Sample records for nanoparticles induced cytotoxicity

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

    PubMed Central

    2011-01-01

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

  2. Reactive oxygen species-induced cytotoxic effects of zinc oxide nanoparticles in rat retinal ganglion cells.

    PubMed

    Guo, Dadong; Bi, Hongsheng; Liu, Bing; Wu, Qiuxin; Wang, Daoguang; Cui, Yan

    2013-03-01

    Recent studies have proved that zinc oxide (ZnO) nanoparticles can cause toxicity in different cell lines, oxidative stress is often hypothesized to be an important factor in cytotoxicity of ZnO nanoparticles. However, the mechanisms are incompletely understood. The present study aimed to investigate the role of oxidative stress in toxicity and possible involvement of mitochondria in the production of reactive oxygen species (ROS) upon exposure of retinal ganglion cells (RGC-5) to ZnO nanoparticles. In this study, the effects of ZnO nanoparticles on mitochondrial membrane potential and ROS levels involved in hydrogen peroxide and hydroxyl radical production were investigated via inverted fluorescence microscope and hydrogen peroxide and hydroxyl radical assay kits, respectively. Furthermore, the mRNA of caspase-12 and the protein secreted into culture supernatant were also determined by means of real-time quantitative PCR and ELISA techniques. Our studies indicate that ZnO nanoparticles could apparently decrease the mitochondrial membrane potential, increase the production of ROS and lead to the overexpression of caspase-12 in RGC-5 cells, suggesting that ZnO nanoparticle-induced toxicity via ROS overproduction will trigger endoplasmic reticulum stress, lead to the RGC-5 cell damage and finally induce apoptosis/necrosis, the overexpression of caspase-12 may be involved in cell death in RGC-5 cells. PMID:23232460

  3. Excess titanium dioxide nanoparticles on the cell surface induce cytotoxicity by hindering ion exchange and disrupting exocytosis processes.

    PubMed

    Wang, Yanli; Yao, Chenjie; Li, Chenchen; Ding, Lin; Liu, Jian; Dong, Peng; Fang, Haiping; Lei, Zhendong; Shi, Guosheng; Wu, Minghong

    2015-07-23

    To date, considerable effort has been devoted to determine the potential toxicity of nanoparticles to cells and organisms. However, determining the mechanism of cytotoxicity induced by different types of nanoparticles remains challenging. Herein, typically low toxicity nanomaterials were used as a model to investigate the mechanism of cytotoxicity induced by low toxicity nanomaterials. We studied the effect of nano-TiO2, nano-Al2O3 and nano-SiO2 deposition films on the ion concentration on a cell-free system simulating the cell membrane. The results showed that the ion concentration of K(+), Ca(2+), Na(+), Mg(2+) and SO4(2-) decreased significantly following filtration of the prepared deposition films. More specifically, at a high nano-TiO2 concentration (200 mg L(-1)) and a long nano-TiO2 deposition time (48 h), the concentration of Na(+) decreased from 2958.01 to 2775.72, 2749.86, 2757.36, and 2719.82 mg L(-1), respectively, for the four types of nano-TiO2 studied. Likewise, the concentration of SO4(2-) decreased from 38.83 to 35.00, 35.80, 35.40, and 35.27 mg L(-1), respectively. The other two kinds of typical low toxicity nanomaterials (nano-Al2O3 and nano-SiO2) have a similar impact on the ion concentration change trend. Adsorption of ions on nanoparticles and the hydrated shell around the ions strongly hindered the ions through the nanoparticle films. The endocytosed nanoparticles could be released from the cells without inducing cytotoxicity. Hindering the ion exchange and disrupting the exocytosis process are the main factors that induce cytotoxicity in the presence of excess nano-TiO2 on the cell surface. The current findings may offer a universal principle for understanding the mechanism of cytotoxicity induced by low toxicity nanomaterials. PMID:26176908

  4. Gold nanoparticles do not induce myotube cytotoxicity but increase the susceptibility to cell death.

    PubMed

    Leite, Paulo Emílio Corręa; Pereira, Mariana Rodrigues; Santos, Carlos Antonio do Nascimento; Campos, Andrea Porto Carreiro; Esteves, Ticiana Mota; Granjeiro, José Mauro

    2015-08-01

    Gold nanoparticles (AuNP) have been widely used for many applications, including as biological carriers. A better understanding concerning AuNP safety on muscle cells is crucial, since it could be a potential tool in the nanomedicine field. Here, we describe the impact of polyethylene glycol-coated gold nanoparticles (PEG-AuNP) interaction with differentiated skeletal muscle C2C12 cells on cell viability, mitochondria function, cell signaling related to survival, cytokine levels and susceptibility to apoptosis. Intracellular localization of 4.5nm PEG-AuNP diameter size was evidenced by STEM-in-SEM in myotube cells. Methods for cytotoxicity analysis showed that PEG-AuNP did not affect cell viability, but intracellular ATP levels and mitochondrial membrane potential increased. Phosphorylation of ERK was not altered but p-AKT levels reduced (p<0.01). Pre-treatment of cells with PEG-AuNP followed by staurosporine induction increased the caspases-3/7 activity. Indeed, cytokines analysis revealed a sharp increase of IFN-? and TGF-?1 levels after PEG-AuNP treatment, suggesting that inflammatory and fibrotic phenotypes process were activated. These data demonstrate that PEG-AuNP affect the myotube physiology leading these cells to be more susceptible to death stimuli in the presence of staurosporine. Altogether, these results present evidence that PEG-AuNP affect the susceptibility to apoptosis of muscle cells, contributing to development of safer strategies for intramuscular delivery. PMID:25790728

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

    PubMed

    Sayes, Christie; Ivanov, Ivan

    2010-11-01

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

  6. Iron oxide nanoparticle enhancement of radiation cytotoxicity

    NASA Astrophysics Data System (ADS)

    Mazur, Courtney M.; Tate, Jennifer A.; Strawbridge, Rendall R.; Gladstone, David J.; Hoopes, P. Jack

    2013-02-01

    Iron oxide nanoparticles (IONPs) have been investigated as a promising means for inducing tumor cell-specific hyperthermia. Although the ability to generate and use nanoparticles that are biocompatible, tumor specific, and have the ability to produce adequate cytotoxic heat is very promising, significant preclinical and clinical development will be required for clinical efficacy. At this time it appears using IONP-induced hyperthermia as an adjunct to conventional cancer therapeutics, rather than as an independent treatment, will provide the initial IONP clinical treatment. Due to their high-Z characteristics, another option is to use intracellular IONPs to enhance radiation therapy without excitation with AMF (production of heat). To test this concept IONPs were added to cell culture media at a concentration of 0.2 mg Fe/mL and incubated with murine breast adenocarcinoma (MTG-B) cells for either 48 or 72 hours. Extracellular iron was then removed and all cells were irradiated at 4 Gy. Although samples incubated with IONPs for 48 hrs did not demonstrate enhanced post-irradiation cytotoxicity as compared to the non-IONP-containing cells, cells incubated with IONPs for 72 hours, which contained 40% more Fe than 48 hr incubated cells, showed a 25% decrease in clonogenic survival compared to their non-IONP-containing counterparts. These results suggest that a critical concentration of intracellular IONPs is necessary for enhancing radiation cytotoxicity.

  7. Iron oxide nanoparticle enhancement of radiation cytotoxicity

    PubMed Central

    Mazur, Courtney M.; A.Tate, Jennifer; Strawbridge, Rendall R.; Gladstone, David J.; Hoopes, P. Jack

    2014-01-01

    Iron oxide nanoparticles (IONPs) have been investigated as a promising means for inducing tumor cell-specific hyperthermia. Although the ability to generate and use nanoparticles that are biocompatible, tumor specific, and have the ability to produce adequate cytotoxic heat is very promising, significant preclinical and clinical development will be required for clinical efficacy. At this time it appears using IONP-induced hyperthermia as an adjunct to conventional cancer therapeutics, rather than as an independent treatment, will provide the initial IONP clinical treatment. Due to their high-Z characteristics, another option is to use intracellular IONPs to enhance radiation therapy without excitation with AMF (production of heat). To test this concept IONPs were added to cell culture media at a concentration of 0.2 mg Fe/mL and incubated with murine breast adenocarcinoma (MTG-B) cells for either 48 or 72 hours. Extracellular iron was then removed and all cells were irradiated at 4 Gy. Although samples incubated with IONPs for 48 hrs did not demonstrate enhanced post-irradiation cytotoxicity as compared to the non-IONP-containing cells, cells incubated with IONPs for 72 hours, which contained 40% more Fe than 48 hr incubated cells, showed a 25% decrease in clonogenic survival compared to their non-IONP-containing counterparts. These results suggest that a critical concentration of intracellular IONPs is necessary for enhancing radiation cytotoxicity. PMID:25301998

  8. Gold Nanoparticles Inhibit Matrix Metalloproteases without Cytotoxicity.

    PubMed

    Hashimoto, M; Sasaki, J I; Yamaguchi, S; Kawai, K; Kawakami, H; Iwasaki, Y; Imazato, S

    2015-08-01

    Nanoparticles (NPs) are currently the focus of considerable attention for dental applications; however, their biological effects have not been fully elucidated. The long-term, slow release of matrix metalloproteases (MMPs) digests collagen fibrils within resin-dentin bonds. Therefore, MMP inhibitors can prolong the durability of resin-dentin bonds. However, there have been few reports evaluating the combined effect of MMP inhibition and the cytotoxic effects of NPs for dentin bonding. The aim of this study was to evaluate MMP inhibition and cytotoxic responses to gold (AuNPs) and platinum nanoparticles (PtNPs) stabilized by polyvinylpyrrolidone (PVP) in cultured murine macrophages (RAW264) by using MMP inhibition assays, measuring cell viability and inflammatory responses (quantitative reverse transcription polymerase chain reaction [RT-qPCR]), and conducting a micromorphological analysis by fluorescence and transmission electron microscopy. Cultured RAW264 cells were exposed to metal NPs at various concentrations (1, 10, 100, and 400 µg/mL). AuNPs and PtNPs markedly inhibited MMP-8 and MMP-9 activity. Although PtNPs were cytotoxic at high concentrations (100 and 400 µg/mL), no cytotoxic effects were observed for AuNPs at any concentration. Transmission electron microscopy images showed a significant nonrandom intercellular distribution for AuNPs and PtNPs, which were mostly observed to be localized in lysosomes but not in the nucleus. RT-qPCR analysis demonstrated inflammatory responses were not induced in RAW264 cells by AuNPs or PtNPs. The cytotoxicity of nanoparticles might depend on the core metal composition and arise from a "Trojan horse" effect; thus, MMP inhibition could be attributed to the surface charge of PVP, which forms the outer coating of NPs. The negative charge of the surface coating of PVP binds to Zn(2+) from the active center of MMPs by chelate binding and results in MMP inhibition. In summary, AuNPs are attractive NPs that effectively inhibit MMP activity without cytotoxicity or inflammatory responses. PMID:26040283

  9. Irradiation stability and cytotoxicity of gold nanoparticles for radiotherapy

    PubMed Central

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

    2009-01-01

    Gold nanoparticles are promising as a kind of novel radiosensitizer in radiotherapy. If gold nanoparticles are shown to have good irradiation stability and biocompatibility, they would play an important role in radiotherapy. In this work, we investigated irradiation effects of gold nanoparticles under 2–10 kR gamma irradiation and cytotoxicity of gold nanoparticles with human K562 cells by using Cell Titre-Glo™ luminescent cell viability assay. The results revealed that gamma irradiation had not induced any obvious instability and size variations in gold nanoparticles. We found that gold nanoparticles showed excellent radiation hardness with an absorbed dose conversation factor of 9.491 rad/R. Meanwhile, the surface plasmon resonance of gold nanoparticles was enhanced obviously after 2–10 kR gamma irradiation. Subsequently, cytotoxicity tests indicated that the extremely high concentration of gold nanoparticles could cause a sharp decrease in K562 cell viability, while the low concentration of gold nanoparticles had no obvious influence on the cell viability. Our results revealed that gold nanoparticles were stable under high-energy ray irradiation and showed concentration-dependent cytotoxicity. PMID:19774115

  10. Effects of surface chemistry on cytotoxicity, genotoxicity, and the generation of reactive oxygen species induced by ZnO nanoparticles.

    PubMed

    Yin, Hong; Casey, Philip S; McCall, Maxine J; Fenech, Michael

    2010-10-01

    The relationship between the toxicity of zinc oxide (ZnO) nanoparticles (NPs) and their surface chemistry was investigated. Cytotoxicity, genotoxicity, and the ability to generate reactive oxygen species (ROS) were assessed for well-characterized ZnO NPs whose surface chemistry was varied from its pristine state by coating with oleic acid (OA), poly(methacrylic acid) (PMAA), or components adsorbed from cell culture medium (medium-soaked). It was found that uncoated NPs showed ROS accumulation and diminished cell viability whereas all tested surface coatings assisted in reducing ROS production and cytotoxicity. The ability of coatings to reduce the cytotoxicity of ZnO NPs was ranked in the following order: medium-soaked ? PMAA > OA. However, PMAA-coated ZnO had significant genotoxicity compared to uncoated ZnO and the other coated NPs, highlighting the need to investigate thoroughly the effects of NP surface modification on both cytotoxicity and genotoxicity assays. The lowest toxicity was achieved with a surface coating of components from a cell culture medium. PMID:20809599

  11. Cytotoxicity of nanoparticle-loaded polymer capsules

    Microsoft Academic Search

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

    2005-01-01

    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

  12. Cytotoxicity and Apoptosis Inducing Activities of 2-Amino-4H-chromene-3-carbonitrile Derivatives Loaded on Gold Nanoparticles Against Human Breast Cancer Cell Line T47D.

    PubMed

    Saffari, Zahra; Zarabi, Maryam Farahnak; Aryapour, Hasan; Foroumadi, Alireza; Farhangi, Ali; Ghassemi, Soheil; Akbarzadeh, Azim

    2015-04-01

    Chemotherapy drugs, used for prevention of uncontrolled cell proliferation in certain tissues as well as inducing apoptosis in tumor cells, are important candidates for treatment of cancer. The synthesized 2-amino-4H-chromene-3-carbonitrile derivatives effective on cancerous cells resistant to other drugs such as Paclitaxel were used due to their ability in induction of apoptosis. The growth inhibitory and inducing apoptosis activities were determined. In order to make it target-oriented, the best compound was conjugated with gold nanoparticles (NPs) by aspartic acid with chemical reduction method. Cytotoxicity effect of 2-amino-4H-chromene-3-carbonitrile derivatives against the T47D breast cancer cell line was determined by MTT assay. The synthesis of gold NPs was confirmed by transmission electron microscopy, UV-Vis and dynamic light scattering. To assess the effects of compounds on the process of apoptosis, staining methods with acridine orange-ethidium bromide and Hoechst staining by fluorescence microscopy and DNA fragmentation by the diphenylamine method were used. The synthesized compounds containing two NH2 groups on benzene rings, demonstrated more cytotoxicity effect. The effect of conjugation with gold NPs and the induction of apoptosis were studied with the best compound. The cytotoxicity effects of the synthesized 2-amino-4H-chromene-3-carbonitrile compounds were changed by replacement of NO2 group on thiol ring with different chemical groups on the benzene ring. Analyses of treated cell lines by conjugated and non-conjugated forms of compounds verified their ability in inducing apoptosis while conjugated form demonstrated higher apoptosis. PMID:25883420

  13. Cytotoxicity and genotoxicity of biogenic silver nanoparticles

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

    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.

  14. Cytotoxicity, DNA damage, and apoptosis induced by titanium dioxide nanoparticles in human non-small cell lung cancer A549 cells.

    PubMed

    Wang, Yurong; Cui, Haiyan; Zhou, Jiaping; Li, Fengjuan; Wang, Jinju; Chen, Mianhua; Liu, Qingdai

    2015-04-01

    Concerns about the risk of titanium dioxide nanoparticles (TiO2 NPs) to human health and environment are gradually increasing due to their wide range of applications. In this study, cytotoxicity, DNA damage, and apoptosis induced by TiO2 NPs (5 nm) in A549 cells were investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays revealed the time- and concentration-dependent cytotoxic effects of TiO2 NPs in a concentration range of 50 to 200 ?g/mL. A statistically significant (p?induced by TiO2 NPs at the above concentrations were observed by scanning electron micrographs. Flow cytometric analysis demonstrated that the cells treated with TiO2 NPs at concentrations of 100 and 200 ?g/mL showed a significant G2/M phase arrest and a significant increased proportion of apoptotic cells. TiO2 NPs also disrupted the mitochondrial membrane potential evaluated by rhodamine 123 staining. Further analysis by quantitative real-time PCR (qRT-PCR) indicated that the expression of caspase-3 and caspase-9 messenger RNA (mRNA) was increased significantly at the concentrations of 100 and 200 ?g/mL TiO2 NPs for 48 h. Taken together, these findings suggest that TiO2 NPs can inhibit A549 cell proliferation, cause DNA damage, and induce apoptosis via a mechanism primarily involving the activation of the intrinsic mitochondrial pathway. The assay data provide strong evidence that TiO2 NPs can induce cytotoxicity, significant DNA damage, and apoptosis of A549 cells, suggesting that exposure to TiO2 NPs could cause cell injury and be hazardous to health. PMID:25339530

  15. Source of cytotoxicity in a colloidal silver nanoparticle suspension.

    PubMed

    Hatipoglu, Manolya Kukut; Kele?temur, Seda; Altunbek, Mine; Culha, Mustafa

    2015-05-15

    Silver nanoparticles (AgNPs) are increasingly used in a variety of applications because of their potential antimicrobial activity and their plasmonic and conductivity properties. In this study, we investigated the source of cytotoxicity, genotoxicity, and reactive oxygen species (ROS) production on human dermal fibroblast and human lung cancer (A549) cell lines upon exposure to AgNP colloidal suspensions prepared with the simplest and most commonly used Lee–Meisel method with a variety of reaction times and the concentrations of the reducing agent. The AgNPs synthesized with shorter reaction times were more cytotoxic and genotoxic due to the presence of a few nanometer-sized AgNP seeds. The suspensions prepared with an increased citrate concentration were not cytotoxic, but they induced more ROS generation on A549 cells due to the high citrate concentration. The genotoxicity of the suspension decreased significantly at the higher citrate concentrations. The analysis of both transmission electron microscopy images from the dried droplet areas of the colloidal suspensions and toxicity data indicated that the AgNP seeds were the major source of toxicity. The completion of the nucleation step and the formation of larger AgNPs effectively decreased the toxicity. PMID:25904404

  16. Cationic additives in nanosystems activate cytotoxicity and inflammatory response of human neutrophils: lipid nanoparticles versus polymeric nanoparticles

    PubMed Central

    Hwang, Tsong-Long; Aljuffali, Ibrahim A; Lin, Chwan-Fwu; Chang, Yuan-Ting; Fang, Jia-You

    2015-01-01

    This report compares the effect of lipid and polymeric nanoparticles upon human neutrophils in the presence of cationic surfactants. Nanostructured lipid carriers and poly(lactic-co-glycolic) acid nanoparticles were manufactured as lipid and polymeric systems, respectively. Some cytotoxic and proinflammatory mediators such as lactate dehydrogenase (LDH), elastase, O2•?, and intracellular Ca2+ were examined. The nanoparticles showed a size of 170–225 nm. Incorporation of cetyltrimethylammonium bromide or soyaethyl morpholinium ethosulfate, the cationic surfactant, converted zeta potential from a negative to a positive charge. Nanoparticles without cationic surfactants revealed a negligible change on immune and inflammatory responses. Cationic surfactants in both nanoparticulate and free forms induced cell death and the release of mediators. Lipid nanoparticles generally demonstrated a greater response compared to polymeric nanoparticles. The neutrophil morphology observed by electron microscopy confirmed this trend. Cetyltrimethylammonium bromide as the coating material showed more significant activation of neutrophils than soyaethyl morpholinium ethosulfate. Confocal microscope imaging displayed a limited internalization of nanoparticles into neutrophils. It is proposed that cationic nanoparticles interact with the cell membrane, triggering membrane disruption and the following Ca2+ influx. The elevation of intracellular Ca2+ induces degranulation and oxidative stress. The consequence of these effects is cytotoxicity and cell death. Caution should be taken when selecting feasible nanoparticulate formulations and cationic additives for consideration of applicability and toxicity. PMID:25609950

  17. Biodegradable nanoparticles designed for drug delivery: The number of nanoparticles impacts on cytotoxicity.

    PubMed

    Mendes, Lívia Palmerston; Delgado, Jorge Miguel Ferreira; Costa, Angela Daniela A; Vieira, Marcelo Sousa; Benfica, Poliana Lopes; Lima, Eliana Martins; Valadares, Marize Campos

    2015-09-01

    Nanostructured drug delivery systems are based on biocompatible and biodegradable components. Composition, size and membrane surface properties are characteristics that may influence cell viability in cytotoxicity assays. In this work, four nanostructured systems commonly used for drug delivery were prepared and cytotoxicity was evaluated on human lymphocytes and Balb/c 3T3 fibroblasts. The hemolytic potential was also investigated. Polymeric nanocapsules (NC) and nanospheres (NS), nanostructured lipid carriers (NLC) and liposomes were prepared and characterized for size, distribution, zeta potential and number per volume of the colloidal dispersion. Cell viability was evaluated, 24 and 48h, by MTT and neutral red assays (NR). Cells were incubated with each particle in eight different dilutions varying from 2.1×10(4) to 2.1×10(11)particles/mL. Diameter of nanoparticles was between 130 and 200nm, all samples exhibited narrow size distribution (polydispersity index below 0.1) and zeta potential varied from -6.8 to -19.5mV. NC, NS and NLC reduced cell viability in a dilution dependent manner. For these nanoparticles, the higher number of particles induced cell death for both cell types. Liposomes did not cause loss of cell viability even at the highest number of particles. Results suggest that, depending on the kind of nanoparticle, the number of particles in the dispersion can negatively influence cell viability in pre-clinical drug development. PMID:25596133

  18. Differential cytotoxicity of metal oxide nanoparticles

    Microsoft Academic Search

    Jian Chen; Jinmin Zhu; Hyun-Hee Cho; Kemi Cui; Fuhai Li; Xiaobo Zhou; Jack T. Rogers; Stephen T. C. Wong; Xudong Huang

    2008-01-01

    Concerns about the potential health hazards of nanomaterials are growing. To determine the potential toxicity of metal oxide nanoparticles, human SH-SY5Y neuroblastoma and H4 neuroglioma cells were exposed to Fe2O3, CuO and ZnO nanoparticles and their metal ion counterparts (Fe, Cu and Zn) at a concentration range of 0.01–100 µM for 48 h, under the cell culture conditions: 95% O2,

  19. Selective cytotoxicity effect of cerium oxide nanoparticles under UV irradiation.

    PubMed

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

    2014-02-01

    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

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

    PubMed Central

    2012-01-01

    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. PMID:22303956

  1. Cytotoxicity of metal and semiconductor nanoparticles indicated by cellular micromotility.

    PubMed

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

    2009-01-27

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

  2. Cytotoxicity of monodispersed chitosan nanoparticles against the Caco-2 cells

    SciTech Connect

    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

    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.

  3. In vitro cytotoxicity of SiO2 or ZnO nanoparticles with different sizes and surface charges on U373MG human glioblastoma cells

    PubMed Central

    Kim, Jung-Eun; Kim, Hyejin; An, Seong Soo A; Maeng, Eun Ho; Kim, Meyoung-Kon; Song, Yoon-Jae

    2014-01-01

    Silicon dioxide (SiO2) and zinc oxide (ZnO) nanoparticles are widely used in various applications, raising issues regarding the possible adverse effects of these metal oxide nanoparticles on human cells. In this study, we determined the cytotoxic effects of differently charged SiO2 and ZnO nanoparticles, with mean sizes of either 100 or 20 nm, on the U373MG human glioblastoma cell line. The overall cytotoxicity of ZnO nanoparticles against U373MG cells was significantly higher than that of SiO2 nanoparticles. Neither the size nor the surface charge of the ZnO nanoparticles affected their cytotoxicity against U373MG cells. The 20 nm SiO2 nanoparticles were more toxic than the 100 nm nanoparticles against U373MG cells, but the surface charge had little or no effect on their cytotoxicity. Both SiO2 and ZnO nanoparticles activated caspase-3 and induced DNA fragmentation in U373MG cells, suggesting the induction of apoptosis. Thus, SiO2 and ZnO nanoparticles appear to exert cytotoxic effects against U373MG cells, possibly via apoptosis. PMID:25565841

  4. Docetaxel loaded chitosan nanoparticles: formulation, characterization and cytotoxicity studies.

    PubMed

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

    2014-08-01

    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

  5. Differences in DNA Damage Pathways Induced by Two Ceramic Nanoparticles

    Microsoft Academic Search

    Jiao Sun; Tingting Ding

    2009-01-01

    In our prophase studies, it has been proved that hydroxyapatite (HAP) and tricalcium phosphate (TCP) nanoparticles (NPs) had obvious cytotoxicity on rat macrophages. So, mechanisms of DNA damage induced by HAP and TCP NPs would be discussed in these studies. Rat peritoneal macrophages were cultured and induced by NPs in vitro. Then, the expressions of P53, P21, growth arrest and

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

    PubMed Central

    2013-01-01

    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. PMID:23968360

  7. Synthesis, colloidal properties and cytotoxicity of biopolymer nanoparticles.

    PubMed

    Moorkoth, Dhanya; Nampoothiri, Kesavan Madhavan

    2014-11-01

    To characterize the physicochemical and biological stability of nanodevices suitable for biomedical applications, polylactic acid (PLA) nanoparticles (NPs) of 112?±?6 nm and polyhydroxy butyrate (PHB) of 15?±?5 nm size were prepared by standardizing the suitable method for each. Morphology of NPs was studied by scanning and transmission electron microscopy and temperature stability by thermogravimetric analysis. Their stability in biological fluids (simulated gastrointestinal and saliva) and tolerance against 0.5 mM NaCl were analyzed. PHB NPs remained stable in all fluids, while after 24 h treatment, the PLA NPs showed the beginning of disintegration with intestinal fluid mimic. In addition to the preparation of polyethylene glycol (PEG) surface-coated NPs, PLA-PEG-PLA triblock copolymer (MW???7,366 Da) was also chemically synthesized and characterized. Cytotoxicity of all forms of nanoparticles was tested by MTT assay and by annexin pi staining. PMID:25172058

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

    PubMed

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

    2014-05-01

    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

  9. In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility.

    PubMed

    Brunner, Tobias J; Wick, Peter; Manser, Pius; Spohn, Philipp; Grass, Robert N; Limbach, Ludwig K; Bruinink, Arie; Stark, Wendelin J

    2006-07-15

    Early indicators for nanoparticle-derived adverse health effects should provide a relative measure for cytotoxicity of nanomaterials in comparison to existing toxicological data. We have therefore evaluated a human mesothelioma and a rodent fibroblast cell line for in vitro cytotoxicity tests using seven industrially important nanoparticles. Their response in terms of metabolic activity and cell proliferation of cultures exposed to 0-30 ppm nanoparticles (microg g(-1)) was compared to the effects of nontoxic amorphous silica and toxic crocidolite asbestos. Solubility was found to strongly influence the cytotoxic response. The results further revealed a nanoparticle-specific cytotoxic mechanism for uncoated iron oxide and partial detoxification or recovery after treatment with zirconia, ceria, or titania. While in vitro experiments may never replace in vivo studies, the relatively simple cytotoxic tests provide a readily available pre-screening method. PMID:16903273

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

    PubMed

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

    2010-09-28

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

  11. Phosphate-enhanced cytotoxicity of zinc oxide nanoparticles and agglomerates.

    PubMed

    Everett, W Neil; Chern, Christina; Sun, Dazhi; McMahon, Rebecca E; Zhang, Xi; Chen, Wei-Jung A; Hahn, Mariah S; Sue, H-J

    2014-02-10

    Zinc oxide (ZnO) nanoparticles (NPs) have been found to readily react with phosphate ions to form zinc phosphate (Zn3(PO4)2) crystallites. Because phosphates are ubiquitous in physiological fluids as well as waste water streams, it is important to examine the potential effects that the formation of Zn3(PO4)2 crystallites may have on cell viability. Thus, the cytotoxic response of NIH/3T3 fibroblast cells was assessed following 24h of exposure to ZnO NPs suspended in media with and without the standard phosphate salt supplement. Both particle dosage and size have been shown to impact the cytotoxic effects of ZnO NPs, so doses ranging from 5 to 50 ?g/mL were examined and agglomerate size effects were investigated by using the bioinert amphiphilic polymer polyvinylpyrrolidone (PVP) to generate water-soluble ZnO ranging from individually dispersed 4 nm NPs up to micron-sized agglomerates. Cell metabolic activity measures indicated that the presence of phosphate in the suspension media can led to significantly reduced cell viability at all agglomerate sizes and at lower ZnO dosages. In addition, a reduction in cell viability was observed when agglomerate size was decreased, but only in the phosphate-containing media. These metabolic activity results were reflected in separate measures of cell death via the lactate dehydrogenase assay. Our results suggest that, while higher doses of water-soluble ZnO NPs are cytotoxic, the presence of phosphates in the surrounding fluid can lead to significantly elevated levels of cell death at lower ZnO NP doses. Moreover, the extent of this death can potentially be modulated or offset by tuning the agglomerate size. These findings underscore the importance of understanding how nanoscale materials can interact with the components of surrounding fluids so that potential adverse effects of such interactions can be controlled. PMID:24362007

  12. Interaction of citrate-coated silver nanoparticles with earthworm coelomic fluid and related cytotoxicity in Eisenia andrei.

    PubMed

    Kwak, Jin Il; Lee, Woo-Mi; Kim, Shin Woong; An, Youn-Joo

    2014-11-01

    Understanding the interaction of nanoparticles with biological fluid is important for predicting the behavior and toxicity of nanoparticles in living systems. The earthworm Eisenia andrei was exposed to citrate-coated silver nanoparticles (cAgNPs), and the interaction of cAgNPs with earthworm coelomic fluid (ECF), the cytotoxicity of cAgNPs in earthworm coelomocytes was assessed. The neutral red retention assay showed a reduction in lysosomal stability after exposure. The toxicity of silver ions dissolved from cAgNPs in the soil medium was not significant. The aggregation and dissolution of cAgNPs increased in ECF, which contains various electrolytes that alter the properties of nanoparticles, and their subsequent toxicity. Microscopic and dissolution studies demonstrated that the aggregation of cAgNPs rapidly increased, and readily dissolved in ECF. The bioavailability of cAgNPs to earthworms induced lysosomal cytotoxicity. This is the first report to test the interaction and lysosomal cytotoxicity of nanoparticles in earthworm biofluids. PMID:24532537

  13. Poly (?-caprolactone) nanoparticles of carboplatin: Preparation, characterization and in vitro cytotoxicity evaluation in U-87 MG cell lines.

