenic, a common environmental pollutant, is toxic to many mammalian cells. However, the arsenic-induced toxicity to aquatic animal species is unclear. This study attempted to compare the arsenic-induced cytotoxicity in various fish cells. Two fish cell lines, JF (fin cells of Therapon jarbua) and TO-2 cells (ovary cells of Tilapia), were treated with sodium arsenite in two ways to mimic

Yu-Chieh Wang; Ren-Haw Chaung; Li-Chu Tung

2004-01-01

216

Enhanced effector function of cytotoxic cells in the induced sputum of COPD patients  

Microsoft Academic Search

BACKGROUND: We have previously shown that NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells are reduced in both numbers and cytotoxicity in peripheral blood. The aim of the present study was to investigate their numbers and function within induced sputum. METHODS: Induced sputum cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry. Immunomagnetically selected CD56+ cells (NK and

Richard A Urbanowicz; Jonathan R Lamb; Ian Todd; Jonathan M Corne; Lucy C Fairclough

2010-01-01

217

Lipid molecules induce the cytotoxic aggregation of Cu/Zn superoxide dismutase with structurally disordered regions.  

PubMed

Cu/Zn-superoxide dismutase (SOD1) is present in the cytosol, nucleus, peroxisomes and mitochondrial intermembrane space of human cells. More than 114 variants of human SOD1 have been linked to familial amyotrophic lateral sclerosis (ALS), which is also known as Lou Gehrig's disease. Although the ultimate mechanisms underlying SOD1-mediated cytotoxicity are largely unknown, SOD1 aggregates have been strongly implicated as a common feature in ALS. This study examined the mechanism for the formation of SOD1 aggregates in vitro as well as the nature of its cytotoxicity. The aggregation propensity of SOD1 species was investigated using techniques ranging from circular dichroism spectroscopy to fluorescence dye binding methods, as well as electron microscopic imaging. The aggregation of SOD1 appears to be related to its structural instability. The demetallated (apo)-SOD1 and aggregated SOD1 species, with structurally disordered regions, readily undergo aggregation in the presence of lipid molecules, whereas metallated (holo)-SOD1 does not. The majority of aggregated SOD1s that are induced by lipid molecules have an amorphous morphology and exhibit significant cytotoxicity. The lipid binding propensity of SOD1 was found to be closely related to the changes in surface hydrophobicity of the proteins, even at very low levels, which induced further binding and assembly with lipid molecules. These findings suggest that lipid molecules induce SOD1 aggregation under physiological conditions and exert cytotoxicity, and might provide a possible mechanism for the pathogenesis of ALS. PMID:20837142

Choi, Inhee; Yang, Young In; Song, Hyeon Don; Lee, Jeong Seon; Kang, Taewook; Sung, Jung-Joon; Yi, Jongheop

2011-01-01

218

The decrease of PAMAM dendrimer-induced cytotoxicity by PEGylation via attenuation of oxidative stress  

NASA Astrophysics Data System (ADS)

Due to their unique structure, poly(amidoamine) (PAMAM) dendrimers have been widely used in medical applications. However, PAMAM dendrimers bearing amino terminals show certain cytotoxicity. In order to improve their biocompatibility, we modified Generation-5 PAMAM dendrimers by conjugating them with poly(ethylene glycol) (PEG) of two different molecular weights and different number of chains. The IC50 values of PEGylated dendrimers were 12-105 fold higher than those of PAMAM dendrimers. To investigate the influence of PEGylation on PAMAM-induced cytotoxicity, the intracellular responses, reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), and apoptosis were examined. The results indicated that conjugation with PEG could effectively reduce the PAMAM-induced cell apoptosis by attenuating the ROS production and inhibiting PAMAM-induced MMP collapse. Meanwhile, dendrimers conjugated with less PEG of lower molecular weight did not significantly change the endocytic properties. Dendrimers conjugated with more PEG of higher molecular weight were much less cytotoxic. This study provided a novel insight into the effects of PEGylation on the decrease of cytotoxicity at the molecular level.

Wang, Wei; Xiong, Wei; Wan, Jiangling; Sun, Xiaohui; Xu, Huibi; Yang, Xiangliang

2009-03-01

219

Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model.  

PubMed

Drug-induced hepatotoxicity is a major reason for withdrawal of drugs from development as well as from the market. A major problem predicting hepatotoxicity is the lack of suitable predictive in vitro system. Drug-induced hepatotoxicity is usually associated with the recruitment of immune cells to the liver accelerating an inflammatory response often initiated by activation of the Kupffer cells. In order to evaluate whether the introduction of inflammatory cells could increase the sensitivity for drug-induced cytotoxicity we developed an in vitro co-culture system based on two human cell lines; a hepatoma (Huh-7) and monocytic (THP-1) cell line. As model drugs we chose two peroxisome proliferator activated receptor gamma (PPAR gamma) agonists, the hepatotoxic troglitazone and the non-hepatotoxic rosiglitazone. In the co-cultures, troglitazone caused an enhanced cytotoxicity as compared to single cultures of either cell line, whereas little cytotoxicity was seen after treatment with rosiglitazone. Troglitazone treatment increased gene expression of pro-inflammatory mediators and stress-related genes in both cell types, which in general was more pronounced in co-cultures than in single cell cultures. Based on these results we suggest that co-cultures of human hepatoma cells and monocytes might provide an important in vitro system for better prediction of cytotoxicity mediated by potential hepatotoxins. PMID:19631733

Edling, Ylva; Sivertsson, Louise K; Butura, Angelica; Ingelman-Sundberg, Magnus; Ek, Monica

2009-10-01

220

Antioxidants and herbal extracts protect HT-4 neuronal cells against glutamate-induced cytotoxicity.  

PubMed

Antioxidant therapy has been shown to be beneficial in neurological disorders including Alzheimer's disease and cerebral ischemia. Glutamate-induced cytotoxicity in HT-4 neuronal cells has been previously demonstrated to be due to oxidative stress caused by depletion of cellular glutathione (GSH). The present study demonstrates that a wide variety of antioxidants inhibit glutamate-induced cytotoxicity in HT-4 neuronal cells. Low concentrations of alpha-tocopherol and its analogs were highly effective in protecting neuronal cells against cytotoxicity. Purified flavonoids and herbal extracts of Gingko biloba (EGb 761) and French maritime pine bark (Pycnogenol) were also effective. We have previously shown that pro-glutathione agents can spare GSH and protect cells from glutamate insult in a C6 glial cell model. The protective effects of nonthiol-based antioxidants tested in the HT-4 line were not mediated via GSH level modulation. In contrast, protective effects of thiol-based pro-glutathione agents alpha-lipoic acid (LA) and N-acetyl cysteine (NAC) corresponded with a sparing effect on GSH levels in glutamate-treated HT-4 cells. Glutamate-induced cytotoxicity in HT-4 cells is a useful model system for testing compounds or mixtures for antioxidant activity. PMID:10653482

Kobayashi, M S; Han, D; Packer, L

2000-02-01

221

Digitoxin-induced cytotoxicity in cancer cells is mediated through distinct kinase and interferon signaling networks.  

PubMed

Cardiac glycosides (e.g., digoxin, digitoxin) constitute a diverse family of plant-derived sodium pump inhibitors that have been in clinical use for the treatment of heart-related diseases (congestive heart failure, atrial arrhythmia) for many years. Recently though, accumulating in vitro and in vivo evidence highlight potential anticancer properties of these compounds. Despite the fact that members of this family have advanced to clinical trial testing in cancer therapeutics, their cytotoxic mechanism is not yet elucidated. In this study, we investigated the cytotoxic properties of cardiac glycosides against a panel of pancreatic cancer cell lines, explored their apoptotic mechanism, and characterized the kinetics of cell death induced by these drugs. Furthermore, we deployed a high-throughput kinome screening approach and identified several kinases of the Na-K-ATPase-mediated signal transduction circuitry (epidermal growth factor receptor, Src, pkC, and mitogen-activated protein kinases) as important mediators downstream of cardiac glycoside cytotoxic action. To further extend our knowledge on their mode of action, we used mass-spectrometry-based quantitative proteomics (stable isotope labeling of amino acids in cell culture) coupled with bioinformatics to capture large-scale protein perturbations induced by a physiological dose of digitoxin in BxPC-3 pancreatic cancer cells and identified members of the interferon family as key regulators of the main protein/protein interactions downstream of digitoxin action. Hence, our findings provide more in-depth information regarding the molecular mechanisms underlying cardiac glycoside-induced cytotoxicity. PMID:21859838

Prassas, Ioannis; Karagiannis, George S; Batruch, Ihor; Dimitromanolakis, Apostolos; Datti, Alessandro; Diamandis, Eleftherios P

2011-11-01

222

Feselol enhances the cytotoxicity and DNA damage induced by cisplatin in 5637 cells.  

PubMed

Transitional cell carcinoma (TCC), which is the most common type of bladder cancer, shows resistance to chemotherapeutic agents due to the overexpression of drug efflux pumps. In this study, the effects of feselol, a sesquiterpene coumarin extracted from Ferula badrakema, on cisplatin cytotoxicity were investigated in 5637 cells, a TCC subline. Cell viability and DNA lesion were evaluated by thiazolyl blue tetrazolium bromide and comet assays, respectively. Feselol had no significant cytotoxic effect in 5637 cells but at 32 microg/mL it increased the cytotoxicity of 1 microg/mL cisplatin by 37% after 24 h. Furthermore, the comet assay revealed that DNA damage induced by cisplatin in 5637 cells is enhanced by 31% when used in combination with feselol. Therefore, feselol might be considered as an effective reversal agent for future in vivo and clinical studies. PMID:22351980

Mollazadeh, Samaneh; Matin, Maryam M; Bahrami, Ahmad Reza; Iranshahi, Mehrdad; Behnam-Rassouli, Morteza; Rassouli, Fatemeh B; Neshati, Vajiheh

2011-01-01

223

Radiation-induced differential optical absorption of metal nanoparticles  

NASA Astrophysics Data System (ADS)

A method of measuring the temperature of metal nanoparticles under ion bombardment is proposed. Optical absorption in the range of the surface plasmon resonance of metal nanoparticles was measured during implantation of 3 MeV Cu2+ ions into silica glass to derive a difference in optical absorption between beam on and off regimes. The radiation-induced differential (RD) spectra were similar to the spectra of thermomodulation (TM) and quite different from the spectra of nonlinear optical response measured by the pump-probe method. Increasing amplitude of RD and TM spectra was assigned to an increase of lattice temperature of Cu nanoparticles.

Plaksin, Oleg; Takeda, Yoshihiko; Amekura, Hiroshi; Kishimoto, Naoki

2006-05-01

224

Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles  

PubMed Central

Gold nanoparticles (Au NPs) are used in many fields, including biomedical applications; however, no conclusive information on their potential cytotoxicity and genotoxicity mechanisms is available. For this reason, experiments in human primary lymphocytes and murine macrophages (Raw264.7) were performed exposing cells to spherical citrate-capped Au NPs with two different nominal diameters (5 nm and 15 nm). The proliferative activity, mitotic, apoptotic, and necrotic markers, as well as chromosomal damage were assessed by the cytokinesis-block micronucleus cytome assay. Fluorescence in situ hybridization with human and murine pancentromeric probes was applied to distinguish between clastogenic and aneuploidogenic effects. Our results indicate that 5 nm and 15 nm Au NPs are able to inhibit cell proliferation by apoptosis and to induce chromosomal damage, in particular chromosome mis-segregation. DNA strand breaks were detected by comet assay, and the modified protocol using endonuclease-III and formamidopyrimidine-DNA glycosylase restriction enzymes showed that pyrimidines and purines were oxidatively damaged by Au NPs. Moreover, we show a size-independent correlation between the cytotoxicity of Au NPs and their tested mass concentration or absolute number, and genotoxic effects which were more severe for Au NP 15 nm compared to Au NP 5 nm. Results indicate that apoptosis, aneuploidy, and DNA oxidation play a pivotal role in the cytotoxicity and genotoxicity exerted by Au NPs in our cell models.

Di Bucchianico, Sebastiano; Fabbrizi, Maria Rita; Cirillo, Silvia; Uboldi, Chiara; Gilliland, Douglas; Valsami-Jones, Eugenia; Migliore, Lucia

2014-01-01

225

Rapid green synthesis of silver nanoparticles from Chrysanthemum indicum L and its antibacterial and cytotoxic effects: an in vitro study.  

PubMed

The present work reports a simple, cost-effective, and ecofriendly method for the synthesis of silver nanoparticles (AgNPs) using Chrysanthemum indicum and its antibacterial and cytotoxic effects. The formation of AgNPs was confirmed by color change, and it was further characterized by ultraviolet-visible spectroscopy (435 nm). The phytochemical screening of C. indicum revealed the presence of flavonoids, terpenoids, and glycosides, suggesting that these compounds act as reducing and stabilizing agents. The crystalline nature of the synthesized particles was confirmed by X-ray diffraction, as they exhibited face-centered cubic symmetry. The size and morphology of the particles were characterized by transmission electron microscopy, which showed spherical shapes and sizes that ranged between 37.71-71.99 nm. Energy-dispersive X-ray spectroscopy documented the presence of silver. The antimicrobial effect of the synthesized AgNPs revealed a significant effect against the bacteria Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Additionally, cytotoxic assays showed no toxicity of AgNPs toward 3T3 mouse embryo fibroblast cells (25 ?g/mL); hence, these particles were safe to use. PMID:24426782

Arokiyaraj, Selvaraj; Arasu, Mariadhas Valan; Vincent, Savariar; Prakash, Nyayirukannaian Udaya; Choi, Seong Ho; Oh, Young-Kyoon; Choi, Ki Choon; Kim, Kyoung Hoon

2014-01-01

226

Rapid green synthesis of silver nanoparticles from Chrysanthemum indicum L and its antibacterial and cytotoxic effects: an in vitro study  

PubMed Central

The present work reports a simple, cost-effective, and ecofriendly method for the synthesis of silver nanoparticles (AgNPs) using Chrysanthemum indicum and its antibacterial and cytotoxic effects. The formation of AgNPs was confirmed by color change, and it was further characterized by ultraviolet–visible spectroscopy (435 nm). The phytochemical screening of C. indicum revealed the presence of flavonoids, terpenoids, and glycosides, suggesting that these compounds act as reducing and stabilizing agents. The crystalline nature of the synthesized particles was confirmed by X-ray diffraction, as they exhibited face-centered cubic symmetry. The size and morphology of the particles were characterized by transmission electron microscopy, which showed spherical shapes and sizes that ranged between 37.71–71.99 nm. Energy-dispersive X-ray spectroscopy documented the presence of silver. The antimicrobial effect of the synthesized AgNPs revealed a significant effect against the bacteria Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Additionally, cytotoxic assays showed no toxicity of AgNPs toward 3T3 mouse embryo fibroblast cells (25 ?g/mL); hence, these particles were safe to use.

Arokiyaraj, Selvaraj; Arasu, Mariadhas Valan; Vincent, Savariar; Prakash, Nyayirukannaian Udaya; Choi, Seong Ho; Oh, Young-Kyoon; Choi, Ki Choon; Kim, Kyoung Hoon

2014-01-01

227

Cytotoxicity, oxidative stress and expression of adhesion molecules in human umbilical vein endothelial cells exposed to dust from paints with or without nanoparticles.  

PubMed

Nanoparticles in primary form and nanoproducts might elicit different toxicological responses. We compared paint-related nanoparticles with respect to effects on endothelial oxidative stress, cytotoxicity and cell adhesion molecule expression. Primary human umbilical vein endothelial cells were exposed to primary nanoparticles (fine, photocatalytic or nanosized TiO(2), aluminium silicate, carbon black, nano-silicasol or axilate) and dust from sanding reference- or nanoparticle-containing paints. Most of the samples increased cell surface expressions of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1), but paint sanding dust samples generally generated less response than primary particles of TiO(2) and carbon black. We found no relationship between the expression of adhesion molecules, cytotoxicity and production of reactive oxygen species. In conclusion, sanding dust from nanoparticle-containing paint did not generate more oxidative stress or expression of cell adhesion molecules than sanding dust from paint without nanoparticles, whereas the primary particles had the largest effect on mass basis. PMID:22263546

Mikkelsen, Lone; Jensen, Keld A; Koponen, Ismo K; Saber, Anne T; Wallin, Hĺkan; Loft, Steffen; Vogel, Ulla; Mřller, Peter

2013-03-01

228

Cerium doping and stoichiometry control for biomedical use of La0.7Sr0.3MnO3 nanoparticles: microwave absorption and cytotoxicity study.  

PubMed

La0.7Sr0.3MnO3 nanoparticles doped with cerium (La0.7-xCe(x)Sr0.3MnO3 where 0 < or = x < or = 0.7) as well as the La(1-y)Sr(y)MnO3 nanoparticles with different values of y (La/Sr ratio) are evaluated for cytotoxicity and heating application. Considering hyperthermia as one of the possible application domains of such materials, the cytotoxicity studies were done on human skin carcinoma and human fibrosarcoma cell lines. All the samples showed the desired heating effect when subjected to high-frequency exposure at 2.45 GHz. Cytotoxicity studies revealed extremely low cytotoxicity in Ce-doped samples as well as in samples with a reduced La/Sr ratio. A maximum percentage cell viability on exposure to these nanoparticles was 95% and 85% for the two groups of samples, respectively, with a dose of 20 microg/mL for the x = 0.4 sample. The issues of dopant solubility and nonstoichiometry are discussed. PMID:17292146

Kale, Sangeeta N; Arora, Sumit; Bhayani, Kavita R; Paknikar, Kishore M; Jani, Mona; Wagh, Ulhas V; Kulkarni, Shailaja D; Ogale, Satish B

2006-12-01

229

Epigallocatechin-3-gallate (EGCG)-Stabilized Selenium Nanoparticles Coated with Tet-1 Peptide To Reduce Amyloid-? Aggregation and Cytotoxicity.  

PubMed

Alzheimer's disease (AD), the most common neurodegenerative disease, is caused by an accumulation of amyloid-? (A?) plaque deposits in the brains. Evidence is increasingly showing that epigallocatechin-3-gallate (EGCG) can partly protect cells from A?-mediated neurotoxicity by inhibiting A? aggregation. In order to better understand the process of A? aggregation and amyloid fibril disaggregation and reduce the cytotoxicity of EGCG at high doses, we attached EGCG onto the surface of selenium nanoparticles (EGCG@Se). Given the low delivery efficiency of EGCG@Se to the targeted cells and the involvement of selenoprotein in antioxidation and neuroprotection, which are the key factors for preventing the onset and progression of AD, we synthesized EGCG-stabilized selenium nanoparticles coated with Tet-1 peptide (Tet-1-EGCG@Se, a synthetic selenoprotein analogue), considering the affinity of Tet-1 peptide to neurons. We revealed that Tet-1-EGCG@Se can effectively inhibit A? fibrillation and disaggregate preformed A? fibrils into nontoxic aggregates. In addition, we found that both EGCG@Se and Tet-1-EGCG@Se can label A? fibrils with a high affinity, and Tet-1 peptides can significantly enhance the cellular uptake of Tet-1-EGCG@Se in PC12 cells rather than in NIH/3T3 cells. PMID:24758520

Zhang, Jingnan; Zhou, Xianbo; Yu, Qianqian; Yang, Licong; Sun, Dongdong; Zhou, Yanhui; Liu, Jie

2014-06-11

230

Cytokine release and cytotoxicity in human keratinocytes and fibroblasts induced by phenols and sodium dodecyl sulfate.  

PubMed

Phenolic compounds used in pharmaceutical and industrial products can cause irritant contact dermatitis. We studied the effects of resorcinol, phenol, 3,5-xylenol, chloroxylenol, and 4-hexyl-resorcinol on normal human epidermal keratinocytes and dermal fibroblasts for cytotoxicity and cytokine release, determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide methodology and enzyme-linked immunosorbent assay, respectively. An inverse correlation between phenol concentrations causing a 50% reduction in keratinocyte and fibroblast viability at 24 h and their octanol water-partition coefficients (i.e., hydrophobicity) was observed. 3,5-xylenol, chloroxylenol, hexyl-resorcinol, and sodium dodecyl sulfate, but not resorcinol or phenol, induced release of interleukin-1alpha from keratinocytes at cytotoxic concentrations. Variable release of tumor necrosis factor-alpha and interleukin-8 from keratinocytes occurred only at toxic threshold concentrations of the phenols or sodium dodecyl sulfate. Subtoxic concentrations of phenols or sodium dodecyl sulfate did not induce cytokine release from keratinocytes. Neither the phenols nor sodium dodecyl sulfate induced release of the chemokines interleukin-8, growth-related oncogene-alpha or monocyte chemotactic protein-1 from fibroblasts. Conditioned media from keratinocytes treated with cytotoxic concentrations of 3,5-xylenol, chloroxylenol, hexyl-resorcinol, or sodium dodecyl sulfate stimulated further release of the chemokines from fibroblasts above that obtained with control media. Rabbit anti-interleukin-1alpha serum inhibited keratinocyte-conditioned media induction of chemokine release. We have shown a structure-cytotoxicity relationship for a series of phenols as well as an association of interleukin-1alpha release with a cytotoxic effect. We demonstrated a cytokine cascade amplification step by the actions of stimulated keratinocyte media on cultured dermal fibroblasts, identifying interleukin-1alpha as the principal initiator of chemokine synthesis. PMID:10951249

Newby, C S; Barr, R M; Greaves, M W; Mallet, A I

2000-08-01

231

Cationic Antimicrobial Peptides and Biogenic Silver Nanoparticles Kill Mycobacteria without Eliciting DNA Damage and Cytotoxicity in Mouse Macrophages  

PubMed Central

With the emergence of multidrug-resistant mycobacterial strains, better therapeutic strategies are required for the successful treatment of the infection. Although antimicrobial peptides (AMPs) and silver nanoparticles (AgNPs) are becoming one of the popular antibacterial agents, their antimycobacterial potential is not fully evaluated. In this study, we synthesized biogenic-silver nanoparticles using bacterial, fungal, and plant biomasses and analyzed their antibacterial activities in combination with AMPs against mycobacteria. Mycobacterium smegmatis was found to be more susceptible to AgNPs compared to M. marinum. We found that NK-2 showed enhanced killing effect with NP-1 and NP-2 biogenic nanoparticles at a 0.5-ppm concentration, whereas LLKKK-18 showed antibacterial activity only with NP-2 at 0.5-ppm dose against M. smegmatis. In case of M. marinum NK-2 did not show any additive activity with NP-1 and NP-2 and LLKKK-18 alone completely inhibited the bacterial growth. Both NP-1 and NP-2 also showed increased killing of M. smegmatis in combination with the antituberculosis drug rifampin. The sizes and shapes of the AgNPs were determined by transmission electron microscopy and dynamic light scattering. AgNPs showed no cytotoxic or DNA damage effects on macrophages at the mycobactericidal dose, whereas treatment with higher doses of AgNPs caused toxicity and micronuclei formation in cytokinesis blocked cells. Macrophages actively endocytosed fluorescein isothiocyanate-labeled AgNPs resulting in nitric oxide independent intracellular killing of M. smegmatis. Apoptosis and cell cycle studies showed that treatment with higher dose of AgNPs arrested macrophages at the G1-phase. In summary, our data suggest the combined effect of biogenic-AgNPs and antimicrobial peptides as a promising antimycobacterial template.

Mohanty, Soumitra; Jena, Prajna; Mehta, Ranjit; Pati, Rashmirekha; Banerjee, Birendranath; Patil, Satish

2013-01-01

232

?-Tetrahydrocannabinol induces cytotoxicity in macrophage J774-1 cells: involvement of cannabinoid receptor 2 and p38 MAPK.  

PubMed

Tetrahydrocannabinol (THC), a psychoactive component of marijuana, is known to exert cytotoxicity in immune cells. In the present study, we examined the cytotoxicity of ??-THC in mouse macrophage J774-1 cells and a possible involvement of cannabinoid receptors and stress-responsive mitogen-activated protein kinases (MAPKs) in the cytotoxic process. J774-1 cells were treated with ??-THC (0-20 ?M) for up to 6 h. As measured by the MTT and LDH assays, ??-THC induced cell death of J774-1 cells in a concentration- and/or exposure time-dependent manner. ??-THC-induced cell damage was associated with vacuole formation, cell swelling, chromatin condensation, and nuclear fragmentation. The cytotoxic effect of ??-THC was significantly prevented by a caspase-1 inhibitor Ac-YVAD-cmk but not a caspase-3 inhibitor z-DEVD-fmk. The pretreatment with SR144528, a CB? receptor-selective antagonist, effectively suppressed ??-THC-induced cytotoxicity in J774-1 cells, which exclusively expressed CB? receptors as indicated by real-time polymerase chain reaction analysis. In contrast, AM251, a CB? receptor-selective antagonist, did not affect the cytotoxicity. Pertussis toxin and ?-tocopherol significantly attenuated ??-THC-induced cytotoxicity suggesting that G(i/o) protein coupling signal transduction and oxidative stress are responsible for the cytotoxicity. ??-THC stimulated the phosphorylation of p38 MAPK and c-Jun N-terminal kinase (JNK) in J774-1 cells, which were effectively antagonized by the pretreatment with SR144528. In addition, SB203580, a p38 MARK inhibitor, significantly attenuated the cytotoxic effect of ??-THC, whereas SP600125, a JNK inhibitor, significantly enhanced the cytotoxicity. These results suggest that the cytotoxicity of ??-THC to J774-1 cells is exerted mediated through the CB? receptor followed by the activation of p38 MAPK. PMID:24184660

Yamaori, Satoshi; Ishii, Hirosuke; Chiba, Kenzo; Yamamoto, Ikuo; Watanabe, Kazuhito

2013-12-15

233

Nanoparticle induced director distortion and disorder in liquid crystal-nanoparticle dispersions.  

PubMed

Colloidal dispersions of nanoparticles in liquid crystals have been investigated experimentally using a model system consisting of the thermotropic liquid crystalline compound 4-n-octyloxy-4'-cyanobiphenyl (8OCB) doped with BaTiO(3) nanoparticles. We show that the physical properties of these dispersions can vary considerably depending on the method of preparation of the dispersions. We also find that aging the sample can improve dispersal of the nanoparticles in the host liquid crystal. Decreases in the isotropic to nematic transition temperature, parallel component of the dielectric constant and orientational order parameter are observed for the dispersions compared to the behaviour of pure 8OCB. These decreases have been explained in terms of orientational disorder and defects induced by the nanoparticles. PMID:20869064

Gupta, Meenal; Satpathy, Ipsita; Roy, Arun; Pratibha, R

2010-12-15

234

Intracellular glutathione regulates Andrographolide-induced cytotoxicity on hepatoma Hep3B cells.  

PubMed

Andrographolide (ANDRO), a diterpenoid lactone isolated from the traditional herbal plant Andrographis paniculata, was reported to induce apoptosis in hepatoma Hep3B cells in our previous study (Ji LL, Liu TY, Liu J, Chen Y, Wang ZT. Andrographolide inhibits human hepatoma-derived Hep3B cells growth through the activation of c-Jun N-terminal kinase. Planta Med 2007; 73: 1397-1401). The present investigation was carried out to observe whether cellular reduced glutathione (GSH) plays important roles in ANDRO-induced apoptosis. ANDRO initially increased intracellular GSH levels which then decreased later, while inhibition of cellular GSH synthesis by L-Buthionine-(S,R)-sulfoximine (BSO) augmented ANDRO-induced cytotoxicity and apoptosis in Hep3B cells. On the other hand, the thiol antioxidant dithiothreitol (DTT) rescued ANDRO-depleted cellular GSH, and abrogated ANDRO-induced cytotoxicity and apoptosis. Furthermore, BSO pretreatment augmented ANDRO-decreased expression of antioxidant protein thioredoxin 1 (Trx1), while DTT reversed this decrease. Further results showed that ANDRO increased the activity of the GSH-related antioxidant enzyme glutathione peroxidase (GPx) and the production of intracellular reactive oxygen species (ROS). Taken together, this study demonstrates that the intracellular redox system plays important roles in regulating the cytotoxicity of ANDRO on hepatoma Hep3B cells. PMID:19695125

Ji, Lili; Shen, Kaikai; Liu, Jun; Chen, Ying; Liu, Tianyu; Wang, Zhengtao

2009-01-01

235

Molecular Mechanisms of Apoptosis Induced by Cytotoxic Chemicals  

Microsoft Academic Search

?? ?? m, mitochondrial membrane potential; NGF, neuronal growth factor; AIF, apoptosis-inducing factor; ICE, interleukin-1?-converting enzyme; FADD, Fas-associated protein with death domain; ICAD, inhibitor of caspase-activated DNase; DFF, DNA fragmentation factor; z-VAD.fmk, benzyloxycarbonyl-Val-Ala-Asp- (Ome) fluoromethyl ketone; DED, death effector domain; BH, Bcl-2 homology domain; TCDD, 2,3,7,8-tetrachlorodibenzo-p- dioxin; PCBs, polychlorinated biphenyls; PAHs, polycyclic aromatic hydrocarbons; AHR, aryl hydrocarbon receptor; ARNT, aryl

John D. Robertson; Sten Orrenius

2000-01-01

236

A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide nanoparticles  

Microsoft Academic Search

Superparamagnetic iron oxide nanoparticles (SPIONs) are increasingly used in medical applications, such as targeting delivery and imaging. In the future, patients are more likely to be exposed to pharmaceutical products containing such particles. The study of toxicity of SPIONs has become of great importance in recent years, although the published data in this arena is limited. The aim of the

Morteza Mahmoudi; Abdolreza Simchi; Mohammad Imani; Mohammad A. Shokrgozar; Abbas S. Milani; Urs O. Häfeli; Pieter Stroeve

2010-01-01

237

Polyphosphazene nanoparticles for cytoplasmic release of doxorubicin with improved cytotoxicity against Dox-resistant tumor cells.  

PubMed

This study involved the construction of self-assembled nanoparticles from novel pH-sensitive amphiphilic polyphosphazenes. These nanoparticles provide fast pH-responsive drug release and have the capability to disturb endosomal membranes. The polymers were prepared by linking N,N-diisopropylethylenediamine (DPA) onto a backbone of PEGylated polyphosphazene. In vitro cell viability measurements demonstrated the superior efficacy of these pH-responsive nanoparticles over free doxorubicin (Dox): the IC50 was over 60 times lower than that of free Dox against a Dox-resistant cell line. Using flow cytometry and confocal microscopy, the further investigation of the intracellular distribution of Dox and fluorescent probes provided evidence that, upon internalization by cells through endocytic pathways, the pH-sensitive polymer would disrupt membranes of endosomal compartments, releasing the cargo drugs into the cytoplasm in a burst-like manner. This resulted in reduced likelihood of drug efflux via exocytosis, and reversal of the drug resistance of the tumor cells. Generally, the pH-responsive nanoparticles designed in this study have achieved their potential as a drug delivery system for tumor therapy applications. PMID:21220138

Zheng, Cheng; Xu, Jing; Yao, Xiaping; Xu, Jian; Qiu, Liyan

2011-03-15

238

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

239

Activation of stress-related signalling pathway in human cells upon SiO2 nanoparticles exposure as an early indicator of cytotoxicity  

PubMed Central

Background Nanomaterials such as SiO2 nanoparticles (SiO2NP) are finding increasing applications in the biomedical and biotechnological fields such as disease diagnostics, imaging, drug delivery, food, cosmetics and biosensors development. Thus, a mechanistic and systematic evaluation of the potential biological and toxic effects of SiO2NP becomes crucial in order to assess their complete safe applicability limits. Results In this study, human monocytic leukemia cell line THP-1 and human alveolar epithelial cell line A549 were exposed to a range of amorphous SiO2NP of various sizes and concentrations (0.01, 0.1 and 0.5 mg/ml). Key biological indicators of cellular functions including cell population density, cellular morphology, membrane permeability, lysosomal mass/pH and activation of transcription factor-2 (ATF-2) were evaluated utilizing quantitative high content screening (HCS) approach and biochemical techniques. Despite the use of extremely high nanoparticle concentrations, our findings showed a low degree of cytotoxicity within the panel of SiO2NP investigated. However, at these concentrations, we observed the onset of stress-related cellular response induced by SiO2NP. Interestingly, cells exposed to alumina-coated SiO2NP showed low level, and in some cases complete absence, of stress response and this was consistent up to the highest dose of 0.5 mg/ml. Conclusions The present study demonstrates and highlights the importance of subtle biological changes downstream of primary membrane and endocytosis-associated phenomena resulting from high dose SiO2NP exposure. Increased activation of transcription factors, such as ATF-2, was quantitatively assessed as a function of i) human cell line specific stress-response, ii) SiO2NP size and iii) concentration. Despite the low level of cytotoxicity detected for the amorphous SiO2NP investigated, these findings prompt an in-depth focus for future SiO2NP-cell/tissue investigations based on the combined analysis of more subtle signalling pathways associated with accumulation mechanisms, which is essential for establishing the bio-safety of existing and new nanomaterials.

2011-01-01

240

Nanoparticles induce raft formation in phospholipid liposomes  

NASA Astrophysics Data System (ADS)

Motivated by general interests in endocytosis, virus transfection and utilization of nanoparticles as cargo for drug delivery, this study focuses on the binding of nanoparticles to model lipid bilayers and the interactions between them. Exploring not only on the ensemble level, with the help of calorimetry, but also on the single-molecule level using fluorescence probes and single-molecule detection, we conclude the following. First, adsorbates capture and slave dynamically the lipids underneath, which results in lipid packing fluctuations, thereby producing rafts in the bilayers. Second, competition between neighboring particles causes further recomposition of heterogeneous lipid distribution. Bearing this insight in mind, we expect coupled motions of lipid and nanoparticles to occur, and confirm this with direct measurements. Going further, collective responses of lipid molecules cast light on the crucial role of support membranes in determining how membrane-based sensors respond to an external stimulus.

Wang, Bo; Zhang, Liangfang; Granick, Steve

2007-03-01

241

CIIA prevents SOD1(G93A)-induced cytotoxicity by blocking ASK1-mediated signaling  

PubMed Central

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with higher selectivity in degeneration of motor neurons. However, the molecular mechanism by which the ALS-linked mutants of human superoxide dismutase 1 (SOD1) gene induce neurotoxicity remains obscure yet. Here, we show that depletion of CIIA expression by RNA interference (RNAi) promoted cytotoxicity caused by ALS-linked G93A mutant of the SOD1 gene. The RNAi-mediated knockdown of CIIA also enhanced the SOD1(G93A)-induced interaction between ASK1 and TRAF2 as well as ASK1 activity. Furthermore, endogenous silencing of CIIA by RNAi augmented the effects of SOD1(G93A) on reduction of mitochondria membrane potential (??m), release of cytochrome c into the cytoplasm, and caspase activation. Together, our results suggest that CIIA negatively modulates ASK1-mediated cytotoxic signaling processes in a SOD1(G93A)-expressing cellular model of ALS.

Lee, Jae Keun; Hwang, Sang Gil; Shin, Jin Hee; Shim, Jaekyung; Choi, Eui-Ju

2014-01-01

242

Nanosecond laser-induced synthesis of nanoparticles with tailorable magneticanisotropy  

NASA Astrophysics Data System (ADS)

Controlling the magnetic orientation of nanoparticles is important for many applications. Recently, it has been shown that single domain ferromagnetic hemispherical Co nanoparticles prepared by nanosecond laser-induced self-organization, show magnetic orientation that was related to the negative sign of the magnetostrictive coefficient ?S [J. Appl. Phys. v103, p073902, 2008]. Here we have extended this work to the Fe 50Co 50 alloy, which has a positive ?S and Ni, which has a negative ?S. Patterned arrays of ferromagnetic nanoparticles of Fe 50Co 50, Ni, (and Co) were synthesized from their ultrathin metal films on SiO 2 substrate by nanosecond laser-induced self-organization. The morphology, nanostructure, and magnetic behavior of the nanoparticle arrays were investigated by a combination of electron microscopy, atomic force microscopy, and magnetic force microscopy techniques. Transmission electron microscopy investigations revealed a granular polycrystalline nanostructure, with the number of grains inside the nanoparticle increasing with their diameter. Magnetic force measurements showed that the magnetization direction of the hemispherical Co and Ni nanoparticles was predominantly out-of-plane while those for the Fe 50Co 50 alloy was in the plane of the substrate. Finite element analysis was used to estimate the average residual strain in the nanoparticles, following laser processing. The difference in behavior is due to the dominating influence of magnetostrictive energy on the magnetization as a result of residual thermal strain following fast laser processing. Since ?S is negative for polycrystalline Co and Ni, and positive for Fe 50Co 50, the tensile residual strain forces the magnetization direction to out-of-plane and in-plane, respectively. This work demonstrates a cost-effective non-epitaxial technique for the synthesis of magnetic nanoparticles with tailored magnetization orientations.

Krishna, H.; Gangopadhyay, A. K.; Strader, J.; Kalyanaraman, R.

2011-02-01

243

Modulating activity of fullerol C 60(OH) 22 on doxorubicin-induced cytotoxicity  

Microsoft Academic Search

Paper presents the effects of the newly synthesized fullerol C60(OH)22 on the growth of tumor cells in vitro and its modulating activity on doxorubicin (DOX)-induced cytotoxicity in human breast cancer cell lines. Cell growth inhibition was evaluated by tetrazolium colorimetric WST1 assay. Electron spin resonance (ESR) “trapping” method was used to investigate OH-radical scavenger activity of fullerol during Fenton's reaction.

Gordana Bogdanovi?; Vesna Koji?; Aleksandar ?or?evi?; Jasna ?anadanovi?-Brunet; Mirjana Vojinovi?-Miloradov; Vladimir Vit. Balti?

2004-01-01

244

Target cell induced activation of NK cells in vitro: cytokine production and enhancement of cytotoxic function  

Microsoft Academic Search

This study examines the effect of fixed AK-5 tumour cells on rat NK cells. Co-culture of NK cells with fixed tumour cells augmented the cytotoxicity of NK cells against NK-sensitive targets, YAC-1 and AK-5, and induced the secretion of IFN-% by NK cells. Antibody against IFN-% suppressed the anti-tumour activity of NK cells, whereas the addition of T cells during

Suvendu Das; C. Varalakshmi; Leela A. Kumari; Megha Patel; Ashok Khar

2001-01-01

245

Nitric oxide is involved in interleukin-1alpha-induced cytotoxicity in polarised human thyrocytes  

Microsoft Academic Search

Nitric oxide (NO) is a well-known mediator of auto- immune processes. In the thyroid gland, it is produced in response to interleukin 1 (IL-1) and may mediate cytokine action at an early stage of autoimmune thyroiditis. In this study, we have investigated whether NO is involved in cytokine-induced cytotoxic effects and epithelial barrier alterations in thyrocytes. Human thyroid epithelial cells

M-F van den Hove; M S Stoenoiu; K Croizet; M Couvreur; P J Courtoy; O Devuyst; I M Colin

2002-01-01

246

Using Dynamic Gene Module Map Analysis To Identify Targets That Modulate Free Fatty Acid Induced Cytotoxicity  

PubMed Central

The objective of this study was to identify pathways that regulate the cytotoxicity induced by free fatty acids (FFAs) in human hepatoblastoma cells (HepG2/C3A). Gene expression profiles of HepG2/C3A cells were obtained at three time points, after 24, 48, and 72 h of exposure to different types of FFA. Saturated fatty acid (palmitate) was found to be cytotoxic. The pathways activated by the different FFAs at the different time points were identified using global gene module map analysis. Unsaturated FFAs exerted transcriptional regulation mainly within the first 24 h, whereas saturated FFA, palmitate, regulated energy production pathways, such as the electron transport chain (ETC) and tricarboxylic acid cycle, within the first 24 h. In the next 24 h, palmitate up-regulated 36 cell death relevant pathways and down-regulated several protective pathways, such as the pentose phosphate pathway and glutathione-related pathways. In the final 24 h, the FFAs did not induce significant transcriptional regulation. We hypothesized that palmitate induced cytotoxicity by first perturbing metabolic pathways in the initial 24 h, resulting in changes to factors, such as metabolites or signaling molecules, which subsequently triggered cell death relevant pathways in the next 24 h. The uptake and release of 27 metabolites were measured to further elucidate the metabolic changes in the first 24 h. It was determined that ketone bodies such as ?-hydroxybutyrate and acetoacetate were important in separating the toxic from the nontoxic phenotypes. A regression model was used to identify the genes relevant to these metabolites. Some of the genes identified to be important were experimentally validated. It was found that ETC genes such as NADH dehydrogenase and succinate dehydrogenase were involved in palmitate induced cytotoxicity.