    PubMed

    Karanam, Vamshikrishna; Marslin, Gregory; Krishnamoorthy, Balakumar; Chellan, Vijayaraghavan; Siram, Karthik; Natarajan, Tamilselvan; Bhaskar, Balaji; Franklin, Gregory

    2015-06-01

    Carboplatin is a platinum based drug used in the treatment of several malignancies. Due to poor cellular uptake, generally, a larger dose of drug is administered to achieve therapeutic levels, causing harmful side-effects such as hematologic toxicity. In order to enhance the cellular uptake of carboplatin, we have developed carboplatin loaded nanoparticles using the biodegradable polymer poly (?-caprolactone) (PCL). Nanoparticles ranging from the size of 23.77±1.37 to 96.73±2.79nm with positive zeta potential and moderate entrapment efficiency (54.21±0.98%) were obtained. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) confirmed the spherical morphology and smooth surface of all nanoformulations. The concentrations of PCL and the stabilizer (DMAB) are found to play a role in determining the size and the entrapment efficiency of the nanoparticles. Drug release from nanoparticles followed a biphasic pattern with an initial burst release followed by a sustained release for 10h. Results of in vitro cellular uptake and cytotoxicity studies revealed that carboplatin in the form of PCL-nanoparticles were efficiently up taken and displayed profound cytotoxicity to U-87 MG (human glioma) cells than the free drug. Importantly, unlike the free carboplatin, carboplatin in the form of PCL nanoparticles did not present any haemolytic activity in rat erythrocytes, a major side effect of this chemotherapeutic drug. This suggests that poly (?-caprolactone) nanoencapsulation of carboplatin might be an efficient approach to treat cancer, while reducing carboplatin induced haemolysis. PMID:25899843

  14. The role of surface functionality in determining nanoparticle cytotoxicity

    PubMed Central

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

    2013-01-01

    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. PMID:23294365

  15. Cytotoxic, genotoxic and the hemolytic effect of titanium dioxide (TiO2 ) nanoparticles on human erythrocyte and lymphocyte cells in vitro.

    PubMed

    Ghosh, Manosij; Chakraborty, Anirban; Mukherjee, Anita

    2013-10-01

    With the increasing clinical use of titanium dioxide (TiO2 ) nanoparticles, a better understanding of their safety in the blood stream is required. The present study evaluates the toxic effect of commercially available TiO2 nanoparticles (~100 nm) using a battery of cytotoxic, genotoxic, hemolytic and morphological parameters. The cytotoxic effects of TiO2 nanoparticles in human lymphocyte cells were studied with respect to membrane damage, mitochondrial function, metabolic activity and lysosomal membrane stability. Genotoxicity in lymphocyte cells was quantitated using a comet assay. The mode of cell death (apoptosis/necrosis) was evaluated using PI/Annexin V staining. TiO2 nanoparticles were also evaluated for their hemolytic properties, osmotic fragility and interaction with hemoglobin. Human erythrocyte cells were studied for morphological alterations using atomic force microscopy (AFM). Results suggest that the particles could induce a significant reduction in mitochondrial dehydrogenase activity in human lymphocyte cells. Membrane integrity remained unaffected by nanoparticle treatment. DNA damage and apoptosis were induced by TiO2 nanoparticles in a dose-dependent manner. A study on human erythrocyte cells revealed a hemolytic property of TiO2 nanoparticles characterized by spherocytosis and echinocytosis. Spectral analysis revealed a hemoglobin TiO2 nanoparticle interaction. Our in vitro study results suggest that commercially available blood contacting nanoparticles (TiO2 nanoparticle) should be carefully evaluated for their toxic potential. PMID:23616399

  16. Cellular Uptake and Cytotoxicity of ?-Lactoglobulin Nanoparticles: The Effects of Particle Size and Surface Charge.

    PubMed

    Ha, Ho-Kyung; Kim, Jin Wook; Lee, Mee-Ryung; Jun, Woojin; Lee, Won-Jae

    2015-03-01

    It is necessary to understand the cellular uptake and cytotoxicity of food-grade delivery systems, such as ?-lactoglobulin (?-lg) nanoparticles, for the application of bioactive compounds to functional foods. The objectives of this study were to investigate the relationships between the physicochemical properties of ?-lg nanoparticles, such as particle size and zeta-potential value, and their cellular uptakes and cytotoxicity in Caco-2 cells. Physicochemical properties of ?-lg nanoparticles were evaluated using particle size analyzer. Flow cytometry and confocal laser scanning microscopy were used to investigate cellular uptake and cytotoxicity of ?-lg nanoparticles. The ?-lg nanoparticles with various particle sizes (98 to 192 nm) and zeta-potential values (-14.8 to -17.6 mV) were successfully formed. A decrease in heating temperature from 70°C to 60°C resulted in a decrease in the particle size and an increase in the zeta-potential value of ?-lg nanoparticles. Non-cytotoxicity was observed in Caco-2 cells treated with ?-lg nanoparticles. There was an increase in cellular uptake of ?-lg nanoparticles with a decrease in particle size and an increase in zeta-potential value. Cellular uptake ?-lg nanoparticles was negatively correlated with particle size and positively correlated with zeta-potential value. Therefore, these results suggest that the particle size and zeta-potential value of ?-lg nanoparticles play an important role in the cellular uptake. The ?-lg nanoparticles can be used as a delivery system in foods due to its high cellular uptake and non-cytotoxicity. PMID:25656189

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

    PubMed Central

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

    2012-01-01

    Nanoparticles (NPs) are tiny materials used in a wide range of industrial and medical applications. Titanium dioxide (TiO2) is a type of nanoparticle that is widely used in paints, pigments, and cosmetics; however, little is known about the impact of TiO2 on human health and the environment. Therefore, considerable research has focused on characterizing the potential toxicity of nanoparticles such as TiO2 and on understanding the mechanism of TiO2 NP-induced nanotoxicity through the evaluation of biomarkers. Uncoated TiO2 NPs tend to aggregate in aqueous media, and these aggregates decrease cell viability and induce expression of stress-related genes, such as those encoding interleukin-6 (IL-6) and heat shock protein 70B’ (HSP70B’), indicating that TiO2 NPs induce inflammatory and heat shock responses. In order to reduce their toxicity, we conjugated TiO2 NPs with polyethylene glycol (PEG) to eliminate aggregation. Our findings indicate that modifying TiO2 NPs with PEG reduces their cytotoxicity and reduces the induction of stress-related genes. Our results also suggest that TiO2 NP-induced effects on cytotoxicity and gene expression vary depending upon the cell type and surface modification. PMID:22489177

  18. Proinflammatory and cytotoxic response to nanoparticles in precision-cut lung slices.

    PubMed

    Hirn, Stephanie; Haberl, Nadine; Loza, Kateryna; Epple, Matthias; Kreyling, Wolfgang G; Rothen-Rutishauser, Barbara; Rehberg, Markus; Krombach, Fritz

    2014-01-01

    Precision-cut lung slices (PCLS) are an established ex vivo alternative to in vivo experiments in pharmacotoxicology. The aim of this study was to evaluate the potential of PCLS as a tool in nanotoxicology studies. Silver (Ag-NPs) and zinc oxide (ZnO-NPs) nanoparticles as well as quartz particles were used because these materials have been previously shown in several in vitro and in vivo studies to induce a dose-dependent cytotoxic and inflammatory response. PCLS were exposed to three concentrations of 70 nm monodisperse polyvinylpyrrolidone (PVP)-coated Ag-NPs under submerged culture conditions in vitro. ZnO-NPs (NM110) served as 'soluble' and quartz particles (Min-U-Sil) as 'non-soluble' control particles. After 4 and 24 h, the cell viability and the release of proinflammatory cytokines was measured. In addition, multiphoton microscopy was employed to assess the localization of Ag-NPs in PCLS after 24 h of incubation. Exposure of PCLS to ZnO-NPs for 4 and 24 h resulted in a strong decrease in cell viability, while quartz particles had no cytotoxic effect. Moreover, only a slight cytotoxic response was detected by LDH release after incubation of PCLS with 20 or 30 µg/mL of Ag-NPs. Interestingly, none of the particles tested induced a proinflammatory response in PCLS. Finally, multiphoton microscopy revealed that the Ag-NP were predominantly localized at the cut surface and only to a much lower extent in the deeper layers of the PCLS. In summary, only 'soluble' ZnO-NPs elicited a strong cytotoxic response. Therefore, we suggest that the cytotoxic response in PCLS was caused by released Zn(2+) ions rather than by the ZnO-NPs themselves. Moreover, Ag-NPs were predominantly localized at the cut surface of PCLS but not in deeper regions, indicating that the majority of the particles did not have the chance to interact with all cells present in the tissue slice. In conclusion, our findings suggest that PCLS may have some limitations when used for nanotoxicology studies. To strengthen this conclusion, however, other NP types and concentrations need to be tested in further studies. PMID:25671139

  19. Proinflammatory and cytotoxic response to nanoparticles in precision-cut lung slices

    PubMed Central

    Haberl, Nadine; Loza, Kateryna; Epple, Matthias; Kreyling, Wolfgang G; Rothen-Rutishauser, Barbara; Rehberg, Markus; Krombach, Fritz

    2014-01-01

    Summary Precision-cut lung slices (PCLS) are an established ex vivo alternative to in vivo experiments in pharmacotoxicology. The aim of this study was to evaluate the potential of PCLS as a tool in nanotoxicology studies. Silver (Ag-NPs) and zinc oxide (ZnO-NPs) nanoparticles as well as quartz particles were used because these materials have been previously shown in several in vitro and in vivo studies to induce a dose-dependent cytotoxic and inflammatory response. PCLS were exposed to three concentrations of 70 nm monodisperse polyvinylpyrrolidone (PVP)-coated Ag-NPs under submerged culture conditions in vitro. ZnO-NPs (NM110) served as ‘soluble’ and quartz particles (Min-U-Sil) as ‘non-soluble’ control particles. After 4 and 24 h, the cell viability and the release of proinflammatory cytokines was measured. In addition, multiphoton microscopy was employed to assess the localization of Ag-NPs in PCLS after 24 h of incubation. Exposure of PCLS to ZnO-NPs for 4 and 24 h resulted in a strong decrease in cell viability, while quartz particles had no cytotoxic effect. Moreover, only a slight cytotoxic response was detected by LDH release after incubation of PCLS with 20 or 30 µg/mL of Ag-NPs. Interestingly, none of the particles tested induced a proinflammatory response in PCLS. Finally, multiphoton microscopy revealed that the Ag-NP were predominantly localized at the cut surface and only to a much lower extent in the deeper layers of the PCLS. In summary, only ‘soluble’ ZnO-NPs elicited a strong cytotoxic response. Therefore, we suggest that the cytotoxic response in PCLS was caused by released Zn2+ ions rather than by the ZnO-NPs themselves. Moreover, Ag-NPs were predominantly localized at the cut surface of PCLS but not in deeper regions, indicating that the majority of the particles did not have the chance to interact with all cells present in the tissue slice. In conclusion, our findings suggest that PCLS may have some limitations when used for nanotoxicology studies. To strengthen this conclusion, however, other NP types and concentrations need to be tested in further studies. PMID:25671139

  20. The noncellular reduction of MTT tetrazolium salt by TiO? nanoparticles and its implications for cytotoxicity assays.

    PubMed

    Lupu, A R; Popescu, T

    2013-08-01

    We report results of noncellular tests, revealing the occurrence of photocatalytic interactions between titanium dioxide (TiO2, titania) nanoparticles and the MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide] cytotoxicity indicator. These interactions induce the reduction of MTT and formation of purple formazan under biologically relevant conditions. Classical MTT assays have been performed to evaluate the production of formazan in DMEM-F12 and RPMI-1640 cell culture media (containing 10% fetal bovine serum-FBS) treated with Degussa-P25 TiO2 nanoparticles, in the absence of cells. The colorimetric determinations revealed the noncellular MTT to formazan transformation induced by TiO2 nanoparticles, under conditions commonly used for in vitro cytotoxicity testing of nanomaterials. The formazan precipitation was found to be proportional to the TiO2 concentration, being enhanced under laboratory daylight exposure. The photocatalytic nature of the studied effect was assessed under UV irradiation at 365nm. The biological significance of the reported reaction was established with respect to cellular reference experiments performed on V79-4, HeLa and B16 cell lines. The results show false viability increases with up to 14% (for TiO2 concentrations generally higher than 50?g/ml), induced by the TiO2-MTT reaction. This type of artifacts may lead to underestimated toxicity or false proliferation results. PMID:23531555

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

    PubMed

    Xu, Min; Zhao, Yuefang; Feng, Min

    2012-08-01

    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

  2. Preparation and cytotoxicity of N,N,N-trimethyl chitosan/alginate beads containing gold nanoparticles.

    PubMed

    Martins, Alessandro F; Facchi, Suelen P; Monteiro, Johny P; Nocchi, Samara R; Silva, Cleiser T P; Nakamura, Celso V; Girotto, Emerson M; Rubira, Adley F; Muniz, Edvani C

    2015-01-01

    Polyelectrolyte complex beads based on N,N,N-trimethyl chitosan (TMC) and sodium alginate (ALG) were obtained. This biomaterial was characterised by FTIR, TGA/DTG, DSC and SEM analysis. The good properties of polyelectrolyte complex hydrogel beads were associated, for the first time, with gold nanoparticles (AuNPs). Through a straightforward methodology, AuNPs were encapsulated into the beads. The in vitro cytotoxicity assays on the Caco-2 colon cancer cells and healthy VERO cells showed that the beads presented good biocompatibility on both cell lines, whereas the beads loaded with gold nanoparticles (beads/AuNPs) was slightly cytotoxic on the Caco-2 and VERO cells. PMID:25159881

  3. Interaction studies between biosynthesized silver nanoparticle with calf thymus DNA and cytotoxicity of silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Roy, Swarup; Sadhukhan, Ratan; Ghosh, Utpal; Das, Tapan Kumar

    2015-04-01

    The interaction of calf thymus DNA (CTDNA) with silver nanoparticles (SNP) has been investigated following spectroscopic studies, analysis of melting temperature (Tm) curves and hydrodynamic measurement. In spectrophotometric titration and thermal denaturation studies of CTDNA it was found that SNP can form a complex with double-helical DNA and the increasing value of Tm also supported the same. The association constant of SNP with DNA from UV-Vis study was found to be 4.1 × 103 L/mol. The fluorescence emission spectra of intercalated ethidium bromide (EB) with increasing concentration of SNP represented a significant reduction of EB intensity and quenching of EB fluorescence. The results of circular dichroism (CD) suggested that SNP can change the conformation of DNA. From spectroscopic, hydrodynamic, and DNA melting studies, SNP has been found to be a DNA groove binder possessing partial intercalating property. Cell cytotoxicity of SNP was compared with that of normal silver salt solution on HeLa cells. Our results show that SNP has less cytotoxicity compared to its normal salt solution and good cell staining property.

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

    SciTech Connect

    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

    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.

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

    Microsoft Academic Search

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

    Zinc oxide (ZnO) nanoparticles have wide-ranging applications in a diverse array of industrial and consumer products, from\\u000a ceramic manufacture and paint formulation to sunscreens and haircare products. Hence, it is imperative to rigorously characterize\\u000a the health and safety aspects of human exposure to ZnO nanoparticles. This study therefore evaluated the cellular association,\\u000a cytotoxic and inflammatory potential of spherical and sheet-shaped

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

    PubMed

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

    2013-06-01

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

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

    PubMed Central

    Varshosaz, Jaleh; Sadeghi Aliabadi, Hojatollah

    2014-01-01

    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

  8. Evaluation of antioxidant, antibacterial and cytotoxic effects of green synthesized silver nanoparticles by Piper longum fruit.

    PubMed

    Reddy, N Jayachandra; Nagoor Vali, D; Rani, M; Rani, S Sudha

    2014-01-01

    Silver nanoparticles synthesized through bio-green method has been reported to have biomedical applications to control pathogenic microbes as it is cost effective compared to commonly used physical and chemical methods. In present study, silver nanoparticles were synthesized using aqueous Piper longum fruit extract (PLFE) and confirmed by UV-visible spectroscopy. The nanoparticles were spherical in shape with an average particle size of 46nm as determined by scanning electronic microscopy (SEM) and dynamic light scattering (DLS) particle size analyzer respectively. FT-IR spectrum revealed the capping of the phytoconstituents, probably polyphenols from P. longum fruit extract and stabilizing the nanoparticles. Further the ferric ion reducing test, confirmed that the capping agents were condensed tannins. The aqueous P. longum fruit extract (PLFE) and the green synthesized silver nanoparticles (PLAgNPs) showed powerful antioxidant properties in in vitro antioxidant assays. The results from the antimicrobial assays suggested that green synthesized silver nanoparticles (PLAgNPs) were more potent against pathogenic bacteria than the P. longum fruit extract (PLFE) alone. The nanoparticles also showed potent cytotoxic effect against MCF-7 breast cancer cell lines with an IC 50 value of 67?g/ml/24h by the MTT assay. These results support the advantages of using bio-green method for synthesizing silver nanoparticles with antioxidant, antimicrobial and cytotoxic activities those are simple and cost effective as well. PMID:24268240

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

    PubMed

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

    2013-11-01

    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

  10. Oxidative stress mediated cytotoxicity of biologically synthesized silver nanoparticles in human lung epithelial adenocarcinoma cell line

    NASA Astrophysics Data System (ADS)

    Han, Jae Woong; Gurunathan, Sangiliyandi; Jeong, Jae-Kyo; Choi, Yun-Jung; Kwon, Deug-Nam; Park, Jin-Ki; Kim, Jin-Hoi

    2014-09-01

    The goal of the present study was to investigate the toxicity of biologically prepared small size of silver nanoparticles in human lung epithelial adenocarcinoma cells A549. Herein, we describe a facile method for the synthesis of silver nanoparticles by treating the supernatant from a culture of Escherichia coli with silver nitrate . The formation of silver nanoparticles was characterized using various analytical techniques. The results from UV-visible (UV-vis) spectroscopy and X-ray diffraction analysis show a characteristic strong resonance centered at 420 nm and a single crystalline nature, respectively. Fourier transform infrared spectroscopy confirmed the possible bio-molecules responsible for the reduction of silver from silver nitrate into nanoparticles. The particle size analyzer and transmission electron microscopy results suggest that silver nanoparticles are spherical in shape with an average diameter of 15 nm. The results derived from in vitro studies showed a concentration-dependent decrease in cell viability when A549 cells were exposed to silver nanoparticles. This decrease in cell viability corresponded to increased leakage of lactate dehydrogenase (LDH), increased intracellular reactive oxygen species generation (ROS), and decreased mitochondrial transmembrane potential (MTP). Furthermore, uptake and intracellular localization of silver nanoparticles were observed and were accompanied by accumulation of autophagosomes and autolysosomes in A549 cells. The results indicate that silver nanoparticles play a significant role in apoptosis. Interestingly, biologically synthesized silver nanoparticles showed more potent cytotoxicity at the concentrations tested compared to that shown by chemically synthesized silver nanoparticles. Therefore, our results demonstrated that human lung epithelial A549 cells could provide a valuable model to assess the cytotoxicity of silver nanoparticles.

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

    PubMed Central

    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

    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. PMID:23885175

  12. Synthesis, Characterization and Cytotoxicity Evaluation of Nitric Oxide-Iron Oxide magnetic Nanoparticles

    NASA Astrophysics Data System (ADS)

    Haddad, P. S.; Britos, T. N.; Santos, M. C.; Seabra, A. B.; Palladino, M. V.; Justo, G. Z.

    2015-05-01

    The present work is focused on the synthesis, characterization and cytotoxic evaluation of superparamagnetic iron oxide nanoparticles (SPIONs). SPIONs have been proposed for an increasing number of biomedical applications, such as drug-delivery. To this end, toxicological studies of their potential effects in biological systems must be better evaluated. The aim of this study was to examine the in vitro cytotoxicity of thiolated (SH) and S-nitrosated (S-NO) SPIONs in cancer cell lines. SPIONs were prepared by the coprecipitation method using ferrous and ferric chlorides in aqueous solution. The nanoparticles (Fe3O4) were coated with thiol containing molecule cysteine (Cys) (molar ratio SPIONs:ligand = 1:20), leading to the formation of an aqueous dispersion of thiolated nanoparticles (SH- SPIONs). These particles were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The results obtained showed that Cys-SPIONs have a mean diameter of 14 nm at solid state and present super paramagnetic behavior at room temperature. Thiol groups on the surface of the nanoparticles were nitrosated through the addition of sodium nitrite leading to the formation of S-NOCys-SPIONs (S-nitrosated-Cys-SPIONs), which act as spontaneous nitric oxide (NO) donor). The cytotoxicity of thiolated and S-nitrosated nanoparticles was evaluated in acute T cell leukemia (Jurkat cell line) and Lewis lung carcinoma (3LL) cells. The results showed that at low concentrations thiolated (Cys) and S- nitrosated (S-NOCyst) SPIONs display low cytotoxicity in both cell types. However, at higher concentrations, Cys-SPIONs exhibited cytotoxic effects, whereas S-NOCys-SPIONs protected them, and also promoted cell proliferation.

  13. Biocompatibility of various ferrite nanoparticles evaluated by in vitro cytotoxicity assays using HeLa cells

    NASA Astrophysics Data System (ADS)

    Tomitaka, Asahi; Hirukawa, Atsuo; Yamada, Tsutomu; Morishita, Shin; Takemura, Yasushi

    2009-05-01

    Magnetic nanoparticles for thermotherapy must be biocompatible and possess high thermal efficiency as heating elements. The biocompatibility of Fe 3O 4 (20-30 nm), ZnFe 2O 4 (15-30 nm) and NiFe 2O 4 (20-30 nm) nanoparticles was studied using a cytotoxicity colony formation assay and a cell viability assay. The Fe 3O 4 sample was found to be biocompatible on HeLa cells. While ZnFe 2O 4 and NiFe 2O 4 were non-toxic at low concentrations, HeLa cells exhibited cytotoxic effects when exposed to concentrations of 100 ?g/ml nanoparticles.

  14. Uptake and cytotoxicity of chitosan nanoparticles in human liver cells

    SciTech Connect

    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

    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.

  15. Heparin and Carboxymethylchitosan Metal Nanoparticles: An Evaluation of Their Cytotoxicity

    PubMed Central

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

    2013-01-01

    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. PMID:23509708

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

    PubMed

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

    2013-04-17

    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

  17. Comparative cytotoxic response of nickel ferrite nanoparticles in human liver HepG2 and breast MFC-7 cancer cells.

    PubMed

    Ahamed, Maqusood; Akhtar, Mohd Javed; Alhadlaq, Hisham A; Khan, M A Majeed; Alrokayan, Salman A

    2015-09-01

    Nickel ferrite nanoparticles (NPs) have received much attention for their potential applications in biomedical fields such as magnetic resonance imaging, drug delivery and cancer hyperthermia. However, little is known about the toxicity of nickel ferrite NPs at the cellular and molecular levels. In this study, we investigated the cytotoxic responses of nickel ferrite NPs in two different types of human cells (i.e., liver HepG2 and breast MCF-7). Nickel ferrite NPs induced dose-dependent cytotoxicity in both types of cells, which was demonstrated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT), neutral red uptake (NRU) and lactate dehydrogenase (LDH) assays. Nickel ferrite NPs were also found to induce oxidative stress, which was evident by the depletion of glutathione and the induction of reactive oxygen species (ROS) and lipid peroxidation. The mitochondrial membrane potential due to nickel ferrite NP exposure was also observed. The mRNA levels for the tumor suppressor gene p53 and the apoptotic genes bax, CASP3 and CASP9 were up-regulated, while the anti-apoptotic gene bcl-2 was down-regulated following nickel ferrite NP exposure. Furthermore, the activities of apoptotic enzymes (caspase-3 and caspase-9) were also higher in both types of cells treated with nickel ferrite NPs. Cytotoxicity induced by nickel ferrite was efficiently prevented by N-acetyl cysteine (ROS scavenger) treatment, which suggested that oxidative stress might be one of the possible mechanisms of nickel ferrite NP toxicity. We also observed that MCF-7 cells were slightly more susceptible to nickel ferrite NP exposure than HepG2 cells. This study warrants further investigation to explore the potential mechanisms of different cytotoxic responses of nickel ferrite NPs in different cell lines. PMID:25966046

  18. Cytotoxicity induced by nanobacteria and nanohydroxyapatites in human choriocarcinoma cells

    NASA Astrophysics Data System (ADS)

    Zhang, Mingjun; Yang, Jinmei; Shu, Jing; Fu, Changhong; Liu, Shengnan; Xu, Ge; Zhang, Dechun

    2014-11-01

    We explored the cytotoxic effects of nanobacteria (NB) and nanohydroxyapatites (nHAPs) against human choriocarcinoma cells (JAR) and the mechanisms of action underlying their cytotoxicity. JAR cells were co-cultured with NB and nHAPs for 48 h, and ultrastructural changes were more readily induced by NB than nHAPs. Autophagy in the plasma of JAR cells were observed in the NB group. The rate of apoptosis induced by NB was higher than that for nHAPs. The expression of Bax and FasR proteins in the NB group was stronger than that for the nHAP group. NB probably resulted in autophagic formation. Apoptosis was possibly activated via FasL binding to the FasR signaling pathway.

  19. Classification Nano-SAR Development for Cytotoxicity of Metal Oxide Nanoparticles

    PubMed Central

    Liu, Rong; Rallo, Robert; George, Saji; Ji, Zhaoxia; Nair, Sumitra; Nel, André E.

    2014-01-01

    A classification based cytotoxicity nano-structure-activity-realtionship (nano-SAR) is presented based on a set of nine metal oxide nanoparticles to which transformed bronchial epithelial cells (BEAS-2B) were exposed over a range of concentrations of 0.375–200 mg·L?1 and exposure times up to 24 h. The nano-SAR is developed using cytotoxicity data from high throughput screening (HTS) assay that was processed to identify and label toxic (in terms of the Propidium Iodide uptake of BEAS-2B cells) versus non-toxic events relative to unexposed control cell population. Starting with a set of fourteen intuitive but fundamental physicochemical nano-SAR input parameters, a number of models were identified which had classification accuracy above 95%. The best performing model had a 100% classification accuracy in both internal and external validation. This model is based on four descriptors including the atomization energy of the metal oxide, period of the nanoparticle metal, nanoparticle primary size, in addition to nanoparticle volume fraction (in solution). Notwithstanding the success of the present modeling approach with a relatively small nanoparticle library, it is important to recognize that a significantly larger data set would be needed in order to expand the applicability domain and increase the confidence and reliability of data-driven nano-SARs. PMID:21456088

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

    PubMed

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

    2010-05-01

    The increased applications of nanoparticles in a wide range of industrial fields raise the concern about their potential toxicity to human. The aim of this study was to assess and compare the toxicity of four different oxide nanoparticles (Al2O3, CeO2, TiO2 and ZnO) to human lung epithelial cells, A549 carcinoma cells and L-132 normal cells, in vitro. We focused on the toxicological effects of the present nanoparticles on cell proliferation, cell viability, membrane integrity and oxidative stress. The long-term cytotoxicity of nanoparticles was also evaluated by employing the clonogenic assay. Among four nanoparticles tested, ZnO exhibited the highest cytotoxicity in terms of cell proliferation, cell viability, membrane integrity and colony formation in both cell lines. Al2O3, CeO2 and TiO2 showed little adverse effects on cell proliferation and cell viability. However, TiO2 induced oxidative stress in a concentration- and time-dependent manner. CeO2 caused membrane damage and inhibited colony formation in long-term, but with different degree depending on cell lines. Al2O3 seems to be less toxic than the other nanoparticles even after long time exposure. These results highlight the need for caution during manufacturing process of nanomaterials as well as further investigation on the toxicity mechanism. PMID:20358977

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

    Microsoft Academic Search

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

    2010-01-01

    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

  2. Cuprous oxide nanoparticles selectively induce apoptosis of tumor cells

    PubMed Central

    Wang, Ye; Zi, Xiao-Yuan; Su, Juan; Zhang, Hong-Xia; Zhang, Xin-Rong; Zhu, Hai-Ying; Li, Jian-Xiu; Yin, Meng; Yang, Feng; Hu, Yi-Ping

    2012-01-01

    In the rapid development of nanoscience and nanotechnology, many researchers have discovered that metal oxide nanoparticles have very useful pharmacological effects. Cuprous oxide nanoparticles (CONPs) can selectively induce apoptosis and suppress the proliferation of tumor cells, showing great potential as a clinical cancer therapy. Treatment with CONPs caused a G1/G0 cell cycle arrest in tumor cells. Furthermore, CONPs enclosed in vesicles entered, or were taken up by mitochondria, which damaged their membranes, thereby inducing apoptosis. CONPs can also produce reactive oxygen species (ROS) and initiate lipid peroxidation of the liposomal membrane, thereby regulating many signaling pathways and influencing the vital movements of cells. Our results demonstrate that CONPs have selective cytotoxicity towards tumor cells, and indicate that CONPs might be a potential nanomedicine for cancer therapy. PMID:22679374

  3. Development of drug-loaded chitosan-vanillin nanoparticles and its cytotoxicity against HT-29 cells.

    PubMed

    Li, Pu-Wang; Wang, Guang; Yang, Zi-Ming; Duan, Wei; Peng, Zheng; Kong, Ling-Xue; Wang, Qing-Huang

    2014-04-01

    Abstract Chitosan as a natural polysaccharide derived from chitin of arthropods like shrimp and crab, attracts much interest due to its inherent properties, especially for application in biomedical materials. Presently, biodegradable and biocompatible chitosan nanoparticles are attractive for drug delivery. However, some physicochemical characteristics of chitosan nanoparticles still need to be further improved in practice. In this work, chitosan nanoparticles were produced by crosslinking chitosan with 3-methoxy-4-hydroxybenzaldehyde (vanillin) through a Schiff reaction. Chitosan nanoparticles were 200-250?nm in diameter with smooth surface and were negatively charged with a zeta potential of?-?17.4?mV in neutral solution. Efficient drug loading and drug encapsulation were achieved using 5-fluorouracil as a model of hydrophilic drug. Drug release from the nanoparticles was constant and controllable. The in vitro cytotoxicity against HT-29 cells and cellular uptake of the chitosan nanoparticles were evaluated by methyl thiazolyl tetrazolium method, confocal laser scanning microscope and flow cytometer, respectively. The results indicate that the chitosan nanoparticles crosslinked with vanillin are a promising vehicle for the delivery of anticancer drugs. PMID:24712731

  4. Physicochemical properties, cytotoxicity, and antimicrobial activity of sulphated zirconia nanoparticles

    PubMed Central

    Mftah, Ae; Alhassan, Fatah H; Al-Qubaisi, Mothanna Sadiq; El Zowalaty, Mohamed Ezzat; Webster, Thomas J; Sh-eldin, Mohammed; Rasedee, Abdullah; Taufiq-Yap, Yun Hin; Rashid, Shah Samiur

    2015-01-01

    Nanoparticle sulphated zirconia with Brřnsted acidic sites were prepared here by an impregnation reaction followed by calcination at 600°C for 3 hours. The characterization was completed using X-ray diffraction, thermal gravimetric analysis, Fourier transform infrared spectroscopy, Brunner-Emmett-Teller surface area measurements, scanning electron microscopy with energy dispersive X-ray spectroscopy, and transmission electron microscopy. Moreover, the anticancer and antimicrobial effects were investigated for the first time. This study showed for the first time that the exposure of cancer cells to sulphated zirconia nanoparticles (3.9–1,000 ?g/mL for 24 hours) resulted in a dose-dependent inhibition of cell growth, as determined by (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Similar promising results were observed for reducing bacteria functions. In this manner, this study demonstrated that sulphated zirconia nanoparticles with Brřnsted acidic sites should be further studied for a wide range of anticancer and antibacterial applications. PMID:25632233

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

    PubMed Central

    Fröhlich, Eleonore

    2013-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

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

    SciTech Connect

    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

    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.