Li, Zheng; Srivastava, Shireesh; Findlan, Robert; Chan, Christina

2014-01-01

247

Signaling Pathways Involved in Lunar Dust Induced Cytotoxicity  

NASA Technical Reports Server (NTRS)

The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (< 3 micron), that is respirable. The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents to assess the health risk of dust exposures to humans. One of the particular interests in the study is to evaluate dust-induced changes of the expression of fibrosis-related genes, and to identify specific signaling pathways involved in lunar dust-induced toxicity. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.1, 21, and 61 mg/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, 1 week, 1 month, and 3 months after the last inhalation exposure. The total RNAs were isolated from the blood or lung tissue after being lavaged, using the Qigen RNeasy kit. The Rat Fibrosis RT2 Profile PCR Array was used to profile the expression of 84 genes relevant to fibrosis. The genes with significant expression changes are identified and the gene expression data were further analyzed using IPA pathway analysis tool to determine the signaling pathways with significant changes.

Zhang, Ye; Lam, Chiu-Wing; Scully, Robert R.; Williams, Kyle; Zalesak, Selina; Wu, Honglu; James, John T.

2014-01-01

248

Cytotoxic and apoptosis-inducing activities of steviol and isosteviol derivatives against human cancer cell lines.  

PubMed

Seventeen steviol derivatives, i.e., 2-18, and 19 isosteviol derivatives, i.e., 19-37, were prepared from a diterpenoid glycoside, stevioside (1). Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines, nine steviol derivatives, i.e., 5-9 and 11-14, and five isosteviol derivatives, i.e., 28-32, exhibited activities with single-digit micromolar IC(50) values against one or more cell lines. All of these active compounds possess C(19)-O-acyl group, and among which, ent-kaur-16-ene-13,19-diol 19-O-4',4',4'-trifluorocrotonate (14) exhibited potent cytotoxicities against four cell lines with IC(50) values in the range of 1.2-4.1 ?M. Compound 14 induced typical apoptotic cell death in HL60 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis. These results suggested that acylation of the 19-OH group of kaurane- and beyerane-type diterpenoids might be useful for enhancement of their cytotoxicities with apoptosis-inducing activity. PMID:23418165

Ukiya, Motohiko; Sawada, Shingo; Kikuchi, Takashi; Kushi, Yasunori; Fukatsu, Makoto; Akihisa, Toshihiro

2013-02-01

249

Human ?? T lymphocytes induce robust NK cell-mediated antitumor cytotoxicity through CD137 engagement  

PubMed Central

Natural killer (NK) cells are innate effector lymphocytes that control the growth of major histocompatibility complex class I negative tumors. We show here that ?? T lymphocytes, expanded in vitro in the presence isopentenylpyrophosphate (IPP), induce NK cell–mediated killing of tumors that are usually resistant to NK cytolysis. The induction of cytotoxicity toward these resistant tumors requires priming of NK cells by immobilized human immunoglobulin G1 and costimulation through CD137L expressed on activated ?? T lymphocytes. This costimulation increases NKG2D expression on the NK-cell surface, which is directly responsible for tumor cell lysis. Moreover, culturing peripheral blood mononuclear cells with zoledronic acid, a ?? T lymphocyte activating agent, enhances NK-cell direct cytotoxicity and antibody-dependent cellular cytotoxicity against hematopoietic and nonhematopoietic tumors. Our data reveal a novel function of human ?? T lymphocytes in the regulation of NK cell–mediated cytotoxicity and provide rationale for the use of strategies to manipulate the CD137 pathway to augment innate antitumor immunity.

Maniar, Amudhan; Zhang, Xiaoyu; Lin, Wei; Gastman, Brian R.; Pauza, C. David; Strome, Scott E.

2010-01-01

250

Comparison of cytotoxicity and DNA damage potential induced by ent-kaurene diterpenoids from Isodon plant.  

PubMed

The cytotoxicity of six ent-kaurene diterpenoids isolated from the leaves of Isodon japonica (Burm.f.) Hara var. galaucocalyx (maxin) Hara was evaluated against three human tumour HepG2, GLC-82 and HL-60 cell lines through SRB assay, and their DNA damage potential (against HepG2 cell line) was assessed by comet assay. Among the six ent-kaurene diterpenoids, Rabdosin B was most cytotoxic, followed by Oridonin, Epinodosin, Rabdosinate, Lasiokaurin and Epinodosinol. All of the six ent-kaurene diterpenoids induced significant DNA damage (p < 0.05) to HepG2 cells in a time- and dose-dependent manner except Lasiokaurin and Eponodosinol at 6 µmol L?ą for 24 h. The structure-activity relationships (SARs) were discussed and it was found that exo-methylene cyclopentanone in the molecular structure was important for maintaining the cytotoxicity and DNA damage potential of the compounds.-OAc group at site C-1 in Lasiokaurin had a higher stereospecific blockade, which made the compound have less cytotoxicity and DNA damage potential than Oridonin (-OH at C-1). PMID:19606380

Ding, Lan; Zhou, Qiyin; Wang, Li; Wang, Wei; Zhang, Shidong; Liu, Bo

2011-09-01

251

The induction of heme oxygenase-1 modulates bismuth oxide-induced cytotoxicity in human dental pulp cells.  

PubMed

The aim of this study was to investigate the cytotoxic and nitric oxide (NO)-inducing effects of bismuth oxide (Bi(2)O(3))-containing Portland cement (BPC) on human dental pulp cells. We also assessed whether heme oxygenase-1 (HO-1) is involved in BPC-induced cytotoxicity in dental pulp cells. Cytotoxicity and NO production induced by BPC were higher than those induced by Portland cement at 12 and 24 hours, and the former gradually decreased to the level observed for PC. HO-1 and inducible nitric oxide synthase messenger RNA expressions in the BPC group showed maximal increase at 24 hours, and it gradually decreased with increasing cultivation time. Hemin treatment reversed the BPC-induced cytotoxicity, whereas zinc protoporphyrin IX treatment increased the cytotoxicity. These results suggested that NO production by BPC correlates with HO-1 expression in dental pulp cells. Moreover, BPC-induced HO-1 expression in dental pulp cells plays a protective role against the cytotoxic effects of BPC. PMID:17963960

Min, Kyung-San; Chang, Hoon-Sang; Bae, Ji-Myung; Park, Sang-Hyuk; Hong, Chan-Ui; Kim, Eun-Cheol

2007-11-01

252

Laser-induced periodic nanoparticle patterns  

NASA Astrophysics Data System (ADS)

Creating the conditions so that matter naturally self-arranges at the nanoscale under a homogeneous excitation is an exciting challenge for the development of efficient and cost-effective processes. Sub-micrometer periodic templates can be formed spontaneously on materials by low-energy ion sputtering or with lasers. In the latter case, the formation of self-organized grating-like structures requires a high temperature rise and generally results from interactions with ultrashort laser pulses. Recently, a few studies have dealt with self-formed periodic patterns of metal nanoparticle assemblies, but they only reported changes in the spatial and size distributions of metal nanoparticles deposited on surfaces prior to interaction with femtosecond lasers. Here, we show that metal nanoparticles can grow in a selforganized manner within a waveguide illuminated from free-space by a continuous wave visible laser. We report the conditions that give rise to the generation of such 1D nanoparticle gratings and describe the parameters that influence the grating characteristics. We explain the mechanisms involved in the formation of such nanostructures on the basis of interference phenomena between the incident wave and guided modes.

Destouches, N.; Vitrant, G.; Crespo-Monteiro, N.; Liu, Z.; Lefkir, Y.; Vocanson, F.; Epicier, T.

2014-03-01

253

In Caenorhabditis elegans Nanoparticle-Bio-Interactions Become Transparent: Silica-Nanoparticles Induce Reproductive Senescence  

PubMed Central

While expectations and applications of nanotechnologies grow exponentially, little is known about interactions of engineered nanoparticles with multicellular organisms. Here we propose the transparent roundworm Caenorhabditis elegans as a simple but anatomically and biologically well defined animal model that allows for whole organism analyses of nanoparticle-bio-interactions. Microscopic techniques showed that fluorescently labelled nanoparticles are efficiently taken up by the worms during feeding, and translocate to primary organs such as epithelial cells of the intestine, as well as secondary organs belonging to the reproductive tract. The life span of nanoparticle-fed Caenorhabditis elegans remained unchanged, whereas a reduction of progeny production was observed in silica-nanoparticle exposed worms versus untreated controls. This reduction was accompanied by a significant increase of the ‘bag of worms’ phenotype that is characterized by failed egg-laying and usually occurs in aged wild type worms. Experimental exclusion of developmental defects suggests that silica-nanoparticles induce an age-related degeneration of reproductive organs, and thus set a research platform for both, detailed elucidation of molecular mechanisms and high throughput screening of different nanomaterials by analyses of progeny production.

Bossinger, Olaf; von Mikecz, Anna

2009-01-01

254

Green synthesis, antimicrobial and cytotoxic effects of silver nanoparticles using Eucalyptus chapmaniana leaves extract  

PubMed Central

Objective To synthesize silver nanopaticles from leaves extract of Eucalyptus chapmaniana (E. chapmaniana) and test the antimicrobial of the nanoparticles against different pathogenic bacteria, yeast and its toxicity against human acute promyelocytic leukemia (HL-60) cell line. Methods Ten milliliter of leaves extract was mixed with 90 mL of 0.01 mmol/mL or 0.02 mmol/mL aqueous AgNO3 and exposed to sun light for 1 h. A change from yellowish to reddish brown color was observed. Characterization using UV-vis spectrophotometery and X-ray diffraction analysis were performed. Antimicrobial activity against six microorganisms was tested using well diffusion method and cytoxicity test using 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole was obtained on the human leukemia cell line (HL-60). Results UV-vis spectral analysis showed silver surface plasmon resonance band at 413 nm. X-ray diffraction showed that the particles were crystalline in nature with face centered cubic structure of the bulk silver with broad beaks at 38.50° and 44.76°. The synthesized silver nanoparticles efficiently inhibited various pathogenic organisms and reduced viability of the HL-60 cells in a dose-dependent manner. Conclusions It has been demonstrated that the extract of E. chapmaniana leaves are capable of producing silver nanoparticles extracellularly and the Ag nanoparticles are quite stable in solution. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the antimicrobial and anticancer activity of these particles.

Sulaiman, Ghassan Mohammad; Mohammed, Wasnaa Hatif; Marzoog, Thorria Radam; Al-Amiery, Ahmed Abdul Amir; Kadhum, Abdul Amir H.; Mohamad, Abu Bakar

2013-01-01

255

Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549  

Microsoft Academic Search

Nanomaterials, especially silver nanoparticles (Ag NPs), are used in a rapidly increasing number of commercial products. Accordingly,\\u000a the hazards associated with human exposure to nanomaterials should be investigated to facilitate the risk assessment process.\\u000a A potential route of exposure to NPs is through the respiratory system. In the present study, we investigated the effects\\u000a of well-characterized PVP-coated Ag NPs and

Rasmus Foldbjerg; Duy Anh Dang; Herman Autrup

2011-01-01

256

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

257

ETHANOL-INDUCED CYTOTOXICITY IN RAT PANCREATIC ACINAR AR42J CELLS: ROLE OF FATTY ACID ETHYL ESTERS  

Microsoft Academic Search

Aims: To understand the mechanism(s) of alcoholic pancreatitis and role of fatty acid ethyl esters (FAEEs, non- oxidative metabolites of ethanol) in ethanol-induced pancreatic injury. Methods: A time- and concentration-dependent synthesis of FAEEs and the cytotoxicity of ethanol and its predominant fatty acid esters were studied in rat pancreatic tumour (AR42J) cells in cultures. Role of FAEEs in ethanol-induced cytotoxicity

HAI WU; KAMLESH K. BHOPALE; G. A. S. ANSARI; BHUPENDRA S. KAPHALIA

258

Association of the physical and chemical properties and the cytotoxicity of metal oxide nanoparticles: metal ion release, adsorption ability and specific surface area.  

PubMed

Association of cellular influences and physical and chemical properties were examined for 24 kinds of industrial metal oxide nanoparticles: ZnO, CuO, NiO, Sb(2)O(3), CoO, MoO(3), Y(2)O(3), MgO, Gd(2)O(3), SnO(2), WO(3), ZrO(2), Fe(2)O(3), TiO(2), CeO(2), Al(2)O(3), Bi(2)O(3), La(2)O(3), ITO, and cobalt blue pigments. We prepared a stable medium dispersion for each nanoparticle and examined the influence on cell viability and oxidative stress together with physical and chemical characterizations. ZnO, CuO, NiO, MgO, and WO(3) showed a large amount of metal ion release in the culture medium. The cellular influences of these soluble nanoparticles were larger than insoluble nanoparticles. TiO(2), SnO(2), and CeO(2) nanoparticles showed strong protein adsorption ability; however, cellular influences of these nanoparticles were small. The primary particle size and the specific surface area seemed unrelated to cellular influences. Cellular influences of metal oxide nanoparticles depended on the kind and concentrations of released metals in the solution. For insoluble nanoparticles, the adsorption property was involved in cellular influences. The primary particle size and specific surface area of metal oxide nanoparticles did not affect directly cellular influences. In conclusion the most important cytotoxic factor of metal oxide nanoparticles was metal ion release. PMID:22419205

Horie, Masanori; Fujita, Katsuhide; Kato, Haruhisa; Endoh, Shigehisa; Nishio, Keiko; Komaba, Lilian Kaede; Nakamura, Ayako; Miyauchi, Arisa; Kinugasa, Shinichi; Hagihara, Yoshihisa; Niki, Etsuo; Yoshida, Yasukazu; Iwahashi, Hitoshi

2012-04-01

259

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

260

Surface Charges and Shell Crosslinks Each Play Significant Roles in Mediating Degradation, Biofouling, Cytotoxicity and Immunotoxicity for Polyphosphoester-based Nanoparticles  

NASA Astrophysics Data System (ADS)

The construction of nanostructures from biodegradable precursors and shell/core crosslinking have been pursued as strategies to solve the problems of toxicity and limited stability, respectively. Polyphosphoester (PPE)-based micelles and crosslinked nanoparticles with non-ionic, anionic, cationic, and zwitterionic surface characteristics for potential packaging and delivery of therapeutic and diagnostic agents, were constructed using a quick and efficient synthetic strategy, and importantly, demonstrated remarkable differences in terms of cytotoxicity, immunotoxicity, and biofouling properties, as a function of their surface characteristics and also with dependence on crosslinking throughout the shell layers. For instance, crosslinking of zwitterionic micelles significantly reduced the immunotoxicity, as evidenced from the absence of secretions of any of the 23 measured cytokines from RAW 264.7 mouse macrophages treated with the nanoparticles. The micelles and their crosslinked analogs demonstrated lower cytotoxicity than several commercially-available vehicles, and their degradation products were not cytotoxic to cells at the range of the tested concentrations. PPE-nanoparticles are expected to have broad implications in clinical nanomedicine as alternative vehicles to those involved in several of the currently available medications.

Elsabahy, Mahmoud; Zhang, Shiyi; Zhang, Fuwu; Deng, Zhou J.; Lim, Young H.; Wang, Hai; Parsamian, Perouza; Hammond, Paula T.; Wooley, Karen L.

2013-11-01

261

Nanoparticle-induced platelet aggregation and vascular thrombosis  

PubMed Central

Ever increasing use of engineered carbon nanoparticles in nanopharmacology for selective imaging, sensor or drug delivery systems has increased the potential for blood platelet–nanoparticle interactions. We studied the effects of engineered and combustion-derived carbon nanoparticles on human platelet aggregation in vitro and rat vascular thrombosis in vivo. Multiplewall (MWNT), singlewall (SWNT) nanotubes, C60 fullerenes (C60CS) and mixed carbon nanoparticles (MCN) (0.2–300??g?ml?1) were investigated. Nanoparticles were compared with standard urban particulate matter (SRM1648, average size 1.4??m). Platelet function was studied using lumi aggregometry, phase-contrast, immunofluorescence and transmission electron microscopy, flow cytometry, zymography and pharmacological inhibitors of platelet aggregation. Vascular thrombosis was induced by ferric chloride and the rate of thrombosis was measured, in the presence of carbon particles, with an ultrasonic flow probe. Carbon particles, except C60CS, stimulated platelet aggregation (MCN?SWNT>MWNT>SRM1648) and accelerated the rate of vascular thrombosis in rat carotid arteries with a similar rank order of efficacy. All particles resulted in upregulation of GPIIb/IIIa in platelets. In contrast, particles differentially affected the release of platelet granules, as well as the activity of thromboxane-, ADP, matrix metalloproteinase- and protein kinase C-dependent pathways of aggregation. Furthermore, particle-induced aggregation was inhibited by prostacyclin and S-nitroso-glutathione, but not by aspirin. Thus, some carbon nanoparticles and microparticles have the ability to activate platelets and enhance vascular thrombosis. These observations are of importance for the pharmacological use of carbon nanoparticles and pathology of urban particulate matter.

Radomski, Anna; Jurasz, Paul; Alonso-Escolano, David; Drews, Magdalena; Morandi, Maria; Malinski, Tadeusz; Radomski, Marek W

2005-01-01

262

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

263

Reduced cadmium-induced cytotoxicity in cultured liver cells following 5-azacytidine pretreatment  

SciTech Connect

Recent work indicated that administration of the pyrimidine analog 5-azacytidine (AZA), either to cells in culture or to rats, results in an enhancement of expression of the metallothionein (MT) gene. Since MT is thought to play a central role in the detoxification of cadmium, the present study was designed to assess the effect of AZA pretreatment on cadmium cytotoxicity. Cultured rat liver cells in log phase of growth were first exposed to AZA (8 microM). Forty-eight hours later, cadmium was added. A modest increase in MT amounts over control was detected after AZA treatment alone. Cadmium alone resulted in a 10-fold increase in MT concentrations. The combination of AZA pretreatment followed by cadmium exposure caused a 23-fold increase in MT concentrations over control. Treatment with the DNA synthesis inhibitor hydroxyurea (HU) eliminated the enhancing effect of AZA pretreatment on cadmium induction of MT, indicating that cell division is required. AZA-pretreated cells were also harvested and incubated in suspension with cadmium for 0 to 90 min. AZA-pretreated cells showed marked reductions in cadmium-induced cytotoxicity as reflected by reduced intracellular potassium loss, glutamic-oxaloacetic transaminase loss, and lipid peroxidation following cadmium exposure. Results suggest that AZA pretreatment induces tolerance to cadmium cytotoxicity which appears to be due to an increased capacity to synthesize MT rather than high quantities of preexisting MT at the time of cadmium exposure.

Waalkes, M.P.; Wilson, M.J.; Poirier, L.A.

1985-11-01

264

Acetaminophen Induced Cytotoxicity and Altered Gene Expression in Cultured Cardiomyocytes of H9C2 Cells  

PubMed Central

Objectives Hepatotoxicity of acetaminophen has been widely studied. However, the adverse effects on the heart have not been sufficiently evaluated. This study was performed to investigate cytotoxicity and alterations of gene expression in cultured cardiomyocytes (H9C2 cells) after exposure to acetaminophen. Methods H9C2 cells were incubated in a 10 mM concentration of acetaminophen for the designated times (6, 12, and 24 hours), and cytotoxicity was determined by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Alteration of gene expression was observed by microarray analysis, and RT-PCR was performed for the three representative oxidative stress-related genes at 24 hours after treatment. Results It revealed that acetaminophen was toxic to cardiomyocytes, and numerous critical genes were affected. Induced genes included those associated with oxidative stress, DNA damage, and apoptosis. Repressed genes included those associated with cell proliferation, myocardial contraction, and cell shape control. Conclusions These findings provide the evidences of acetaminophen-induced cytotoxicity and changes in gene expression in cultured cardiomyocytes of H9C2 cells.

Jin, Seon Mi

2012-01-01

265

Optically induced cell fusion using bispecific nanoparticles.  

PubMed

Redirecting the immune system to eliminate tumor cells is a promising alternative to traditional cancer therapies, most often requiring direct interaction between an immune system effector cell and its target. Herein, a novel approach for selective attachment of malignant cells to antigen-presenting cells by using bispecific nanoparticles is presented. The engaged cell pairs are then irradiated by a sequence of resonant femtosecond pulses, which results in widespread cell fusion and the consequent formation of hybrid cells. The dual role of gold nanoparticles as conjugating agents and fusion promoters offers a simple yet effective means for specific fusion between different cells. This technology could be useful for a variety of in vitro and in vivo applications that call for selective fusion between cells within a large heterogenic cell population. PMID:23788508

Yeheskely-Hayon, Daniella; Minai, Limor; Golan, Lior; Dann, Eldad J; Yelin, Dvir

2013-11-25

266

Continuous hypoxia attenuates paraquat-induced cytotoxicity in the human A549 lung carcinoma cell line.  

PubMed

Paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride; PQ), an effective and widely used herbicide, was commercially introduced in 1962. It is reduced by the electron donor NADPH, and then reduced PQ transfers the electrons to molecular oxygen, resulting in the production of reactive oxygen species (ROS), which are related to cellular toxicity. However, the influence of continuous hypoxia on PQ-induced ROS production has not fully been investigated. We evaluated in vitro the protective effect of continuous hypoxia on PQ-induced cytotoxicity in the human carcinogenic alveolar basal epithelial cell line (A549 cells) by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and live and dead assay, and by measuring lactate dehydrogenase (LDH) release. To elucidate the mechanism underlying this effect, we monitored the immunofluorescence of intracellular ROS and measured malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Continuous hypoxia protected the A549 cells from PQ-induced cytotoxicity. Continuous hypoxia for a period of 24 h significantly reduced intracellular ROS, decreased MDA concentration in the supernatant, and normalized SOD and GPx activities. Continuous hypoxia attenuated PQ-induced cell toxicity in A549 cells. This protective effect might be attributable to the suppression of PQ-induced ROS generation. PMID:21734449

Kim, Hoon; Lee, Suk Woo; Baek, Kyung Min; Park, Jung Soo; Min, Jin Hong

2011-09-30

267

Zinc at Sub-Cytotoxic Concentrations Induces Heme Oxygenase-1 Expression in Human Cancer Cells  

PubMed Central

Background/Aims This study investigated the effects of zinc on heme oxygenase-1 (HO-1) expression in human cancer cells. Methods/Results Zinc at sub-cytotoxic concentrations (50–100 µM) induces HO-1 expression in the MDA-MB-231 (human breast cancer) and A2780 (human ovarian cancer) cell lines in a concentration- and time-dependent manner. The induction of HO-1 by zinc was detected after 4–6 hours of treatment, reached maximal level at 8 hours, and declined thereafter. Using a human HO-1 gene promoter reporter construct, we identified two antioxidant response elements (AREs) that mediated the zinc-induced increase in HO-1 gene transcription, indicating that the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway is involved in this event. This assumption was supported by the observations that knockdown of Nrf2 expression compromised the zinc-induced increase in HO-1 gene transcription, and that zinc increased Nrf2 protein expression and the Nrf2 binding to the AREs. Additionally, we found that the zinc-induced HO-1 gene transcription can be enhanced by clioquinol, a zinc ionophore, and reversed by pretreatment with TPEN, a known zinc chelator, indicating that an increase in intracellular zinc levels is responsible for this induction. Conclusion These findings demonstrate that zinc at sub-cytotoxic concentrations induces HO-1 expression in human cancer cells. The biological significance of this induction merits further investigation.

Xue, Jing; Wang, Shuai; Wu, Jinchang; Hannafon, Bethany N.; Ding, Wei-Qun

2013-01-01

268

The in vitro enzyme-inducing and cytotoxic properties of South African laboratory animal contact bedding and nesting materials.  

PubMed

Enzyme-inducing and cytotoxic effects of South African bedding materials were investigated using a mouse hepatoma cell line, Hepa-1, cell culture system. This cell culture system is a convenient and sensitive method for the screening of bedding materials for the presence of compounds that could be potentially harmful to animals and thus the experimental outcome. Cells were exposed to acetone extracts of the different materials or their components. Corn cobs displayed very little or no CYP1A1-inducing or cytotoxic effects, whilst vermiculite and unbleached pulp from pine and eucalyptus showed greater induction and cytotoxic properties. The latter properties were lower than those produced by the different recycled paper extracts. Pine shavings (Pinus elliottii) and the different wood components making up industrial sawdust expressed the highest cytotoxic and CYP1A1-inducing properties. PMID:7603002

Potgieter, F J; Törrönen, R; Wilke, P I

1995-04-01

269

SiO2 nanoparticle-induced impairment of mitochondrial energy metabolism in hepatocytes directly and through a Kupffer cell-mediated pathway in vitro  

PubMed Central

The liver has been shown to be a primary target organ for SiO2 nanoparticles in vivo, and may be highly susceptible to damage by these nanoparticles. However, until now, research focusing on the potential toxic effects of SiO2 nanoparticles on mitochondria-associated energy metabolism in hepatocytes has been lacking. In this work, SiO2 nanoparticles 20 nm in diameter were evaluated for their ability to induce dysfunction of mitochondrial energy metabolism. First, a buffalo rat liver (BRL) cell line was directly exposed to SiO2 nanoparticles, which induced cytotoxicity and mitochondrial damage accompanied by decreases in mitochondrial dehydrogenase activity, mitochondrial membrane potential, enzymatic expression in the Krebs cycle, and activity of the mitochondrial respiratory chain complexes I, III and IV. Second, the role of rat-derived Kupffer cells was evaluated. The supernatants from Kupffer cells treated with SiO2 nanoparticles were transferred to stimulate BRL cells. We observed that SiO2 nanoparticles had the ability to activate Kupffer cells, leading to release of tumor necrosis factor-?, nitric oxide, and reactive oxygen species from these cells and subsequently to inhibition of mitochondrial respiratory chain complex I activity in BRL cells.

Xue, Yang; Chen, Qingqing; Ding, Tingting; Sun, Jiao

2014-01-01

270

Protection from radiation-induced pneumonitis using cerium oxide nanoparticles.  

PubMed

In an effort to combat the harmful effects of radiation exposure, we propose that rare-earth cerium oxide (CeO(2)) nanoparticles (free-radical scavengers) protect normal tissue from radiation-induced damage. Preliminary studies suggest that these nanoparticles may be a therapeutic regenerative nanomedicine that will scavenge reactive oxygen species, which are responsible for radiation-induced cell damage. The effectiveness of CeO(2) nanoparticles in radiation protection in murine models during high-dose radiation exposure is investigated, with the ultimate goal of offering a new approach to radiation protection, using nanotechnology. We show that CeO(2) nanoparticles are well tolerated by live animals, and they prevent the onset of radiation-induced pneumonitis when delivered to live animals exposed to high doses of radiation. In the end, these studies provide a tremendous potential for radioprotection and can lead to significant benefits for the preservation of human health and the quality of life for humans receiving radiation therapy. PMID:19285453

Colon, Jimmie; Herrera, Luis; Smith, Joshua; Patil, Swanand; Komanski, Chris; Kupelian, Patrick; Seal, Sudipta; Jenkins, D Wayne; Baker, Cheryl H

2009-06-01

271

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

PubMed Central

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.

2012-01-01

272

Hexokinase II detachment from the mitochondria potentiates cisplatin induced cytotoxicity through a caspase-2 dependent mechanism.  

PubMed

Cancer cells are frequently glycolytic and overexpress hexokinase II (HXK II). In cancer cells, the majority of hexokinase II is localized to the mitochondria through interaction with the voltage dependent anion channel (VDAC). Disruption in the binding of hexokinase II to the mitochondria has been shown to promote mitochondrial injury provoked by pro-apoptotic proteins. The present study demonstrates that cisplatin induces the PIDD (p53 induced protein with a death domain) dependent activation of caspase-2. In turn, caspase-2 cleaves and activates Bid, resulting in the oligomerization of Bak and the release of cytochrome c. Notably, the detachment of hexokinase II from the mitochondria markedly potentiates the onset of caspase-2 induced mitochondrial damage, thus resulting in a synergistic induction of cisplatin induced cytotoxicity. PMID:19770592

Shulga, Nataly; Wilson-Smith, Robin; Pastorino, John G

2009-10-15

273

Hexokinase II Detachment from the Mitochondria Potentiates Cisplatin Induced Cytotoxicity through a Caspase-2 dependent Mechanism  

PubMed Central

Cancer cells are frequently glycolytic and over-express hexokinase II (HXK II). In cancer cells, the majority of hexokinase II is localized to the mitochondria through interaction with the voltage dependent anion channel (VDAC). Disruption in the binding of hexokinase II to the mitochondria has been shown to promote mitochondrial injury provoked by pro-apoptotic proteins. The present study demonstrates that cisplatin induces the PIDD (P53 induced protein with a death domain) dependent activation of caspase-2. In turn, caspase-2 cleaves and activates Bid, resulting in the oligomerization of Bak and the release of cytochrome c. Notably, the detachment of hexokinase II from the mitochondria markedly potentiates the onset of caspase-2 induced mitochondrial damage, thus resulting in a synergistic induction of cisplatin induced cytotoxicity.

Shulga, Nataly; Wilson-Smith, Robin; Pastorino, John G.

2010-01-01

274

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

275

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

276

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

2009-01-01

277

Magnetic and Cytotoxicity Properties of La1?xSrxMnO3(0 <= x <= 0.5) Nanoparticles Prepared by a Simple Thermal Hydro-Decomposition  

PubMed Central

This study reports the magnetic and cytotoxicity properties of magnetic nanoparticles of La1?xSrxMnO3(LSMO) withx = 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 ofx ? 0.3. Basic magnetic characteristics such as saturated magnetization (MS) and coercive field (HC) were evaluated by vibrating sample magnetometry at room temperature (20 °C). The samples show paramagnetic behavior for all the samples withx = 0 or LMO, and a superparamagnetic behavior for the other samples havingMSvalues of ~20–47 emu/g and theHCvalues 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.

2009-01-01

278

Protective effects of betulin and betulinic acid against ethanol-induced cytotoxicity in HepG2 cells.  

PubMed

Plant triterpenes, such as oleanolic acid and betulin were described as hepatoprotectants active against cytotoxicity of acetaminophen or cadmium. The aim of this paper is to compare the cytoprotective activity of betulin, betulinic acid and oleanolic acid against ethanol-induced cytotoxicity in HepG2 cells. The influence of three triterpenes on ethanol-induced production of superoxide anion and hydrogen peroxide was also examined. Among the examined triterpenes, betulin was the most active protectant of HepG2 cells against ethanol-induced cytotoxicity. Betulin and betulinic acid significantly decreased ethanol-induced production of superoxide anion. Oleanolic acid inhibited only ethanol- and phorbol ester-induced production of hydrogen peroxide. The results indicate that cytoprotective or antioxidative activity of triterpenes depends on their chemical structure. PMID:16227641

Szuster-Ciesielska, Agnieszka; Kandefer-Szersze?, Martyna

2005-01-01

279

Paclitaxel-loaded glyceryl palmitostearate nanoparticles: in vitro release and cytotoxic activity.  

PubMed

Solid lipid nanoparticles (SLNs) of paclitaxel using glyceryl palmitostearate (GPS) as matrix were prepared by modified hot homogenization method. The SLNs were characterized for mean particle size, percent entrapment efficiency, and zeta potential, which were found to be 207 nm, 96.26%, and -28.26 mV, respectively. Transmission electron microscopic studies revealed that the prepared SLNs were of spherical shape. Drug retarding efficiency of the lipid (GPS) was better in pH 7.4 compared with pH 3.5. The release profile showed tendency to follow Higuchi diffusion pattern in both the media. Chemosensitivity assay carried out using B16F10 cell lines showed that antiproliferative activity of paclitaxel was not hindered because of encapsulation. PMID:19255897

Shenoy, Vikram S; Gude, Rajiv P; Murthy, Rayasa S Ramchandra

2009-05-01

280

Peptide-induced patterning of gold nanoparticle thin films  

NASA Astrophysics Data System (ADS)

In this work, the use of patterned proteins and peptides for the deposition of gold nanoparticles on several substrates with different surface chemistries is presented. The patterned biomolecule on the surface acts as a catalyst to precipitate gold nanoparticles from a precursor solution of HAuCl 4 onto the substrate. The peptide patterning on the surfaces was accomplished by physical adsorption or covalent attachment. It was shown that by using covalent attachment with a linker molecule, the influence of the surface properties from the different substrates on the biomolecule adsorption and subsequent nanoparticle deposition could be avoided. By adjusting the reaction conditions such as pH or HAuCl 4 concentration, the sizes and morphologies of deposited gold nanoparticle agglomerates could be controlled. Two biomolecules were used for this experiment, 3XFLAG peptide and bovine serum albumin (BSA). A micro-transfer molding technique was used to pattern the peptides on the substrates, in which a pre-patterned poly(dimethylsiloxane) (PDMS) mold was used to deposit a lift-off pattern of polypropylmethacrylate (PPMA) on the various substrates. The proteins were either physically adsorbed or covalently attached to the substrates, and an aqueous HAuCl 4 solution was applied on the substrates with the protein micropatterns, causing the precipitation of gold nanoparticles onto the patterns. SEM, AFM, and Electron Beam Induced Current (EBIC) were used for characterization.

Borteh, Hassan M.; Ferrell, Nicholas J.; Butler, Randall T.; Olesik, Susan V.; Hansford, Derek J.

2011-10-01

281

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

Microsoft Academic Search

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

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

2011-01-01

282

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

PubMed

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 (10(7) 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. PMID:22264036

Nguyen, Kathy C; Seligy, Vern L; Tayabali, Azam F

2013-03-01

283

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

284

Protective effect of hydroxytyrosol against acrylamide-induced cytotoxicity and DNA damage in HepG2 cells  

Microsoft Academic Search

The chemoprotective effect of hydroxytyrosol (HT) against acrylamide (AA)-induced cytotoxicity and DNA damage was investigated in a human hepatoma cell line, HepG2. The cytotoxicity was estimated by methyl thiazol tetrazolium bromide (MTT) assay. The comet assay was used to monitor DNA damage. The intracellular reactive oxygen species (ROS) formation and the level of oxidative DNA damage were estimated by using

Xiaomei Zhang; Jun Cao; Liping Jiang; Chenyan Geng; Laifu Zhong

2009-01-01

285

Adiponectin protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity.  

PubMed

1-Methyl-4-phenylpyridinium ion (MPP+), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome characterized by elevation of intracellular reactive oxygen species level and apoptotic death. Adiponectin, secreted from adipose tissue, mediates systemic insulin sensitivity with liver and muscle as target organs. Adiponectin can also suppress superoxide generation in endothelial cells. In the present study, we investigated the protective effects of adiponectin on MPP+-induced cytotoxicity in human neuroblastoma SH-SY5Y cells, as well as the underlying mechanism. Our results suggest that the protective effects of adiponectin on MPP+-induced apoptosis may be ascribed to its anti-oxidative properties, anti-apoptotic activity via inducing expression of SOD and catalase, and regulation of Bcl-2 and Bax expression. These data indicated that adiponectin might provide a useful therapeutic strategy for the treatment of progressive neurodegenerative diseases such as Parkinson's disease. PMID:16554029

Jung, Tae Woo; Lee, Ji Young; Shim, Wan Sub; Kang, Eun Seok; Kim, Jong Sun; Ahn, Chul Woo; Lee, Hyun Chul; Cha, Bong Soo

2006-05-01

286

Potentiation of etoposide-induced cytotoxicity and DNA damage in CCRF-CEM cells by pretreatment with non-cytotoxic concentrations of arabinosyl cytosine.  

PubMed

Pretreatment of the human lymphoblastoid cell line CCRF-CEM with 0.02 microM arabinosyl cytosine (ara C) enhances both the cytotoxic and the DNA-damaging effects of etoposide. This concentration of ara C is itself non-cytotoxic and results in no detectable DNA damage as measured by alkaline elution. Ara C pretreatment results in the synchronisation of cells, a 24-h pretreatment resulting in the accumulation of cells in the early S phase. The sensitivity of cells to etoposide-induced cytotoxicity was increased 2.5 times and DNA damage was enhanced 1.66 times by this pretreatment. Maximal potentiation of etoposide-induced DNA damage (2.06-fold increase) was observed after 48 h continuous treatment with ara C, but no further enhancement of cytotoxicity occurred. Cell-cycle analysis demonstrated that 48 h ara C treatment resulted in the accumulation of cells in the late S/G2M phase. Cells returned to a normal cell-cycle distribution within 24 h of the removal of ara C, and the potentiation of etoposide activity was then reduced to a 1.3- to 1.4-fold level. DNA damage induced by etoposide following ara C pretreatment was qualitatively identical to that produced by etoposide alone, suggesting a mechanism involving topoisomerase II. To investigate this possibility, we measured topoisomerase II protein levels by immunoblotting. Measurement of topoisomerase II levels in whole-cell lysates of ara C-pretreated cells showed a 3- to 5-fold increase in topoisomerase levels relative to total protein content. This suggests that elevated enzyme levels may be responsible for the increased sensitivity of ara C-pretreated cells to etoposide. PMID:1333370

Chresta, C M; Hicks, R; Hartley, J A; Souhami, R L

1992-01-01

287

Cytotoxicity effects of metal oxide nanoparticles in human tumor cell lines  

NASA Astrophysics Data System (ADS)

Metallic and metal oxide nanoparticles (Nps) have a wide range of applications in various settings including household, cosmetics and chemical industries, as well as for coatings. Nevertheless, an in-depth study of the potential toxic effects of these Nps is still needed, in order to fulfill the mandatory requirement of ensuring the safety of workers, patients and the general public. In this study, Quick Cell colorimetric assays were used to evaluate the in vitro toxicity of different metal oxide Nps [Fe(II,III)Ox, TiOx, ZnO and CeO2] in several cell lines. The ZnO Nps were found to be highly toxic, with a lethal dose <=100 ?g/ml for all the cell lines studied. Western blot was also used to test the ability of the different Nps to activate the complement pathway. However, no activation of this cascade was observed when the Nps were added. In addition, the aggregation state and charge of the Nps in culture media was studied by dynamic light scattering (DLS) and measurement of zeta potential. Transmission Electron Microscopy was used to analyze Np uptake and localization at the cellular level.