  8. Functional up-converting SrTiO3:Er(3+)/Yb(3+) nanoparticles: structural features, particle size, colour tuning and in vitro RBC cytotoxicity.

    PubMed

    Pazik, R; Maczka, M; Malecka, M; Marciniak, L; Ekner-Grzyb, A; Mrowczynska, L; Wiglusz, R J

    2015-05-27

    SrTiO3 nanoparticles co-doped with a broad concentration range of Er(3+) and Yb(3+) ions were fabricated using the citric route as a function of annealing temperatures of 500-1000 °C. The effect of a broad co-dopant concentration range and sintering temperature on structural and up-conversion properties was investigated in detail by X-ray diffraction techniques and optical spectroscopy. The TEM technique was used to estimate the mean particle size, which was around 30 nm for the inorganic product annealed at 600 °C. Up-conversion emission color tuning was achieved by particle size control. Power dependence of the green and red emissions was found to be a result of temperature determination in the operating range of SrTiO3 nanoparticles and a candidate for the fast and local microscopic heating and heat release induced by IR irradiation. The color changed from white-red-yellow-green upon an increase of sintering temperature, inducing changes in the surface-to-volume ratio and the number of optically active ions in particle surface regions. The cytotoxic activity of nanoparticles on human red blood cells was investigated, showing no harmful effects up to a particle concentration of 0.1 mg ml(-1). The cytotoxic response of a colloidal suspension of nanoparticles to RBC cells was connected with the strong affinity of SrTiO3 particles to the cell membranes, blocking the transport of important biological solutes. PMID:25962584

  9. Computer-aided nanotoxicology: assessing cytotoxicity of nanoparticles under diverse experimental conditions by using a novel QSTR-perturbation approach

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

    Nowadays, the interest in the search for new nanomaterials with improved electrical, optical, catalytic and biological properties has increased. Despite the potential benefits that can be gathered from the use of nanoparticles, only little attention has been paid to their possible toxic effects that may affect human health. In this context, several assays have been carried out to evaluate the cytotoxicity of nanoparticles in mammalian cells. Owing to the cost in both resources and time involved in such toxicological assays, there has been a considerable increase in the interest towards alternative computational methods, like the application of quantitative structure-activity/toxicity relationship (QSAR/QSTR) models for risk assessment of nanoparticles. However, most QSAR/QSTR models developed so far have predicted cytotoxicity against only one cell line, and they did not provide information regarding the influence of important factors rather than composition or size. This work reports a QSTR-perturbation model aiming at simultaneously predicting the cytotoxicity of different nanoparticles against several mammalian cell lines, and also considering different times of exposure of the cell lines, as well as the chemical composition of nanoparticles, size, conditions under which the size was measured, and shape. The derived QSTR-perturbation model, using a dataset of 1681 cases (nanoparticle-nanoparticle pairs), exhibited an accuracy higher than 93% for both training and prediction sets. In order to demonstrate the practical applicability of our model, the cytotoxicity of different silica (SiO2), nickel (Ni), and nickel(ii) oxide (NiO) nanoparticles were predicted and found to be in very good agreement with experimental reports. To the best of our knowledge, this is the first attempt to simultaneously predict the cytotoxicity of nanoparticles under multiple experimental conditions by applying a single unique QSTR model.Nowadays, the interest in the search for new nanomaterials with improved electrical, optical, catalytic and biological properties has increased. Despite the potential benefits that can be gathered from the use of nanoparticles, only little attention has been paid to their possible toxic effects that may affect human health. In this context, several assays have been carried out to evaluate the cytotoxicity of nanoparticles in mammalian cells. Owing to the cost in both resources and time involved in such toxicological assays, there has been a considerable increase in the interest towards alternative computational methods, like the application of quantitative structure-activity/toxicity relationship (QSAR/QSTR) models for risk assessment of nanoparticles. However, most QSAR/QSTR models developed so far have predicted cytotoxicity against only one cell line, and they did not provide information regarding the influence of important factors rather than composition or size. This work reports a QSTR-perturbation model aiming at simultaneously predicting the cytotoxicity of different nanoparticles against several mammalian cell lines, and also considering different times of exposure of the cell lines, as well as the chemical composition of nanoparticles, size, conditions under which the size was measured, and shape. The derived QSTR-perturbation model, using a dataset of 1681 cases (nanoparticle-nanoparticle pairs), exhibited an accuracy higher than 93% for both training and prediction sets. In order to demonstrate the practical applicability of our model, the cytotoxicity of different silica (SiO2), nickel (Ni), and nickel(ii) oxide (NiO) nanoparticles were predicted and found to be in very good agreement with experimental reports. To the best of our knowledge, this is the first attempt to simultaneously predict the cytotoxicity of nanoparticles under multiple experimental conditions by applying a single unique QSTR model. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01285b

  10. Deoxynivalenol induces cytotoxicity and genotoxicity in animal primary cell culture.

    PubMed

    Singh, Shweta; Banerjee, Subham; Chattopadhyay, Pronobesh; Borthakur, Sashin Kumar; Veer, Vijay

    2015-03-01

    Deoxynivalenol (DON), a mycotoxin produced by Fusarium graminearum, is widely found as a contaminant of food. DON is responsible for a wide range of toxic activities, including gastro-intestinal, lymphoid, bone-marrow and cardiotoxicity. But, the complete explorations of toxicity in terms of hepatotoxicity, nephrotoxicity, cytotoxicity and genotoxicity as well have not been documented well. Again, the mechanisms through which DON damages the DNA and promotes cellular toxicity are not well established. Considering the above fact, this research article is focused on the effects of DON-induced toxicities on experimental animal model as well as its effects on cellular level via various toxicological investigations. DON treatment showed cytotoxicity and DNA damage. Further, flow cytometric analysis of hepatocytes showed cellular apoptosis, suggesting that DON-induced hepatotoxicity is, may be partly, mediated by apoptosis. Moreover, significant differences were found in each haematology and clinical chemistry value, either (p?>?0.05). No abnormality of any organ was found during histopathological examination. Hence, it can be concluded that DON induces oxidative DNA damage and increases the formation of centromere positive micronuclei due to aneugenic activity. PMID:25578892

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

    SciTech Connect

    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

    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.

  12. Cytotoxicity evaluation of carbon-encapsulated iron nanoparticles in melanoma cells and dermal fibroblasts.

    PubMed

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

    2013-01-01

    Carbon-encapsulated iron nanoparticles (CEINs) are emerging as promising biomedical tools due to their unique physicochemical properties. In this study, the cytotoxic effect of CEINs (the mean diameter distribution ranges 46-56 nm) has been explored by MTT, LDH leakage, Calcein-AM/propidium iodide (PI) and Annexin V-FITC/PI assays in human melanoma (HTB-140), mouse melanoma (B16-F10) cells, and human dermal fibroblasts (HDFs). The results demonstrated that CEINs produce mitochondrial and cell membrane cytotoxicities in a dose (0.0001-100 ?g/ml)-dependent manner. Moreover, the studies elucidated some differences in cytotoxic effects between CEINs used as raw and purified materials composing of the carbon surface with acidic groups. Experiments showed that HTB-140 cells are more sensitive to prone early apoptotic events due to raw CEINs as compared to B16-F10 or HDF cells, respectively. Taken together, these results suggest that the amount of CEINs administered to cells and the composition of CEINs containing different amounts of iron as well as the carbon surface modification type is critical determinant of cytotoxic responses in both normal and cancer (melanoma) cells. PMID:23990753

  13. Enhanced cellular uptake and cytotoxicity of folate decorated doxorubicin loaded PLA-TPGS nanoparticles

    NASA Astrophysics Data System (ADS)

    Nguyen, Hoai Nam; Nhung Hoang, Thi My; Thu Trang Mai, Thi; Quynh Trang Nguyen, Thi; Doan Do, Hai; Hien Pham, Thi; Lap Nguyen, Thi; Thu Ha, Phuong

    2015-01-01

    Doxorubicin (DOX) is one of the most effective anticancer drugs for treating many types of cancer. However, the clinical applications of DOX were hindered because of serious side-effects resulting from the unselective delivery to cancer cell including congestive heart failure, chronic cardiomyopathy and drug resistance. Recently, it has been demonstrated that loading anti-cancer drugs onto drug delivery nanosystems helps to maximize therapeutic efficiency and minimize unwanted side-effects via passive and active targeting mechanisms. In this study we prepared folate decorated DOX loaded PLA-TPGS nanoparticles with the aim of improving the potential as well as reducing the side-effects of DOX. Characteristics of nanoparticles were investigated by field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS) method and Fourier transform infrared spectroscopy (FTIR). Anticancer activity of the nanoparticles was evaluated through cytotoxicity and cellular uptake assays on HeLa and HT29 cancer cell lines. The results showed that prepared drug delivery system had size around 100 nm and exhibited higher cytotoxicity and cellular uptake on both tested HeLa and HT29 cells.

  14. Cytotoxicity of curcumin silica nanoparticle complexes conjugated with hyaluronic acid on colon cancer cells.

    PubMed

    Singh, Surya Prakash; Sharma, Mrinalini; Gupta, Pradeep Kumar

    2015-03-01

    We report results of our investigations on the cytotoxic efficacy of Organically modified silica nanoparticle (SiNp)-curcumin complex conjugated with hyaluronic acid (HA) (HA-SiNp-cur) and HA free SiNp-cur complex in human colon carcinoma (colo-205) cells. Curcumin was loaded in SiNp and resulting complexes were conjugated with HA, which has a strong affinity for cancer cells expressing CD44. After conjugation with HA, the average size of the SiNp-cur nanoparticles increased from 45 nm to 70 nm, and zeta potential changed to -33 mV from -26 mV. Compared to free curcumin and SiNp-cur, curcumin in HA-SiNp was more stable. The uptake and cytotoxicity of curcumin delivered through HA-SiNp-cur was significantly higher in monolayer and spheroids as compared to free curcumin and HA free SiNp-cur. Concomitantly, HA-SiNp-cur complex treatment resulted in higher inhibition of growth and migration of cells in spheroids. Further, incubation of colo-205 cancer cells with an excess of HA impaired the uptake of HA-SiNp-cur confirming the involvement of receptor mediated endocytosis in the uptake of HA conjugated nanocomplex. Time dependent increase in the fluorescence of curcumin observed in the release media when HA-SiNp-cur was incubated with hyaluronidase suggests involvement of enzyme in release of curcumin from nanoparticle. PMID:25511568

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

    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.

  16. Physiological changes induced in cardiac myocytes by cytotoxic T lymphocytes

    SciTech Connect

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

    1987-01-01

    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.

  17. Effect of radiation energy and intracellular iron dose on iron oxide nanoparticle enhancement of radiation cytotoxicity

    NASA Astrophysics Data System (ADS)

    Mazur, Courtney M.; Strawbridge, Rendall R.; Thompson, Ella S.; Petryk, Alicia A.; Gladstone, David J.; Hoopes, P. Jack

    2015-03-01

    Iron oxide nanoparticles (IONPs) are one of several high-Z materials currently being investigated for their ability to enhance the cytotoxic effects of therapeutic ionizing radiation. Studies with iron oxide, silver, gold, and hafnium oxide suggest radiation dose, radiation energy, cell type, and the type and level of metallic nanoparticle are all critical factors in achieving radiation enhancement in tumor cells. Using a single 4 Gy radiation dose, we compared the level of tumor cell cytotoxicity at two different intracellular iron concentrations and two different radiation energies in vitro. IONPs were added to cell culture media at concentrations of 0.25 mg Fe/mL and 1.0 mg Fe/mL and incubated with murine breast adenocarcinoma (MTG-B) cells for 72 hours. Extracellular iron was then removed and cells were irradiated at either 662 keV or 10 MV. At the 0.25 mg Fe/mL dose (4 pg Fe/cell), radiation energy did not affect the level of cytotoxicity. However with 1.0 mg Fe/mL (9 pg Fe/cell), the higher 10 MV radiation energy resulted in 50% greater cytotoxicity as compared to cells without IONPs irradiated at this energy. These results suggest IONPs may be able to significantly enhance the cytotoxic effects of radiation and improve therapeutic ratio if they can be selectively associated with cancer cells and/or tumors. Ongoing in vivo studies of IONP radiation enhancement in a murine tumor model are too immature to draw conclusions from at this time, however preliminary data suggests similar effectiveness of IONP radiation enhancement at 6 MV and 18 MV energy levels. In addition to the IONP-based radiation enhancement demonstrated here, the use of tumor-localized IONP with an externally delivered, non-toxic alternating magnetic field affords the opportunity to selectively heat and kill tumor cells. Combining IONP-based radiation sensitization and heat-based cytotoxicity provides a unique and potentially highly effective opportunity for therapeutic ratio enhancement.

  18. In vitro cytotoxicity and in vivo sub-acute oral toxicity assessment of porphyran reduced gold nanoparticles

    Microsoft Academic Search

    Vinod Venkatpurwar; Vishal Mali; Subhash Bodhankar; Varsha Pokharkar

    2012-01-01

    The aim of this study was to establish a toxicologic profile of gold nanoparticles (AuNP) (surface plasmon resonance at 520?nm and average particle size 14?±?2?nm) synthesized using novel polysaccharide porphyran isolated from marine red algae. The toxicology profile includes in vitro cytotoxicity and in vivo sub-acute oral toxicity study (OECD guideline 407) of porphyran-reduced AuNP. In vitro cytotoxicity study of porphyran-reduced AuNP (10,

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

    PubMed Central

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

    2013-01-01

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

  20. Cerium Oxide Nanoparticles Induce Oxidative Stress and Genotoxicity in Human Skin Melanoma Cells.

    PubMed

    Ali, Daoud; Alarifi, Saud; Alkahtani, Saad; AlKahtane, Abdullah A; Almalik, Abdulaziz

    2014-11-14

    Extensive applications of cerium oxide (CeO2) nanoparticles require a better understanding of their possible effects on human health. However, data demonstrating the effect of CeO2 nanoparticles on the human skin melanoma cell remain scanty. In the current study, we determined the mechanism through which CeO2 nanoparticles (APS <25 nm) induce toxicity in human skin melanoma cells (A375). The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and neutral red uptake assays showed concentration and time-dependent cytotoxicity of CeO2 nanoparticles in A375 cells. CeO2 nanoparticles significantly induced the generation reactive oxygen species (ROS) and malondialdehyde, superoxide dismutase, and decreased glutathione levels in A375 cells. It was also observed that the CeO2 nanoparticles induced chromosomal condensation and caspase-3 activity. CeO2 nanoparticles exposed cells revealed the formation of DNA double-strand breakage as measured by percent tail DNA and olive tail moment through comet assay. The decline of cell viability, production of ROS, and DNA damage in A375 cells specifies that CeO2 nanoparticles have less capable to induce cyto and genotoxicity. PMID:25395198

  1. Fluoromica nanoparticle cytotoxicity in macrophages decreases with size and extent of uptake

    PubMed Central

    Tee, Nicolin; Zhu, Yingdong; Mortimer, Gysell M; Martin, Darren J; Minchin, Rodney F

    2015-01-01

    Polyurethanes are widely used in biomedical devices such as heart valves, pacemaker leads, catheters, vascular devices, and surgical dressings because of their excellent mechanical properties and good biocompatibility. Layered silicate nanoparticles can significantly increase tensile strength and breaking strain of polyurethanes potentially increasing the life span of biomedical devices that suffer from wear in vivo. However, very little is known about how these nanoparticles interact with proteins and cells and how they might exert unwanted effects. A series of fluoromica nanoparticles ranging in platelet size from 90 to over 600 nm in diameter were generated from the same base material ME100 by high energy milling and differential centrifugation. The cytotoxicity of the resulting particles was dependent on platelet size but in a manner that is opposite to many other types of nanomaterials. For the fluoromicas, the smaller the platelet size, the less toxicity was observed. The small fluoromica nanoparticles (<200 nm) were internalized by macrophages via scavenger receptors, which was dependent on the protein corona formed in serum. This internalization was associated with apoptosis in RAW cells but not in dTHP-1 cells. The larger particles were not internalized efficiently but mostly decorated the surface of the cells, causing membrane disruption, even in the presence of 80% serum. This work suggests the smaller fluoromica platelets may be safer for use in humans but their propensity to recognize macrophage scavenger receptors also suggests that they will target the reticulo-endoplasmic system in vivo. PMID:25848256

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

    PubMed

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

    2013-08-01

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

  3. In Vitro Cytotoxic Evaluation of MgO Nanoparticles and Their Effect on the Expression of ROS Genes

    PubMed Central

    Kumaran, Rangarajulu Senthil; Choi, Yong-Keun; Singh, Vijay; Song, Hak-Jin; Song, Kyung-Guen; Kim, Kwang Jin; Kim, Hyung Joo

    2015-01-01

    Water-dispersible MgO nanoparticles were tested to investigate their cytotoxic effects on oxidative stress gene expression. In this in vitro study, genes related to reactive oxygen species (ROS), glutathione S-transferase (GST) and catalase, were quantified using real-time polymerase chain reactions (molecular level) and molecular beacon technologies (cellular level). The monodispersed MgO nanoparticles, 20 nm in size, were used to treat human cancer cell lines (liver cancer epithelial cells) at different concentrations (25, 75 and 150 µg/mL) and incubation times (24, 48 and 72 h). Both the genetic and cellular cytotoxic screening methods produced consistent results, showing that GST and catalase ROS gene expression was maximized at 150 µg/mL nanoparticle treatment with 48 h incubation. However, the genotoxic effect of MgO nanoparticles was not significant compared with control experiments, which indicates its significant potential applications in nanomedicine as a diagnostic and therapeutic tool. PMID:25854426

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

    PubMed

    Mandal, A; Sekar, S; Chandrasekaran, N; Mukherjee, A; Sastry, T P

    2013-11-01

    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

  5. Design of LVFFARK and LVFFARK-functionalized nanoparticles for inhibiting amyloid ?-protein fibrillation and cytotoxicity.

    PubMed

    Xiong, Neng; Dong, Xiao-Yan; Zheng, Jie; Liu, Fu-Feng; Sun, Yan

    2015-03-18

    Aggregation of amyloid ?-protein (A?) into amyloid oligomers and fibrils is pathologically linked to Alzheimer's disease (AD). Hence, the inhibition of A? aggregation is essential for the prevention and treatment of AD, but the development of potent agents capable of inhibiting A? fibrillogenesis has posed significant challenges. Herein, we designed Ac-LVFFARK-NH2 (LK7) by incorporating two positively charged residues, R and K, into the central hydrophobic fragment of A?17-21 (LVFFA) and examined its inhibitory effect on A?42 aggregation and cytotoxicity by extensive physical, biophysical, and biological analyses. LK7 was observed to inhibit A?42 fibrillogenesis in a dose-dependent manner, but its strong self-assembly characteristic also resulted in high cytotoxicity. In order to prevent the cytotoxicity that resulted from the self-assembly of LK7, the peptide was then conjugated to the surface of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to fabricate a nanosized inhibitor, LK7@PLGA-NPs. It was found that LK7@PLGA-NPs had little cytotoxicity because the self-assembly of the LK7 conjugated on the NPs was completely inhibited. Moreover, the NPs-based inhibitor showed remarkable inhibitory capability against A?42 aggregation and significantly alleviated its cytotoxicity at a low LK7@PLGA-NPs concentration of 20 ?g/mL. At the same peptide concentration, free LK7 showed little inhibitory effect. It is considered that several synergetic effects contributed to the strong inhibitory ability of LK7@PLGA-NPs, including the enhanced interactions between A?42 and LK7@PLGA-NPs brought on by inhibiting LK7 self-assembly, restricting conformational changes of A?42, and thus redirecting A?42 aggregation into unstructured, off-pathway aggregates. The working mechanisms of the inhibitory effects of LK7 and LK7@PLGA-NPs on A?42 aggregation were proposed based on experimental observations. This work provides new insights into the design and development of potent NPs-based inhibitors against A? aggregation and cytotoxicity. PMID:25700145

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

    PubMed

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

    2012-02-01

    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

  7. Stress-Induced Nanoparticle Crystallization

    PubMed Central

    2015-01-01

    We demonstrate for the first time a new mechanical annealing method that can significantly improve the structural quality of self-assembled nanoparticle arrays by eliminating defects at room temperature. Using in situ high-pressure small-angle X-ray scattering, we show that deformation of nanoparticle assembly in the presence of gigapascal level stress rebalances interparticle forces within nanoparticle arrays and transforms the nanoparticle film from an amorphous assembly with defects into a quasi-single crystalline superstructure. Our results show that the existence of the hydrostatic pressure field makes the transformation both thermodynamically and kinetically possible/favorable, thus providing new insight for nanoparticle self-assembly and integration with enhanced mechanical performance. PMID:24829089

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

    PubMed

    Zaki, Noha M

    2014-06-01

    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

  9. Cytotoxicity of water-soluble mPEG-SH-coated silver nanoparticles in HL-7702 cells.

    PubMed

    Song, Xiu-ling; Li, Bo; Xu, Kun; Liu, Juan; Ju, Wen; Wang, Juan; Liu, Xiao-dong; Li, Juan; Qi, Yan-fei

    2012-08-01

    Silver nanoparticles (AgNPs) are being used widely and increasingly in various products and medical supplies due to their antibacterial activity. However, little is known about the impacts of the AgNPs. Herein, The primary purpose of this study was to investigate the cytotoxic effect of AgNPs in the human liver cell line (HL-7702). The water-soluble ?-Methoxy-poly (ethylene glycol)-?-mercapto (mPEG-SH)-coated AgNPs (40 nm) were synthesized, which showed superior stabilization and uniform dispersion in culture medium. The effect of mPEG-SH-coated silver nanoparticles on cell viability, leakage of lactate dehydrogenase (LDH), oxidative stress, mitochondrial membrane potential (MMP), and cell cycle was evaluated after the cells were treated with nanoparticles. The results showed that the coated AgNPs could be taken up by cells, decreased cell viability in dose- and time-dependent manners at dosage levels between 6.25 and 100.00 ?g/mL, caused membrane damage (LDH leakage), and decreased the activities of superoxide dismutase and glutathione peroxides. The level of malondialdehyde, an end product of lipid peroxidation, was also increased in AgNPs-exposed cells. Moreover, flow cytometric analysis showed that AgNP exposure decrease MMP and cause G?/M phase arrest. Thus, our data suggest that mPEG-SH-coated AgNPs have the potential toxicity that is associated with oxidative stress, apoptosis, and DNA damage. PMID:22415596

  10. Size-dependent cytotoxicity of silver nanoparticles in human lung cells: the role of cellular uptake, agglomeration and Ag release

    PubMed Central

    2014-01-01

    Background Silver nanoparticles (AgNPs) are currently one of the most manufactured nanomaterials. A wide range of toxicity studies have been performed on various AgNPs, but these studies report a high variation in toxicity and often lack proper particle characterization. The aim of this study was to investigate size- and coating-dependent toxicity of thoroughly characterized AgNPs following exposure of human lung cells and to explore the mechanisms of toxicity. Methods BEAS-2B cells were exposed to citrate coated AgNPs of different primary particle sizes (10, 40 and 75 nm) as well as to 10 nm PVP coated and 50 nm uncoated AgNPs. The particle agglomeration in cell medium was investigated by photon cross correlation spectroscopy (PCCS); cell viability by LDH and Alamar Blue assay; ROS induction by DCFH-DA assay; genotoxicity by alkaline comet assay and ?H2AX foci formation; uptake and intracellular localization by transmission electron microscopy (TEM); and cellular dose as well as Ag release by atomic absorption spectroscopy (AAS). Results The results showed cytotoxicity only of the 10 nm particles independent of surface coating. In contrast, all AgNPs tested caused an increase in overall DNA damage after 24 h assessed by the comet assay, suggesting independent mechanisms for cytotoxicity and DNA damage. However, there was no ?H2AX foci formation and no increased production of intracellular reactive oxygen species (ROS). The reasons for the higher toxicity of the 10 nm particles were explored by investigating particle agglomeration in cell medium, cellular uptake, intracellular localization and Ag release. Despite different agglomeration patterns, there was no evident difference in the uptake or intracellular localization of the citrate and PVP coated AgNPs. However, the 10 nm particles released significantly more Ag compared with all other AgNPs (approx. 24 wt% vs. 4–7 wt%) following 24 h in cell medium. The released fraction in cell medium did not induce any cytotoxicity, thus implying that intracellular Ag release was responsible for the toxicity. Conclusions This study shows that small AgNPs (10 nm) are cytotoxic for human lung cells and that the toxicity observed is associated with the rate of intracellular Ag release, a ‘Trojan horse’ effect. PMID:24529161

  11. Effect of the protein corona on nanoparticles for modulating cytotoxicity and immunotoxicity

    PubMed Central

    Lee, Yeon Kyung; Choi, Eun-Ju; Webster, Thomas J; Kim, Sang-Hyun; Khang, Dongwoo

    2015-01-01

    Although the cytotoxicity of nanoparticles (NPs) is greatly influenced by their interactions with blood proteins, toxic effects resulting from blood interactions are often ignored in the development and use of nanostructured biomaterials for in vivo applications. Protein coronas created during the initial reaction with NPs can determine the subsequent immunological cascade, and protein coronas formed on NPs can either stimulate or mitigate the immune response. Along these lines, the understanding of NP-protein corona formation in terms of physiochemical surface properties of the NPs and NP interactions with the immune system components in blood is an essential step for evaluating NP toxicity for in vivo therapeutics. This article reviews the most recent developments in NP-based protein coronas through the modification of NP surface properties and discusses the associated immune responses. PMID:25565807

  12. Preparation, characterization, cytotoxicity, and genotoxicity evaluations of thiolated- and s-nitrosated superparamagnetic iron oxide nanoparticles: implications for cancer treatment.

    PubMed

    Seabra, Amedea B; Pasquôto, Tatiane; Ferrarini, Ana Carolina F; Santos, Marconi da Cruz; Haddad, Paula S; de Lima, Renata

    2014-07-21

    Iron oxide magnetic nanoparticles have been proposed for an increasing number of biomedical applications, such as drug delivery. To this end, toxicological studies of their potent effects in biological media must be better evaluated. The aim of this study was to synthesize, characterize, and examine the potential in vitro cytotoxicity and genotoxicity of thiolated (SH) and S-nitrosated (S-NO) iron oxide superparamagnetic nanoparticles toward healthy and cancer cell lines. Fe3O4 nanoparticles were synthesized by coprecipitation techniques and coated with small thiol-containing molecules, such as mercaptosuccinic acid (MSA) or meso-2,3-dimercaptosuccinic acid (DMSA). The physical-chemical, morphological, and magnetic properties of thiol-coating Fe3O4 nanoparticles were characterized by different techniques. The thiol groups on the surface of the nanoparticles were nitrosated, leading to the formation of S-nitroso-MSA- or S-nitroso-DMSA-Fe3O4 nanoparticles. The cytotoxicity and genotoxicity of thiolated and S-nitrosated nanoparticles were more deeply evaluated in healthy (3T3, human lymphocytes cells, and chinese hamster ovary cells) and cancer cell lines (MCF-7). The results demonstrated that thiol-coating iron oxide magnetic nanoparticles have few toxic effects in cells, whereas S-nitrosated-coated particles did cause toxic effects. Moreover, due to the superaramagnetic behavior of S-nitroso-Fe3O4 nanoparticles, those particles can be guided to the target site upon the application of an external magnetic field, leading to local toxic effects in the tumor cells. Taken together, the results suggest the promise of S-nitroso-magnetic nanoparticles in cancer treatment. PMID:24949992

  13. Detection of nitric oxide in macrophage cells for the assessment of the cytotoxicity of gold nanoparticles.

    PubMed

    Du, Libo; Miao, Xiaoxiang; Jia, Hongying; Gao, Yanli; Liu, Ke; Zhang, Xueji; Liu, Yang

    2012-11-15

    In this paper, an electrochemical method using a nitric oxide sensor was employed for quantitative evaluation of NO released from AuNPs-treated macrophage cells. Our results indicate that the AuNPs initiate NO release from macrophage cells and the amount of NO released is positively correlated with concentration of AuNPs. Meanwhile, total nitrite/nitrate concentrations in the AuNPs-treated macrophage cells have been determined via the Griess reaction and we demonstrate that the variation of the nitrite/nitrate concentrations is in accordance with that measured by the electrochemical method. In contrast to the citrate-coated gold nanoparticles (CT-AuNPs), when AuNPs were protected by thiolated poly ethylene glycol (PEG), the NO-releasing in macrophage upon the addition of AuNPs was relieved, implying that the PEG-coated AuNPs having less cytotoxicity and oxidative stress potential is probably due to inhibition of NO production. In conclusion, this work has demonstrated an effective sensing platform for the evaluation of the cytotoxicity of AuNPs by detecting the extracellular NO released from macrophage cells. PMID:23158284

  14. Enhanced cytotoxic activity of cetuximab in EGFR-positive lung cancer by conjugating with gold nanoparticles

    PubMed Central

    Qian, Yichun; Qiu, Mantang; Wu, Qingquan; Tian, Yanyan; Zhang, Yu; Gu, Ning; Li, Suyi; Xu, Lin; Yin, Rong

    2014-01-01

    Cetuximab (C225) is a unique agent, targeting epidermal growth factor receptor (EGFR)-positive cancer. However, the therapeutic effect of C225 in EGFR high-expressing non-small cell lung cancer (NSCLC) remains poor. Here, we report that conjugation of C225 with gold nanoparticles (AuNPs) enhances the cytotoxicity of C225 in NSCLC both in vitro and in vivo. The NSCLC cell lines A549 (EGFRhigh) and H1299 (EGFRlow) were employed to investigate different responses to C225, IgG-AuNPs and C225-AuNPs. The antitumor properties of C225-AuNPs were explored in vivo by establishing a tumor xenograft model in nude mice. Overall, the therapeutic effect of C225-AuNPs was more pronounced in EGFRhigh A549 cells compared with EGFRlow H1299 cells. The cytotoxic effect of C225-AuNPs in A549 cells increased in a dose-dependent manner. C225-AuNPs significantly suppressed A549 cell proliferation and migration capacity and accelerated apoptosis compared with C225, and this effect was probably due to enhanced EGFR endocytosis and the subsequent suppression of downstream signaling pathway. Finally in the tumor xenograft of nude mice, treatment with C225-AuNPs also led to a significant reduction in tumor weight and volume with low toxicity. Our findings suggest that C225-AuNPs conjugate has promising potential for targeted therapy of EGFR positive NSCLC patients. PMID:25502402

  15. Oleanolic Acid Loaded PEGylated PLA and PLGA Nanoparticles with Enhanced Cytotoxic Activity against Cancer Cells.

    PubMed

    Man, Dede K W; Casettari, Luca; Cespi, Marco; Bonacucina, Giulia; Palmieri, Giovanni Filippo; Sze, Stephen C W; Leung, George P H; Lam, Jenny K W; Kwok, Philip C L

    2015-06-01

    Oleanolic acid (OA) is a natural triterpenoid with anticancer properties, but its hydrophobic nature and poor aqueous solubility pose challenges in pharmaceutical formulation development. The present study aimed at developing OA-loaded mPEG-PLGA or mPEG-PLA nanoparticles (NPs) to improve the delivery of OA. The NPs were prepared by nanoprecipitation, and their physicochemical properties were characterized. The OA encapsulation efficiency of the NPs was between 40 and 75%. The size of the OA-loaded NPs was around 200-250 nm, which fell within the range required for tumor targeting by means of the enhanced permeability and retention (EPR) effect, and the negatively charged NPs remained physically stable for over 20 weeks with no aggregation observed. The OA-loaded NPs produced significant cytotoxic effects through apoptosis in cancer cell lines. Overall, the OA-loaded mPEG-PLGA NPs and mPEG-PLA NPs shared similar physicochemical properties. The former, especially the OA-loaded mPEG-P(D,L)LGA NPs, were more cytotoxic to cancer cells and therefore were more efficient for OA delivery. PMID:25881668

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

    PubMed Central

    Fröhlich, Eleonore

    2012-01-01

    Many types of nanoparticles (NPs) are tested for use in medical products, particularly in imaging and gene and drug delivery. For these applications, cellular uptake is usually a prerequisite and is governed in addition to size by surface characteristics such as hydrophobicity and charge. Although positive charge appears to improve the efficacy of imaging, gene transfer, and drug delivery, a higher cytotoxicity of such constructs has been reported. This review summarizes findings on the role of surface charge on cytotoxicity in general, action on specific cellular targets, modes of toxic action, cellular uptake, and intracellular localization of NPs. Effects of serum and intercell type differences are addressed. Cationic NPs cause more pronounced disruption of plasma-membrane integrity, stronger mitochondrial and lysosomal damage, and a higher number of autophagosomes than anionic NPs. In general, nonphagocytic cells ingest cationic NPs to a higher extent, but charge density and hydrophobicity are equally important; phagocytic cells preferentially take up anionic NPs. Cells do not use different uptake routes for cationic and anionic NPs, but high uptake rates are usually linked to greater biological effects. The different uptake preferences of phagocytic and nonphagocytic cells for cationic and anionic NPs may influence the efficacy and selectivity of NPs for drug delivery and imaging. PMID:23144561

  17. Cytotoxicity of Biologically Synthesized Silver Nanoparticles in MDA-MB-231 Human Breast Cancer Cells

    PubMed Central

    Gurunathan, Sangiliyandi; Han, Jae Woong; Eppakayala, Vasuki; Jeyaraj, Muniyandi; Kim, Jin-Hoi

    2013-01-01

    Silver nanoparticles (AgNPs) have been used as an antimicrobial and disinfectant agents. However, there is limited information about antitumor potential. Therefore, this study focused on determining cytotoxic effects of AgNPs on MDA-MB-231 breast cancer cells and its mechanism of cell death. Herein, we developed a green method for synthesis of AgNPs using culture supernatant of Bacillus funiculus, and synthesized AgNPs were characterized by various analytical techniques such as UV-visible spectrophotometer, particle size analyzer, and transmission electron microscopy (TEM). The toxicity was evaluated using cell viability, metabolic activity, and oxidative stress. MDA-MB-231 breast cancer cells were treated with various concentrations of AgNPs (5 to 25??g/mL) for 24?h. We found that AgNPs inhibited the growth in a dose-dependent manner using MTT assay. AgNPs showed dose-dependent cytotoxicity against MDA-MB-231 cells through activation of the lactate dehydrogenase (LDH), caspase-3, reactive oxygen species (ROS) generation, eventually leading to induction of apoptosis which was further confirmed through resulting nuclear fragmentation. The present results showed that AgNPs might be a potential alternative agent for human breast cancer therapy. PMID:23936814

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

    PubMed

    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

    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

  19. Uremic toxins enhance statin-induced cytotoxicity in differentiated human rhabdomyosarcoma cells.

    PubMed

    Uchiyama, Hitoshi; Tsujimoto, Masayuki; Shinmoto, Tadakazu; Ogino, Hitomi; Oda, Tomoko; Yoshida, Takuya; Furukubo, Taku; Izumi, Satoshi; Yamakawa, Tomoyuki; Tachiki, Hidehisa; Minegaki, Tetsuya; Nishiguchi, Kohshi

    2014-09-01

    The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF). Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins-hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate-on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated). In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated). However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated). These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins. PMID:25192420

  20. Uremic Toxins Enhance Statin-Induced Cytotoxicity in Differentiated Human Rhabdomyosarcoma Cells

    PubMed Central

    Uchiyama, Hitoshi; Tsujimoto, Masayuki; Shinmoto, Tadakazu; Ogino, Hitomi; Oda, Tomoko; Yoshida, Takuya; Furukubo, Taku; Izumi, Satoshi; Yamakawa, Tomoyuki; Tachiki, Hidehisa; Minegaki, Tetsuya; Nishiguchi, Kohshi

    2014-01-01

    The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF). Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins—hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate—on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated). In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated). However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated). These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins. PMID:25192420

  1. Influence of surface properties of zinc oxide nanoparticles on their cytotoxicity.

    PubMed

    Altunbek, Mine; Baysal, Asl?; Çulha, Mustafa

    2014-09-01

    The toxicity of nanoparticles (NPs) depends on several factors including size, shape, surface properties and chemical nature of the NPs. The release of toxic ions due to the dissolution of NPs is another important factor. In addition, impurities or reaction products from synthesis procedures on the NP surfaces may contribute to the toxicity. Zinc oxide nanoparticles (ZnO NPs) are one of the unique NPs showing toxicity through all of these mentioned factors. In this study, we demonstrate that the treatment of the ZnO NPs with hydrogen peroxide (H2O2) alters the surface properties of the ZnO NPs by decomposing organic impurities remained from synthesis procedures. The changes on the surface chemistry and properties of the ZnO NPs influence their behavior in cell culture media and the NPs-cell interactions. Finally, a decrease in the cytotoxicity of H2O2 treated ZnO NPs is observed on HDF and A549 cells through the decrease of the membrane damage and oxidative stress. PMID:25042418

  2. Evaluation of azathioprine-induced cytotoxicity in an in vitro rat hepatocyte system.

    PubMed

    Al Maruf, Abdullah; Wan, Luke; O'Brien, Peter J

    2014-01-01

    Azathioprine (AZA) is widely used in clinical practice for preventing graft rejection in organ transplantations and various autoimmune and dermatological diseases with documented unpredictable hepatotoxicity. The potential molecular cytotoxic mechanisms of AZA towards isolated rat hepatocytes were investigated in this study using "Accelerated Cytotoxicity Mechanism Screening" techniques. The concentration of AZA required to cause 50% cytotoxicity in 2?hrs at 37°C was found to be 400??M. A significant increase in AZA-induced cytotoxicity and reactive oxygen species (ROS) formation was observed when glutathione- (GSH-) depleted hepatocytes were used. The addition of N-acetylcysteine decreased cytotoxicity and ROS formation. Xanthine oxidase inhibition by allopurinol decreased AZA-induced cytotoxicity, ROS, and hydrogen peroxide (H2O2) formation and increased % mitochondrial membrane potential (MMP). Addition of N-acetylcysteine and allopurinol together caused nearly complete cytoprotection against AZA-induced hepatocyte death. TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl), a known ROS scavenger and a superoxide dismutase mimic, and antioxidants, like DPPD (N,N'-diphenyl-p-phenylenediamine), Trolox (a water soluble vitamin E analogue), and mesna (2-mercaptoethanesulfonate), also decreased hepatocyte death and ROS formation. Results from this study suggest that AZA-induced cytotoxicity in isolated rat hepatocytes may be partly due to ROS formation and GSH depletion that resulted in oxidative stress and mitochondrial injury. PMID:25101277

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

    PubMed Central

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

    2012-01-01

    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. PMID:23055734

  4. Cytotoxicity study of iron oxide nanoparticles, single-wall carbon nanotubes and their complexes applied to MCF7 breast cancer cells

    NASA Astrophysics Data System (ADS)

    Mege, Karine

    Reactive Oxygen Species (ROS) are radicals of great concern to biologists. Their role in several diseases---such as neurodegenerative disease, diabetes, premature aging and cancer---has been intensively investigated during the last decade. Since a major focus in cancer research is to better understand how it is induced and therefore how it can be cured, the study of the cytotoxic effects of ROS production within cancer cells is vital. Nanotechnology is an emerging field of science that promises great improvements in a number of disciplines. Nano medicine is one of its daughter fields. Various nanomaterials are used for diagnosis and disease detection, therapy and medical imaging, and many are already being used in oncology medicine. The two most frequently used nanomaterials in cancer research are Carbon nanotubes (CNTs) and iron oxide nanoparticles (IONPs). They have been proven to play a significant role in the ROS production of various cancer cells. In this context, this thesis emphasizes the need to study the impact of nanoparticles, such as single-walled carbon nanotubes (SWCNTs), iron oxide nanoparticles (IONPs) and their complexes, on a human breast cancer cell line (MCF-7). To date, there have been very few studies assessing the effect on the oxidative stress activity of this cell line using these nanoparticles and their complexes.

  5. Diabetes exacerbates nanoparticles induced brain pathology.

    PubMed

    Lafuente, José Vicente; Sharma, Aruna; Patnaik, Ranjana; Muresanu, Dafin Fior; Sharma, Hari Shanker

    2012-02-01

    Long term exposure of nanoparticles e.g., silica dust (SiO2) from desert environments, or engineered nanoparticles from metals viz., Cu, Al or Ag from industry, ammunition, military equipment and related products may lead to adverse effects on mental health. However, it is unclear whether these nanoparticles may further adversely affect human health in cardiovascular or metabolic diseases e.g., hypertension or diabetes. It is quite likely that in diabetes or hypertension where the body immune system is already compromised there will be greater adverse effects following nanoparticles exposure on human health as compared to their exposure to healthy individuals. Previous experiments from our laboratory showed that diabetic or hypertensive animals are more susceptible to heat stress-induced neurotoxicity. Furthermore, traumatic injury to the spinal cord in SiO2 exposed rats resulted in exacerbation of cord pathology. However, whether nanoparticles such as Cu, Ag or SiO2 exposure will lead to enhanced neurotoxicity in diabetic animals are still not well investigated. Previous data from our laboratory showed that Cu or Ag intoxication (50 mg/kg, i.p. per day for 7 days) in streptozotocine induced diabetic rats exhibited enhanced neurotoxicity and exacerbation of sensory, motor and cognitive function as compared to normal animals under identical conditions. Thus the diabetic animals showed exacerbation of regional blood-brain barrier (BBB) disruption, edema formation and cell injuries along with greater reduction in the local cerebral blood flow (CBF) as compared to normal rats. These observations suggest that diabetic animals are more vulnerable to nanoparticles induced brain damage than healthy rats. The possible mechanisms and functional significance of these findings are discussed in this review largely based on our own investigations. PMID:22229323

  6. Size-dependent cytotoxicity of europium doped NaYF ? nanoparticles in endothelial cells.

    PubMed

    Chen, Shizhu; Zhang, Cuimiao; Jia, Guang; Duan, Jianlei; Wang, Shuxiang; Zhang, Jinchao

    2014-10-01

    Lanthanide-doped sodium yttrium fluoride (NaYF4) nanoparticles exhibit novel optical properties which make them be widely used in various fields. The extensive applications increase the chance of human exposure to these nanoparticles and thus raise deep concerns regarding their riskiness. In the present study, we have synthesized europium doped NaYF4 (NaYF4:Eu(3+)) nanoparticles with three diameters and used endothelial cells (ECs) as a cell model to explore the potential toxic effect. The cell viability, cytomembrane integrity, cellular uptake, intracellular localization, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), apoptosis detection, caspase-3 activity and expression of inflammatory gene were studied. The results indicated that these nanoparticles could be uptaken into ECs and decrease the cell viability, induce the intracellular lactate dehydrogenase (LDH) release, increase the ROS level, and decrease the cell MMP in a size-dependent manner. Besides that, the cells were suffered to apoptosis with the caspase-3 activation, and the inflammation specific gene expressions (ICAM1 and VCAM1) were also increased. Our results suggest that the damage pathway may be related to the ROS generation and mitochondrial damage. The results provide novel evidence to elucidate their toxicity mechanisms and may be helpful for more rational applications of these compounds in the future. PMID:25175221

  7. Differential cytotoxic and radiosensitizing effects of silver nanoparticles on triple-negative breast cancer and non-triple-negative breast cells

    PubMed Central

    Swanner, Jessica; Mims, Jade; Carroll, David L; Akman, Steven A; Furdui, Cristina M; Torti, Suzy V; Singh, Ravi N

    2015-01-01

    Identification of differential sensitivity of cancer cells as compared to normal cells has the potential to reveal a therapeutic window for the use of silver nanoparticles (AgNPs) as a therapeutic agent for cancer therapy. Exposure to AgNPs is known to cause dose-dependent toxicities, including induction of oxidative stress and DNA damage, which can lead to cell death. Triple-negative breast cancer (TNBC) subtypes are more vulnerable to agents that cause oxidative stress and DNA damage than are other breast cancer subtypes. We hypothesized that TNBC may be susceptible to AgNP cytotoxicity, a potential vulnerability that could be exploited for the development of new therapeutic agents. We show that AgNPs are highly cytotoxic toward TNBC cells at doses that have little effect on nontumorigenic breast cells or cells derived from liver, kidney, and monocyte lineages. AgNPs induced more DNA and oxidative damage in TNBC cells than in other breast cells. In vitro and in vivo studies showed that AgNPs reduce TNBC growth and improve radiation therapy. These studies show that unmodified AgNPs act as a self-therapeutic agent with a combination of selective cytotoxicity and radiation dose-enhancement effects in TNBC at doses that are nontoxic to noncancerous breast and other cells. PMID:26185437

  8. Antioxidant studies of chitosan nanoparticles containing naringenin and their cytotoxicity effects in lung cancer cells.

    PubMed

    Kumar, Sekar Praveen; Birundha, Kannan; Kaveri, Kannan; Devi, K T Ramya

    2015-07-01

    Chitosan based nano carrier systems have been widely explored owing to its reliability and simpler synthesis route. In the current study, chitosan (CS) encapsulated naringenin (NAR) nanoparticles (CS-NPs/NAR) were synthesized by ionic gelation method mediated by tripolyphosphate (TPP) as a cross-linker and characterized by DLS, SEM, Zeta potential, FT-IR and EDS analyses. The encapsulation efficiency of CS-NPs/NAR was determined by Folin-Ciocalteau (FC) and high performance liquid chromatography (HPLC) techniques. The native CS-NPs were found to be sized at 53.2nm, while an increase in the size to 407.47nm was observed upon loading with NAR. The encapsulation efficiency of CS-NPs/NAR was identified to be ?70% by FC method and ?80% by HPLC method, respectively. The release of NAR from CS-NPs/NAR in simulated gastric fluid was found to be ?15% and remaining 85% of NAR was entrapped in CS-NPs/NAR. Furthermore, the free radical scavenging ability of CS-NPs/NAR was studied by Nitrate scavenging, 2, 2-diphenyl-2-picryl hydrazyl hydrate and hydroxyl radical scavenging assays. The free radical scavenging activity was significantly higher in CS-NPs/NAR. MTT based cytotoxic analysis also depicted the non-toxic nature of CS-NPs/NAR towards normal fibroblast 3T3 cells, while cytotoxic effects were noticed against A549 lung cancer cells. Hence, the current investigations showed the superiority of chitosan encapsulated NAR over free NAR and suggested an efficient system for delivering NAR with antioxidant and anticancer activities. PMID:25840152

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

    PubMed Central

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

    2014-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

  11. Mechanisms of cell penetration and cytotoxicity of ultrasmall Au nanoparticles conjugated to doxorubicin and/or targeting peptides

    NASA Astrophysics Data System (ADS)

    Nadeau, Jay; Poon, Wilson; Zhang, Xuan

    2015-03-01

    The goals of this work were to determine whether conjugation of any of four selected peptides to Au nanoparticles improved their delivery to B16 melanoma in vitro and in vivo. In in vitro cytotoxicity assays, peptides and conjugates were endocytosed but did not escape from endosomes. None of the peptides showed any cytotoxicity, with or without conjugation to the nanoparticles. The combination of peptides and doxorubicin did not improve upon the cytotoxicity of gold-doxorubicin alone. We then tested targeting in vivo using inductively coupled plasma mass spectrometry to quantify the concentration of Au in the organs of B16 tumor-bearing mice 4, 24, and 72 h after intravenous Au nanoparticle injection. These experiments showed that in some cases, peptide conjugation improved upon the enhanced permeability and retention (EPR) effect. A peptide based upon the myxoma virus and the cyclic RGD peptide were both effective at tumor targeting; myxoma was more effective with un-PEGylated particles, and cRGD with PEGylated particles. The FREG and melanocyte stimulating hormone (MSH) peptides did not improve targeting. These results suggest that these peptides may improve delivery of Au particles to tumors, but also may prevent entry of particles into cell nuclei.

  12. Zinc oxide nanoparticles induce rat retinal ganglion cell damage through bcl-2, caspase-9 and caspase-12 pathways.

    PubMed

    Guo, Dadong; Bi, Hongsheng; Wu, Qiuxin; Wang, Daoguang; Cui, Yan

    2013-06-01

    Nanomaterials, including zinc oxide (ZnO) nanoparticles, are being developed for a variety of commercial products. Recent reports showed that cells exposed to ZnO nanoparticles produced severe cytotoxicity accompanied by oxidative stress and genotoxicity. To understand the possible mechanism underlying oxidative stress of ZnO nanoparticles, the present investigation focused on the direct bioactivity of ZnO nanoparticles using a rat retinal ganglion cell (RGC-5) culture. At concentrations relevant to those used in vitro exposure of RGC-5 cells to ZnO nanoparticles, it was found that ZnO nanoparticles could inhibit cell proliferation in time- and concentration-dependent manners. Meanwhile, cell cycle arrest of S and G2/M phases occurred in RGC-5 cells induced by ZnO nanoparticles. Moreover, our results also demonstrated that the overproduction of reactive oxygen species (ROS) and elevated level of caspase-12 as well as decreased levels of bcl-2 and caspase-9 occurred after treatment with different concentrations of ZnO nanoparticles when compared to those in untreated cells. In summary, our findings suggest that ZnO nanoparticles could lead to the over generations of ROS and caspase-12 as well as decreased levels of bcl-2 and caspase-9. These results indicate that bcl-2, caspase-9 and caspase-12 may play significant roles in ZnO nanoparticle-induced RGC-5 cell damage. PMID:23862406

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

    NASA Astrophysics Data System (ADS)

    Ispas, Cristina R.

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

  14. Antibacterial and cytotoxic potential of silver nanoparticles synthesized using latex of Calotropis gigantea L.

    PubMed

    Rajkuberan, Chandrasekaran; Sudha, Kannaiah; Sathishkumar, Gnanasekar; Sivaramakrishnan, Sivaperumal

    2015-02-01

    The present study aimed to synthesis silver nanoparticles (AgNPs) in a greener route using aqueous latex extract of Calotropis gigantea L. toward biomedical applications. Initially, synthesis of AgNPs was confirmed through UV-Vis spectroscopy which shows the surface plasmonic resonance peak (SPR) at 420 nm. Fourier transform infrared spectroscopy (FTIR) analysis provides clear evidence that protein fractions present in the latex extract act as reducing and stabilizing bio agents. Energy dispersive X-ray (EDAX) spectroscopy confirms the presence of silver as a major constituent element. X-ray diffractograms displays that the synthesized AgNPs were biphasic crystalline nature. Electron microscopic studies such as Field emission scanning electron microscopic (Fe-SEM) and Transmission electron microscope (TEM) reveals that synthesized AgNPs are spherical in shape with the size range between 5 and 30 nm. Further, crude latex aqueous extract and synthesized AgNPs were evaluated against different bacterial pathogens such as Bacillus cereus, Enterococci sp, Shigella sp, Pseudomonas aeruginosa, Klebsiella pneumonia, Staphylococcus aureus and Escherichia coli. Compared to the crude latex aqueous extract, biosynthesized AgNPs exhibits a remarkable antimicrobial activity. Likewise in vitro anticancer study manifests the cytotoxicity value of synthesized AgNPs against tested HeLa cells. The output of this study clearly suggesting that biosynthesized AgNPs using latex of C. gigantea can be used as promising nanomaterial for therapeutic application in context with nanodrug formulation. PMID:25459618

  15. Antibacterial and cytotoxic potential of silver nanoparticles synthesized using latex of Calotropis gigantea L.

    NASA Astrophysics Data System (ADS)

    Rajkuberan, Chandrasekaran; Sudha, Kannaiah; Sathishkumar, Gnanasekar; Sivaramakrishnan, Sivaperumal

    2015-02-01

    The present study aimed to synthesis silver nanoparticles (AgNPs) in a greener route using aqueous latex extract of Calotropis gigantea L. toward biomedical applications. Initially, synthesis of AgNPs was confirmed through UV-Vis spectroscopy which shows the surface plasmonic resonance peak (SPR) at 420 nm. Fourier transform infrared spectroscopy (FTIR) analysis provides clear evidence that protein fractions present in the latex extract act as reducing and stabilizing bio agents. Energy dispersive X-ray (EDAX) spectroscopy confirms the presence of silver as a major constituent element. X-ray diffractograms displays that the synthesized AgNPs were biphasic crystalline nature. Electron microscopic studies such as Field emission scanning electron microscopic (Fe-SEM) and Transmission electron microscope (TEM) reveals that synthesized AgNPs are spherical in shape with the size range between 5 and 30 nm. Further, crude latex aqueous extract and synthesized AgNPs were evaluated against different bacterial pathogens such as Bacillus cereus, Enterococci sp, Shigella sp, Pseudomonas aeruginosa, Klebsiella pneumonia, Staphylococcus aureus and Escherichia coli. Compared to the crude latex aqueous extract, biosynthesized AgNPs exhibits a remarkable antimicrobial activity. Likewise invitro anticancer study manifests the cytotoxicity value of synthesized AgNPs against tested HeLa cells. The output of this study clearly suggesting that biosynthesized AgNPs using latex of C. gigantea can be used as promising nanomaterial for therapeutic application in context with nanodrug formulation.

  16. Silver nanoparticles with antimicrobial activities against Streptococcus mutans and their cytotoxic effect.

    PubMed

    Pérez-Díaz, Mario Alberto; Boegli, Laura; James, Garth; Velasquillo, Cristina; Sánchez-Sánchez, Roberto; Martínez-Martínez, Rita-Elizabeth; Martínez-Castańón, Gabriel Alejandro; Martinez-Gutierrez, Fidel

    2015-10-01

    Microbial resistance represents a challenge for the scientific community to develop new bioactive compounds. The goal of this research was to evaluate the antimicrobial activity of silver nanoparticles (AgNPs) against a clinical isolate of Streptococcus mutans, antibiofilm activity against mature S. mutans biofilms and the compatibility with human fibroblasts. The antimicrobial activity of AgNPs against the planktonic clinical isolate was size and concentration dependent, with smaller AgNPs having a lower minimum inhibitory concentration. A reduction of 2.3 log in the number of colony-forming units of S. mutans was observed when biofilms grown in a CDC reactor were exposed to 100ppm of AgNPs of 9.5±1.1nm. However, AgNPs at high concentrations (>10ppm) showed a cytotoxic effect upon human dermal fibroblasts. AgNPs effectively inhibited the growth of a planktonic S. mutans clinical isolate and killed established S. mutans biofilms, which suggests that AgNPs could be used for prevention and treatment of dental caries. Further research and development are necessary to translate this technology into therapeutic and preventive strategies. PMID:26117766

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

    PubMed

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

    2012-02-01

    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

  18. MWCNT uptake in Allium cepa root cells induces cytotoxic and genotoxic responses and results in DNA hyper-methylation.

    PubMed

    Ghosh, Manosij; Bhadra, Sreetama; Adegoke, Aremu; Bandyopadhyay, Maumita; Mukherjee, Anita

    2015-04-01

    Advances in nanotechnology have led to the large-scale production of nanoparticles, which, in turn, increases the chances of environmental exposure. While humans (consumers/workers) are primarily at risk of being exposed to the adverse effect of nanoparticles, the effect on plants and other components of the environment cannot be ignored. The present work investigates the cytotoxic, genotoxic, and epigenetic (DNA methylation) effect of MWCNT on the plant system- Allium cepa. MWCNT uptake in root cells significantly altered cellular morphology. Membrane integrity and mitochondrial function were also compromised. The nanotubes induced significant DNA damage, micronucleus formation and chromosome aberration. DNA laddering assay revealed the formation of internucleosomal fragments, which is indicative of apoptotic cell death. This finding was confirmed by an accumulation of cells in the sub-G0 phase of the cell cycle. An increase in CpG methylation was observed using the isoschizomers MspI/HpaII. HPLC analysis of DNA samples revealed a significant increase in the levels of 5-methyl-deoxy-cytidine (5mdC). These results confirm the cyto-genotoxic effect of MWCNT in the plant system and simultaneously highlight the importance of this epigenetic study in nanoparticle toxicity. PMID:25829105

  19. Selenite-induced toxicity in cancer cells is mediated by metabolic generation of endogenous selenium nanoparticles.

    PubMed

    Bao, Peng; Chen, Zheng; Tai, Ren-Zhong; Shen, Han-Ming; Martin, Francis L; Zhu, Yong-Guan

    2015-02-01

    Selenite has been a touted cancer chemopreventative agent but generates conflicting outcomes. Multiple mechanisms of selenite cytotoxicity in cancer cells are thought to be induced by metabolites of selenite. We observed that intracellular metabolism of selenite generates endogenous selenium nanoparticles (SeNPs) in cancer cells. Critical proteins that bind with high affinity to elemental selenium during SeNPs self-assembly were identified through proteomics analysis; these include glycolytic enzymes, insoluble tubulin, and heat shock proteins 90 (HSP90). Sequestration of glycolytic enzymes by SeNPs dramatically inhibits ATP generation, which leads to functional and structural disruption of mitochondria. Transcriptome sequencing showed tremendous down-regulation of mitochondrial respiratory NADH dehydrogenase (complex I), cytochrome c oxidase (complex IV), and ATP synthase (complex V) in response to glycolysis-dependent mitochondrial dysfunction. Sequestration of insoluble tubulin led to microtubule depolymerization, altering microtubule dynamics. HSP90 sequestration led to degradation of its downstream effectors via autophagy, ultimately resulting in a cell-signaling switch to apoptosis. Additionally, the surface effects of SeNPs generated oxidative stress, thus contributing to selenite cytotoxicity. Herein, we reveal that the multiple mechanisms of selenite-induced cytotoxicity are caused by endogenous protein-assisted self-assembly of SeNPs and suggest that endogenous SeNPs could potentially be the primary cause of selenite-induced cytotoxicity. PMID:25567070

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

    PubMed Central

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

    2013-01-01

    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. PMID:24265551

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

    PubMed

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

    2014-05-01

    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

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

    Microsoft Academic Search

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

    2009-01-01

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

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

    PubMed

    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

    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

  4. Cytotoxicity and morphological transforming potential of cobalt nanoparticles, microparticles and ions in Balb/3T3 mouse fibroblasts: an in vitro model.