Lozano, T.; Rey, M.; Rojas, E.; Moya, S.; Fleddermann, J.; Estrela-Lopis, I.; Donath, E.; Wang, B.; Mao, Z.; Gao, C.; González-Fernández, África

2011-07-01

288

Synergistic Cytotoxicity of Irinotecan and Cisplatin in Dual-Drug PSMA-Targeted Polymeric Nanoparticles  

PubMed Central

Aim Two unexplored aspects for irinotecan and cisplatin (I&C) combination chemotherapy are (1) actively targeting both drugs to a specific diseased cell type and (2) delivering both drugs on the same vehicle to ensure their synchronized entry into the cell at a well-defined ratio. In this work we report the use of targeted polymeric nanoparticles (NPs) to co-encapsulate and deliver I&C to cancer cells expressing the Prostate Specific Membrane Antigen (PSMA). Method We prepared targeted NPs in a single-step by mixing four different precursors inside microfluidic devices. Results I&C were encapsulated in 55-nm NPs and showed an 8-fold increase in internalization by PSMA-expressing LNCaP cells compared to non-targeted NPs. NPs co-encapsulating both drugs exhibited strong synergism in LNCaP cells with a combination index of 0.2. Conclusion The strategy of co-encapsulating both irinotecan and cisplatin in a single NP targeted to a specific cell type could potentially be used to treat different types of cancer.

Valencia, Pedro M.; Pridgen, Eric M.; Perea, Brian; Gadde, Suresh; Sweeney, Christopher; Kantoff, Philip W.; Lippard, Stephen J.; Langer, Robert; Karnik, Rohit; Farokhzad, Omid C.

2013-01-01

289

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?ą 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?ą after 2?h, at 5, 10, 100?µg?ml?ą after 4?h and at 10?µg?ml?ą 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

2012-06-01

290

Fluorescence behavior of non-functionalized carbon nanoparticles and their in vitro applications in imaging and cytotoxic analysis of cancer cells.  

PubMed

We report fluorescence behavior in non-functionalized carbon nanoparticles (NCNP) prepared from lamp soot and their application in imaging of normal and cancer cells. Structural characterization of these particles by Raman spectroscopy showed characteristic peaks located at 1350 and 1590 cm(-1) corresponding to the diamond-like (D) and graphite-like (G) bands of the carbon allotropes respectively with the characteristic ratio I(D)/I(G)=2.24. X-ray diffraction study confirmed the presence of amorphous as well as graphitized carbon in these nanostructures with minimum grain size ?2 nm. A typical luminescence lifetime measured by time resolved fluorescence spectroscopy was obtained 3.54 ns. The photoluminescence behavior of these particles was excitation dependent and gave off blue, green and red fluorescence under UV, blue and green excitation, respectively. Cellular uptake of these NCNP yielded excellent results for cell imaging of human embryonic kidney, lung carcinoma and breast adenocarcinoma cells. Cell imaging was further correlated with cytotoxicity in the above mentioned cell lines and also in leukemia cell lines. Dose dependant cytotoxicity was observed after 24 h up to 48 h of incubation of nanoparticles. Fluorescence microscopy of nanoparticle-cell interaction clearly indicated aggregation of the particles. PMID:22088754

Kumar, Pradip; Meena, Ramavtar; Paulraj, R; Chanchal, A; Verma, A K; Bohidar, H B

2012-03-01

291

Potentiation of cannabinoid-induced cytotoxicity in Mantle Cell Lymphoma through modulation of ceramide metabolism  

PubMed Central

Ceramide levels are elevated in Mantle Cell Lymphoma cells following treatment with cannabinoids. Here, we investigated the pathways of ceramide accumulation in the MCL cell line Rec-1 using the stable endocannabinoid analogue R(+)-methanandamide (R-MA). We further interfered with the conversion of ceramide into sphingolipids that promote cell growth. Treatment with R-MA led to increased levels of ceramide species C16, C18, C24 and C24:1 and transcriptional induction of ceramide synthases (CerSs) 3 and 6. The effects were attenuated using SR141716A, which has high affinity to cannabinoid receptor 1 (CB1). The CB1-mediated induction of CerS3 and CerS6 mRNA was confirmed using Win-55,212-2. Simultaneous silencing of CerS3 and CerS6 using siRNA abrogated the R-MA-induced accumulation of C16 and C24. Inhibition of either of the enzymes serine palmiotyl transferase, ceramide synthase, and dihydroceramide desaturase within the de novo ceramide pathway reversed ceramide accumulation and cell death induced by R-MA treatment. In order to enhance the cytotoxic effect R-MA, sphingosine kinase-1 (SK-1) and glucosylceramide synthase (GCS), enzymes that convert ceramide to the pro-proliferative sphingolipids sphingosine-1-phospate and glucosylceramide, respectively, were inhibited. Suppression of either enzyme using inhibitors or siRNA potentiated the decreased viability, induction of cell death and ceramide accumulation induced by R-MA treatment. Our findings suggest that R-MA induces cell death in MCL via CB1-mediated upregulation of the de novo ceramide synthesis pathway. Furthermore, inhibition of SK-1 and GCS potentiated ceramide accumulation and cell death induced by R-MA. This is the first study were the cytotoxic effect of a cannabinoid is enhanced by modulation of ceramide metabolism.

Gustafsson, Kristin; Sander, Birgitta; Bielawski, Jacek; Hannun, Yusuf A.; Flygare, Jenny

2011-01-01

292

Self-reporter shikonin-Act-loaded solid lipid nanoparticle: formulation, physicochemical characterization and geno/cytotoxicity evaluation.  

PubMed

Shikonin and some of its derivative have approved apoptotic potential in different human cancer cell lines, and moreover have a dominant fluorescent emission at ?600nm. Here, to enhance shikonin-Act anti-proliferation properties, it was successfully incorporated in Solid Lipid Nanoparticles (SLNs) by the hot homogenization and entrapment efficiency (EE) of drug in SLNs was determined by ultrafiltration method. Scanning electron microscopy (SEM), laser diffractometry and zeta-sizer indicated that shikonin-Act-SLN were spherical and regular particles in the range of 70-120nm with polydispersity index (PI) of less than 0.10. The physical stability of shikonin-Act-loaded SLN in aqueous dispersion was evaluated in terms of size, PI, EE and drug leakage and the results showed that SLNs were stable upon storing three month. Long term in vitro release of the shikonin-Act was also approved. Cellular uptake of the shikonin-Act-SLN was examined by the in vitro fluorescent microscopy and facs flow cytometry analyses. In vivo rat imaging approved the penetrating capability of shikonin-Act-SLN emission through living tissues. In vitro anti-proliferation and genotoxicity evaluation by MTT and comet assay confirmed that shikonin-Act-SLN showed higher cytotoxic/antitumor potential than intact shikonin in terms of IC50 and DNA damage. This work provide sufficient information about improving of the therapeutic efficacy of the shikonin-Act, and also using of the shikonin-Act-SLN in bio-distribution studies during drug delivery investigation by incorporating in lipidic and colloidal drug delivery particles such as SLNs. PMID:24768857

Eskandani, Morteza; Nazemiyeh, Hossein

2014-08-01

293

In vivo and in vitro evaluation of the cytotoxic effects of Photosan-loaded hollow silica nanoparticles on liver cancer  

PubMed Central

This study aimed to compare the inhibitory effects of photosensitizers loaded in hollow silica nanoparticles and conventional photosensitizers on HepG2 human hepatoma cell proliferation and determine the underlying mechanisms. Photosensitizers (conventional Photosan-II or nanoscale Photosan-II) were administered to in vitro cultured HepG2 hepatoma cells and treated by photodynamic therapy (PDT) with various levels of light exposure. To assess photosensitizers' effects, cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, apoptotic and necrotic cells were measured by flow cytometry and the expression of caspase-3 and caspase-9 evaluated by western blot. Finally, the in vivo effects of nanoscale and conventional photosensitizers on liver cancer were assessed in nude mice. Nanoscale Photosan-II significantly inhibited hepatoma cell viability in a concentration-dependent manner and this effect was more pronounced with high laser doses. Moreover, nanoscale photosensitizers performed better than the conventional ones under the same experimental conditions (p?induced cell death was markedly increased after treatment with nanoscale Photosan-II in comparison with free Photosan-II (p?nanoparticles than free Photosan-II (p?nanoparticles containing photosensitizer more efficiently inhibited hepatoma cells than photosensitizer alone, through induction of apoptosis, both in vivo and in vitro.

2014-01-01

294

Mesoporous silica shell alleviates cytotoxicity and inflammation induced by colloidal silica particles.  

PubMed

Core-shell mesoporous silica (MPS) materials have been proven to perform multiple simultaneous functions in biological systems and they demonstrate a vast potential for applications in the medical arena. Exploring such extensive potential requires a meticulous evaluation of their interactions with cells. The aim of this study is to investigate the influence of MPS-shells on the viability and activation of human THP-1 macrophages by comparing core-shell MPS with colloidal silica particles. In the present study we find core-shell MPS particles with a solid colloidal silica core and a thin MPS-shell deliver significantly less cytotoxicity than their nonporous counterparts and induce lower expression and release of the pro-inflammatory cytokines in macrophages. Moreover, core-shell MPS particles show no effect on the activation of mitogen-activated protein kinases (MAPKs), while colloidal silica particles do activate MAPKs under identical conditions. The corona of core-shell MPS particles is composed of a greater amount and variety of proteins as compared with colloidal silica particles. The abundant protein composition of the corona may inhibit the cellular toxicity by masking surface silanol groups at the MPS-cellular interface. In conclusion, the MPS-shell significantly alleviates both cytotoxicity and immune responses induced by colloidal silica particles while greatly improving the biocompatibility of colloidal silica materials. PMID:24513963

Wang, Jie; Shen, Yuqing; Bai, Ling; Lv, Dan; Zhang, Aifeng; Miao, Fengqin; Tang, Meng; Zhang, Jianqiong

2014-04-01

295

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 IC?? 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

2013-09-27

296

Cytotoxic Effect of Icaritin and Its Mechanisms in Inducing Apoptosis in Human Burkitt Lymphoma Cell Line  

PubMed Central

Icaritin (ICT), a hydrolytic product of icariin from Epimedium genus, exhibits antitumor activities in several human solid-tumor and myeloid leukemia cells with extensive influence on various cell signal molecules, such as MAPKs being involved in cell proliferation and Bcl-2 participating in cell apoptosis. However, the effect of icaritin on Burkitt Lymphoma has not been elucidated. In the present study, we first screened the potential effect of icaritin on Burkitt lymphoma Raji and P3HR-1 cell lines and found that icaritin showed cytotoxicity in both cell lines. We further found that icaritin could significantly inhibit Raji cells proliferation with S-phase arrest of cell cycle and induced cell apoptosis accompanied by activation of caspase-8 and caspase-9 and cleavage of PARP. We also observed that icaritin was able to decrease Bcl-2 levels, thus shifting the Bcl-2/Bax ratio, and it could obviously reduce c-Myc, a specific molecular target in Burkitt lymphoma. Our findings demonstrated that icaritin showed cytotoxicity, inhibited cell growth, caused S arrest, and induced apoptosis in Burkitt lymphoma cells and provided a rationale for the further evaluation of icaritin for Burkitt lymphoma therapy.

Yao, Can; Liu, Su-Fang; Chen, Long; Xi, Ya-Ming; Zhang, Wen; Zhang, Guang-Sen

2014-01-01

297

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. PMID:23950208

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

2013-10-01

298

SN38 polymeric nanoparticles: In vitro cytotoxicity and in vivo antitumor efficacy in xenograft balb/c model with breast cancer versus irinotecan.  

PubMed

SN38 (7-ethyl-10-hydroxyl camptothecin), a potent metabolite of irinotecan, has been considered as an anticancer candidate. Its clinical development has been hampered due to its poor solubility. As a result, SN38 loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) was developed in current study to solve its poor water solubility problem while maintaining its cytotoxicity against cancer cells. PLGA NPs were prepared using modified emulsification-solvent evaporation technique and their characteristics were optimized by central composite experimental design in which average size, entrapment efficiency and drug loading were 170.5±11.87nm, 77.35%±2.314 and 5.95%±0.087, respectively. Scanning electron microscopy and in vitro studies consisting of drug release and cytotoxicity in 4T1 breast cancer cells followed by in vivo biodistribution and blood cytotoxicity were carried out. Therapeutic efficacy of SN38-NPs was evaluated in xenograft balb/c animal with 4T1 breast cancer. The results demonstrated that the treatment with SN38-NPs was more efficacious in comparison with irinotecan. In conclusion, superior cytotoxic effect and improved in vivo antitumor efficacy of SN38-NPs versus irinotecan introduced SN38-NPs as a promising candidate for cancer treatment investigation. PMID:24879937

Sepehri, Nima; Rouhani, Hasti; Tavassolian, Faranak; Montazeri, Hamed; Khoshayand, Mohammad Reza; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Atyabi, Fatemeh; Dinarvand, Rassoul

2014-08-25

299

Nanoparticle-induced vascular blockade in human prostate cancer  

PubMed Central

The tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) specifically homes to tumors by binding to fibrin and fibrin-associated clotted plasma proteins in tumor vessels. Previous results show that CREKA-coated superparamagnetic iron oxide particles can cause additional clotting in tumor vessels, which creates more binding sites for the peptide. We have used this self-amplifying homing system to develop theranostic nanoparticles that simultaneously serve as an imaging agent and inhibit tumor growth by obstructing tumor circulation through blood clotting. The CREKA nanoparticles were combined with nanoparticles coated with another tumor-homing peptide, CRKDKC, and nanoparticles with an elongated shape (nanoworms) were used for improved binding efficacy. The efficacy of the CREKA peptide was then increased by replacing some residues with nonproteinogenic counterparts, which increased the stability of the peptide in the circulation. Treatment of mice bearing orthotopic human prostate cancer tumors with the targeted nanoworms caused extensive clotting in tumor vessels, whereas no clotting was observed in the vessels of normal tissues. Optical and magnetic resonance imaging confirmed tumor-specific targeting of the nanoworms, and ultrasound imaging showed reduced blood flow in tumor vessels. Treatment of mice with prostate cancer with multiple doses of the nanoworms induced tumor necrosis and a highly significant reduction in tumor growth.

Agemy, Lilach; Sugahara, Kazuki N.; Kotamraju, Venkata Ramana; Gujraty, Kunal; Girard, Olivier M.; Kono, Yuko; Mattrey, Robert F.; Park, Ji-Ho; Sailor, Michael J.; Jimenez, Ana I.; Cativiela, Carlos; Zanuy, David; Sayago, Francisco J.; Aleman, Carlos; Nussinov, Ruth

2010-01-01

300

Nickel (II)-induced cytotoxicity and apoptosis in human proximal tubule cells through a ROS- and mitochondria-mediated pathway  

SciTech Connect

Nickel compounds are known to be toxic and carcinogenic in kidney and lung. In this present study, we investigated the roles of reactive oxygen species (ROS) and mitochondria in nickel (II) acetate-induced cytotoxicity and apoptosis in the HK-2 human renal cell line. The results showed that the cytotoxic effects of nickel (II) involved significant cell death and DNA damage. Nickel (II) increased the generation of ROS and induced a noticeable reduction of mitochondrial membrane potential (MMP). Analysis of the sub-G1 phase showed a significant increase in apoptosis in HK-2 cells after nickel (II) treatment. Pretreatment with N-acetylcysteine (NAC) not only inhibited nickel (II)-induced cell death and DNA damage, but also significantly prevented nickel (II)-induced loss of MMP and apoptosis. Cell apoptosis triggered by nickel (II) was characterized by the reduced protein expression of Bcl-2 and Bcl-xL and the induced the protein expression of Bad, Bcl-Xs, Bax, cytochrome c and caspases 9, 3 and 6. The regulation of the expression of Bcl-2-family proteins, the release of cytochrome c and the activation of caspases 9, 3 and 6 were inhibited in the presence of NAC. These results suggest that nickel (II) induces cytotoxicity and apoptosis in HK-2 cells via ROS generation and that the mitochondria-mediated apoptotic signaling pathway may be involved in the positive regulation of nickel (II)-induced renal cytotoxicity.

Wang, Yi-Fen; Shyu, Huey-Wen [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Chang, Yi-Chuang [Department of Nursing, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Nursing, Fooyin University, Kaohsiung, Taiwan (China); Tseng, Wei-Chang [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Huang, Yeou-Lih [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Lin, Kuan-Hua; Chou, Miao-Chen; Liu, Heng-Ling [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Chen, Chang-Yu, E-mail: mt037@mail.fy.edu.tw [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)

2012-03-01

301

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

302

Endoplasmic reticulum stress induced by zinc oxide nanoparticles is an earlier biomarker for nanotoxicological evaluation.  

PubMed

Zinc oxide nanoparticles (ZnO NPs) have been widely used in cosmetics and sunscreens, advanced textiles, self-charging and electronic devices; the potential for human exposure and the health impact at each stage of their manufacture and use are attracting great concerns. In addition to pulmonary damage, nanoparticle exposure is also strongly correlated with the increase in incidences of cardiovascular diseases; however, their toxic potential remains largely unclear. Herein, we investigated the cellular responses and endoplasmatic reticulum (ER) stress induced by ZnO NPs in human umbilical vein endothelial cells (HUVECs) in comparison with the Zn2+ ions and CeO2 NPs. We found that the dissolved zinc ion was the most significant factor for cytotoxicity in HUVECs. More importantly, ZnO NPs at noncytotoxic concentration, but not CeO2 NPs, can induce significant cellular ER stress response with higher expression of spliced xbp-1, chop, and caspase-12 at the mRNA level, and associated ER marker proteins including BiP, Chop, GADD34, p-PERK, p-eIF2?, and cleaved Caspase-12 at the protein levels. Moreover, ER stress was widely activated after treatment with ZnO NPs, while six of 84 marker genes significantly increased. ER stress response is a sensitive marker for checking the interruption of ER homeostasis by ZnO NPs. Furthermore, higher dosage of ZnO NPs (240 ?M) quickly rendered ER stress response before inducing apoptosis. These results demonstrate that ZnO NPs activate ER stress-responsive pathway and the ER stress response might be used as an earlier and sensitive end point for nanotoxicological study. PMID:24490819

Chen, Rui; Huo, Lingling; Shi, Xiaofei; Bai, Ru; Zhang, Zhenjiang; Zhao, Yuliang; Chang, Yanzhong; Chen, Chunying

2014-03-25

303

Tetrahydroxystilbene glucoside protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity.  