    PubMed

    Sabbioni, Enrico; Fortaner, Salvador; Farina, Massimo; Del Torchio, Riccardo; Olivato, Iolanda; Petrarca, Claudia; Bernardini, Giovanni; Mariani-Costantini, Renato; Perconti, Silvia; Di Giampaolo, Luca; Gornati, Rosalba; Di Gioacchino, Mario

    2014-06-01

    We previously described the behaviour of different cobalt forms, i.e., cobalt nanoparticles (CoNP), cobalt microparticles (CoMP) and cobalt ions (Co(2+)), in culture medium (dissolution, interaction with medium components, bioavailability) as well as their uptake and intracellular distribution in Balb/3T3 mouse fibroblasts (Sabbioni, Nanotoxicology, 2012). Here, we assess the cytotoxicity and morphological transformation of CoNP compared not only to Co(2+), but also to CoMP and to released Co products. Cytotoxicity reached maximum at 4-h exposure, with ranking CoMP > CoNP > Co(2+). However, if we consider toxicity as a function of intracellular Co, toxicity of the ionic forms seems to prevail over the particles. Co forms other than Co(2+) released from particles had toxicity intermediate between particles and ions. Alterations in concentrations of essential elements (Cu, Mg, Zn) in cells exposed to Co particles may contribute to toxicity. Both CoMP and CoNP (but not Co(2+) and other released Co forms) induced morphological transformation (CoMP > CoNP). This was dependent on reactive oxygen species production and lipid peroxidation, as indicated by inhibition of type III foci with ascorbic acid. The present results suggest that the previously demonstrated massive mitochondrial and nuclear Co internalisation and DNA adduct formation by CoMP and CoNP (Sabbioni, Nanotoxicology, 2012) induce toxicity and transformation. On the contrary, the role of ions released by particles in culture medium is negligible. Thus, both the chemical and the physical properties of Co particles contribute to cytotoxicity and morphological transformation. PMID:23586465

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

    PubMed

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

    2011-09-01

    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

  6. Cytotoxicity of magnetic nanoparticles derived from green chemistry against human cells

    NASA Astrophysics Data System (ADS)

    Hanumandla, Pranitha

    The core-shelled Fe3O4 magnetic nanoparticles (MNPs) have been extensively investigated by the researchers due to their diversified applications. Recently, the study on the toxicity of nanomaterials has been drawn increasing attention to reduce or mitigate the environmental hazards and health risk. The objectives of this thesis are three fold: 1) prepare series functionalized Fe3O4 MNPs and optimize the synthesis variables of; 2) characterize their nanostructures using the state-of-the-art instrumental techniques; and 3) evaluate their cytotoxicity by measurement of nitrogen monoxide (NO) release, reactive oxygen species (ROS) and single oxygen species (SOS) generation. In order to prepare the crystalline Fe3O4 MNPs, a cost-effective and user-friendly wet chemistry (Sol-Gel) method was used. Two Indian medicinal plants were extracted to derive the active chemicals, which were used to functionalize the Fe3O 4 MNPs. The results indicated that the Fe3O4 MNPs were well-indexed with the standard inverse spinel structure (PDF 65-3107, a=8.3905A, ? = 90°). The particle's sizes varied from 6-10 nm with the Fe3O 4 MNPs acting as cores and medicinal extracts as shell. The active chemical components extracted from two Hygrophila auriculata/ Chlorophytum borivilianum are fatty acid, Saponins, sterols, carbohydrates and amino acids, which are in agreement with the reported data. Toxicological evaluations of MNPs indicated that the Fe3O4 MNPs functionalized with Hygrophila auriculata/ Chlorophytum borivilianum extract prepared at room temperature were toxic to the cells when compared to the control, and act in a mechanism similar to the actions of hydrogen peroxide (H2O2). These functionalized MNPs, which were prepared at 100 ° C, displayed similar mechanism of action to the anticancer drug (SN-38). It was also found that the MNPs prepared at lower temperatures are less toxic and showed similar mechanism of action as the sodium nitrite (NaNO 2).

  7. Extracellular biosynthesis of silver nanoparticle using Streptomyces sp. 09 PBT 005 and its antibacterial and cytotoxic properties

    NASA Astrophysics Data System (ADS)

    Saravana Kumar, P.; Balachandran, C.; Duraipandiyan, V.; Ramasamy, D.; Ignacimuthu, S.; Al-Dhabi, Naif Abdullah

    2015-02-01

    The application of microorganisms for the synthesis of nanoparticles as an eco-friendly and promising approach is welcome due to its non-toxicity and simplicity. The aim of this study was to synthesize silver nanoparticle using Streptomyces sp. (09 PBT 005). 09 PBT 005 was isolated from the soil sample of the agriculture field in Vengodu, Thiruvannamalai district, Tamil Nadu, India. 09 PBT 005 was subjected to molecular characterization by 16S rRNA sequence analysis. It was found that 09 PBT 005 belonged to Streptomyces sp. The isolate Streptomyces sp. 09 PBT 005 was inoculated in fermentation medium and incubated at 30 şC for 12 days in different pH conditions. The 0.02 molar concentration showed good antibacterial activity against Gram-positive and Gram-negative bacteria at pH-7. The synthesis of silver nanoparticles was investigated by UV-Vis spectroscopy, scanning electron microscopy and Fourier Transform Infrared analysis. The synthesized AgNPs sizes were found to be in the dimensions ranging between 198 and 595 nm. The cytotoxicity of the synthesized nanoparticles was studied against A549 adenocarcinoma lung cancer cell line. It showed 83.23 % activity at 100 ?l with IC 50 value of 50 ?l. This method will be useful in the biosynthesis of nanoparticles.

  8. Cytotoxicity of zinc nanoparticles fabricated by Justicia adhatoda L. on root tips of Allium cepa L.-a model approach.

    PubMed

    Taranath, T C; Patil, Bheemanagouda N; Santosh, T U; Sharath, B S

    2015-06-01

    Zinc nanoparticles were synthesized using aqueous leaf extract of Justicia adhatoda L. The characterization of nanoparticles was done by ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), and high-resolution transmission electron microscopy (HR-TEM). The characteristic absorption peak of the UV spectrum was recorded at 379 nm. The FTIR data revealed the possible biomolecules involved in bioreduction and capping of zinc nanoparticles for efficient stabilization. AFM and HR-TEM images have shown that the size of zinc nanoparticles ranges from 55 to 83 nm and they are spherical in shape. The biogenic zinc nanoparticles were evaluated for their toxic effect on mitotic chromosomes of Allium cepa as a model system. Experiments were conducted in triplicate to assay the effect of 25, 50, 75, and 100 % of zinc nanoparticles on mitotic chromosomes at an interval of 6 h duration for 24 h. The investigation revealed that the mitotic index (MI) was decreased with increased concentration of zinc nanoparticles and exposure duration. The results revealed that zinc nanoparticles have induced abnormalities like anaphase bridge formation, diagonal anaphase, C-metaphase, sticky metaphase, laggards, and sticky anaphase at different percentages and times of exposure. It is evident from the observation that mitotic cell division becomes abortive at 100 % treatment of zinc nanoparticles. PMID:25586613

  9. Use of genetically modified mouse models to assess pathways of benzene-induced bone marrow cytotoxicity and genotoxicity

    Microsoft Academic Search

    Leslie Recio; Alison Bauer; Brenda Faiola

    2005-01-01

    Benzene induces bone marrow cytotoxicity and chromosomal breaks as a primary mode of action for the induction of bone marrow toxicity. Our research group has used genetically modified mouse models to examine metabolic and genomic response pathways involved in benzene induced cytotoxicity and genotoxicity in bone marrow and in hematopoietic stem cells (HSC). We review our studies using NQO1?\\/? mice

  10. Protection from radiation-induced pneumonitis using cerium oxide nanoparticles

    Microsoft Academic Search

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

    2009-01-01

    In an effort to combat the harmful effects of radiation exposure, we propose that rare-earth cerium oxide (CeO2) 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 CeO2 nanoparticles in radiation protection

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

    PubMed

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

    2013-01-01

    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

  12. The progress of silver nanoparticles in the antibacterial mechanism, clinical application and cytotoxicity.

    PubMed

    You, Chuangang; Han, Chunmao; Wang, Xingang; Zheng, Yurong; Li, Qiyin; Hu, Xinlei; Sun, Huafeng

    2012-09-01

    Nanotechnology is a highly promising field, with nanoparticles produced and utilized in a wide range of commercial products. Silver nanoparticles (AgNPs) has been widely used in clothing, electronics, bio-sensing, the food industry, paints, sunscreens, cosmetics and medical devices, all of which increase human exposure and thus the potential risk related to their short- and long-term toxicity. Many studies indicate that AgNPs are toxic to human health. Interestingly, the majority of these studies focus on the interaction of the nano-silver particle with single cells, indicating that AgNPs have the potential to induce the genes associated with cell cycle progression, DNA damage and mitochondrial associated apoptosis. AgNPs administered through any method were subsequently detected in blood and were found to cause deposition in several organs. There are very few studies in rats and mice involving the in vivo bio-distribution and toxicity, organ accumulation and degradation, and the possible adverse effects and toxicity in vivo are only slowly being recognized. In the present review, we summarize the current data associated with the increased medical usage of nano-silver and its related nano-materials, compare the mechanism of antibiosis and discuss the proper application of nano-silver particles. PMID:22722996

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

    PubMed

    Gürbay, Aylin

    2012-07-01

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

  14. NSAID-manufacturing plant effluent induces geno- and cytotoxicity in common carp (Cyprinus carpio).

    PubMed

    SanJuan-Reyes, Nely; Gómez-Oliván, Leobardo Manuel; Galar-Martínez, Marcela; García-Medina, Sandra; Islas-Flores, Hariz; González-González, Edgar David; Cardoso-Vera, Jesús Daniel; Jiménez-Vargas, Juan Manuel

    2015-10-15

    The pharmaceutical industry generates wastewater discharges of varying characteristics and contaminant concentrations depending on the nature of the production process. The main chemicals present in these effluents are solvents, detergents, disinfectants - such as sodium hypochlorite (NaClO) - and pharmaceutical products, all of which are potentially ecotoxic. Therefore, this study aimed to evaluate the geno- and cytotoxicity induced in the common carp Cyprinus carpio by the effluent emanating from a nonsteroidal anti-inflammatory drug (NSAID)-manufacturing plant. Carp were exposed to the lowest observed adverse effect level (LOAEL, 0.1173%) for 12, 24, 48, 72 and 96h, and biomarkers of genotoxicity (comet assay and micronucleus test) and cytotoxicity (caspase-3 activity and TUNEL assay) were evaluated. A significant increase with respect to the control group (p<0.05) occurred with all biomarkers from 24h on. Significant positive correlations were found between NSAID concentrations and biomarkers of geno- and cytotoxicity, as well as among geno- and cytotoxicity biomarkers. In conclusion, exposure to this industrial effluent induces geno- and cytotoxicity in blood of C. carpio. PMID:26026403

  15. Phagocytic uptake and cytotoxicity of solid lipid nanoparticles (SLN) sterically stabilized with poloxamine 908 and poloxamer 407.

    PubMed

    Müller, R H; Maassen, S; Weyhers, H; Mehnert, W

    1996-01-01

    Solid lipid nanoparticles (SLN) as alternative intravenous colloidal drug carriers were produced by high pressure homogenisation of melted lipids (glycerolbehenate, cetylpalmitate). Their surface was modified by using hydrophilic poloxamine 908 and poloxamer 407 blockcopolymers in order to reduce the phagocytic uptake by the reticuloendothelial system (RES) after i. v. injection. The phagocytosis reducing effect of the polymers was investigated in vitro in cultures of human granulocytes, uptake was quantified by chemiluminescence. Modification of the SLN with poloxamine 908 and poloxamer 407 reduced the phagocytic uptake to appr. 8-15% compared to the phagocytosis of hydrophobic polystyrene particles. The modified SLN proved more efficient in avoiding phagocytic uptake than polystyrene particles surface-modified with these blockcopolymers (48% and 38%, respectively). Viability determinations revealed the SLN to be 10 fold less cytotoxic than polylactide nanoparticles and 100 fold less than butylcyanoacrylate particles. PMID:8959488

  16. Cytotoxic T-Lymphocyte Epitopes Fused to Anthrax Toxin Induce Protective Antiviral Immunity

    Microsoft Academic Search

    AMY M. DOLING; JIMMY D. BALLARD; HAO SHEN; KAJA MURALI KRISHNA; RAFI AHMED; R. JOHN COLLIER; MICHAEL N. STARNBACH

    1999-01-01

    We have investigated the use of the protective antigen (PA) and lethal factor (LF) components of anthrax toxin as a system for in vivo delivery of cytotoxic T-lymphocyte (CTL) epitopes. During intoxication, PA directs the translocation of LF into the cytoplasm of mammalian cells. Here we demonstrate that antiviral immunity can be induced in BALB\\/c mice immunized with PA plus

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

    PubMed Central

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

    2010-01-01

    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. PMID:21053278

  18. Blocking autophagy enhanced cytotoxicity induced by recombinant human arginase in triple-negative breast cancer cells

    PubMed Central

    Wang, Z; Shi, X; Li, Y; Fan, J; Zeng, X; Xian, Z; Wang, Z; Sun, Y; Wang, S; Song, P; Zhao, S; Hu, H; Ju, D

    2014-01-01

    Depletion of arginine by recombinant human arginase (rhArg) has proven to be an effective cancer therapeutic approach for a variety of malignant tumors. Triple-negative breast cancers (TNBCs) lack of specific therapeutic targets, resulting in poor prognosis and limited therapeutic efficacy. To explore new therapeutic approaches for TNBC we studied the cytotoxicity of rhArg in five TNBC cells. We found that rhArg could inhibit cell growth in these five TNBC cells. Intriguingly, accumulation of autophagosomes and autophagic flux was observed in rhArg-treated MDA-MB-231 cells. Inhibition of autophagy by chloroquine (CQ), 3-methyladenine (3-MA) and siRNA targeting Beclin1 significantly enhanced rhArg-induced cytotoxic effect, indicating the cytoprotective role of autophagy in rhArg-induced cell death. In addition, N-acetyl-l-cysteine (NAC), a common antioxidant, blocked autophagy induced by rhArg, suggesting that reactive oxygen species (ROS) had an essential role in the cytotoxicity of rhArg. This study provides new insights into the molecular mechanism of autophagy involved in rhArg-induced cytotoxicity in TNBC cells. Meanwhile, our results revealed that rhArg, either alone or in combination with autophagic inhibitors, might be a potential novel therapy for the treatment of TNBC. PMID:25501824

  19. Neuroprotection by Pergolide Against Levodopa-Induced Cytotoxicity of Neural Stem Cells

    Microsoft Academic Search

    Wei-Guo Liu; Yan Chen; Biao Li; Guo-Qiang Lu; Sheng-Di Chen

    2004-01-01

    Neural stem cells (NSCs) are currently considered very hopeful candidates for cell replacement therapy in neurodegenerative pathologies such as Parkinson’s disease (PD), but like embryonic neural tissue transplantation, levodopa medication may still be required to improve symptoms even after cell transplantation. The issues of whether levodopa induces cytotoxicity and apoptosis of NSCs following transplantation, as well as the means to

  20. Apoptosis signal-regulating kinase 1 promotes Ochratoxin A-induced renal cytotoxicity.

    PubMed

    Liang, Rui; Shen, Xiao Li; Zhang, Boyang; Li, Yuzhe; Xu, Wentao; Zhao, Changhui; Luo, YunBo; Huang, Kunlun

    2015-01-01

    Oxidative stress and apoptosis are involved in Ochratoxin A (OTA)-induced renal cytotoxicity. Apoptosis signal-regulating kinase 1 (ASK1) is a Mitogen-Activated Protein Kinase Kinase Kinase (MAPKKK, MAP3K) family member that plays an important role in oxidative stress-induced cell apoptosis. In this study, we performed RNA interference of ASK1 in HEK293 cells and employed an iTRAQ-based quantitative proteomics approach to globally investigate the regulatory mechanism of ASK1 in OTA-induced renal cytotoxicity. Our results showed that ASK1 knockdown alleviated OTA-induced ROS generation and ??m loss and thus desensitized the cells to OTA-induced apoptosis. We identified 33 and 24 differentially expressed proteins upon OTA treatment in scrambled and ASK1 knockdown cells, respectively. Pathway classification and analysis revealed that ASK1 participated in OTA-induced inhibition of mRNA splicing, nucleotide metabolism, the cell cycle, DNA repair, and the activation of lipid metabolism. We concluded that ASK1 plays an essential role in promoting OTA-induced renal cytotoxicity. PMID:25627963

  1. Functionalized nanoparticles for AMF-induced gene and drug delivery

    NASA Astrophysics Data System (ADS)

    Biswas, Souvik

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

  2. Green Synthesis of Small Silver Nanoparticles Using Geraniol and Its Cytotoxicity against Fibrosarcoma-Wehi 164

    Microsoft Academic Search

    Mona Safaepour; Ahmad Reza Shahverdi; Hamid Reza Shahverdi; Mohammad Reza Khorramizadeh; Ahmad Reza Gohari; Ahmad-Reza Shahverdi

    Many reports have been published about the biogenesis of silver nanoparticles using several plant extracts such as Pelargonium graveolens (P.graveolens- geranium) and Azadirachta indica (neem) but the capacity of their natural reducing constituents to form silver nanoparticles has not yet been studied. In this research the synthesis of silver nanoparticles using geraniol has been investigated. We successfully synthesized uniformly dispersed

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

    PubMed

    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

    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

  4. Antibacterial and cytotoxic effect of biologically synthesized silver nanoparticles using aqueous root extract of Erythrina indica lam

    NASA Astrophysics Data System (ADS)

    Rathi Sre, P. R.; Reka, M.; Poovazhagi, R.; Arul Kumar, M.; Murugesan, K.

    2015-01-01

    Simple, yet an effective and rapid approach for the green synthesis of silver nanoparticles (Ag NPs) using root extract of Erythrina indica and its in vitro antibacterial activity was tried against human pathogenic bacteria and its cytotoxic effect in breast and lung cancer cell lines has been demonstrated in this study. Various instrumental techniques were adopted to characterize the synthesized Ag NPs viz. UV-Vis (Ultra violet), FTIR (Fourier Transform Infrared), XRD (X-ray diffraction), DLS (Dynamic light scattering), HR TEM (High-resolution transmission electron microscopy), EDX (Energy-dispersive X-ray spectroscopy). Surface plasmon spectra for Ag NPs are centered nearly at 438 nm with dark brown color. FTIR analysis revealed the presence of terpenes, phenol, flavonols and tannin act as effective reducing and capping agents for converting silver nitrate to Ag NPs. The synthesized Ag NPs were found to be spherical in shape with size in the range of 20-118 nm. Moreover, the synthesized Ag NPs showed potent antibacterial activity against Gram positive and Gram negative bacteria and these biologically synthesized nanoparticles were also proved to exhibit excellent cytotoxic effect on breast and lung cancer cell lines.

  5. Antibacterial and cytotoxic effect of biologically synthesized silver nanoparticles using aqueous root extract of Erythrina indica lam.

    PubMed

    Rathi Sre, P R; Reka, M; Poovazhagi, R; Arul Kumar, M; Murugesan, K

    2015-01-25

    Simple, yet an effective and rapid approach for the green synthesis of silver nanoparticles (Ag NPs) using root extract of Erythrina indica and its in vitro antibacterial activity was tried against human pathogenic bacteria and its cytotoxic effect in breast and lung cancer cell lines has been demonstrated in this study. Various instrumental techniques were adopted to characterize the synthesized Ag NPs viz. UV-Vis (Ultra violet), FTIR (Fourier Transform Infrared), XRD (X-ray diffraction), DLS (Dynamic light scattering), HR TEM (High-resolution transmission electron microscopy), EDX (Energy-dispersive X-ray spectroscopy). Surface plasmon spectra for Ag NPs are centered nearly at 438 nm with dark brown color. FTIR analysis revealed the presence of terpenes, phenol, flavonols and tannin act as effective reducing and capping agents for converting silver nitrate to Ag NPs. The synthesized Ag NPs were found to be spherical in shape with size in the range of 20-118 nm. Moreover, the synthesized Ag NPs showed potent antibacterial activity against Gram positive and Gram negative bacteria and these biologically synthesized nanoparticles were also proved to exhibit excellent cytotoxic effect on breast and lung cancer cell lines. PMID:25189525

  6. Docetaxel Loaded PEG-PLGA Nanoparticles: Optimized Drug Loading, In-vitro Cytotoxicity and In-vivo Antitumor Effect

    PubMed Central

    Noori Koopaei, Mona; Khoshayand, Mohammad Reza; Mostafavi, Seyed Hossein; Amini, Mohsen; Khorramizadeh, Mohammad Reza; Jeddi Tehrani, Mahmood; Atyabi, Fatemeh; Dinarvand, Rassoul

    2014-01-01

    In this study a 3-factor, 3-level Box-Behnken design was used to prepare optimized docetaxel (DTX) loaded pegylated poly lactide-co-glycolide (PEG-PLGA) Nanoparticles (NPs) with polymer concentration (X1), drug concentration (X2) and ratio of the organic to aqueous solvent (X3) as the independent variables and particle size (Y1), poly dispersity index (PDI) (Y2) and drug loading (Y3) as the responses. The cytotoxicity of optimized DTX loaded PEG-PLGA NPs was studied in SKOV3 tumor cell lines by standard MTT assay. The in-vivo antitumor efficacy of DTX loaded PLGA-PEG NPs was assessed in tumor bearing female BALB/c mice. The optimum level of Y1, Y2 and Y3 predicted by the model were 188 nm, 0.16 and 9% respectively with perfect agreement with the experimental data. The in-vitro release profile of optimum formulation showed a burst release of approximately 20% (w/w) followed by a sustained release profile of the loaded drug over 288 h. The DTX loaded optimized nanoparticles showed a greater cytotoxicity against SKOV3 cancer cells than free DTX. Enhanced tumor-suppression effects were achieved with DTX-loaded PEG-PLGA NPs. These results demonstrated that optimized NPs could be a potentially useful delivery system for DTX as an anticancer agent. PMID:25276182

  7. Interferon-? gene transfer induces a strong cytotoxic bystander effect on melanoma cells.

    PubMed

    Rossi, Úrsula A; Gil-Cardeza, María L; Villaverde, Marcela S; Finocchiaro, Liliana M E; Glikin, Gerardo C

    2015-05-01

    A local gene therapy scheme for the delivery of type I interferons could be an alternative for the treatment of melanoma. We evaluated the cytotoxic effects of interferon-? (IFN?) gene lipofection on tumor cell lines derived from three human cutaneous and four canine mucosal melanomas. The cytotoxicity of human IFN? gene lipofection resulted higher or equivalent to that of the corresponding addition of the recombinant protein (rhIFN?) to human cells. IFN? gene lipofection was not cytotoxic for only one canine melanoma cell line. When cultured as monolayers, three human and three canine IFN?-lipofected melanoma cell lines displayed a remarkable bystander effect. As spheroids, the same six cell lines were sensitive to IFN? gene transfer, two displaying a significant multicell resistance phenotype. The effects of conditioned IFN?-lipofected canine melanoma cell culture media suggested the release of at least one soluble thermolabile cytotoxic factor that could not be detected in human melanoma cells. By using a secretion signal-free truncated human IFN?, we showed that its intracellular expression was enough to induce cytotoxicity in two human melanoma cell lines. The lower cytoplasmatic levels of reactive oxygen species detected after intracellular IFN? expression could be related to the resistance displayed by one human melanoma cell line. As IFN? gene transfer was effective against most of the assayed melanomas in a way not limited by relatively low lipofection efficiencies, the clinical potential of this approach is strongly supported. PMID:26054674

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

    NASA Astrophysics Data System (ADS)

    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

    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.

  9. Flutamide-induced cytotoxicity and oxidative stress in an in vitro rat hepatocyte system.

    PubMed

    Al Maruf, Abdullah; O'Brien, Peter

    2014-01-01

    Flutamide (FLU) is a competitive antagonist of the androgen receptor which has been reported to induce severe liver injury in some patients. Several experimental models suggested that an episode of inflammation during drug treatment predisposes animals to tissue injury. The molecular cytotoxic mechanisms of FLU in isolated rat hepatocytes using an in vitro oxidative stress inflammation system were investigated in this study. When a nontoxic hydrogen peroxide (H2O2) generating system (glucose/glucose oxidase) with peroxidase or iron(II) [Fe(II)] (to partly simulate in vivo inflammation) was added to the hepatocytes prior to the addition of FLU, increases in FLU-induced cytotoxicity and lipid peroxidation (LPO) were observed that were decreased by 6-N-propyl-2-thiouracil or deferoxamine, respectively. N-Acetylcysteine decreased FLU-induced cytotoxicity in this system. Potent antioxidants, for example, Trolox ((±)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), resveratrol (3,5,4'-trihydroxy-trans-stilbene), and DPPD (N,N'-diphenyl-1,4-phenylenediamine) also significantly decreased FLU-induced cytotoxicity and LPO and increased mitochondrial membrane potential (MMP) and glutathione (GSH) levels in the H2O2 generating system with peroxidase. TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl), a known reactive oxygen species (ROS) scavenger and superoxide dismutase mimetic, also significantly decreased toxicity caused by FLU in this system. These results raise the possibility that the presence or absence of inflammation may be another susceptibility factor for drug-induced hepatotoxicity. PMID:25371773

  10. Photoexpulsion of Surface-Grafted Ruthenium Complexes and Subsequent Release of Cytotoxic Cargos to Cancer Cells from Mesoporous Silica Nanoparticles

    PubMed Central

    Frasconi, Marco; Liu, Zhichang; Lei, Juying; Wu, Yilei; Strekalova, Elena; Malin, Dmitry; Ambrogio, Michael W.; Chen, Xinqi; Botros, Youssry Y.; Cryns, Vincent L.; Sauvage, Jean-Pierre; Stoddart, J. Fraser

    2014-01-01

    Ruthenium(II) polypyridyl complexes have emerged both as promising probes of DNA structure and as anticancer agents because of their unique photophysical and cytotoxic properties. A key consideration in the administration of those therapeutic agents is the optimization of their chemical reactivities to allow facile attack on the target sites, yet avoid unwanted side effects. Here, we present a drug delivery platform technology, obtained by grafting the surface of mesoporous silica nanoparticles (MSNPs) with ruthenium(II) dipyridophenazine (dppz) complexes. This hybrid nanomaterial displays enhanced luminescent properties relative to that of the ruthenium(II) dppz complex in a homogeneous phase. Since the coordination between the ruthenium(II) complex and a monodentate ligand linked covalently to the nanoparticles can be cleaved under irradiation with visible light, the ruthenium complex can be released from the surface of the nanoparticles by selective substitution of this ligand with a water molecule. Indeed, the modified MSNPs undergo rapid cellular uptake, and after activation with light, the release of an aqua ruthenium(II) complex is observed. We have delivered, in combination, the ruthenium(II) complex and paclitaxel, loaded in the mesoporous structure, to breast cancer cells. This hybrid material represents a promising candidate as one of the so-called theranostic agents that possess both diagnostic and therapeutic functions. PMID:23815127

  11. Aldose reductase regulates acrolein-induced cytotoxicity in human small airway epithelial cells

    PubMed Central

    Yadav, Umesh CS; Ramana, KV; Srivastava, SK

    2013-01-01

    Aldose reductase (AR), a glucose metabolizing enzyme, reduces lipid aldehydes and their glutathione conjugates with more than 1000-fold efficiency (Km aldehydes 5-30?M) than glucose. Acrolein, a major endogenous lipid peroxidation product as well as component of environmental pollutant and cigarette smoke, is known to be involved in various pathologies including atherosclerosis, airway inflammation, COPD, and age-related disorders but the mechanism of acrolein-induced cytotoxicity is not clearly understood. We have investigated the role of AR in acrolein-induced cytotoxicity in primary human small airway epithelial cells SAECs. Exposure of SAECs to varying concentrations of acrolein caused cell-death in a concentration- and time-dependent manner. AR inhibition by fidarestat prevented the low (5 to 10 ?M) but not high (>10 ?M) concentrations of acrolein-induced SAECs cell death. AR inhibition protected SAECs from low dose (5 ?M) acrolein-induced cellular reactive oxygen species (ROS). Inhibition of acrolein-induced apoptosis by fidarestat was confirmed by decreased condensation of nuclear chromatin, DNA fragmentation, comet tail-moment, and annexin-V fluorescence. Further, fidarestat inhibited acrolein-induced translocation of pro-apoptotic proteins Bax and Bad from cytosol to the mitochondria, and that of Bcl2 and BclXL from mitochondria to cytosol. Acrolein-induced cytochrome c release from mitochondria was also prevented by AR inhibition. The mitogen-activated protein kinases (MAPK) such as extracellular signal-regulated kinases 1 and 2 (ERK1/2), stress-activated protein kinases/c-jun NH2-terminal kinases (SAPK/JNK) and p38MAPK, and c-jun were transiently activated in airway epithelial cells by acrolein in a concentration and time-dependent fashion, which were significantly prevented by AR inhibition. These results suggest that AR inhibitors could prevent acrolein-induced cytotoxicity in the lung epithelial cells. PMID:23770200

  12. Genotoxicity and cytotoxicity induced by municipal effluent in multiple organs of Wistar rats.

    PubMed

    da Silva, Victor Hugo Pereira; de Moura, Carolina Foot Gomes; Ribeiro, Flavia Andressa Pidone; Cesar, Augusto; Pereira, Camilo Dias Seabra; Silva, Marcelo Jose Dias; Vilegas, Wagner; Ribeiro, Daniel Araki

    2014-11-01

    The aim of this study was to evaluate cytotoxicity and genotoxicity in multiple organs of rats induced by municipal effluent released by submarine outfall in city of Santos. A total of 20 male Wistar rats were exposed to effluents by drinking water ad libitum at concentrations of 0, 10, 50, and 100 % for 30 days. Microscopic analysis revealed severe lesions such as necrosis and hemorrhagic areas in liver and kidney from animals exposed to effluent at 50 and 100 % concentration. DNA damage in peripheral blood, liver, and kidney cells were detected by comet assay at higher concentrations of effluent. Moreover, a decrease DNA repair capacity was detected in liver cells. Significant statistical differences (p<0.05) for micronucleated cells from liver were noticed at 50 % concentration of effluent. Taken together, our results demonstrate that municipal effluent is able to induce cytotoxicity and genotoxicity in multiple organs of Wistar rats. PMID:24996946

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

    PubMed

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

    2010-01-01

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

  14. Sonodynamically-induced cytotoxicity by rose bengal derivative and microbubbles in isolated sarcoma 180 cells

    NASA Astrophysics Data System (ADS)

    Sugita, Nami; Hosokawa, Mami; Sunaga, Naoki; Iwase, Yumiko; Yumita, Nagahiko; Ikeda, Toshihiko; Umemura, Shin-ichiro

    2015-07-01

    It is known that the combination of ultrasound and sonodynamic sensitizer (SDS) is effective in noninvasive tumor treatment, referred to as sonodynamic therapy (SDT). Microbubbles have been used in ultrasound therapy as well. The purpose of this paper is to clarify the effect of microbubbles on SDT. Sarcoma 180 cells were suspended in air-saturated phosphate-buffered saline and exposed to ultrasound with the SDS rose bengal derivative (RBD) in standing wave mode in the presence and absence of microbubbles [sonazoid (SZ)]. The ultrasonically induced cytotoxicity with RBD and SZ was about 20 times higher than without either, and about 80% of the SZ microbubbles were destructed by ultrasonic exposure in as short as five seconds. Since microbubbles induce significant cytotoxicity even with short duration, low intensity ultrasound, the application of microbubbles in SDT shows promise in anti-tumor treatment.