PubMed

1-methyl-4-phenylpyridinium (MPP+), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin for inducing a cell model of Parkinson's disease. This study aimed to evaluate the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-?-D-glucoside (TSG), an active component extracted from Polygonum multiflorum, on MPP+-induced cytotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells. The results from the MTT and lactate dehydrogenase (LDH) assays showed that incubating cells with 500 ?M MPP+ for 24 h decreased cell viability and increased LDH leakage, whereas preincubating cells with 3.125 to 50 ?M TSG for 24 h protected the cells against MPP+-induced cell damage. Using 2',7'-dichlorofluorescin diacetate (DCFH-DA) and rhodamine 123, respectively, we found that TSG inhibited both the elevation of intracellular reactive oxygen species and the disruption of mitochondrial membrane potential induced by MPP+. In addition, TSG suppressed both the upregulation of the ratio of Bax to Bcl-2 and the activation of caspase-3 induced by MPP+, and TSG inhibited apoptosis as detected by flow cytometric analysis using Annexin-V and propidium (PI) label. These results suggest that TSG may protect neurons against MPP+-induced cell death through improving mitochondrial function, decreasing oxidative stress and inhibiting apoptosis, and this may provide a potentially new strategy for preventing and treating neurodegenerative disorders such as Parkinson's disease. PMID:21497157

Sun, Fang-ling; Zhang, Lan; Zhang, Ru-yi; Li, Lin

2011-06-25

304

Synthesis, Characterization, In Vitro Cytotoxicity, and Apoptosis-Inducing Properties of Ruthenium(II) Complexes  

PubMed Central

Two new Ru(II) complexes, [Ru(bpy)2(FAMP)](ClO4)2 1 and 2, are synthesized and characterized by elemental analysis, electrospray mass spectrometry, and 1H nuclear magnetic resonance. The in vitro cytotoxicities and apoptosis-inducing properties of these complexes are extensively studied. Complexes 1 and 2 exhibit potent antiproliferative activities against a panel of human cancer cell lines. The cell cycle analysis shows that complexes 1 and 2 exhibit effective cell growth inhibition by triggering G0/G1 phase arrest and inducing apoptosis by mitochondrial dysfunction. The in vitro DNA binding properties of the two complexes are investigated by different spectrophotometric methods and viscosity measurements.

Xu, Li; Zhong, Nan-Jing; Xie, Yang-Yin; Huang, Hong-Liang; Jiang, Guang-Bin; Liu, Yun-Jun

2014-01-01

305

Streptozotocin-Induced Cytotoxicity, Oxidative Stress and Mitochondrial Dysfunction in Human Hepatoma HepG2 Cells  

PubMed Central

Streptozotocin (STZ) is an antibiotic often used in the treatment of different types of cancers. It is also highly cytotoxic to the pancreatic beta-cells and therefore is commonly used to induce experimental type 1 diabetes in rodents. Resistance towards STZ-induced cytotoxicity in cancer cells has also been reported. Our previous studies have reported organ-specific toxicity and metabolic alterations in STZ-induced diabetic rats. STZ induces oxidative stress and metabolic complications. The precise molecular mechanism of STZ-induced toxicity in different tissues and carcinomas is, however, unclear. We have, therefore, investigated the mechanism of cytotoxicity of STZ in HepG2 hepatoma cells in culture. Cells were treated with different doses of STZ for various time intervals and the cytotoxicity was studied by observing the alterations in oxidative stress, mitochondrial redox and metabolic functions. STZ induced ROS and RNS formation and oxidative stress as measured by an increase in the lipid peroxidation as well as alterations in the GSH-dependent antioxidant metabolism. The mitochondria appear to be a highly sensitive target for STZ toxicity. The mitochondrial membrane potential and enzyme activities were altered in STZ treated cells resulting in the inhibition of ATP synthesis. ROS-sensitive mitochondrial aconitase activity was markedly inhibited suggesting increased oxidative stress in STZ-induced mitochondrial toxicity. These results suggest that STZ-induced cytotoxicity in HepG2 cells is mediated, at least in part, by the increase in ROS/RNS production, oxidative stress and mitochondrial dysfunction. Our study may be significant for better understanding the mechanisms of STZ action in chemotherapy and drug induced toxicity.

Raza, Haider; John, Annie

2012-01-01

306

Survivin-miRNA-loaded nanoparticles as auxiliary tools for radiation therapy: preparation, characterisation, drug release, cytotoxicity and therapeutic effect on colorectal cancer cells.  

PubMed

One of the main challenges in radiation oncology is to overcome the resistance of cancer cells against treatment by molecular targeted approaches. Among the most promising targets is the inhibitor of apoptosis protein survivin, known to be associated with increased tumour aggressiveness and therapy resistance. The objective of this study was the development of a human serum albumin-based nanoparticulate carrier system for plasmid-mediated RNA interference (miRNA) and the investigation of its in vitro efficacy on survivin knockdown and cellular toxicity in SW480 colorectal cancer cells. The results demonstrate a robust nanoparticulate system of a size around 220?nm with a plasmid incorporation efficacy of about 90%. Moreover, treatment of carcinoma cells with survivin-miRNA nanoparticles resulted in reduction of survivin expression by 50% and increased cytotoxicity if combined with ionising irradiation. These nanoparticles comprise a promising option to enhance the response of carcinoma cells to therapy with ionising irradiation. PMID:22703230

Gaca, Sebastian; Reichert, Sebastian; Rödel, Claus; Rödel, Franz; Kreuter, Jörg

2012-01-01

307

Schisandra fructus extract ameliorates doxorubicin-induce cytotoxicity in cardiomyocytes: altered gene expression for detoxification enzymes  

PubMed Central

The effect of Schisandra fructus extract (SFE) on doxorubicin (Dox)-induced cardiotoxicity was investigated in H9c2 cardiomyocytes. Dox, which is an antineoplastic drug known to induce cardiomyopathy possibly through production of reactive oxygen species, induced significant cytotoxicity, intracellular reactive oxygen species (ROS), and lipid peroxidation. SFE treatment significantly increased cell survival up to 25%, inhibited intracellular ROS production in a time- and dose-dependent manner, and inhibited lipid peroxidation induced by Dox. In addition, SFE treatment induced expression of cellular glutathione S-transferases (GSTs), which function in the detoxification of xenobiotics, and endogenous toxicants including lipid peoxides. Analyses of 31,100 genes using Affymetrix cDNA microarrays showed that SFE treatment up-regulated expression of genes involved in glutathione metabolism and detoxification [GST theta 1, mu 1, and alpha type 2, heme oxygenase 1 (HO-1), and microsomal epoxide hydrolase (mEH)] and energy metabolism [carnitine palmitoyltransferase-1 (CPT-1), transaldolase, and transketolase]. These data indicated that SFE might increase the resistance to cardiac cell injury by Dox, at least partly, together with altering gene expression, especially induction of phase II detoxification enzymes.

Choi, Eun Hye; Lee, Nari; Kim, Hyun Jung; Kim, Mi Kyung; Chi, Sung-Gil; Kwon, Dae Young

2007-01-01

308

Stress-induced phase transformation and optical coupling of silver nanoparticle superlattices into mechanically stable nanowires.  

PubMed

One-dimensional silver materials display unique optical and electrical properties with promise as functional blocks for a new generation of nanoelectronics. To date, synthetic approaches and property engineering of silver nanowires have primarily focused on chemical methods. Here we report a simple physical method of metal nanowire synthesis, based on stress-induced phase transformation and sintering of spherical Ag nanoparticle superlattices. Two phase transformations of nanoparticles under stress have been observed at distinct length scales. First, the lattice dimensions of silver nanoparticle superlattices may be reversibly manipulated between 0-8?GPa compressive stresses to enable systematic and reversible changes in mesoscale optical coupling between silver nanoparticles. Second, stresses greater than 8?GPa induced an atomic lattice phase transformation, which induced sintering of silver nanoparticles into micron-length scale nanowires. The nanowire synthesis mechanism displays a dependence on both nanoparticle crystal surface orientation and presence of particular grain boundaries to enable nanoparticle consolidation into nanowires. PMID:24957078

Li, Binsong; Wen, Xiaodong; Li, Ruipeng; Wang, Zhongwu; Clem, Paul G; Fan, Hongyou

2014-01-01

309

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

2012-08-01

310

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

PubMed Central

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 and by flow cytometry. The mitochondrial membrane potential and reactive oxygen species production was evaluated by flow cytometry analysis. The role of caspase activities were assayed using caspase apoptosis detection kit . Western blot analysis was used to evaluate the level of Cyto-C, Bcl-2, Bax, Bid, caspase 3, -9, -8 and PARP expression Results After treatment with NCTD, a decrease in the viability of HepG2 cells and increase in apoptosis were observed. NCTD-induced apoptosis was accompanied by an increase in ROS production, loss of mitochondrial membrane potential and release of cytochrome c(cyto-c) from the mitochondria to the cytosol and down-regulation of anti-apoptotic protein Bcl-2 levels with concurrent up-regulation in pro-apoptotic protein Bax levels. However, another pro-apoptotic molecule, Bid, showed no change in such same treatment. NCTD-increased activity of caspase 9,caspase 3 and the subsequent cleavage caspase substrate PARP were also observed. The expression levels of pro-caspase-8 were not changed after NCTD treatment. Conclusion These results indicate that NCTD induced cytotoxicity in HepG2 cells by apoptosis, which is mediated through ROS generation and mitochondrial pathway.

2010-01-01

311

Protective and curative effects of Cocos nucifera inflorescence on alloxan-induced pancreatic cytotoxicity in rats  

PubMed Central

Objectives: This study was planned to investigate the effects of pre and post-treatment of young inflorescence of Cocos nucifera (CnI) on alloxan-induced diabetic rats. Materials and Methods: Male albino Sprague Dawely rats were divided into five groups of six animals each. Group I was normal control, Group II was diabetic control, Cocos nucifera Inflorescence (CnI) was fed along with diet [20% (w/w)] orally (Group III) for a period of 11 days prior to alloxan injection (150 mg/kg i.p.). The curative effect of CnI was evaluated at the same feeding levels in alloxan-induced diabetic rats (Group IV) for a period of 30 days. The effects of both pretreatment and post-treatment (Group V) were also evaluated. Biochemical parameters such serum glucose, hepatic glycogen, and enzymes involving carbohydrate metabolism (hexokinase, phosphoglucomutase, pyruvate kinase, glucose-6-phosphatase, fructose 1, 6-diphosphatase, glucose-6 phosphate dehydrogenase, and glycogen phosphorylase) were assayed along with pancreatic histopathology. Data were analyzed using one-way analysis of variance followed by Duncan's post hoc multiple variance test. P < 0.05 was considered statistical significant. Results: Diabetic control rats showed significant increase in serum glucose (P < 0.05) and decrease in hepatic glycogen levels (P < 0.05) compared to normal rats, which was reversed to near normal in both CnI pretreated and post-treated rats. Treatment with CnI resulted in significant decrease (P < 0.05) in activities of gluconeogenic enzymes in Group III and IV on compared to the diabetic control group, while glycolytic enzyme activities were improved in these groups. The cytotoxicity of pancreatic islets also ameliorated by treatment with CnI on histopathological examination. Conclusion: The results obtained in the study indicate the protective and curative effects of CnI on alloxan-induced pancreatic cytotoxicity, which is mediated through the regulation of carbohydrate metabolic enzyme activities and islets cell repair.

Renjith, Raveendran S.; Rajamohan, Thankappan

2012-01-01

312

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

313

Murine cytomegalovirus-induced suppression of antigen-specific cytotoxic T lymphocyte maturation.  

PubMed

Antigen-specific cytotoxic T lymphocyte (CTL) maturation was inhibited in mice acutely infected with murine cytomegalovirus (MCMV). When immunization with Simian virus 40 (SV40) either preceded or followed infection with MCMV by 1 day, the frequency of SV40-specific CTL precursors among lymph node cells (LNC) was significantly reduced compared to noninfected mice. Replication of the herpesvirus in LNC could not be detected; however, MCMV rendered noninfectious by heat treatment was not suppressive to CTL development. Lymph node cells from nonimmunized, MCMV-infected mice contained a cell(s) present in low frequency which suppressed in vitro maturation of SV40 CTL in immune lymph nodes from mice not infected with MCMV. These suppressor cells did not affect the antigen- and interleukin-2-dependent growth nor cytotoxic activity of a mature, SV40-specific CTL clone. These results indicate that MCMV interferes with immunoregulatory functions required for development of antigen-specific CTL precursors to mature effector CTL. The immunosuppression is mediated at least in part by the MCMV-induced suppressor cell(s). PMID:2554572

Campbell, A E; Slater, J S; Futch, W S

1989-11-01

314

Contrasting effect of recombinant human erythropoietin on breast cancer cell response to cisplatin induced cytotoxicity  

PubMed Central

Background Human recombinant erythropoietin (rHuEpo) that is used for the treatment of the chemotherapy-induced anaemia in cancer patients was shown to cause detrimental effects on the course of disease due to increased adverse events inflicting patient’s survival, potentially related to rHuEpo-induced cancer progression. In this study, we elucidate the effect of rHuEpo administration on breast cancer cell proliferation and gene expression after cisplatin (cDDP) induced cytotoxicity. Materials and methods Two breast carcinoma models, MCF-7 and MDA-MB-231 cell lines, were used differing in oestrogen (ER) and progesterone (PR) receptors and p53 status. Cells were cultured with or without rHuEpo for 24 h or 9 weeks and their growth characteristics after cDDP treatment were assessed together with expression of genes involved in the p53-signaling pathway. Results Short-term exposure of breast cancer cells to rHuEpo lowers their proliferation and reduces cDDP cytotoxic potency. In contrast, long-term exposure of MCF-7 cells to rHuEpo increases proliferation and predisposes MCF-7 cells to cDDP cytotoxicity, but has no effect on MDA-MB-231 cells. MDA-MB-231 cells show altered level of ERK phosphorylation, indicating involvement of MAPK signalling pathway. Gene expression analysis of p53-dependent genes and bcl-2 gene family members confirmed differences between long and short-term rHuEpo effects, indicating the most prominent changes in BCL2 and BAD expression. Conclusions Proliferation and survival characteristics of MCF-7 cells are reversely modulated by the length of the rHuEpo exposure. On the other hand, MDA-MB-231 cells are almost irresponsive to long-term rHuEpo, supposedly due to the mutated p53 and ER(+)/PR(?) status. The p53 and ER/PR status may predict tumour response on rHuEpo and cDDP treatment.

Trost, Nina; Juvan, Peter; Sersa, Gregor; Debeljak, Natasa

2012-01-01

315

Cisplatin Induces a Mitochondrial-ROS Response That Contributes to Cytotoxicity Depending on Mitochondrial Redox Status and Bioenergetic Functions  

PubMed Central

Cisplatin is one of the most effective and widely used anticancer agents for the treatment of several types of tumors. The cytotoxic effect of cisplatin is thought to be mediated primarily by the generation of nuclear DNA adducts, which, if not repaired, cause cell death as a consequence of DNA replication and transcription blockage. However, the ability of cisplatin to induce nuclear DNA (nDNA) damage per se is not sufficient to explain its high degree of effectiveness nor the toxic effects exerted on normal, post-mitotic tissues. Oxidative damage has been observed in vivo following exposure to cisplatin in several tissues, suggesting a role for oxidative stress in the pathogenesis of cisplatin-induced dose-limiting toxicities. However, the mechanism of cisplatin-induced generation of ROS and their contribution to cisplatin cytotoxicity in normal and cancer cells is still poorly understood. By employing a panel of normal and cancer cell lines and the budding yeast Saccharomyces cerevisiae as model system, we show that exposure to cisplatin induces a mitochondrial-dependent ROS response that significantly enhances the cytotoxic effect caused by nDNA damage. ROS generation is independent of the amount of cisplatin-induced nDNA damage and occurs in mitochondria as a consequence of protein synthesis impairment. The contribution of cisplatin-induced mitochondrial dysfunction in determining its cytotoxic effect varies among cells and depends on mitochondrial redox status, mitochondrial DNA integrity and bioenergetic function. Thus, by manipulating these cellular parameters, we were able to enhance cisplatin cytotoxicity in cancer cells. This study provides a new mechanistic insight into cisplatin-induced cell killing and may lead to the design of novel therapeutic strategies to improve anticancer drug efficacy.

Marullo, Rossella; Werner, Erica; Degtyareva, Natalya; Moore, Bryn; Altavilla, Giuseppe; Ramalingam, Suresh S.; Doetsch, Paul W.

2013-01-01

316

Spred2 is involved in imatinib-induced cytotoxicity in chronic myeloid leukemia cells  

SciTech Connect

Spreds, a recently established class of negative regulators of the Ras-ERK (extracellular signal-regulated kinase) pathway, are involved in hematogenesises, allergic disorders and tumourigenesis. However, their role in hematologic neoplasms is largely unknown. Possible effects of Spreds on other signal pathways closely related to Ras-ERK have been poorly investigated. In this study, we investigated the in vitro effects of Spred2 on chronic myeloid leukemia (CML) cells. In addition to inhibiting the well-established Ras-ERK cascade, adenovirus-mediated Spred2 over-expression inhibits constitutive and stem cell factor (SCF)-stimulated sphingosine kinase-1 (SPHK1) and Mcl-1 expression, as well as inhibiting proliferation and inducing apoptosis in CML cells. In K562 cells and primary CML cells, imatinib induces endogenous Spred2 expression. Spred2 silencing by stable RNA interference partly protects K562 cells against imatinib-induced apoptosis. Together, these data implicate Spred2 in imatinib-induced cytotoxicity in CML cells, possibly by inhibiting the Ras-ERK cascade and the pro-survival signaling molecules SPHK1 and Mcl-1. These findings reveal potential targets for selective therapy of CML.

Liu, Xiao-Yun; Yang, Yue-Feng; Wu, Chu-Tse; Xiao, Feng-Jun; Zhang, Qun-Wei [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)] [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Ma, Xiao-Ni [Lanzhou University of Technology, Lanzhou 730050 (China)] [Lanzhou University of Technology, Lanzhou 730050 (China); Li, Qing-Fang; Yan, Jun [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)] [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Wang, Hua, E-mail: wanghualjh@gmail.com [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)] [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Wang, Li-Sheng, E-mail: wangls@nic.bmi.ac.cn [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)] [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)

2010-03-19

317

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

318

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

319

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

2012-12-16

320

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

2011-09-01

321

Micro-Raman Spectroscopy of Silver Nanoparticle Induced Stress on Optically-Trapped Stem Cells  

PubMed Central

We report here results of a single-cell Raman spectroscopy study of stress effects induced by silver nanoparticles in human mesenchymal stem cells (hMSCs). A high-sensitivity, high-resolution Raman Tweezers set-up has been used to monitor nanoparticle-induced biochemical changes in optically-trapped single cells. Our micro-Raman spectroscopic study reveals that hMSCs treated with silver nanoparticles undergo oxidative stress at doping levels in excess of 2 µg/ml, with results of a statistical analysis of Raman spectra suggesting that the induced stress becomes more dominant at nanoparticle concentration levels above 3 µg/ml.

Bankapur, Aseefhali; Krishnamurthy, R. Sagar; Zachariah, Elsa; Santhosh, Chidangil; Chougule, Basavaraj; Praveen, Bhavishna; Valiathan, Manna; Mathur, Deepak

2012-01-01

322

The effects of conjugate and light dose on photo-immunotherapy induced cytotoxicity  

PubMed Central

Background Photoimmunotherapy (PIT) is a highly cell-selective cancer therapy, which employs monoclonal antibodies conjugated to a potent photosensitizer (mAb-IR700). Once the conjugate has bound to the target cell, exposure to near infrared (NIR) light induces necrosis only in targeted cells with minimal damage to adjacent normal cells in vivo. Herein, we report on the effect of altering mAb-IR700 and light power and dose on effectiveness of PIT. Methods For evaluating cytotoxicity, we employed ATP-dependent bioluminescence imaging using a luciferase-transfected MDA-MB-468luc cell line, which expresses EGFR and luciferase. In in vitro experiments, panitumumab-IR700 (Pan-IR700) concentration was varied in combination with varying NIR light doses administered by an LED at one of three power settings, 100 mA and 400 mA continuous wave and 1733 mA intermittent wave. For in vivo experiments, the MDA-MB-468luc orthotopic breast cancer was treated with varying doses of Pan-IR700 and light. Results The in vitro cell study demonstrated that PIT induced cytotoxicity depended on light dose, when the conjugate concentration was kept constant. Increasing the dose of Pan-IR700 allowed lowering of the light dose to achieve equal effects thus indicating that for a given level of efficacy, the conjugate concentration multiplied by the light dose was a constant. A similar relationship between conjugate and light dose was observed in vivo. Conclusions The efficacy of PIT is defined by the product of the number of bound antibody conjugates and the dose of NIR light and can be achieve equally with continuous and pulse wave LED light using different power densities.