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

    PubMed Central

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

    2011-01-01

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

  16. The effects and underlying mechanism of excessive iodide on excessive fluoride-induced thyroid cytotoxicity.

    PubMed

    Liu, Hongliang; Zeng, Qiang; Cui, Yushan; Yu, Linyu; Zhao, Liang; Hou, Changchun; Zhang, Shun; Zhang, Lei; Fu, Gang; Liu, Yeming; Jiang, Chunyang; Chen, Xuemin; Wang, Aiguo

    2014-07-01

    In many regions, excessive fluoride and excessive iodide coexist in groundwater, which may lead to biphasic hazards to human thyroid. To explore fluoride-induced thyroid cytotoxicity and the mechanism underlying the effects of excessive iodide on fluoride-induced cytotoxicity, a thyroid cell line (Nthy-ori 3-1) was exposed to excessive fluoride and/or excessive iodide. Cell viability, lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) formation, apoptosis, and the expression levels of inositol-requiring enzyme 1 (IRE1) pathway-related molecules were detected. Fluoride and/or iodide decreased cell viability and increased LDH leakage and apoptosis. ROS, the expression levels of glucose-regulated protein 78 (GRP78), IRE1, C/EBP homologous protein (CHOP), and spliced X-box-binding protein-1 (sXBP-1) were enhanced by fluoride or the combination of the two elements. Collectively, excessive fluoride and excessive iodide have detrimental influences on human thyroid cells. Furthermore, an antagonistic interaction between fluoride and excessive iodide exists, and cytotoxicity may be related to IRE1 pathway-induced apoptosis. PMID:25104093

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

    PubMed

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

    2013-02-01

    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

  18. Vanadium accumulation and subcellular distribution in relation to vanadate induced cytotoxicity in vitro.

    PubMed

    Bracken, W M; Sharma, R P; Elsner, Y Y

    1985-10-01

    A bovine kidney cell culture system was used to assess the relationship of vandium uptake and subcellular distribution to orthovanadate induced cytotoxicity. Twenty-four hr incubations with 20-1000 microM vanadium elicited 15-75% cytotoxicity. Concentration-related morphological changes from the control polygonal shape to the treated biopolar appearance were detected. Vanadium accumulated in cells via a multiphasic process; peak accumulation was achieved by 1 hr post-treatment and was followed by apparent decline, completed by 3 hr. A slower second phase of accumulation occurred during the remainder of the 24 hr incubation period. A concentration-dependent accumulation resulted in a 50-fold increase in cellular vanadium content. Near maximum toxicity was achieved at a cellular vanadium burden of approximately 5 nmoles/10(6) cells; further accumulation (up to 35 nmoles/10(6) cells) resulted in only a slight increase in the degree of toxicity. Subcellular distribution studies indicated 90% accumulation of vanadium in the soluble supernatant fraction (105,000xg supernatant) at varying stages of cytotoxicity. It was concluded that the multifaceted dependency of vanadium cytotoxicity on its cellular content may have resulted from a cellular balancing between proposed regulatory functions for vanadium and the interactions incurred with an excessive content. PMID:3916984

  19. Weakly Charged Cationic Nanoparticles Induce DNA Bending and Strand Separation

    SciTech Connect

    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

    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.

  20. Characterization, antioxidant and cytotoxicity evaluation of green synthesized silver nanoparticles using Cleistanthus collinus extract as surface modifier

    SciTech Connect

    Kanipandian, Nagarajan [Laboratory of Aquabiotics/Nanoscience, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu (India); Kannan, Soundarapandian [Proteomics and Molecular Cell Physiology Laboratory, Department of Zoology, Periyar University, Salem 636 011, Tamil Nadu (India); Ramesh, Ramar; Subramanian, Periyasamy [Laboratory of Aquabiotics/Nanoscience, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu (India); Thirumurugan, Ramasamy, E-mail: ramthiru72@gmail.com [Laboratory of Aquabiotics/Nanoscience, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu (India)

    2014-01-01

    Graphical abstract: The figure is the TEM image of green synthesized silver nanoparticles from Cleistanthus collinus. In this investigation we have used the poisonous plant as a reducing and capping agent. This is a first time data to synthesis the metal nanoparticles using poisonous plant. - Highlights: • A hitherto unreported venomous plant mediated AgNPs synthesis. • The particle size is observed in the range of 20–40 nm. • Surface morphology of the well-dispersed silver nanoparticles is studied using SEM and TEM. • Crystalline nature of AgNPs is confirmed by X-ray diffraction analysis. • Antioxidant activities of green synthesized AgNPs are tested in vitro. - Abstract: We report, here a simple green method for the preparation of silver nanoparticles (AgNPs) using the plant extract of Cleistanthus collinus as potential phyto reducer. The synthesized AgNPs were characterized by UV–vis spectra, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The obtained results confirmed that the AgNPs were crystalline in nature and the morphological studies reveal the spherical shape of AgNPs with size ranging from 20 to 40 nm. The in vitro antioxidant activity of AgNPs showed a significant effect on scavenging of free radicals. The cytotoxicity study exhibited a dose-dependent effect against human lung cancer cells (A549) and normal cells (HBL-100), the inhibitory concentration (IC{sub 50}) were found to be 30 ?g/mL and 60 ?g/mL respectively. The in vivo histopathology of mouse organs proved that AgNPs does not possess toxic effect and can be extensively applied in biomedical sciences.

  1. Signaling Pathways Involved in Lunar Dust Induced Cytotoxicity

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

    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.

  2. Action of silver nanoparticles towards biological systems: cytotoxicity evaluation using hen's egg test and inhibition of Streptococcus mutans biofilm formation.

    PubMed

    Freire, Priscila L L; Stamford, Thayza C M; Albuquerque, Allan J R; Sampaio, Fabio C; Cavalcante, Horacinna M M; Macedo, Rui O; Galembeck, André; Flores, Miguel A P; Rosenblatt, Aronita

    2015-02-01

    This study aimed to evaluate the cytotoxicity and bactericidal properties of four silver nanoparticle (AgNP) colloids and their ability to inhibit Streptococcus mutans biofilm formation on dental enamel. The cytotoxicity of AgNPs was evaluated based on signs of vascular change on the chorioallantoic membrane using the hen's egg test (HET-CAM). Bactericidal properties and inhibition of S. mutans biofilm formation were determined using a parallel-flow cell system and a dichromatic fluorescent stain. The percentage of viable cells was calculated from regression data generated from a viability standard. AgNP colloids proved to be non-irritating, as they were unable to promote vasoconstriction, haemorrhage or coagulation. AgNP colloids inhibited S. mutans biofilm formation on dental enamel, and cell viability measured by fluorescence was 0% for samples S1, S2, S3 and S4 and 36.5% for the positive control (diluted 30% silver diamine fluoride). AgNPs are new products with a low production cost because they have a lower concentration of silver, with low toxicity and an effective bactericidal effect against a cariogenic oral bacterium. Moreover, they do not promote colour change in dental enamel, which is an aesthetic advantage compared with traditional silver products. PMID:25455849

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

    PubMed Central

    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

    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

  4. Reversion of pH-Induced Physiological Drug Resistance: A Novel Function of Copolymeric Nanoparticles

    PubMed Central

    Li, Rutian; Xie, Li; Zhu, Zhenshu; Liu, Qin; Hu, Yong; Jiang, Xiqun; Yu, Lixia; Qian, Xiaoping; Guo, Wanhua; Ding, Yitao; Liu, Baorui

    2011-01-01

    Aims The extracellular pH of cancer cells is lower than the intracellular pH. Weakly basic anticancer drugs will be protonated extracellularly and display a decreased intracellular concentration. In this study, we show that copolymeric nanoparticles (NPs) are able to overcome this “pH-induced physiological drug resistance” (PIPDR) by delivering drugs to the cancer cells via endocytosis rather than passive diffussion. Materials and Methods As a model nanoparticle, Tetradrine (Tet, Pka 7.80) was incorporated into mPEG-PCL. The effectiveness of free Tet and Tet-NPs were compared at different extracellular pHs (pH values 6.8 and 7.4, respectively) by MTT assay, morphological observation and apoptotic analysis in vitro and on a murine model by tumor volume measurement, PET-CT scanning and side effect evaluation in vivo. Results The cytotoxicity of free Tet decreased prominently (P<0.05) when the extracellular pH decreased from 7.4 to 6.8. Meanwhile, the cytotoxicity of Tet-NPs was not significantly influenced by reduced pH. In vivo experiment also revealed that Tet-NPs reversed PIPDR more effectively than other existing methods and with much less side effects. Conclusion The reversion of PIPDR is a new discovered mechanism of copolymeric NPs. This study emphasized the importance of cancer microenvironmental factors in anticancer drug resistance and revealed the superiority of nanoscale drug carrier from a different aspect. PMID:21966359

  5. Xanthohumol induces different cytotoxicity and apoptotic pathways in malignant and normal astrocytes.

    PubMed

    Zajc, I; Filipi?, M; Lah, T T

    2012-11-01

    Cytotoxicity and the mechanisms of cell death induced by xanthohumol (XN) were compared in normal and cancerous human cells as the differences may be relevant for the potential use of XN in cancer therapy. The cancer cells seemed to be more susceptible to the cytotoxicity of XN than normal cells, but a significant difference was observed only in astrocytic cells. XN induced a higher rate of apoptosis in glioblastoma cells than in normal astrocytes, which was associated with activation of p53 and an elevated Bax/Bcl-2 ratio in glioblastoma cells, indicating an intrinsic caspase-dependent apoptotic pathway. In contrast, a reduced Bax/Bcl-2 ratio was observed in normal human astrocytes. This was also associated with higher expression of the cell cycle inhibitor, p21, in glioblastoma cells than in normal astrocytes. In addition, at a lower, non-cytotoxic concentration, XN partially inhibited the invasiveness of glioblastoma cells. Due to the selective sensitivity of astrocytic cells to XN, this compound should be studied further as a candidate for adjuvant therapy in the treatment of glioma. PMID:22407755

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

    PubMed Central

    Jin, Seon Mi

    2012-01-01

    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. PMID:22639738

  7. Neuroprotective effect of crocin on acrylamide-induced cytotoxicity in PC12 cells.

    PubMed

    Mehri, Soghra; Abnous, Khalil; Mousavi, Seyed Hadi; Shariaty, Vahideh Motamed; Hosseinzadeh, Hossein

    2012-03-01

    Acrylamide (ACR) is a potent neurotoxic in human and animal models. In this study, the effect of crocin, main constituent of Crocus sativus L. (Saffron) on ACR-induced cytotoxicity was evaluated using PC12 cells as a suitable in vitro model. The exposure of PC12 cells to ACR reduced cell viability, increased DNA fragmented cells and phosphatidylserine exposure, and elevated Bax/Bcl-2 ratio. Results showed that ACR increased intracellular reactive oxygen species (ROS) in cells and ROS played an important role in ACR cytotoxicity. The pretreatment of cells with 10-50 ?M crocin before ACR treatment significantly attenuated ACR cytotoxicity in a dose-dependent manner. Crocin inhibited the downregulation of Bcl-2 and the upregulation of Bax and decreased apoptosis in treated cells. Also, crocin inhibited ROS generation in cells exposed to ACR. In conclusion, our results indicated that pretreatment with crocin protected cells from ACR-induced apoptosis partly by inhibition of intracellular ROS production. PMID:21901509

  8. Protective effect of kombucha mushroom (KM) tea on phenol-induced cytotoxicity in albino mice.

    PubMed

    Yapar, Kursad; Cavusoglu, Kultigin; Oruc, Ertan; Yalcin, Emine

    2010-09-01

    The present study was carried out to evaluate the protective role of kombucha mushroom (KM) tea on cytotoxicity induced by phenol (PHE) in mice. We used weight gain and micronucleus (MN) frequency as indicators of cytotoxicity and supported these parameters with pathological findings. The animals were randomly divided into seven groups: (Group I) only tap water (Group II) 1000 microl kg(-1) b. wt KM-tea, (Group III) 35 mg kg(-1) body wt. PHE (Group IV) 35 mg kg(-1) body wt. PHE + 250 microl kg(-1) b. wt KM-tea (Group V) 35 mg kg(-1) b. wt PHE + 500 microl kg(-1) b. wt KM-tea (Group VI) 35 mg kg(-1) b. wt PHE + 750 microl kg(-1) b. wt KM-tea, (Group VII) 35 mg kg(-1) b. wt PHE + 1000 microl kg(-1) b. wt KM-tea, for 20 consecutive days by oral gavage. The results indicated that all KM-tea supplemented mice showed a lower MN frequency than erythrocytes in only PHE-treated group. There was an observable regression on account of lesions in tissues of mice supplemented with different doses of KM-tea in histopathological observations. In conclusion, the KM-tea supplementation decreases cytotoxicity induced by PHE and its protective role is dose-dependent. PMID:21387911

  9. Biosynthesis of silver nanoparticles from deep sea bacterium Pseudomonas aeruginosa JQ989348 for antimicrobial, antibiofilm, and cytotoxic activity.

    PubMed

    Ramalingam, V; Rajaram, R; PremKumar, C; Santhanam, P; Dhinesh, P; Vinothkumar, S; Kaleshkumar, K

    2014-09-01

    Pseudomonas aeruginosa (JQ989348) was isolated from deep sea water sample and used for synthesis of silver nanoparticles (AgNPs). AgNPs were confirmed by analyzing surface plasmon resonance using UV-visible spectrophotometer at 420?nm. Further scanning electron microscope analysis confirmed the range of particle size between 13 and 76?nm and XRD pattern authorizes the anisotropic crystalline nature of AgNPs. Fourier transform infrared spectrum endorsed the presence of high amount of proteins and other secondary metabolites in synthesized AgNPs influence the reduction process and stabilization of nanoparticles. The inhibitory activity of AgNPs was tested against human pathogens showed high activity against Eschericia coli, Vibrio cholerae, Aeromonas sp., and Cornebacterium sp. demonstrating its antimicrobial value against pathogenic diseases. Additionally, biologically synthesized AgNPs have notable anti-biofilm activity against primary biofilm forming bacteria P. aeruginosa and Staphylococcus aureus. The MTT assay method was evaluated using human cervical cancer cells exposed the AgNPs have excellent cytotoxic activity. PMID:24136453

  10. Genetic variants associated with carboplatin-induced cytotoxicity in cell lines derived from Africans

    PubMed Central

    Huang, R. Stephanie; Duan, Shiwei; Kistner, Emily O.; Hartford, Christine M.; Dolan, M. Eileen

    2009-01-01

    To gain a better understanding of the genetic variants associated with carboplatin-induced cytotoxicity in individuals of African descent, we present a step-wise approach integrating genotypes, gene expression, and sensitivity of HapMap cell lines to carboplatin. Cell lines derived from 30 trios of African descent (YRI) were used to develop a preclinical model to identify genetic variants and gene expression that contribute to carboplatin-induced cytotoxicity. Cytotoxicity was determined as cell growth inhibition at increasing concentrations of carboplatin for 72 h. Gene expression of 89 HapMap YRI cell lines was determined using the Affymetrix GeneChip Human Exon 1.0 ST Array. Single nucleotide polymorphism genotype and the percent survival at different treatment concentrations along with carboplatin IC50 were linked through whole genome association. A second association test was done between single nucleotide polymorphism genotype and gene expression, and linear regression was then used to capture those genes whose expression correlated to drug sensitivity phenotypes. This approach allows us to identify genetic variants that significantly associate with sensitivity to the cytotoxic effects of carboplatin through their effect on gene expression. We found a gene (GPC5) whose expression is important in all carboplatin treatment concentrations as well as many genes unique to either low (e.g., MAPK1) or high (e.g., BRAF, MYC, and BCL2L1) concentrations of drug. Our whole genome approach enables us to evaluate the contribution of genetic and gene expression variation to a wide range of cellular phenotypes. The identification of concentration specific genetic signatures allows for potential integration of pharmacokinetics, pharmacodynamics, and pharmacogenetics in tailoring chemotherapy. PMID:18765826

  11. Changes in Cardiopulmonary Function Induced by Nanoparticles

    PubMed Central

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

    2012-01-01

    Nanoparticles (NP) are highly applicable in a variety of technological and biomedical fields due to their unique physicochemical properties. The increased development and utilization of NP has amplified human exposure and raised concerns regarding their potential to generate toxicity. The biological impacts of NP exposures have been shown to be dependent on aerodynamic size, chemical composition, and the route of exposure (oral, dermal, intravenous, and inhalation), while recent research has demonstrated the cardiovascular (CV) system as an important site of toxicity. Proposed mechanisms responsible for these effects include inflammation, oxidative stress, autonomic dysregulation, and direct interactions of NP with CV cells. Specifically, NP have been shown to impact vascular endothelial cell (EC) integrity, which may disrupt the dynamic endothelial regulation of vascular tone, possibly altering systemic vascular resistance and impairing the appropriate distribution of blood flow throughout the circulation. Cardiac consequences of NP-induced toxicity include disruption of heart rate and electrical activity via catecholamine release, increased susceptibility to ischemia/reperfusion injury, and modified baroreceptor control of cardiac function. These and other CV outcomes likely contribute to adverse health effects promoting myocardial infarction, hypertension, cardiac arrhythmias, and thrombosis. This review will assess the current knowledge regarding the principle sites of CV toxicity following NP exposure. Furthermore, we will propose mechanisms contributing to altered CV function and hypothesize possible outcomes resulting in decrements in human health. PMID:22915448

  12. Cytotoxicity and GMI bio-sensor detection of maghemite nanoparticles internalized into cells

    NASA Astrophysics Data System (ADS)

    Blanc-Béguin, F.; Nabily, S.; Gieraltowski, J.; Turzo, A.; Querellou, S.; Salaun, P. Y.

    2009-02-01

    In this work we determine conditions to produce cell samples for imaging with detection of the modification of the magnetic field by maghemite (Fe 2O 3) nanoparticles acting as a high sensitivity magnetic bio-sensor based on the giant magneto-impedance (GMI) effect. Mat Ly Lu cells are grown for 24 h with various maghemite nanoparticles concentrations (from 0 to 6 mg/ml). The percentage of viable cells is determined by counting labeled cells with trypan blue under an optical microscope. The quantity of nanoparticles internalized into the cells is evaluated by X-ray fluorescence analysis and expressed in iron moles per cell. The GMI bio-sensor was tested with the various samples. We observed that the best sensitivity of the GMI bio-sensor was obtained at a frequency of 1 MHz. To confirm these results in the presence of cell samples, four measurement frequencies were pre-selected (from 1 to 100 MHz) and tested. Cell growth conditions compatible with an acceptable percentage of cell viability for various concentrations of nanoparticles were also determined. These experiments allow us to conclude that cell growth with 0.1 mg/ml of nanoparticles for 24 h shows modifications of the magnetic field detectable optimally at 1 MHz frequency.

  13. Nanoparticles and nanotubes induced by femtosecond lasers

    Microsoft Academic Search

    S. Eliezer; N. Eliaz; E. Grossman; D. Fisher; I. Gouzman; Z. Henis; S. Pecker; Y. Horovitz; M. Fraenkel; S. Maman; V. Ezersky; D. Eliezer

    2005-01-01

    In this paper, we suggest the creation of a nanoparticles and nanotubes by using the interaction of a femtosecond laser with a solid target in a vacuum. A simple model is used to predict the optimal target and the laser parameters for the production of efficient nanoparticles. At the Soreq laboratory, experiments are performed with aluminium and carbon targets using

  14. Natural phenylpropanoids protect endothelial cells against oxidized LDL-induced cytotoxicity.

    PubMed

    Martin-Nizard, Françoise; Sahpaz, Sevser; Furman, Christophe; Fruchart, Jean-Charles; Duriez, Patrick; Bailleul, François

    2003-03-01

    There is increasing evidence that oxidized low-density lipoproteins (Ox-LDL) might be involved in the pathogenesis of atherosclerosis and it has been reported that polyphenols inhibit LDL peroxidation and atherosclerosis. Minimally oxidized LDL (mOx-LDL) induce cytotoxicity in cultured bovine aortic endothelial cells (BAEC). The goal of this study was to test the protective effect of five natural polyphenols isolated from the aerial parts of Marrubium vulgare L. against mOx-LDL-induced cytotoxicity in BAEC. Four phenylpropanoid glycosides (acteoside 1, forsythoside B 2, arenarioside 3, ballotetroside 4) and one non-glycosidic derivative (caffeoyl-l-malic acid 5) were tested. These compounds inhibited both copper (Cu 2+)- and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced in vitro LDL oxidation and preserved the morphological aspects of BAEC during their incubation with mOx-LDL. Furthermore, they reduced the accumulation of aldehydes in the cultured medium during the incubation of BAEC with mOx-LDL and prevented cellular LDH leakage during this period. These data suggest that natural phenylpropanoids inhibit mOx-LDL-induced cellular toxicity and that inhibition of lipid peroxidation could be a key mechanism in the cytoprotective effect of these molecules. PMID:12677522

  15. Identification of an epithelial cell receptor responsible for Clostridium difficile TcdB-induced cytotoxicity.

    PubMed

    LaFrance, Michelle E; Farrow, Melissa A; Chandrasekaran, Ramyavardhanee; Sheng, Jinsong; Rubin, Donald H; Lacy, D Borden

    2015-06-01

    Clostridium difficile is the leading cause of hospital-acquired diarrhea in the United States. The two main virulence factors of C. difficile are the large toxins, TcdA and TcdB, which enter colonic epithelial cells and cause fluid secretion, inflammation, and cell death. Using a gene-trap insertional mutagenesis screen, we identified poliovirus receptor-like 3 (PVRL3) as a cellular factor necessary for TcdB-mediated cytotoxicity. Disruption of PVRL3 expression by gene-trap mutagenesis, shRNA, or CRISPR/Cas9 mutagenesis resulted in resistance of cells to TcdB. Complementation of the gene-trap or CRISPR mutants with PVRL3 resulted in restoration of TcdB-mediated cell death. Purified PVRL3 ectodomain bound to TcdB by pull-down. Pretreatment of cells with a monoclonal antibody against PVRL3 or prebinding TcdB to PVRL3 ectodomain also inhibited cytotoxicity in cell culture. The receptor is highly expressed on the surface epithelium of the human colon and was observed to colocalize with TcdB in both an explant model and in tissue from a patient with pseudomembranous colitis. These data suggest PVRL3 is a physiologically relevant binding partner that can serve as a target for the prevention of TcdB-induced cytotoxicity in C. difficile infection. PMID:26038560

  16. Copper Oxide Nanoparticles Induced Mitochondria Mediated Apoptosis in Human Hepatocarcinoma Cells

    PubMed Central

    Siddiqui, Maqsood A.; Alhadlaq, Hisham A.; Ahmad, Javed; Al-Khedhairy, Abdulaziz A.; Musarrat, Javed; Ahamed, Maqusood

    2013-01-01

    Copper oxide nanoparticles (CuO NPs) are heavily utilized in semiconductor devices, gas sensor, batteries, solar energy converter, microelectronics and heat transfer fluids. It has been reported that liver is one of the target organs for nanoparticles after they gain entry into the body through any of the possible routes. Recent studies have shown cytotoxic response of CuO NPs in liver cells. However, the underlying mechanism of apoptosis in liver cells due to CuO NPs exposure is largely lacking. We explored the possible mechanisms of apoptosis induced by CuO NPs in human hepatocellular carcinoma HepG2 cells. Prepared CuO NPs were spherical in shape with a smooth surface and had an average diameter of 22 nm. CuO NPs (concentration range 2–50 µg/ml) were found to induce cytotoxicity in HepG2 cells in dose-dependent manner, which was likely to be mediated through reactive oxygen species generation and oxidative stress. Tumor suppressor gene p53 and apoptotic gene caspase-3 were up-regulated due to CuO NPs exposure. Decrease in mitochondrial membrane potential with a concomitant increase in the gene expression of bax/bcl2 ratio suggested that mitochondria mediated pathway involved in CuO NPs induced apoptosis. This study has provided valuable insights into the possible mechanism of apoptosis caused by CuO NPs at in vitro level. Underlying mechanism(s) of apoptosis due to CuO NPs exposure should be further invested at in vivo level. PMID:23940521

  17. Copper oxide nanoparticles induced mitochondria mediated apoptosis in human hepatocarcinoma cells.

    PubMed

    Siddiqui, Maqsood A; Alhadlaq, Hisham A; Ahmad, Javed; Al-Khedhairy, Abdulaziz A; Musarrat, Javed; Ahamed, Maqusood

    2013-01-01

    Copper oxide nanoparticles (CuO NPs) are heavily utilized in semiconductor devices, gas sensor, batteries, solar energy converter, microelectronics and heat transfer fluids. It has been reported that liver is one of the target organs for nanoparticles after they gain entry into the body through any of the possible routes. Recent studies have shown cytotoxic response of CuO NPs in liver cells. However, the underlying mechanism of apoptosis in liver cells due to CuO NPs exposure is largely lacking. We explored the possible mechanisms of apoptosis induced by CuO NPs in human hepatocellular carcinoma HepG2 cells. Prepared CuO NPs were spherical in shape with a smooth surface and had an average diameter of 22 nm. CuO NPs (concentration range 2-50 µg/ml) were found to induce cytotoxicity in HepG2 cells in dose-dependent manner, which was likely to be mediated through reactive oxygen species generation and oxidative stress. Tumor suppressor gene p53 and apoptotic gene caspase-3 were up-regulated due to CuO NPs exposure. Decrease in mitochondrial membrane potential with a concomitant increase in the gene expression of bax/bcl2 ratio suggested that mitochondria mediated pathway involved in CuO NPs induced apoptosis. This study has provided valuable insights into the possible mechanism of apoptosis caused by CuO NPs at in vitro level. Underlying mechanism(s) of apoptosis due to CuO NPs exposure should be further invested at in vivo level. PMID:23940521

  18. Protective effect of ebselen against hydrogen peroxide-induced cytotoxicity and DNA damage in HepG 2 cells

    Microsoft Academic Search

    Cheng-Feng Yang; Han-Ming Shen; Choon-Nam Ong

    1999-01-01

    The protective effect of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a selenoorganic compound, against hydrogen peroxide (H2O2)-induced cytotoxicity and DNA damage was investigated in a human hepatoma cell line, HepG2. The inhibitory effect of H2O2 on cell growth was determined using the tetrazolium dye colorimetric test (MTT test), and the cytotoxicity and lipid peroxidation were estimated by lactate dehydrogenase (LDH) leakage and malondialdehyde (MDA)

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

    Microsoft Academic Search

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

    2009-01-01

    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

  20. Effect of enhanced expression of connexin 43 on sunitinib-induced cytotoxicity in mesothelioma cells.

    PubMed

    Uzu, Miaki; Sato, Hiromi; Yamada, Ryota; Kashiba, Tatsuro; Shibata, Yukihiro; Yamaura, Katsunori; Ueno, Koichi

    2015-05-01

    Connexin (Cx) makes up a type of intercellular channel called gap junction (GJ). GJ plays a regulatory role in cellular physiology. The Cx expression level is often decreased in cancer cells compared to that in healthy ones, and the restoration of its expression has been shown to exert antiproliferative effects. This work aims to evaluate the effect of the restoration of connexin 43 (Cx43) (the most ubiquitous Cx subtype) expression on sunitinib (SU)-induced cytotoxicity in malignant mesothelioma (MM) cells. Increased Cx43 expression in an MM cell line (H28) improved the ability of SU to inhibit receptor tyrosine kinase (RTK) signaling. Moreover, higher Cx43 expression promoted SU-induced apoptosis. The cell viability test revealed that Cx43 enhanced the cytotoxic effect of SU in a GJ-independent manner. The effect of Cx43 on a proapoptotic factor, Bax, was then investigated. The interaction between Cx43 and Bax was confirmed by immunoprecipitation. Furthermore, higher Cx43 expression increased the production of a cleaved (active) form of Bax during SU-induced apoptosis with no alteration in total Bax expression. These findings indicate that Cx43 most likely increases sensitivity to SU in H28 through direct interaction with Bax. In conclusion, we found that Cx43 overcame the chemoresistance of MM cells. PMID:26003083

  1. Dodecanol-poly(D,L-lactic acid)-b-poly (ethylene glycol)-folate (Dol-PLA-PEG-FA) nanoparticles: evaluation of cell cytotoxicity and selecting capability in vitro.

    PubMed

    Wang, Sujun; Luo, Yanfeng; Zeng, Suyun; Luo, Chunhua; Yang, Li; Liang, Zhiqing; Wang, Yuanliang

    2013-02-01

    Folate-conjugated Dol-poly(D,L-lactic acid)-b-poly (ethylene glycol)-folate (Dol-PLA-PEG-FA), was synthesized from dodecanol-poly(D,L-lactic acid), amino-terminated poly(ethylene glycol) and folate. (1)H NMR proved the successful synthesis of Dol-PLA-PEG-FA. Nanoparticles (NPs) were further fabricated from Dol-PLA-PEG-FA by using solvent evaporation-induced interfacial self-assembly method. The size, critical micelle concentration (CMC), cytotoxicity and selecting capability to cancer cells in vitro were examined for Dol-PLA-PEG-FA NPs. The size of NPs showed polymer concentration-dependent phenomenon in the fabrication process, and its polydispersity index (PDI) was very narrow. The CMC was determined as 1.995×10(-4) g/L in aqueous solution, which is much lower than the reported CMC of block copolymer self-assemble micelles. The cytotoxicity evaluation revealed that the obtained NPs2 are non-toxic to either breast cancer cell or normal endothelial cells, and the cell uptake of NPs indicated that the NPs demonstrated much higher selecting capability to breast cancer cells compared to normal fibroblast cells. The possible receptor-mediated endocytosis pathway mechanism was proposed. Based on the above results, it could be concluded that Dol-PLA-PEG-FA polymer and its nanoparticles can be potentially used as a safe drug carrier with strong tumor cells targeting capability for tumor chemotherapy. PMID:23000678

  2. Nanoparticles and nanotubes induced by femtosecond lasers

    NASA Astrophysics Data System (ADS)

    Eliezer, S.; Eliaz, N.; Grossman, E.; Fisher, D.; Gouzman, I.; Henis, Z.; Pecker, S.; Horovitz, Y.; Fraenkel, M.; Maman, S.; Ezersky, V.; Eliezer, D.

    2005-01-01

    In this paper, we suggest the creation of a nanoparticles and nanotubes by using the interaction of a femtosecond laser with a solid target in a vacuum. A simple model is used to predict the optimal target and the laser parameters for the production of efficient nanoparticles. At the Soreq laboratory, experiments are performed with aluminium and carbon targets using a femtosecond laser. The irradiated targets are composed of either a thin layer of aluminium or of carbon, deposited on a transparent heat-insulating glass substrate. The nanoparticle debris is collected on a silicone wafer for X-ray diffraction (XRD), for scanning electron microscopy (SEM), and for atomic force microscopy (AFM). For transmission electron microscopy (TEM), the debris is caught on a copper grid covered on one side with a carbon membrane. Our experiments confirm the creation of crystal nanoparticles for aluminium and nanotubes for carbon experiments.

  3. Acrolein-induced cytotoxicity in cultured human bronchial epithelial cells. Modulation by alpha-tocopherol and ascorbic acid

    Microsoft Academic Search

    Mirella Nardini; E. I Finkelstein; S Reddy; G Valacchi; M Traber; C. E Cross; A van der Vliet

    2002-01-01

    Acrolein is a highly reactive unsaturated hazardous air pollutant of human health concern, particularly as a component of cigarette smoke. In this study, the mechanisms of acrolein-induced cytotoxicity in human bronchial epithelial cells (HBE1) and the modulating effects of antioxidants were examined. Our results show that acrolein induces a cell death pathway in human bronchial epithelial cells, which retain key

  4. Cytotoxicity, cell uptake and microscopic analysis of titanium dioxide and silver nanoparticles in vitro.

    PubMed

    Tomankova, Katerina; Horakova, Jana; Harvanova, Monika; Malina, Lukas; Soukupova, Jana; Hradilova, Sarka; Kejlova, Kristina; Malohlava, Jakub; Licman, Libor; Dvorakova, Marketa; Jirova, Dagmar; Kolarova, Hana

    2015-08-01

    Commercially manufactured nanomaterials are used massively for modification of products of everyday use, including products intended for children. Therefore their potential risks have to be ultimately studied. Aside from toxicity of nanomaterials with known specific parameters, the end-consumer is potentially endangered by materials with unknown specification. Commercially available products are not usually accompanied by parameter/specification sheet providing the consumer with sufficient chemico-physical parameters allowing the evaluation of possible toxic effects. The aim of this work was to evaluate the declared parameters of commercially available TiO2 and Ag NPs employing chemico-physical methods and consequently in vitro cytotoxicity and genotoxicity tests performed on non-cancer cell lines. Based on the results of our complex study we can conclude that the data provided by the producers are not in good agreement with the performed measurements. Furthermore, all tested NPs penetrated into the SVK14 cells and all NPs had significant effect on the kinetics of ROS production in all cell lines (note: the ROS production has not been established as the major mechanism of cell damage elicited by Ag NPs). The study revealed greater cytotoxic potential of Ag NPs in comparison with TiO2 NPs and all of the studied NPs caused significant DNA damage. PMID:25846500

  5. 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)

    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

    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.

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

    PubMed Central

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

    2013-01-01

    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. PMID:24264796

  7. Evaluation of the antimicrobial activity and cytotoxicity of phytogenic gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Sreekanth, T. V. M.; Nagajyothi, P. C.; Supraja, N.; Prasad, T. N. V. K. V.

    2014-09-01

    Among the nanoscale materials, noble metal nanoparticles have been attracting the scientific community due to their unique properties and selectivity in biological applications. In the present investigation, gold nanoparticles (AuNPs) were synthesized using rhizome extract of Dioscorea batatas through a simple, clean, inexpensive and eco-friendly method. Treating 1 mM chloroauric acid (HAuCl4) with the rhizome extract at 50 °C resulted in the formation of AuNPs. The reduction of AuNPs was observed by the color change of the solution from colorless to dark red wine. The synthesized nanoparticles were characterized using the techniques UV-Vis spectrophotometers, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and transmission electron microscopy. Green synthesized AuNPs were found to be toxic against gram-positive and gram-negative bacteria in liquid media. MTT (dimethyl thiazolyl diphenyl tetrazolium salt) assay showed 21.5 % cell inhibition in lower concentration (0.2 mM) and >50 % cell inhibition after 48 h exposure at higher concentrations (0.8-1 mM).

  8. Evaluation of the antimicrobial activity and cytotoxicity of phytogenic gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Sreekanth, T. V. M.; Nagajyothi, P. C.; Supraja, N.; Prasad, T. N. V. K. V.

    2015-06-01

    Among the nanoscale materials, noble metal nanoparticles have been attracting the scientific community due to their unique properties and selectivity in biological applications. In the present investigation, gold nanoparticles (AuNPs) were synthesized using rhizome extract of Dioscorea batatas through a simple, clean, inexpensive and eco-friendly method. Treating 1 mM chloroauric acid (HAuCl4) with the rhizome extract at 50 °C resulted in the formation of AuNPs. The reduction of AuNPs was observed by the color change of the solution from colorless to dark red wine. The synthesized nanoparticles were characterized using the techniques UV-Vis spectrophotometers, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and transmission electron microscopy. Green synthesized AuNPs were found to be toxic against gram-positive and gram-negative bacteria in liquid media. MTT (dimethyl thiazolyl diphenyl tetrazolium salt) assay showed 21.5 % cell inhibition in lower concentration (0.2 mM) and >50 % cell inhibition after 48 h exposure at higher concentrations (0.8-1 mM).

  9. Impact of inflammation on chlorpromazine-induced cytotoxicity and cholestatic features in HepaRG cells.

    PubMed

    Bachour-El Azzi, Pamela; Sharanek, Ahmad; Abdel-Razzak, Ziad; Antherieu, Sebastien; Al-Attrache, Houssein; Savary, Camille C; Lepage, Sylvie; Morel, Isabelle; Labbe, Gilles; Guguen-Guillouzo, Christiane; Guillouzo, André

    2014-09-01

    Several factors are thought to be implicated in the occurrence of idiosyncratic adverse drug reactions. The present work aimed to question as to whether inflammation is a determinant factor in hepatic lesions induced by chlorpromazine (CPZ) using the human HepaRG cell line. An inflammation state was induced by a 24-hour exposure to proinflammatory cytokines interleukin-6 (IL-6) and IL-1?; then the cells were simultaneously treated with CPZ and/or cytokine for 24 hours or daily for 5 days. The inflammatory response was assessed by induction of C-reactive protein and IL-8 transcripts and proteins as well as inhibition of CPZ metabolism and down-regulation of cytochrome 3A4 (CYP3A4) and CYP1A2 transcripts, two major cytochrome P450 (P450) enzymes involved in its metabolism. Most effects of cotreatments with cytokines and CPZ were amplified or only observed after five daily treatments; they mainly included increased cytotoxicity and overexpression of oxidative stress-related genes, decreased Na(+)-taurocholate cotransporting polypeptide mRNA levels and activity, a key transporter involved in bile acids uptake, and deregulation of several other transporters. However, CPZ-induced inhibition of taurocholic acid efflux and pericanalicular F-actin distribution were not affected. In addition, a time-dependent induction of phospholipidosis was noticed in CPZ-treated cells, without obvious influence of the inflammatory stress. In summary, our results show that an inflammatory state induced by proinflammatory cytokines increased cytotoxicity and enhanced some cholestatic features induced by the idiosyncratic drug CPZ in HepaRG cells. These changes, together with inhibition of P450 activities, could have important consequences if extrapolated to the in vivo situation. PMID:25002748

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

    PubMed Central

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

    2011-01-01

    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. PMID:19609004

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

    PubMed

    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

    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

  12. Evaluation of zinc oxide nanoparticles toxicity on marine algae chlorella vulgaris through flow cytometric, cytotoxicity and oxidative stress analysis.

    PubMed

    Suman, T Y; Radhika Rajasree, S R; Kirubagaran, R

    2015-03-01

    The increasing industrial use of nanomaterials during the last decades poses a potential threat to the environment and in particular to organisms living in the aquatic environment. In the present study, the toxicity of zinc oxide nanoparticles (ZnO NPs) was investigated in Marine algae Chlorella vulgaris (C. vulgaris). High zinc dissociation from ZnONPs, releasing ionic zinc in seawater, is a potential route for zinc assimilation and ZnONPs toxicity. To examine the mechanism of toxicity, C. vulgaris were treated with 50mg/L, 100mg/L, 200mg/L and 300 mg/L ZnO NPs for 24h and 72h. The detailed cytotoxicity assay showed a substantial reduction in the viability dependent on dose and exposure. Further, flow cytometry revealed the significant reduction in C. vulgaris viable cells to higher ZnO NPs. Significant reductions in LDH level were noted for ZnO NPs at 300 mg/L concentration. The activity of antioxidant enzyme superoxide dismutase (SOD) significantly increased in the C. vulgaris exposed to 200mg/L and 300 mg/L ZnO NPs. The content of non-enzymatic antioxidant glutathione (GSH) significantly decreased in the groups with a ZnO NPs concentration of higher than 100mg/L. The level of lipid peroxidation (LPO) was found to increase as the ZnO NPs dose increased. The 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 (FESEM and CM). PMID:25483368

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

    SciTech Connect

    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

    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.

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

    PubMed

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

    2014-04-01

    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

  15. Cytotoxic effect of icaritin and its mechanisms in inducing apoptosis in human burkitt lymphoma cell line.

    PubMed

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

    2014-01-01

    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. PMID:24895574

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

    PubMed Central

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

    2014-01-01

    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. PMID:24895574

  17. Effects of soyasaponin I and soyasaponins-rich extract on the alternariol-induced cytotoxicity on Caco-2 cells.

    PubMed

    Vila-Donat, Pilar; Fernández-Blanco, Celia; Sagratini, Gianni; Font, Guillermina; Ruiz, María-José

    2015-03-01

    Alternariol (AOH) is a mycotoxin produced by Alternaria spp. Soyasaponin I (Ss-I) is present naturally in legumes, and it has antioxidant properties. Cytotoxic and genotoxic effects of AOH have been demonstrated previously in vitro. In the present study, the cytotoxicity of AOH, Ss-I, and soyasaponins-rich extract from lentils was investigated; as well as, the cytoprotective effects of Ss-I and lentil extracts against AOH induced-cytotoxicity on Caco-2 cells. Cytotoxicity was carried out using MTT and PC assays (AOH: 3.125-100?µM, Ss-I: 3.125-50?µM, and lentil extracts: 1:0-1:32) during 24?h of exposure. Only AOH showed cytotoxic effect. The reduction in cell proliferation ranged from 25% to 47%. Simultaneous combination of Ss-I with AOH (1:1) increased cell proliferation (35%) compared to AOH tested alone. The Ss-I and extracts showed synergistic cytoprotective effects against cytotoxicity induced by AOH on Caco-2 cells. Food commodities containing Ss-I could contribute to diminish the toxicological risk that natural contaminant as AOH in diet can produce to humans. PMID:25542527

  18. Electromagnetic forces on plasmonic nanoparticles induced by fast electron beams

    NASA Astrophysics Data System (ADS)

    Reyes-Coronado, Alejandro; Barrera, Rubén G.; Batson, Philip E.; Echenique, Pedro M.; Rivacoba, Alberto; Aizpurua, Javier

    2010-12-01

    The total momentum transfer from fast electron beams, like those employed in scanning transmission electron microscopy (STEM), to plasmonic nanoparticles is calculated. The momentum transfer is obtained by integrating the electromagnetic forces acting on the particles over time. Numerical results for single and dimer metallic nanoparticles are presented, for sizes ranging between 2 and 80 nm. We analyze the momentum transfer in the case of metallic dimers where the different relevant parameters such as particle size, interparticle distance, and electron beam impact parameter are modified. It is shown that depending on the specific values of the parameters, the total momentum transfer yields a force that can be either attractive or repulsive. The time-average forces calculated for electron beams commonly employed in STEM are on the order of piconewtons, comparable in magnitude to optical forces and are thus capable of producing movement in the nanoparticles. This effect can be exploited in mechanical control of nanoparticle induced motion.

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

    NASA Astrophysics Data System (ADS)

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

    2011-04-01

    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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24804832

  1. Contribution of hydrazines-derived alkyl radicals to cytotoxicity and transformation induced in normal c-myc-overexpressing mouse fibroblasts.

    PubMed

    Gamberini, M; Cidade, M R; Valotta, L A; Armelin, M C; Leite, L C

    1998-01-01

    Several hydrazine derivatives (HD) tested so far have pharmacological activities, but many also have toxic side effects, including carcinogenesis. Their toxicity has been ascribed to carbocations (via formation of azoxy intermediates), alkyl radicals or reactive oxygen species. Cytotoxicity and transformation by carbocations is widely accepted, but the role of alkyl radicals is still questioned. We have investigated the cytotoxicity of HD to mouse fibroblasts in three activation systems in which enhanced alkyl radical formation is demonstrated by electron spin resonance/spin-trapping. Cytotoxicity was assayed by inhibition of [3H-methyl]thymidine uptake into DNA of Balb/c 3T3 and/or Myc 9E fibroblasts (normal Balb/c 3T3 cells over-expressing the c-myc proto-oncogene). Based on the results obtained in the cytotoxicity assays we also investigated the transforming potential of procarbazine (PCZ) and methylhydrazine (MeH) activated by horseradish peroxidase (HRP) using the Myc 9E cell line, which aims at the activation of a second cooperating oncogene. Our results show that: (i) cytotoxicity of HD to mouse fibroblasts is increased by HRP activation of MeH, phenelzine and PCZ, which displayed enhanced alkyl radical formation, but not of 1,2-dimethylhydrazine (DMH), which did not produce increased alkyl radical formation under these conditions; (ii) cytotoxicity of neutrophil-activated MeH (producing a 10-fold higher concentration of methyl radicals), is more pronounced than DMH; (iii) MeH and DMH activated by prolonged auto-oxidation in 24-h incubations have comparable cytotoxicity and alkyl radical formation; and (iv) PCZ and MeH activation by HRP to alkyl radicals increased the transformation induced in Myc 9E cells. Taken together, our results strongly support a role for hydrazine-derived alkyl radicals in HD-induced cytotoxicity and cell transformation. PMID:9472706

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

    SciTech Connect

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

    2005-11-01

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

  3. Sunroot mediated synthesis and characterization of silver nanoparticles and evaluation of its antibacterial and rat splenocyte cytotoxic effects

    PubMed Central

    Aravinthan, Adithan; Govarthanan, Muthusamy; Selvam, Kandasamy; Praburaman, Loganathan; Selvankumar, Thangasamy; Balamurugan, Rangachari; Kamala-Kannan, Seralathan; Kim, Jong-Hoon

    2015-01-01

    A rapid, green phytosynthesis of silver nanoparticles (AgNPs) using the aqueous extract of Helianthus tuberosus (sunroot tuber) was reported in this study. The morphology of the AgNPs was determined by transmission electron microscopy (TEM). Scanning electron microscopy–energy-dispersive spectroscopy (SEM–EDS) and X-ray powder diffraction (XRD) analysis confirmed the presence of AgNPs. Fourier transform infrared spectroscopy (FTIR) analysis revealed that biomolecules in the tuber extract were involved in the reduction and capping of AgNPs. The energy-dispersive spectroscopy (EDS) analysis of the AgNPs, using an energy range of 2–4 keV, confirmed the presence of elemental silver without any contamination. Further, the synthesized AgNPs were evaluated against phytopathogens such as Ralstonia solanacearum and Xanthomonas axonopodis. The AgNPs (1–4 mM) extensively reduced the growth rate of the phytopathogens. In addition, the cytotoxic effect of the synthesized AgNPs was analyzed using rat splenocytes. The cell viability was decreased according to the increasing concentration of AgNPs and 67% of cell death was observed at 100 ?g/mL. PMID:25792831

  4. Sunroot mediated synthesis and characterization of silver nanoparticles and evaluation of its antibacterial and rat splenocyte cytotoxic effects.

    PubMed

    Aravinthan, Adithan; Govarthanan, Muthusamy; Selvam, Kandasamy; Praburaman, Loganathan; Selvankumar, Thangasamy; Balamurugan, Rangachari; Kamala-Kannan, Seralathan; Kim, Jong-Hoon

    2015-01-01

    A rapid, green phytosynthesis of silver nanoparticles (AgNPs) using the aqueous extract of Helianthus tuberosus (sunroot tuber) was reported in this study. The morphology of the AgNPs was determined by transmission electron microscopy (TEM). Scanning electron microscopy-energy-dispersive spectroscopy (SEM-EDS) and X-ray powder diffraction (XRD) analysis confirmed the presence of AgNPs. Fourier transform infrared spectroscopy (FTIR) analysis revealed that biomolecules in the tuber extract were involved in the reduction and capping of AgNPs. The energy-dispersive spectroscopy (EDS) analysis of the AgNPs, using an energy range of 2-4 keV, confirmed the presence of elemental silver without any contamination. Further, the synthesized AgNPs were evaluated against phytopathogens such as Ralstonia solanacearum and Xanthomonas axonopodis. The AgNPs (1-4 mM) extensively reduced the growth rate of the phytopathogens. In addition, the cytotoxic effect of the synthesized AgNPs was analyzed using rat splenocytes. The cell viability was decreased according to the increasing concentration of AgNPs and 67% of cell death was observed at 100 ?g/mL. PMID:25792831

  5. Mucin Secretion Induced by Titanium Dioxide Nanoparticles

    Microsoft Academic Search

    Eric Y. T. Chen; Maria Garnica; Yung-Chen Wang; Chi-Shuo Chen; Wei-Chun Chin; Meni Wanunu

    2011-01-01

    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 (TiO2), one of the PM10 components, is widely utilized in the

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

    PubMed Central

    Nguyen, Kathy C; Seligy, Vern L

    2013-01-01

    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. PMID:22264036

  7. Glycans coated silver nanoparticles induces autophagy and necrosis in HeLa cells

    NASA Astrophysics Data System (ADS)

    Panzarini, Elisa; Mariano, Stefania; Dini, Luciana

    2015-06-01

    This study reports the induction of autophagy by two concentrations (2×103 or 2×104 NPs/cell) of 30 nm sized ?-D-Glucose- and ?-D-Glucose/Sucrose-coated silver NanoParticles (AgNPs-G and AgNPs-GS respectively) in HeLa cells treated for 6, 12, 24 and 48 hrs. Cell viability was assessed by Neutral Red (NR) test and morphological evaluation. In addition ROS generation (NBT test) and induction of apoptosis/necrosis (Annexin V/Propidium Iodide-Annexin V/PI staining) and autophagy (Monodansylcadaverine-MDC staining) were evaluated. Cytotoxicity, ROS generation and morphology changes depend on NPs type and amount, and incubation time. As a general result, AgNPs-G are more toxic than AgNPs-GS. Moreover, the lowest AgNPs-GS concentration is ineffective on cell viability and ROS generation. Only 10% and 25% of viable HeLa cells were found at the end of incubation time in the presence of higher amount of AgNPs - G and AgNPs-GS respectively and in parallel ROS generation is induced. To elucidate the type of cell death, Annexin V/PI and MDC staining was performed. Interestingly, irrespective of coating type and NPs amount the percentage of apoptotic cells (Annexin V+/PI-) is similar to viable HeLa cells. At contrary, we observed a NPs amount dependent autophagy and necrosis induction. In fact, the lower amount of NPs induces autophagy (MDC+/PI- cells) whereas the higher one induces necrosis (Annexin V+/PI+ cells). Our findings suggest that AgNPs-induced cytotoxicity depends on AgNPs amount and type and provide preliminary evidence of induction of autophagy in HeLa cells cultured in the presence of AgNPs.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24959077

  9. SiO? nanoparticle-induced impairment of mitochondrial energy metabolism in hepatocytes directly and through a Kupffer cell-mediated pathway in vitro.

    PubMed

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

    2014-01-01

    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. PMID:24959077

  10. Methyllycaconitine Alleviates Amyloid-? Peptides-Induced Cytotoxicity in SH-SY5Y Cells

    PubMed Central

    Zheng, XiaoLei; Xie, ZhaoHong; Zhu, ZhengYu; Liu, Zhen; Wang, Yun; Wei, LiFei; Yang, Hui; Yang, HongNa; Liu, YiQing; Bi, JianZhong

    2014-01-01

    Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. As the most common form of dementia, it affects more than 35 million people worldwide and is increasing. Excessive extracellular deposition of amyloid-? peptide (A?) is a pathologic feature of AD. Accumulating evidence indicates that macroautophagy is involved in the pathogenesis of AD, but its exact role is still unclear. Although major findings on the molecular mechanisms have been reported, there are still no effective treatments to prevent, halt, or reverse Alzheimer's disease. In this study, we investigated whether A?25–35 could trigger an autophagy process and inhibit the growth of SH-SY5Y cells. Furthermore, we examined the effect of methyllycaconitine (MLA) on the cytotoxity of A?25–35. MLA had a protective effect against cytotoxity of A?, which may be related to its inhibition of A?-induced autophagy and the involvement of the mammalian target of rapamycin pathway. Moreover, MLA had a good safety profile. MLA treatment may be a promising therapeutic tool for AD. PMID:25360664

  11. Real-time monitoring of copper ions-induced cytotoxicity by EIS cell chips.

    PubMed

    Primiceri, Elisabetta; Chiriacň, Maria Serena; D'Amone, Eliana; Urso, Emanuela; Ionescu, Rodica Elena; Rizzello, Antonia; Maffia, Michele; Cingolani, Roberto; Rinaldi, Ross; Maruccio, Giuseppe

    2010-08-15

    An important goal of biomedical research is the development of tools for high-throughput evaluation of drug effects and cytotoxicity tests. Here we demonstrate EIS cell chips able to monitor cell growth, morphology, adhesion and their changes as a consequence of treatment with drugs or toxic compounds. As a case study, we investigate the uptake of copper ions and its effect on two cell lines: B104 and HeLa cells. For further understanding, we also carried out in parallel with EIS studies, a complete characterization of cell morphology and changes induced by copper ions through complementary methodologies (including state-of-the-art AFM, viability test and Western blot). Our results reveal a strong correlation between EIS data and both MTT test and AFM characterization so our chip can be used as powerful tools in all biology lab in combination with other standard methods giving additional information that can be useful in a complete and deep investigation of a biological process. This chip can be used even alone replacing in vitro drug tests based on conventional biochemical methods, being very cheap and reusable and allowing to perform cytotoxicity tests without using any expensive reagent or equipment. PMID:20547054

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

    SciTech Connect

    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

    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.

  13. Role for ceramide as an endogenous mediator of Fas-induced cytotoxicity.

    PubMed Central

    Tepper, C G; Jayadev, S; Liu, B; Bielawska, A; Wolff, R; Yonehara, S; Hannun, Y A; Seldin, M F

    1995-01-01

    Triggering of the Fas/APO-1 cell-surface receptor induces apoptosis through an uncharacterized chain of events. Exposure of Fas-sensitive cells to an agonist monoclonal antibody induced cell death and a 200-300% elevation in endogenous levels of the sphingolipid ceramide, a proposed intracellular mediator of apoptosis. In contrast, similar treatment of Fas-resistant cells caused insignificant changes in ceramide levels. Because resistant cell lines expressed the Fas antigen, these results indicate that these cells have a defect in the proximal signaling events leading to ceramide generation. Exposure of the resistant cell lines to a synthetic analog of ceramide induced apoptosis, thus bypassing Fas resistance and indicating that the signaling pathways downstream of ceramide were intact. Furthermore, activation of protein kinase C with the diacylglycerol analog phorbol 12-myristate 13-acetate significantly reduced Fas-induced cytotoxicity, suggesting opposing roles for ceramide and protein kinase C in regulation of apoptosis. These results provide evidence for ceramide as a necessary and sufficient lipid mediator of Fas-mediated apoptosis and suggest this process may be modulated via activation of additional signal-transduction pathways. Images Fig. 1 PMID:7545303

  14. Alpha-Tocopherol Counteracts the Cytotoxicity Induced by Ochratoxin A in Primary Porcine Fibroblasts

    PubMed Central

    Fusi, Eleonora; Rebucci, Raffaella; Pecorini, Chiara; Campagnoli, Anna; Pinotti, Luciano; Saccone, Francesca; Cheli, Federica; Purup, Stig; Sejrsen, Kristen; Baldi, Antonella

    2010-01-01

    The aims of the current study were to determine the half-lethal concentration of ochratoxin A (OTA) as well as the levels of lactate dehydrogenase release and DNA fragmentation induced by OTA in primary porcine fibroblasts, and to examine the role of ?-tocopherol in counteracting its toxicity. Cells showed a dose-, time- and origin-dependent (ear vs. embryo) sensitivity to ochratoxin A. Pre-incubation for 3 h with 1 nM ?-tocopherol significantly (P < 0.01) reduced OTA cytotoxicity, lactate dehydrogenase release and DNA damage in both fibroblast cultures. These findings indicate that ?-tocopherol supplementation may counteract short-term OTA toxicity, supporting its defensive role in the cell membrane. PMID:22069637

  15. Protection from radiation-induced pneumonitis using cerium oxide nanoparticles.

    PubMed

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

    2009-06-01

    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

  16. Humic Acid Increases Amyloid ?-Induced Cytotoxicity by Induction of ER Stress in Human SK-N-MC Neuronal Cells

    PubMed Central

    Li, Hsin-Hua; Lu, Fung-Jou; Hung, Hui-Chih; Liu, Guang-Yaw; Lai, Te-Jen; Lin, Chih-Li

    2015-01-01

    Humic acid (HA) is a possible etiological factor associated with for several vascular diseases. It is known that vascular risk factors can directly increase the susceptibility to Alzheimer’s disease (AD), which is a neurodegenerative disorder due to accumulation of amyloid ? (A?) peptide in the brain. However, the role that HA contributes to A?-induced cytotoxicity has not been demonstrated. In the present study, we demonstrate that HA exhibits a synergistic effect enhancing A?-induced cytotoxicity in cultured human SK-N-MC neuronal cells. Furthermore, this deterioration was mediated through the activation of endoplasmic reticulum (ER) stress by stimulating PERK and eIF2? phosphorylation. We also observed HA and A?-induced cytotoxicity is associated with mitochondrial dysfunction caused by down-regulation of the Sirt1/PGC1? pathway, while in contrast, treating the cells with the ER stress inhibitor Salubrinal, or over-expression of Sirt1 significantly reduced loss of cell viability by HA and A?. Our findings suggest a new mechanism by which HA can deteriorate A?-induced cytotoxicity through modulation of ER stress, which may provide significant insights into the pathogenesis of AD co-occurring with vascular injury. PMID:25961951

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

    PubMed Central

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

    2013-01-01

    Autophagy is a critical mechanism in both cancer therapy resistance and tumor suppression. Monoclonal antibodies have been documented to kill tumor cells via apoptosis, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In this study, we report for the first time that chLym-1, a chimeric anti-human HLA-DR monoclonal antibody, induces autophagy in Raji Non-Hodgkin’s Lymphoma (NHL) cells. Interestingly, inhibition of autophagy by pharmacological inhibitors (3-methyladenine and NH4Cl) or genetic approaches (siRNA targeting Atg5) suppresses chLym-1-induced growth inhibition, apoptosis, ADCC and CDC in Raji cells, while induction of autophagy could accelerate cytotoxic effects of chLym-1 on Raji cells. Furthermore, chLym-1-induced autophagy can mediate apoptosis through Caspase 9 activation, demonstrating the tumor-suppressing role of autophagy in antilymphoma effects of chLym-1. Moreover, chLym-1 can activate several upstream signaling pathways of autophagy including Akt/mTOR and extracellular signal-regulated kinase 1/2 (Erk1/2). These results elucidate the critical role of autophagy in cytotoxicity of chLym-1 antibody and suggest a potential therapeutic strategy of NHL therapy by monoclonal antibody chLym-1 in combination with autophagy inducer. PMID:24015249

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

    Microsoft Academic Search

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

    1992-01-01

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

  19. Maackia amurensis agglutinin enhances paclitaxel induced cytotoxicity in cultured non-small cell lung cancer cells.

    PubMed

    Chhetra Lalli, Rakhee; Kaur, Kiranjeet; Dadsena, Shashank; Chakraborti, Anuradha; Srinivasan, Radhika; Ghosh, Sujata

    2015-08-01

    Maackia amurensis agglutinin (MAA) is gaining recognition as the potential diagnostic agent for cancer. Previous studies from our laboratory have demonstrated that this lectin could interact specifically with the cells and biopsy samples of non-small cell lung cancer (NSCLC) origin but not with normal lung fibroblast cells. Moreover, this lectin was also found to induce apoptosis in NSCLC cells. Further, the biological activity of this lectin was shown to survive gastrointestinal proteolysis and inhibit malignant cell growth and tumorigenesis in mice model of melanoma thereby indicating the therapeutic potential of this lectin. Paclitaxel is one of the widely used traditional chemotherapeutic drugs for treatment of NSCLC but it exerts side-effects on normal healthy cells too. Studies have revealed that lectins have potential to act as an adjuvant chemotherapeutic agent in cancer of different origin. Thus, in the present study, an attempt was made to assess the chemo-adjuvant role of MAA in three types of NSCLC cell lines [adenocarcinoma cell line (A549), squamous cell carcinoma cell line (NCI-H520) and large cell carcinoma cell line (NCI-H460)]. We have observed that the non-cytotoxic concentration of this lectin was able to enhance the cytotoxic activity of Paclitaxel even at low dose by inducing apoptosis through intrinsic/mitochondrial pathway in all the three types of NSCLC cell lines, although the involvement of extrinsic pathway of apoptosis in case of NCI-H460 cell line could not be ruled out. Further, this lectin was also found to augment the chemo-preventive activity of this drug by arresting cells in G2-M phase of the cell cycle. Collectively, our results have suggested that Maackia amurensis agglutinin may have the potential to be used as adjuvant chemotherapeutic agent in case of NSCLC. PMID:25978938

  20. Cytotoxic effects induced in vitro by organic extracts from urban air particulate matter in human leukocytes.

    PubMed

    Cimino, Francesco; Speciale, Antonio; Siracusa, Laura; Naccari, Clara; Saija, Antonella; Mancari, Ferdinando; Raciti, Roberto; Cristani, Mariateresa; Trombetta, Domenico

    2014-01-01

    Urban areas represent major pollution sources as a result of anthropogenic activities located in these districts. Among the legislated air pollutants, polycyclic aromatic hydrocarbons (PAHs), which are mostly adsorbed on the surface of dust particles, are known for their adverse health effects. The present study has been carried out to examine the cytotoxic effects induced in vitro on human peripheral monocytes (PBMCs) by extractable organic matter (EOM) from PM10 (characterized for its PAH content) collected at four sites in the urban center of Messina, Italy. Chromatographic analyses showed the presence of PAHs in all EOM. Only EOM from one site induced a marked cell death probably resulting from the highest PAH content in this sample. Conversely, apoptosis activation was evident after PBMC exposure to all the EOM tested. These apoptotic effects do not appear related only to the total PAH content, but are probably influenced by chemical composition. In conclusion, our findings confirm that the cytotoxic potential of organic matter associated to ambient respirable air particles depends predominantly on the quantity and quality of the chemicals contained in it. In particular, the present data strongly evidence that the only evaluation of air concentration of particulate matter and benzo[a]pyrene, as well as the generally used risk models based on additivity, are not sufficient to evaluate air quality and PAH effect on human health because they do not take into account the possible inhibitory or synergic or antagonistic effect of combined exposure and the interference of other organic compounds present in respirable matter. PMID:24195653

  1. Design of cationic lipid nanoparticles for ocular delivery: development, characterization and cytotoxicity.

    PubMed

    Fangueiro, Joana F; Andreani, Tatiana; Egea, Maria A; Garcia, Maria L; Souto, Selma B; Silva, Amélia M; Souto, Eliana B

    2014-01-30

    In the present study we have developed lipid nanoparticle (LN) dispersions based on a multiple emulsion technique for encapsulation of hydrophilic drugs or/and proteins by a full factorial design. In order to increase ocular retention time and mucoadhesion by electrostatic attraction, a cationic lipid, namely cetyltrimethylammonium bromide (CTAB), was added in the lipid matrix of the optimal LN dispersion obtained from the factorial design. There are a limited number of studies reporting the ideal concentration of cationic agents in LN for drug delivery. This paper suggests that the choice of the concentration of a cationic agent is critical when formulating a safe and stable LN. CTAB was included in the lipid matrix of LN, testing four different concentrations (0.25%, 0.5%, 0.75%, or 1.0%wt) and how composition affects LN behavior regarding physical and chemical parameters, lipid crystallization and polymorphism, and stability of dispersion during storage. In order to develop a safe and compatible system for ocular delivery, CTAB-LN dispersions were exposed to Human retinoblastoma cell line Y-79. The toxicity testing of the CTAB-LN dispersions was a fundamental tool to find the best CTAB concentration for development of these cationic LN, which was found to be 0.5 wt% of CTAB. PMID:24275449

  2. Docetaxel-loaded polylactic acid-co-glycolic acid nanoparticles: formulation, physicochemical characterization and cytotoxicity studies.