2014-01-01

323

Alcohol oxidizing enzymes and ethanol-induced cytotoxicity in rat pancreatic acinar AR42J cells.  

PubMed

Alcoholic chronic pancreatitis (ACP) is a serious inflammatory disease causing significant morbidity and mortality. Due to lack of a suitable animal model, the underlying mechanism of ACP is poorly understood. Chronic alcohol abuse inhibits alcohol dehydrogenase (ADH) and facilitates nonoxidative metabolism of ethanol to fatty acid ethyl esters (FAEEs) in the pancreas frequently damaged during chronic ethanol abuse. Earlier, we reported a concentration-dependent formation of FAEEs and cytotoxicity in ethanol-treated rat pancreatic tumor (AR42J) cells, which express high FAEE synthase activity as compared to ADH and cytochrome P450 2E1. Therefore, the present study was undertaken to investigate the role of various ethanol oxidizing enzymes in ethanol-induced pancreatic acinar cell injury. Confluent AR42J cells were pre-treated with inhibitors of ADH class I and II [4-methylpyrazole (MP)] or class I, II, and III [1,10-phenanthroline (PT)], cytochrome P450 2E1 (trans-1,2-dichloroethylene) or catalase (sodium azide) followed by incubation with 800 mg% ethanol at 37°C for 6 h. Ethanol metabolism, cell viability, cytotoxicity (apoptosis and necrosis), cell proliferation status, and formation of FAEEs in AR42J cells were measured. The cell viability and cell proliferation rate were significantly reduced in cells pretreated with 1,10-PT + ethanol followed by those with 4-MP + ethanol. In situ formation of FAEEs was twofold greater in cells incubated with 1,10-PT + ethanol and ?1.5-fold in those treated with 4-MP + ethanol vs. respective controls. However, cells treated with inhibitors of cytochrome P450 2E1 or catalase in combination of ethanol showed no significant changes either for FAEE formation, cell death or proliferation rate. Therefore, an impaired ADH class I-III catalyzed oxidation of ethanol appears to be a key contributing factor in ethanol-induced pancreatic injury via formation of nonoxidative metabolites of ethanol. PMID:24281792

Bhopale, Kamlesh K; Falzon, Miriam; Ansari, G A S; Kaphalia, Bhupendra S

2014-04-01

324

Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells.  

PubMed

We investigated if the antileukemic drug idarubicin induces autophagy, a process of programmed cellular self-digestion, in leukemic cell lines and primary leukemic cells. Transmission electron microscopy and acridine orange staining demonstrated the presence of autophagic vesicles and intracellular acidification, respectively, in idarubicin-treated REH leukemic cell line. Idarubicin increased punctuation/aggregation of microtubule-associated light chain 3B (LC3B), enhanced the conversion of LC3B-I to autophagosome-associated LC3B-II in the presence of proteolysis inhibitors, and promoted the degradation of the selective autophagic target p62, thus indicating the increase in autophagic flux. Idarubicin inhibited the phosphorylation of the main autophagy repressor mammalian target of rapamycin (mTOR) and its downstream target p70S6 kinase. The treatment with the mTOR activator leucine prevented idarubicin-mediated autophagy induction. Idarubicin-induced mTOR repression was associated with the activation of the mTOR inhibitor AMP-activated protein kinase and down-regulation of the mTOR activator Akt. The suppression of autophagy by pharmacological inhibitors or LC3B and beclin-1 genetic knockdown rescued REH cells from idarubicin-mediated oxidative stress, mitochondrial depolarization, caspase activation and apoptotic DNA fragmentation. Idarubicin also caused mTOR inhibition and cytotoxic autophagy in K562 leukemic cell line and leukocytes from chronic myeloid leukemia patients, but not healthy controls. By demonstrating mTOR-dependent cytotoxic autophagy in idarubicin-treated leukemic cells, our results warrant caution when considering combining idarubicin with autophagy inhibitors in leukemia therapy. PMID:24907655

Ristic, Biljana; Bosnjak, Mihajlo; Arsikin, Katarina; Mircic, Aleksandar; Suzin-Zivkovic, Violeta; Bogdanovic, Andrija; Perovic, Vladimir; Martinovic, Tamara; Kravic-Stevovic, Tamara; Bumbasirevic, Vladimir; Trajkovic, Vladimir; Harhaji-Trajkovic, Ljubica

2014-08-01

325

4-aminobenzoic acid-coated maghemite nanoparticles as potential anticancer drug magnetic carriers: a case study on highly cytotoxic Cisplatin-like complexes involving 7-azaindoles.  

PubMed

This study describes a one-pot synthesis of superparamagnetic maghemite-based 4-aminobenzoic acid-coated spherical core-shell nanoparticles (PABA@FeNPs) as suitable nanocomposites potentially usable as magnetic carriers for drug delivery. The PABA@FeNPs system was subsequently functionalized by the activated species (1* and 2*) of highly in vitro cytotoxic cis-[PtCl2(3Claza)2] (1; 3Claza stands for 3-chloro-7-azaindole) or cis-[PtCl2(5Braza)2] (2; 5Braza stands for 5-bromo-7-azaindole), which were prepared by a silver(I) ion assisted dechlorination of the parent dichlorido complexes. The products 1*@PABA@FeNPs and 2*@PABA@FeNPs, as well as an intermediate PABA@FeNPs, were characterized by a combination of various techniques, such as Mössbauer, FTIR and EDS spectroscopy, thermal analysis, SEM and TEM. The results showed that the products consist of well-dispersed maghemite-based nanoparticles of 13 nm average size that represent an easily obtainable system for delivery of highly cytotoxic cisplatin-like complexes in oncological practice. PMID:24476602

Starha, Pavel; Stavárek, Martin; Tu?ek, Ji?í; Trávní?ek, Zden?k

2014-01-01

326

Micro-Raman Spectroscopy of Silver Nanoparticle Induced Stress on Optically-Trapped Stem Cells  

Microsoft Academic Search

We report here results of a single-cell Raman spectroscopy study of stress effects induced by silver nanoparticles in human mesenchymal stem cells (hMSCs). A high-sensitivity, high-resolution Raman Tweezers set-up has been used to monitor nanoparticle-induced biochemical changes in optically-trapped single cells. Our micro-Raman spectroscopic study reveals that hMSCs treated with silver nanoparticles undergo oxidative stress at doping levels in excess

Aseefhali Bankapur; R. Sagar Krishnamurthy; Elsa Zachariah; Chidangil Santhosh; Basavaraj Chougule; Bhavishna Praveen; Manna Valiathan; Deepak Mathur

2012-01-01

327

Protective effects of Gastrodia elata Blume on MPP +-induced cytotoxicity in human dopaminergic SH-SY5Y cells  

Microsoft Academic Search

Aim of the studyGastrodia elata (GE) Blume (Orchidaceae) has been traditionally used as a folk medicine in Oriental countries since centuries for their variety of therapeutic benefits. This study is an attempt to investigate the protective effects of GE extract against MPP+-induced cytotoxicity in human dopaminergic SH-SY5Y cells and explore the neuroprotective mechanisms involved.

Hua An; In Su Kim; Sushruta Koppula; Byung Wook Kim; Pyo Jam Park; Beong Ou Lim; Wahn Soo Choi; Kwang Ho Lee; Dong Kug Choi

2010-01-01

328

Pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide attenuate glutamate-induced nNOS activation and cytotoxicity  

Microsoft Academic Search

Both vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) act as neurotransmitters in the central and peripheral nervous systems. Attention has been focused on these neuropeptides because among their numerous biological activities, they have been confirmed to show neuroprotective effects against ischemia and glutamate-induced cytotoxicity. It is well established that glutamate has excitatory effects on neuronal cells, and

Satomi Onoue; Kosuke Endo; Takehiko Yajima; Kazuhisa Kashimoto

2002-01-01

329

Effect of poly(ethylene glycol)-block-polylactide nanoparticles on hepatic cells of mouse: Low cytotoxicity, but efflux of the nanoparticles by ATP-binding cassette transporters  

Microsoft Academic Search

The objective of this paper is to study the effects of poly(ethylene glycol)-block-polylactide (PLA–PEG) nanoparticles on hepatic cells of mouse. Blank PLA–PEG nanoparticles have been successfully prepared and MTT assay suggested that the nanoparticles with HepG2 cell co-culture model did not cause significant changes in membrane integrity in controlled concentration range (0.001–0.1mg\\/ml). Immunohistochemical analysis demonstrated that large dose of PLA–PEG

Yangde Zhang; Zhiyuan Hu; Maoying Ye; Yifeng Pan; Jiji Chen; Yulin Luo; Yanqiong Zhang; Lianxiang He; Jiwei Wang

2007-01-01

330

Cytotoxic and cytokine inducing properties of Candida glabrata in single and mixed oral infection models  

PubMed Central

Oral candidiasis is a common opportunistic infection, with Candida albicans being the most prevalent etiologic agent and Candida glabrata emerging as an important pathogen. C. glabrata is frequently co-isolated with C. albicans from oral lesions. Although C. albicans has been shown to trigger significant cytokine responses and cell damage, C. glabrata has not been systematically studied yet. The purpose of this study was to characterize the ability of C. glabrata to induce proinflammatory cytokine responses and host damage as a single infecting organism and in combination with C. albicans, using in vitro models of the oral mucosa. In monolayer oral epithelial cell cultures, C. glabrata failed to induce a significant interleukin-1? and interleukin-8 cytokine response and showed lower cytotoxicity, compared to C. albicans. However, C. glabrata triggered a significantly higher granulocyte macrophage colony stimulating factor response than C. albicans. C. glabrata strains showed a strain-dependent tissue damaging ability and a superficial invasion of the mucosal compartment in a 3-dimensional (3-D) in vitro model of the human oral mucosa and submucosa. In the 3-D system, co-infection failed to promote host damage beyond the levels of infection with C. albicans alone. These studies indicate that C. glabrata induces cytokines in human oral epithelium in a strain-specific manner, but its tissue/cell damaging ability, compared to C. albicans, is low. Synergy between C. glabrata and C. albicans in cytokine induction and host damage was not observed with the strains tested.

Li, Lulu; Kashleva, Helena; Dongari-Bagtzoglou, Anna

2007-01-01

331

Antioxidant action of ellagic acid ameliorates paraquat-induced A549 cytotoxicity.  

PubMed

Ellagic acid (EA) is a natural dietary polyphenol whose benefits in a variety of diseases shown in epidemiological and experimental studies involve anti-inflammation, anti-proliferation, anti-angiogenesis, anti-carcinogenesis and anti-oxidation properties. This study aimed to evaluate the effect of EA against paraquat (PQ)-induced oxidative stress. PQ decreased the viability of A549 cells in dose- and time-dependent manners, which was associated with the massive generation of reactive oxygen species (ROS). However, cell viability was significantly recovered by the treatment of EA, from 47.01±1.59% to 66.04±2.84%. The release of lactate dehydrogenase (LDH) was also decreased with the treatment of EA in PQ-treated A549 cells. EA induced the level of expression and activation of nuclear factor-erythroid 2-related factor (Nrf2) and its target cytoprotective and antioxidant genes, heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1). The antioxidant potential of EA might be directly correlated with the increased expression of HO-1 and NQO1, whose expression may have surmounted the oxidative stress generated by PQ. Notably, EA treatment significantly reduced the levels of biochemical markers as lipid peroxidation, reduced the intracellular ROS level, and surmounted total glutathione level in A549 cells. Data indicate that the antioxidant and cytoprotective properties of EA reduce PQ-induced cytotoxicity in human alveolar A549 cells. PMID:23546295

Kim, Yong-Sik; Zerin, Tamanna; Song, Ho-Yeon

2013-01-01

332

Neoechinulin a impedes the progression of rotenone-induced cytotoxicity in PC12 cells.  

PubMed

Neoechinulin A, an indole alkaloid from marine fungi, can protect PC12 cells from the cytotoxicity of 1-methyl-4-phenylpyridinium (MPP(+)), a Parkinson disease-inducing neurotoxin, by ameliorating downstream events resulting from mitochondrial complex I inactivation. However, the cytoprotective mechanisms remained unclear. In this study, by using rotenone, another parkinsonian-inducing neurotoxin targeting mitochondrial complex I, we investigated the cytoprotective mechanism of neoechinulin A. Rotenone-induced cell death was associated with accelerated glucose consumption, and excess glucose supplementation in the culture medium almost completely suppressed cell death, suggesting that glucose deficiency in the medium is critical for triggering cell death in this model. Co-treatment with neoechinulin A, but not neoechinulin A pre-treatment before rotenone exposure, significantly impeded cell death by rotenone. Although the presence of neoechinulin A did not affect the accelerated glycolytic turnover in rotenone-treated cells, it paradoxically decreased ATP levels in the cells, suggesting increased ATP consumption. Although the link between the decreased ATP levels and cytoprotection is not clear at present, it suggests that neoechinulin A may ameliorate rotenone toxicity by activating a cytoprotective machinery that requires ATP. PMID:21415535

Akashi, Soichiro; Kimura, Tomonori; Takeuchi, Toshifumi; Kuramochi, Kouji; Kobayashi, Susumu; Sugawara, Fumio; Watanabe, Nobuo; Arai, Takao

2011-01-01

333

Low cytotoxicity porous Nd2(SiO4)3 nanoparticles with near infrared excitation and emission  

Microsoft Academic Search

Porous Nd2(SiO4)3 nanoparticles were successfully synthesized by a controlled route. This kind of silicate nanoparticle could be excited by near-infrared (NIR) radiation (808 nm) and triggered a NIR emission (1066 nm) at room temperature. By monitoring the 1066 nm emission, the long-lived luminescent lifetime was determined to be 19.5 µs. These NIR nanoparticles with appropriate diameters (<100 nm) were suitable

Xian-Hua Zhang; Dequan Zeng; Lei Zhang; Haomiao Zhu; Guang-Hui Jin; Zhaoxiong Xie; Xueyuan Chen; Junyong Kang; Lansun Zheng

2011-01-01

334

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

335

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

2013-01-01

336

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

337

Comparison of the cytotoxicity induced by different exposure to sodium arsenite in two fish cell lines.  

PubMed

Arsenic, a common environmental pollutant, is toxic to many mammalian cells. However, the arsenic-induced toxicity to aquatic animal species is unclear. This study attempted to compare the arsenic-induced cytotoxicity in various fish cells. Two fish cell lines, JF (fin cells of Therapon jarbua) and TO-2 cells (ovary cells of Tilapia), were treated with sodium arsenite in two ways to mimic acute and subacute exposure. The distinguishable alterations of cell morphology and microtubule network were observed in the cells treated by two arsenite exposure protocols. By the colony-forming assay, we demonstrated that the survival of both cell lines, treated with the high concentrations of arsenite (20-160 microM) for 2 h or with the low concentrations (0.125-10 microM) for 24 h, was decreased in a dose-dependent manner. The difference between the susceptibility of JF and TO-2 cells to arsenite was revealed by the factorial ANOVA to compare the survival rates of the arsenite-treated cells; JF cells were more sensitive than TO-2 cells (P = 0.008 and 0.013 for the high-concentration and the low-concentration treatment, respectively). The possible mechanisms to provoke the cytotoxicity of arsenite in two cell lines were also addressed. Antioxidants, N-acetyl-cysteine and dithiothreitol, significantly prevented JF cells, but not TO-2 cells, from the arsenite-induced inhibition of survival. Additionally, apparent apoptosis of JF cells and a mitotic arrest of TO-2 cells in response to the treatment of arsenite were also demonstrated by the DNA-fragmentation analysis and the flow cytometric analysis of cell-cycle progression. The results indicate that sodium arsenite induces apoptosis in JF cells probably by causing oxidative stress and disturbs the cell cycle of TO-2 cells. These two fish cell lines can serve as the potential tools to in detail study the toxicity and the hazards of arsenic compounds to aquatic animals at molecular level in the future. PMID:15210298

Wang, Yu-Chieh; Chaung, Ren-Haw; Tung, Li-Chu

2004-07-30

338

A comparative study of CdTe quantum dots and CdTe@SiO2 nanoparticles: fabrication and cytotoxicity in HEK293 cells.  

PubMed

Quantum Dots have shown remarkable potentials in biomedical research. Herein, we reported the effects of CdTe quantum dots (QDs) and CdTe@SiO2 nanoparticles (NPs) on human embryonic kidney 293 (HEK 293A) cells with the aim of investigating their in vitro cytotoxicity. The CdTe@SiO2 particles were prepared by reverse microemulsion method. The structural morphology of the CdTe and hydrophilic silica-coated CdTe particles were characterized by transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) spectrometry and photoluminescence (PL) spectrometry. The in vitro cytotoxicity of CdTe QDs and CdTe@SiO2 nanoparticles was assessed in 293A cells using standard MTT assay, western blot and fluorescent microscopy. The results showed that the CdTe and CdTe@SiO2 particles were relatively uniform with the diameter of about 3.8 nm, 75 nm respectively. The cell viability and the adhesion ability were similar to the control 293A cells. The level of the fibronectin protein expression was decreased with the increasing concentration of CdTe while the no effects were observed on expression of beta-actin in CdTe as well as CdTe@SiO2 treated cells even at highest concentration of 45 microg/mL which demonstrated their good biocompatibility to 293A cells. The results indicate that the CdTe@SiO2 nanoparticles are attractive candidates for biological imaging studies as expected. PMID:23035412

Sadaf, Asma; Zeshan, Basit; Wang, Zhuyuan; Zhang, Ruohu; Xu, Shuhong; Wang, Chunlei; Yang, Jing; Cui, Yiping

2012-09-01

339

A review on radiation-induced nucleation and growth of colloidal metallic nanoparticles  

PubMed Central

This review presents an introduction to the synthesis of metallic nanoparticles by radiation-induced method, especially gamma irradiation. This method offers some benefits over the conventional methods because it provides fully reduced and highly pure nanoparticles free from by-products or chemical reducing agents, and is capable of controlling the particle size and structure. The nucleation and growth mechanism of metallic nanoparticles are also discussed. The competition between nucleation and growth process in the formation of nanoparticles can determine the size of nanoparticles which is influenced by certain parameters such as the choice of solvents and stabilizer, the precursor to stabilizer ratio, pH during synthesis, and absorbed dose.

2013-01-01

340

Protective effect of vitamin E on chromium (VI)-induced cytotoxicity and lipid peroxidation in primary cultures of rat Hepatocytes  

Microsoft Academic Search

Pretreatment of primary cultures of rat hepatocytes with ?-tocopherol succinate (vitamin E) for 20?h prior to exposure to\\u000a K2Cr2O7 resulted in a marked decrease of chromium (VI)-induced cytotoxicity, as evaluated by the leakage of lactate dehydrogenase,\\u000a without affecting cellular uptake and subcellular distribution of chromium. The levels of chromium (VI)-induced lipid peroxidation,\\u000a as monitored by malondialdehyde formation, were also inhibited

Nobuyuki Susa; Shunji Ueno; Yoshinori Furukawa; Masayasu Sugiyama

1996-01-01

341

Aldose Reductase Mediates Endotoxin-Induced Production of Nitric oxide and Cytotoxicity in Murine Macrophages.  

PubMed Central

Aldose reductase (AR) is a ubiquitously expressed protein with pleiotrophic roles as an efficient catalyst for the reduction of toxic lipid aldehydes and mediator of hyperglycemia, cytokine and growth factor –induced redox sensitive signals that cause secondary diabetic complications. Although AR inhibition has been shown to be protective against oxidative stress signals, the role of AR in regulating nitric oxide (NO) synthesis and NO-mediated apoptosis has not been elucidated to date. We therefore investigated the role of AR in regulating lipopolysaccharide (LPS)-induced NO synthesis and apoptosis in RAW 264.7 macrophages. Inhibition or RNA interference ablation of AR suppressed LPS-stimulated production of NO and over-expression of iNOS mRNA. Inhibition or ablation of AR also prevented the LPS-induced apoptosis, cell cycle arrest, activation of caspase-3, p38-MAPK, JNK, NF-?B and AP1. In addition, AR inhibition prevented the LPS-induced down-regulation of Bcl-xl and up-regulation of Bax and Bak in macrophages. L-arginine increased and L-NAME decreased the severity of cell death caused by LPS and AR inhibitors prevented it. Furthermore, inhibition of AR prevents cell death caused by HNE and GS-HNE, but not GS-DHN. Our findings for the first time suggest that AR catalyzed lipid aldehyde-glutathione conjugates regulates the LPS-induced production of inflammatory marker NO and cytotoxicity in RAW 264.7 cells. Inhibition or ablation of AR activity may be potential therapeutic target in endotoximia and other inflammatory diseases.

Ramana, Kota V; Reddy, Aramati BM.; Tammali, Ravinder; Srivastava, Satish K.

2007-01-01

342

Curcumin Protects Human Keratinocytes against Inorganic Arsenite-Induced Acute Cytotoxicity through an NRF2-Dependent Mechanism  

PubMed Central

Human exposure to inorganic arsenic leads to various dermal disorders, including hyperkeratosis and skin cancer. Curcumin is demonstrated to induce remarkable antioxidant activity in a variety of cells and tissues. The present study aimed at identifying curcumin as a potent activator of nuclear factor erythroid 2-related factor 2 (NRF2) and demonstrating its protective effect against inorganic arsenite- (iAs3+-) induced cytotoxicity in human keratinocytes. We found that curcumin led to nuclear accumulation of NRF2 protein and increased the expression of antioxidant response element- (ARE-) regulated genes in HaCaT keratinocytes in concentration- and time-dependent manners. High concentration of curcumin (20??M) also increased protein expression of long isoforms of NRF1. Treatment with low concentrations of curcumin (2.5 or 5??M) effectively increased the viability and survival of HaCaT cells against iAs3+-induced cytotoxicity as assessed by the MTT assay and flow cytometry and also attenuated iAs3+-induced expression of cleaved caspase-3 and cleaved PARP protein. Selective knockdown of NRF2 or KEAP1 by lentiviral shRNAs significantly diminished the cytoprotection conferred by curcumin, suggesting that the protection against iAs3+-induced cytotoxicity is dependent on the activation of NRF2. Our results provided a proof of the concept of using curcumin to activate the NRF2 pathway to alleviate arsenic-induced dermal damage.

Zhao, Rui; Yang, Bei; Wang, Linlin; Xue, Peng; Deng, Baocheng; Zhang, Guohua; Jiang, Shukun; Zhang, Miao; Liu, Min; Pi, Jingbo; Guan, Dawei

2013-01-01

343

Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin.  

PubMed

Ganoderma lucidum (G. lucidum) is a medicinal mushroom long used in Asia as a folk remedy to promote health and longevity. Recent studies indicate that G. lucidum activates NK cells, but the molecular mechanism underlying this effect has not been studied so far. To address this question, we prepared a water extract of G. lucidum and examined its effect on NK cells. We observed that G. lucidum treatment increases NK cell cytotoxicity by stimulating secretion of perforin and granulysin. The mechanism of activation involves an increased expression of NKG2D and natural cytotoxicity receptors (NCRs), as well as increased phosphorylation of intracellular MAPKs. Our results indicate that G. lucidum induces NK cell cytotoxicity against various cancer cell lines by activating NKG2D/NCR receptors and MAPK signaling pathways, which together culminate in exocytosis of perforin and granulysin. These observations provide a cellular and molecular mechanism to account for the reported anticancer effects of G. lucidum extracts in humans. PMID:23803412

Chang, Chih-Jung; Chen, Yi-Yuan M; Lu, Chia-Chen; Lin, Chuan-Sheng; Martel, Jan; Tsai, Sheng-Hui; Ko, Yun-Fei; Huang, Tsung-Teng; Ojcius, David M; Young, John D; Lai, Hsin-Chih

2014-04-01

344

Development and validation of TOF-SIMS and CLSM imaging method for cytotoxicity study of ZnO nanoparticles in HaCaT cells.  

PubMed

Zinc oxide nanoparticles (ZnO NPs) exhibit novel physiochemical properties and have found increasing use in sunscreen products and cosmetics. The potential toxicity is of increasing concern due to their close association with human skin. A time-of-flight secondary ion mass spectrometry (TOF-SIMS) and confocal laser scanning microscopy (CLSM) imaging method was developed and validated for rapid and sensitive cytotoxicity study of ZnO NPs using human skin equivalent HaCaT cells as a model system. Assorted material, chemical, and toxicological analysis methods were used to confirm their shape, size, crystalline structure, and aggregation properties as well as dissolution behavior and effect on HaCaT cell viability in the presence of various concentrations of ZnO NPs in aqueous media. Comparative and correlative analyses of aforementioned results with TOF-SIMS and CLSM imaging results exhibit reasonable and acceptable outcome. A marked drop in survival rate was observed with 50?g/ml ZnO NPs. The CLSM images reveal the absorption and localization of ZnO NPs in cytoplasm and nuclei. The TOF-SIMS images demonstrate elevated levels of intracellular ZnO concentration and associated Zn concentration-dependent (40)Ca/(39)K ratio, presumably caused by the dissolution behavior of ZnO NPs. Additional validation by using stable isotope-labeled (68)ZnO NPs as tracers under the same experimental conditions yields similar cytotoxicity effect. The imaging results demonstrate spatially-resolved cytotoxicity relationship between intracellular ZnO NPs, (40)Ca/(39)K ratio, phosphocholine fragments, and glutathione fragments. The trend of change in TOF-SIMS spectra and images of ZnO NPs treated HaCaT cells demonstrate the possible mode of actions by ZnO NP involves cell membrane disruption, cytotoxic response, and ROS mediated apoptosis. PMID:24731914

Lee, Pei-Ling; Chen, Bo-Chia; Gollavelli, Ganesh; Shen, Sin-Yu; Yin, Yu-Sheng; Lei, Shiu-Ling; Jhang, Cian-Ling; Lee, Woan-Ruoh; Ling, Yong-Chien

2014-07-30

345

Effect of prolactin on carcinoembryonic antigen-specific cytotoxic T lymphocyte response induced by dendritic cells.  

PubMed

The cytokine hormone prolactin (PRL) has been shown previously to modulate native cellular responses and maturation of antigen-presenting cells. Here we have addressed its effect on the antigen-specific response of cytotoxic T lymphocytes (CTL). CTL were generated from HLA-A2 lymphocytes after three rounds of stimulation with autologous dendritic cells loaded with HLA-A2-restricted carcinoembrionic antigen (CEA) Cap-1 (YLSGANLNL) peptide. Selected cultures were expanded on cytokine-supplemented feeder-layers, enriched for CD8+ lymphocytes and analysed for PRL-receptor (PRL-R) expression and PRL responsiveness. Resting CD8+ lymphocytes were negative for PRL-R, whereas antigen-activated CD8+ lymphocytes derived from long-term cultures were highly positive. Results of a 51Cr release assay showed CTL killing of CEA-loaded, but not unloaded, T2 cell line and the CEA-positive gastric carcinoma cell line KATO, but not of the CEA-negative T leukaemia cell line Jurkat. Interferon (IFN)-gamma release, evaluated in an ELISPOT assay against CEA-loaded T2, was enhanced (P < 0.05) by concentrations of PRL (12-25 ng/ml) very close to the physiological levels (6-20 ng/ml), but was decreased (P < 0.05) by high concentrations (200 ng/ml). Pre-incubation of the stimulators with the anti-MHC class I MoAb W6.32 induced a 40-60% decrease of the PRL-boosted IFN-gamma release, thus proving the MHC restriction of the lymphocyte response. Cytotoxicity against CEA-loaded T2 and KATO cell lines was also increased by 12-25 ng (P < 0.05) and decreased (P < 0.05) by 200 ng PRL. Pre-incubation of CTL with an antibody specific for the PRL-R almost completely abrogated this effect. PMID:15270849

Matera, L; Beltramo, E; Martinuzzi, E; Buttiglieri, S

2004-08-01

346

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

2013-11-01

347

Novel magnetic iron oxide nanoparticles coated with poly(ethylene imine)-g-poly(ethylene glycol) for potential biomedical application: synthesis, stability, cytotoxicity and MR imaging.  

PubMed

Magnetic iron oxide nanoparticles have found application as contrast agents for magnetic resonance imaging (MRI) and as switchable drug delivery vehicles. Their stabilization as colloidal carriers remains a challenge. The potential of poly(ethylene imine)-g-poly(ethylene glycol) (PEGPEI) as stabilizer for iron oxide (?-Fe?O?) nanoparticles was studied in comparison to branched poly(ethylene imine) (PEI). Carrier systems consisting of ?-Fe?O?-PEI and ?-Fe?O?-PEGPEI were prepared and characterized regarding their physicochemical properties including magnetic resonance relaxometry. Colloidal stability of the formulations was tested in several media and cytotoxic effects in adenocarcinomic epithelial cells were investigated. Synthesized ?-Fe?O? cores showed superparamagnetism and high degree of crystallinity. Diameters of polymer-coated nanoparticles ?-Fe?O?-PEI and ?-Fe?O?-PEGPEI were found to be 38.7 ± 1.0 nm and 40.4 ± 1.6 nm, respectively. No aggregation tendency was observable for ?-Fe?O?-PEGPEI over 12 h even in high ionic strength media. Furthermore, IC?? values were significantly increased by more than 10-fold when compared to ?-Fe?O?-PEI. Formulations exhibited r? relaxivities of high numerical value, namely around 160 mM?ą s?ą. In summary, novel carrier systems composed of ?-Fe?O?-PEGPEI meet key quality requirements rendering them promising for biomedical applications, e.g. as MRI contrast agents. PMID:21315813

Schweiger, Christoph; Pietzonka, Clemens; Heverhagen, Johannes; Kissel, Thomas

2011-04-15

348

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

349

Discrete nanoparticles induce loss of Legionella pneumophila biofilms from surfaces.  

PubMed

Nanoparticles (NPs) have been shown to induce dispersal events in microbial biofilms but the mechanism of the dispersal is unknown. Biofilms contaminate many man-made aquatic systems such as cooling towers, spas and dental lines. Within these biofilms, Legionella pneumophila is a primary pathogen, leading to these environments serving as sources for disease outbreaks. Here we show a reduction in biofilm bio-volume upon treatment with citrate-coated 6-nm platinum NPs, polyethylene glycol (PEG)-coated 11-nm gold NPs, and PEG-coated 8-nm iron oxide NPs. Treatment with citrate-coated 8-nm silver NPs, however, did not reduce biomass. The synthesis of NPs that remain dispersed and resist irreversible aggregation in the exposure media appears to be a key factor in the ability of NPs to induce biofilm dispersal. PMID:23586422

Raftery, Tara D; Kerscher, Petra; Hart, Ashley E; Saville, Steven L; Qi, Bin; Kitchens, Christopher L; Mefford, Olin Thompson; McNealy, Tamara L

2014-08-01

350

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. PMID:23529952

Wang, Gang; Wang, JunJie; Luo, Jie; Wang, Lei; Chen, XuanLi; Zhang, LiPing; Jiang, ShanQing

2013-11-01

351

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

PubMed Central

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.

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

2013-01-01

352

Emodin elicits cytotoxicity in human lung adenocarcinoma A549 cells through inducing apoptosis.  

PubMed

This study investigated the mechanism of the cytotoxic effect of emodin, an active anthraquinone, on human lung adenocarcinoma A549 cells. In vitro growth inhibition and suppression on colony forming were used to evaluate the effects of emodin on A549 cells. Emodin's ability in changing the expressions of apoptosis-related genes was studied by real-time RT-PCR. Emodin could significantly inhibit the growth of A549 cells with IC50 = 16.85 ?g/ml (~60 ?M). It also concentration dependently inhibited the colony-forming ability of A549 cells with IC50 = 7.60 ?g/ml (~30 ?M). Hallmarks of apoptosis, such as single-strand DNA breakage and DNA fragmentation, were observed in A549 cells treated with emodin. Emodin (72 h) treatment could up-regulate the gene expression of FASL (p < 0.05) and down-regulate the gene expression of C-MYC (p < 0.01), but induce no significant changes in the gene expressions of MCL1, GAPDH, BAX and CCND1. These results suggest that emodin could induce growth inhibition and apoptosis in A549 cells through modifying the extrinsic apoptotic pathways and the induction of cell cycle arrest. PMID:23975033

Li, Wing-Yan; Ng, Yam-Fung; Zhang, Huan; Guo, Zi-Dong; Guo, De-Jian; Kwan, Yiu-Wa; Leung, George Pak-Heng; Lee, Simon Ming-Yuen; Yu, Peter Hoi-Fu; Chan, Shun-Wan

2014-04-01

353

The morphology of silver nanoparticles prepared by enzyme-induced reduction  

PubMed Central

Summary Silver nanoparticles were synthesized by an enzyme-induced growth process on solid substrates. In order to customize the enzymatically grown nanoparticles (EGNP) for analytical applications in biomolecular research, a detailed study was carried out concerning the time evolution of the formation of the silver nanoparticles, their morphology, and their chemical composition. Therefore, silver-nanoparticle films of different densities were investigated by using scanning as well as transmission electron microscopy to examine their structure. Cross sections of silver nanoparticles, prepared for analysis by transmission electron microscopy were additionally studied by energy-dispersive X-ray spectroscopy in order to probe their chemical composition. The surface coverage of substrates with silver nanoparticles and the maximum particle height were determined by Rutherford backscattering spectroscopy. Variations in the silver-nanoparticle films depending on the conditions during synthesis were observed. After an initial growth state the silver nanoparticles exhibit the so-called desert-rose or nanoflower-like structure. This complex nanoparticle structure is in clear contrast to the auto-catalytically grown spherical particles, which maintain their overall geometrical appearance while increasing their diameter. It is shown, that the desert-rose-like silver nanoparticles consist of single-crystalline plates of pure silver. The surface-enhanced Raman spectroscopic (SERS) activity of the EGNP structures is promising due to the exceptionally rough surface structure of the silver nanoparticles. SERS measurements of the vitamin riboflavin incubated on the silver nanoparticles are shown as an exemplary application for quantitative analysis.

Schuler, Thomas; Strelau, Katharina K; Weber, Karina; Cialla, Dana; Diegel, Marco; Mattheis, Roland; Berger, Andreas; Moller, Robert; Popp, Jurgen

2012-01-01

354

Mechanisms of Nanoparticle-Induced Oxidative Stress and Toxicity  

PubMed Central

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.

Wang, Liying

2013-01-01

355

Fabrication of chitosan nanoparticles with aggregation-induced emission characteristics and their applications in long-term live cell imaging.  

PubMed

Chitosan with tetraphenylethene pendants (TPE-CS) are synthesized by reaction between amine and isothiocyanate groups of chitosan and tetraphenylethene (TPE), respectively. Nanoparticles of TPE-CS (TPE-CS NPs) are fabricated by ionic gelation method. The NPs are uniform in size, spherical in shape, monodispersed, and positive in surface charge. The suspension of TPE-CS NPs emits strong blue fluorescence under photoexcitation due to the aggregation-induced emission characteristics of the TPE moieties. The NPs can be internalized into cytoplasm through endocytosis pathway and retain inside the live cells to image the cells. Cytotoxicity assay reveals that TPE-CS NPs are cytocompatible and thus can be used for long-term live cell imaging. PMID:23401040

Li, Min; Hong, Yuning; Wang, Zhengke; Chen, Sijie; Gao, Meng; Kwok, Ryan T K; Qin, Wei; Lam, Jacky W Y; Zheng, Qichang; Tang, Ben Zhong

2013-05-14

356

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

357

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

358

Genotoxicity of copper oxide and silver nanoparticles in the mussel Mytilus galloprovincialis.  

PubMed

Though there is some information on cytotoxicity of copper nanoparticles and silver nanoparticles on human cell lines, there is no information on their genotoxic and cytotoxic behaviour in bivalve molluscs. The aim of this study was to investigate the genotoxic impact of copper oxide and silver nanoparticles using mussels Mytilus galloprovincialis. Mussels were exposed to 10 ?g L?ą of CuO nanoparticles and Cu˛? and Ag nanoparticles and Ag? for 15 days to assess genotoxic effects in hemocytes using the comet assay. The results obtained indicated that copper and silver forms (nanoparticles and ionic) induced DNA damage in hemolymph cells and a time-response effect was evident when compared to unexposed mussels. Ionic forms presented higher genotoxicity than nanoparticles, suggesting different mechanisms of action that may be mediated through oxidative stress. DNA strand breaks proved to be a useful biomarker of exposure to genotoxic effects of CuO and Ag nanoparticles in marine molluscs. PMID:23294529

Gomes, Tânia; Araújo, Olinda; Pereira, Rita; Almeida, Ana C; Cravo, Alexandra; Bebianno, Maria Joăo

2013-03-01

359

In vitro evaluation of cellular responses induced by ZnO nanoparticles, zinc ions and bulk ZnO in fish cells.  

PubMed

Zinc oxide nanoparticles (ZnO-NPs) are inevitably released into the environment and are potentially dangerous for aquatic life. However, the potential mechanisms of cytotoxicity of zinc nanoparticles remain unclear. Studying the toxicity of ZnO-NPs with In vitro systems will help to determine their interactions with cellular biomolecules. The aim of this study was to evaluate the cytotoxic potentials of ZnO-NPs in established fish cell lines (RTG-2, RTH-149 and RTL-W1) and compare them with those of bulk ZnO and Zn(2+) ions. Membrane function (CFDA-AM assay), mitochondrial function (MTT assay), cell growth (KBP assay), cellular stress (?-galactosidase assay), reductase enzyme activity (AB assay), reactive oxygen species (ROS), total glutathione cellular content (tGSH assay) and glutathione S-transferase (GST) activities were assessed for all cell lines. ZnO-NPs cytotoxicity was greater than those of bulk ZnO and Zn(2+). ZnO-NPs induced oxidative stress is dependent on their dose. Low cost tests, such as CFDA-AM, ROS, GST activity and tGSH cell content test that use fish cell lines, may be used to detect oxidative stress and redox status changes. Particle dissolution of the ZnO-NPs did not appear to play an important role in the observed toxicity in this study. PMID:23523724

Fernández, Dolores; García-Gómez, Concepción; Babín, Mar

2013-05-01

360

Stable nanoparticle aggregates/agglomerates of different sizes and the effect of their size on hemolytic cytotoxicity.  

PubMed

To study the toxicity of nanoparticles under relevant conditions, it is critical to disperse nanoparticles reproducibly in different agglomeration states in aqueous solutions compatible with cell-based assays. Here, we disperse gold, silver, cerium oxide, and positively-charged polystyrene nanoparticles in cell culture media, using the timing between mixing steps to control agglomerate size in otherwise identical media. These protein-stabilized dispersions are generally stable for at least two days, with mean agglomerate sizes of ?23 nm silver nanoparticles ranging from 43-1400 nm and average relative standard deviations of less than 10%. Mixing rate, timing between mixing steps and nanoparticle concentration are shown to be critical for achieving reproducible dispersions. We characterize the size distributions of agglomerated nanoparticles by further developing dynamic light scattering theory and diffusion limited colloidal aggregation theory. These theories frequently affect the estimated size by a factor of two or more. Finally, we demonstrate the importance of controlling agglomeration by showing that large agglomerates of silver nanoparticles cause significantly less hemolytic toxicity than small agglomerates. PMID:21142841

Zook, Justin M; Maccuspie, Robert I; Locascio, Laurie E; Halter, Melissa D; Elliott, John T

2011-12-01