    PubMed

    Pradhan, Roshan; Poudel, Bijay Kumar; Ramasamy, Thiruganesh; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2013-08-01

    In the present study, we developed novel docetaxel (DTX)-loaded polylactic acid-co-glycolic acid (PLGA) nanoparticles (NPs) using the combination of sodium lauryl sulfate (SLS) and poloxamer 407, the anionic and non-ionic surfactants respectively for stabilization. The NPs were prepared by emulsification/solvent evaporation method. The combination of these surfactants at weight ratio of 1:0.5 was able to produce uniformly distributed small sized NPs and demonstrated the better stability of NP dispersion with high encapsulation efficiency (85.9 +/- 0.6%). The drug/polymer ratio and phase ratio were 2:10 and 1:10, respectively. The optimized formulation of DTX-loaded PLGA NPs had a particle size and polydispersity index of 104.2 +/- 1.5 nm and 0.152 +/- 0.006, respectively, which was further supported by TEM image. In vitro release study was carried out with dialysis membrane and showed 32% drug release in 192 h. When in vitro release data were fitted to Korsmeyer-Peppas model, the n value was 0.481, which suggested the drug was released by anomalous or non-Fickian diffusion. In addition, DTX-loaded PLGA NPs in 72 h, displayed approximately 75% cell viability reduction at 10 microg/ml DTX concentration, in MCF-7 cell lines, indicating sustained release from NPs. Therefore, our results demonstrated that incorporation of DTX into PLGA NPs could provide a novel effective nanocarrier for the treatment of cancer. PMID:23882865

  3. Significance of Persistent Inflammation in Respiratory Disorders Induced by Nanoparticles

    PubMed Central

    Morimoto, Yasuo; Izumi, Hiroto; Kuroda, Etsushi

    2014-01-01

    Pulmonary inflammation, especially persistent inflammation, has been found to play a key role in respiratory disorders induced by nanoparticles in animal models. In inhalation studies and instillation studies of nanomaterials, persistent inflammation is composed of neutrophils and alveolar macrophages, and its pathogenesis is related to chemokines such as the cytokine-induced neutrophil chemoattractant (CINC) family and macrophage inflammatory protein-1? and oxidant stress-related genes such as heme oxygenase-1 (HO-1). DNA damages occur chemically or physically by nanomaterials. Chemical and physical damage are associated with point mutation by free radicals and double strand brake, respectively. The failure of DNA repair and accumulation of mutations might occur when inflammation is prolonged, and finally normal cells could become malignant. These free radicals can not only damage cells but also induce signaling molecules containing immunoreaction. Nanoparticles and asbestos also induce the production of free radicals. In allergic responses, nanoparticles act as Th2 adjuvants to activate Th2 immune responses such as activation of eosinophil and induction of IgE. Taken together, the presence of persistent inflammation may contribute to the pathogenesis of a variety of diseases induced by nanomaterials. PMID:25097864

  4. Cytotoxic effects of cytoplasmic-targeted and nuclear-targeted gold and silver nanoparticles in HSC-3 cells--a mechanistic study.

    PubMed

    Austin, Lauren A; Ahmad, Samera; Kang, Bin; Rommel, Kathryn R; Mahmoud, Mahmoud; Peek, Mary E; El-Sayed, Mostafa A

    2015-06-01

    Nanoparticles (NPs), in particular noble metal nanoparticles, have been incorporated into many therapeutic and biodiagnostic applications. While these particles have many advantageous physical and optical properties, little is known about their intrinsic intracellular effects in biological environments. Here, we report the possible cell death mechanisms triggered in human oral squamous cell carcinoma (HSC-3) cells after exposure to extracellular, cytoplasm, and nuclear localized AuNPs and AgNPs. NP uptake and localization, cell viability, ATP levels, modes of cell death, ROS generation, mitochondrial depolarization, and the levels and/or translocation of caspase-dependent and caspase-independent proteins were assessed under control and localized metal nanoparticle exposure. Exposure to AuNPs resulted the adoption of a quiescent cellular state, as AuNPs caused a decrease in intracellular ATP, but no change in viability or cell death populations. However, AgNP exposure significantly reduced HSC-3 cell viability and increased apoptotic populations, especially when localized at the cytoplasm and nucleus. Increased cell death populations were linked to an increase in intracellular ROS generation. Western blot analysis indicated cytoplasm localized AgNPs and nuclear localized AgNPs utilized a caspase-independent apoptotic pathway that involved the nuclear translocation of AIF and p38 MAPK proteins. These results demonstrate that the degree of cytotoxicity increases as AgNPs move from extracellular localization to nuclear localization, whereas changing AuNP localization does not trigger any significant cytotoxicity. PMID:25462594

  5. The prosurvival role of autophagy in resveratrol-induced cytotoxicity in GH3 cells.

    PubMed

    Zhang, Xuexin; Xu, Wanhai; Su, Jun; Chu, Ming; Jin, Hua; Li, Guofu; Tan, Chunlei; Wang, Xin; Wang, Chao

    2014-04-01

    In a previous study, we reported that resveratrol exerts antitumor effects through the estrogen receptor in prolactinoma. The autophagy/lysosomal degradation pathway plays an important role in damage control and energy efficiency. In this study, we investigated the involvement of autophagy and the related signaling pathways in resveratrol-induced apoptosis of GH3 cells. We demonstrate that resveratrol inhibits cell proliferation and induces apoptosis in a dose-dependent manner in GH3 cells. The cleavage of PARP was also observed, and the activation of caspase-3 and caspase-8 was detected. Consistent with this finding, the inhibition of caspase activation effectively attenuated resveratrol-induced cell apoptosis. In addition, the decreased level of Bcl-2 was also observed. The induction of autophagy was confirmed by the detection of the formation of autophagic vacuoles, and the increase in microtubule-associated protein 1 light chain 3 (LC3)-II and beclin-1 levels, two hallmarks of autophagy. Pre-treatment with bafilomycin A1 or 3-methyladenine, inhibitors of autophagy, enhanced the resveratrol-mediated caspase activation and cell death. Moreover, resveratrol induced the activation of ERK1/2, as well as the downregulation of Akt and mTOR phosphorylation. Taken together, these findings indicate that resveratrol induces caspase-dependent apoptosis and decreases Bcl-2 levels. In addition, resveratrol-induced autophagy is regulated by the PI3K/Akt/mTOR and ERK1/2 pathways. Furthermore, the inhibition of autophagy increases the cytotoxicity of resveratrol to GH3 cells. PMID:24534837

  6. Virus inhibition induced by polyvalent nanoparticles of different sizes

    NASA Astrophysics Data System (ADS)

    Vonnemann, Jonathan; Sieben, Christian; Wolff, Christopher; Ludwig, Kai; Böttcher, Christoph; Herrmann, Andreas; Haag, Rainer

    2014-01-01

    The development of antiviral agents is one of the major challenges in medical science. So far, small monovalent molecular drugs that inhibit the late steps in the viral replication cycle, i.e., virus budding, have not worked well which emphasizes the need for alternative approaches. Polyvalently presented viral receptors, however, show potential as good inhibitors of virus-cell binding, which is the first step in the viral infection cycle. By gradually increasing the size of ligand functionalized gold nanoparticles, up to virus-like dimensions, we are now able to quantify the polyvalent enhancement of virus-cell binding inhibition and to identify varying mechanisms of virus inhibition with different efficacies: by employing a new binding assay we found that surface area-normalized polysulfated gold nanoparticles of diameters equal to and larger than the virus diameter (>50 nm) more efficiently inhibit the binding of vesicular stomatitis virus (VSV) to cells than smaller particles. On a per particle basis, larger sized gold nanoparticles were surprisingly shown to inhibit the viral infection up to two orders of magnitude more efficiently than smaller particles, which suggests different mechanisms of virus inhibition. Based on complementary electron microscopic data, we noticed that larger gold nanoparticles act as efficient cross-linkers between virions, whereas smaller gold nanoparticles decorate the surface of individual virus particles. Our systematic study accentuates the need for the design of biodegradable, virus-sized inhibitors capitalizing on polyvalent binding.The development of antiviral agents is one of the major challenges in medical science. So far, small monovalent molecular drugs that inhibit the late steps in the viral replication cycle, i.e., virus budding, have not worked well which emphasizes the need for alternative approaches. Polyvalently presented viral receptors, however, show potential as good inhibitors of virus-cell binding, which is the first step in the viral infection cycle. By gradually increasing the size of ligand functionalized gold nanoparticles, up to virus-like dimensions, we are now able to quantify the polyvalent enhancement of virus-cell binding inhibition and to identify varying mechanisms of virus inhibition with different efficacies: by employing a new binding assay we found that surface area-normalized polysulfated gold nanoparticles of diameters equal to and larger than the virus diameter (>50 nm) more efficiently inhibit the binding of vesicular stomatitis virus (VSV) to cells than smaller particles. On a per particle basis, larger sized gold nanoparticles were surprisingly shown to inhibit the viral infection up to two orders of magnitude more efficiently than smaller particles, which suggests different mechanisms of virus inhibition. Based on complementary electron microscopic data, we noticed that larger gold nanoparticles act as efficient cross-linkers between virions, whereas smaller gold nanoparticles decorate the surface of individual virus particles. Our systematic study accentuates the need for the design of biodegradable, virus-sized inhibitors capitalizing on polyvalent binding. Electronic supplementary information (ESI) available: NMR, zeta-potential, extinction coefficients, DLS, TEM, stereoscopic cryo-TEM, calculation models, cytotoxicity. See DOI: 10.1039/c3nr04449a

  7. Non-specific interaction of carbon nanotubes with the resazurin assay reagent: impact on in vitro assessment of nanoparticle cytotoxicity.

    PubMed

    Breznan, Dalibor; Das, Dharani; MacKinnon-Roy, Christine; Simard, Benoit; Kumarathasan, Premkumari; Vincent, Renaud

    2015-02-01

    In vitro cytotoxicity assays are essential tools in the screening of engineered nanomaterials (NM) for cellular toxicity. The resazurin live cell assay is widely used because it is non-destructive and is well suited for high-throughput platforms. However, NMs, in particular carbon nanotubes (CNT) can interfere in assays through quenching of transmitted light or fluorescence. We show that using the resazurin assay with time-point reading of clarified supernatants resolves this problem. Human lung epithelial (A549) and murine macrophage (J774A.1) cell lines were exposed to NMs in 96-well plates in 200 ?L of media/well. After 24 h incubation, 100 ?L of supernatant was removed, replaced with resazurin reagent in culture media and aliquots at 10 min and 120 min were transferred to black-wall 96-well plates. The plates were quick-spun to sediment the residual CNTs and fluorescence was top-read (?Ex=540 nm, ?Em=600 nm). The procedure was validated for CNTs as well as silica nanoparticles (SiNP). There was no indication of reduction of resazurin by the CNTs. Stability of resorufin, the fluorescent product of the resazurin reduction was then assessed. We found that polar CNTs could decrease the fluorescence signal for resorufin, possibly through oxidation to resazurin or hyper-reduction to hydroxyresorufin. This effect can be easily quantified for elimination of the bias. We recommend that careful consideration must be given to fluorimetric/colorimetric in vitro toxicological assessments of optically/chemically active NMs in order to relieve any potential artifacts due to the NMs themselves. PMID:25283091

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

    PubMed

    Eskandani, Morteza; Nazemiyeh, Hossein

    2014-08-01

    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

  9. Curcumin inhibits PhIP induced cytotoxicity in breast epithelial cells through multiple molecular targets.

    PubMed

    Jain, Ashok; Samykutty, Abhilash; Jackson, Carissa; Browning, Darren; Bollag, Wendy B; Thangaraju, Muthusamy; Takahashi, Satoru; Singh, Shree Ram

    2015-08-28

    Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), found in cooked meat, is a known food carcinogen that causes several types of cancer, including breast cancer, as PhIP metabolites produce DNA adduct and DNA strand breaks. Curcumin, obtained from the rhizome of Curcuma longa, has potent anticancer activity. To date, no study has examined the interaction of PhIP with curcumin in breast epithelial cells. The present study demonstrates the mechanisms by which curcumin inhibits PhIP-induced cytotoxicity in normal breast epithelial cells (MCF-10A). Curcumin significantly inhibited PhIP-induced DNA adduct formation and DNA double stand breaks with a concomitant decrease in reactive oxygen species (ROS) production. The expression of Nrf2, FOXO targets; DNA repair genes BRCA-1, H2AFX and PARP-1; and tumor suppressor P16 was studied to evaluate the influence on these core signaling pathways. PhIP induced the expression of various antioxidant and DNA repair genes. However, co-treatment with curcumin inhibited this expression. PhIP suppressed the expression of the tumor suppressor P16 gene, whereas curcumin co-treatment increased its expression. Caspase-3 and -9 were slightly suppressed by curcumin with a consequent inhibition of cell death. These results suggest that curcumin appears to be an effective anti-PhIP food additive likely acting through multiple molecular targets. PMID:26004342

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

    PubMed

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

    2013-01-01

    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

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

    SciTech Connect

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

    2011-05-01

    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.

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

    Microsoft Academic Search

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

    2008-01-01

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

  13. Peptide-induced patterning of gold nanoparticle thin films

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

    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.

  14. Induced phase transitions of nanoparticle-stabilized emulsions

    NASA Astrophysics Data System (ADS)

    Frijters, Stefan; Günther, Florian; Harting, Jens

    2013-11-01

    Nanoparticles can stabilize fluid-fluid interfaces over long timescales and are nowadays commonly used, e.g. in emulsions. However, their fundamental properties are as of yet poorly understood. Nanoparticle-stabilized emulsions can exhibit different phases, such as Pickering emulsions or bijels, which can be characterized by their different topologies and rheology. We investigate the effect of various initial conditions on random mixtures of two fluids and nanoparticles - in particular, the final state these systems will reach. For this, we use the well-established 3D lattice Boltzmann method, extended to allow for the added nanoparticles. After the evolution of the emulsions has stopped, we induce transitions from one state to another by gradually changing the wettability of the nanoparticles over time. This changes the preferential local curvature of the interfaces, which strongly affects the global state. We observe strong hysteresis effects because of the energy barrier presented by the necessary massive reordering of the particles. Being able to change emulsion states in situ has potential application possibilities in filtering technology, or creating particle scaffolds.

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

    PubMed Central

    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

    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. PMID:23710286

  16. Effect of protein calorie malnutrition on the levels of natural and inducible cytotoxic activities in mouse spleen cells.

    PubMed Central

    Saxena, Q B; Saxena, R K; Adler, W H

    1984-01-01

    Six-week-old C57B1/6 female mice were fed a normal (24% protein) or an isocaloric but protein-deficient (4% protein) diet. At different time periods after the initiation of diets, basal natural killer (NK) activity, interleukin-2 (IL-2) and concanavalin-A (Con-A)-induced cytotoxic activity, Con-A-induced IL-2 production and levels of allospecific cytotoxic T cell activity generated in a mixed lymphocyte culture (MLC), were studied in spleen cells derived from control and protein deficient (PD) mice. Results indicated that (a) levels of spleen NK activity increased initially in PD mice, but after 7 weeks on PD diet declined to normal and subnormal levels, (b) IL-2 generation in response to Con-A as well as IL-2 activation of NK activity were comparable in spleen cells of control and PD mice at all time points tested, (c) Con-A-induced cytotoxic activity was significantly greater in spleen cells from PD mice, the difference being greater at higher doses of Con-A, and (d) generation of alloimmune cytotoxic T cells in a MLC reaction was normal in PD mouse spleen cells until 4 weeks after the beginning of PD diet, but declined markedly thereafter. Relevance of these observations to other related findings in protein calorie malnutrition are discussed. PMID:6423525

  17. Photoinitiators enhanced 1,2-dichloropropane-induced cytotoxicity in human normal embryonic lung fibroblasts cells in vitro.

    PubMed

    Kawasaki, Yoichi; Tsuboi, Chiaki; Yagi, Kenta; Morizane, Miwa; Masaoka, Yasuyuki; Esumi, Satoru; Kitamura, Yoshihisa; Sendo, Toshiaki

    2015-03-01

    Dichloromethane (DCM) and 1,2-dichloropsropane (DCP) have various uses, including being solvents for paint removers. Photoinitiators are also used in a wide range of commercial applications such as printing. These chemicals have been shown to induce cytotoxic effects. In the present study, we evaluated the combined effects of DCM or DCP from paint removers and photoinitiators used in printing on normal human embryonic lung fibroblasts with the aim of preventing occupational injuries. We showed that DCP, 2,2-dimethoxy-2-phenylacetophenone (2,2-DMPAP), 2-ethylhexyl-4-(dimethylamino) benzoate (2-EHDAB), 1-hydroxycyclohexyl phenyl ketone (1-HCHPK), and methyl 2-benzoylbenzoate (MBB) induced cytotoxicity, whereas DCM and 2-isopropylthioxanthone (2-ITX) did not. In addition, 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) caused a slight increase in cytotoxicity. The combination of DCP and the four photoinitiators (2,2-DMPAP, 2-EHDAB, MBB, and MTMP) significantly induced cytotoxicity and also led to apoptosis. In conclusion, the combination of DCP and photoinitiators may increase the risk of respiratory diseases. PMID:25501643

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

    PubMed

    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

    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

  19. In depth analysis of apoptosis induced by silica coated manganese oxide nanoparticles in vitro.

    PubMed

    Yu, Chao; Zhou, Zhiguo; Wang, Jun; Sun, Jin; Liu, Wei; Sun, Yanan; Kong, Bin; Yang, Hong; Yang, Shiping

    2015-02-11

    Manganese oxide nanoparticles (MnO NPs) have been regarded as a new class of T1-positive contrast agents. The cytotoxicity of silica coated MnO NPs (MnO@SiO2 NPs) was investigated in human cervical carcinoma cells (HeLa) and mouse fibroblast cells (L929). The changes of cell viability, cell morphology, cellular oxidative stress, mitochondrial membrane potential and cell cycle induced by MnO@SiO2 NPs were evaluated. Compared to HeLa cells, L929 cells showed lower cell viability, more strongly response to oxidative stress and higher percentage in the G2/M phase of cell cycle. The appearance of sub-G1 peak, double staining with Annexin V-FITC/PI and the increase of Caspase-3 activity further confirmed apoptosis should be the major form of cell death. Moreover, the apoptotic pathway was clarified as follows. Firstly, reactive oxygen species (ROS) is generated induced by MnO@SiO2 NPs, then p53 is activated followed by an increase in the bax and a decrease in the bcl-2, ultimately leading to G2/M phase arrest, increasing the activity of caspase-3 and inducing apoptosis. PMID:25464291

  20. Inhibition of antioxidants and hyperthermia enhance bleomycin-induced cytotoxicity and lipid peroxidation in Chinese hamster ovary cells.

    PubMed

    Khadir, A; Verreault, J; Averill, D A

    1999-10-15

    Regional hyperthermia has potential for human cancer treatment, particularly in combination with systemic chemotherapy or radiotherapy. Heat enhances the cytotoxic effect of certain anticancer agents such as bleomycin, but the mechanisms involved in cell killing are currently unknown. Bleomycin generates reactive oxygen species. It is likely that hyperthermia itself also increases oxidative stress in cells. We evaluate whether oxidative stress has a role in the mechanism of cell death caused by bleomycin and heat in Chinese hamster ovary cells. Heat (41 to 44 degrees C) increased cytotoxicity of bleomycin, evaluated by clonogenic cell survival. Decreased levels of cellular antioxidants should create an imbalance between prooxidant and antioxidant systems, thus enhancing cytotoxic responses to heat and to oxidant-generating drugs. We determine the involvement of four major cellular antioxidant defenses, superoxide dismutase (SOD), the glutathione redox cycle (GSH cycle), catalase, and glutathione S-transferase (GST), in cellular sensitivity to bleomycin, alone or combined with hyperthermia. These cellular defenses were inhibited by diethyldithiocarbamate, l-buthionine sulfoximine, aminotriazole, and ethacrynic acid, respectively. We show that levels of antioxidants (SOD, GSH cycle, and GST) affect cellular cytotoxic responses to bleomycin, at normal and elevated temperatures (41 to 44 degrees C), suggesting the involvement of oxidative stress. Bleomycin and iron caused oxidative damage to membrane lipids in intact cells, at 37 and 43 degrees C. Lipid peroxidation was evaluated by fluorescence detection of thiobarbituric acid-reactive products. There was an increase in damage to membrane lipids when the antioxidant defenses, SOD and catalase, were inhibited. The differing effects of antioxidant inhibitors on bleomycin-induced cytotoxicity and membrane lipid damage suggest that different mechanisms are involved in these two processes. However, free radicals appear to be involved in both cases. The marked sensitization of cells by diethyldithiocarbamate, to both bleomycin-induced cytotoxicity and lipid peroxidation, suggests that superoxide could be involved in both of these processes. PMID:10510274

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

    PubMed

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

    2014-03-25

    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

  2. Studies on mouse Moloney virus induced tumours: I. The detection of p30 as a cytotoxic target on murine Moloney leukaemic spleen cells, and on an in vitro Moloney sarcoma line by antibody mediated cytotoxicity.

    PubMed Central

    Epstein, L. B.; Knight, R. A.

    1975-01-01

    Antigenic determinants of p30, the most abundant internal virion protein of C type RNA viruses, were detected on the surface of spleen cells from mice bearing Moloney leukaemia and on an in vitro line of Moloney sarcoma, MSC. On both cell types, these determinants on the p30 molecules served as cytotoxic targets in a xenogenic complement dependent antibody mediated 51Cr release assay. Two antisera were used: a rat anti MLV -M induced lymphoma serum, and an antiserum raised in goats to either disrupted FeLV. The cytotoxic target antigens of these antisera were analysed by inhibition of cytotoxicity with viral and cellular proteins. PMID:50852

  3. The biology of cytotoxic cell granule exocytosis pathway: granzymes have evolved to induce cell death and inflammation.

    PubMed

    Pardo, Julián; Aguilo, Juan Ignacio; Anel, Alberto; Martin, Praxedis; Joeckel, Lars; Borner, Christoph; Wallich, Reiner; Müllbacher, Arno; Froelich, Christopher J; Simon, Markus M

    2009-04-01

    The granule exocytosis pathway of cytotoxic lymphocytes (Tc and NK cells) is critical for control of tumor development and viral infections. Granule-associated perforin and granzymes are key components in Tc cell-mediated function(s). On the basis of studies that showed granzymes A, B, C, K and M, to induce apoptosis in vitro, all granzymes were thought to also induce cell death in vivo. This review summarizes our present understanding of the biological processes elicited by purified granzyme A and granzyme as well as the processes induced by the more physiologically relevant cytotoxic cells secreting these proteases. The combined evidence supports the concept that the granule secretion pathway is not mono-specific but rather poly-functional including induction of pro-inflammatory cytokines, besides their widely appreciated apoptotic properties. PMID:19249384

  4. A possible role of oxidative stress in the vanadium-induced cytotoxicity in the MC3T3E1 osteoblast and UMR106 osteosarcoma cell lines

    Microsoft Academic Search

    Ana Mar??a Cortizo; Liliana Bruzzone; Silvina Molinuevo; Susana Beatriz Etcheverry

    2000-01-01

    The cytotoxicity and free radical production induced by vanadium compounds were investigated in an osteoblast (MC3T3E1) and an osteosarcoma (UMR106) cell lines in culture. Vanadate induced cell toxicity, reactive oxygen species (ROS) formation and thiobarbituric acid reactive substances (TBARS) increased in a concentration-dependent manner (0.1–10 mM) after 4 h. The concentration–response curve of vanadate-induced cytotoxicity and oxidative stress in MC3T3E1

  5. Light induced cytosolic drug delivery from liposomes with gold nanoparticles.

    PubMed

    Lajunen, Tatu; Viitala, Lauri; Kontturi, Leena-Stiina; Laaksonen, Timo; Liang, Huamin; Vuorimaa-Laukkanen, Elina; Viitala, Tapani; Le Guével, Xavier; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto

    2015-04-10

    Externally triggered drug release at defined targets allows site- and time-controlled drug treatment regimens. We have developed liposomal drug carriers with encapsulated gold nanoparticles for triggered drug release. Light energy is converted to heat in the gold nanoparticles and released to the lipid bilayers. Localized temperature increase renders liposomal bilayers to be leaky and triggers drug release. The aim of this study was to develop a drug releasing system capable of releasing its cargo to cell cytosol upon triggering with visible and near infrared light signals. The liposomes were formulated using either heat-sensitive or heat- and pH-sensitive lipid compositions with star or rod shaped gold nanoparticles. Encapsulated fluorescent probe, calcein, was released from the liposomes after exposure to the light. In addition, the pH-sensitive formulations showed a faster drug release in acidic conditions than in neutral conditions. The liposomes were internalized into human retinal pigment epithelial cells (ARPE-19) and human umbilical vein endothelial cells (HUVECs) and did not show any cellular toxicity. The light induced cytosolic delivery of calcein from the gold nanoparticle containing liposomes was shown, whereas no cytosolic release was seen without light induction or without gold nanoparticles in the liposomes. The light activated liposome formulations showed a controlled content release to the cellular cytosol at a specific location and time. Triggering with visual and near infrared light allows good tissue penetration and safety, and the pH-sensitive liposomes may enable selective drug release in the intracellular acidic compartments (endosomes, lysosomes). Thus, light activated liposomes with gold nanoparticles are an attractive option for time- and site-specific drug delivery into the target cells. PMID:25701610

  6. Synthetic wogonin derivatives suppress lipopolysaccharide-induced nitric oxide production and hydrogen peroxide-induced cytotoxicity

    Microsoft Academic Search

    Wanjoo Chun; Hee Jae Lee; Pil-Jae Kong; Gun Hee Lee; ll-Young Cheongsu; Sung-Soo Kim

    2005-01-01

    Wogonin (5,7-dihydroxy-8-methoxyflavone) has been reported to exhibit a variety of biological properties including anti-inflammatory\\u000a and neuroprotective functions. In this study, biological activities of diverse synthetic wogonin derivatives have been evaluated\\u000a in two experimental cell culture models. Inhibitory activities of wogonin derivatives on lipopolysaccharide (LPS)-induced\\u000a nitric oxide (NO) production in BV2 microglial cells and on hydrogen peroxide (H202)-induced neuronal cell death

  7. ALDEHYDE DEHYDROGENASE 3A1 PROTECTS AIRWAY EPITHELIAL CELLS FROM CIGARETTE SMOKE-INDUCED DNA DAMAGE AND CYTOTOXICITY

    PubMed Central

    Jang, Jun-Ho; Bruse, Shannon; Liu, Yushi; Duffy, Veronica; Zhang, Chunyu; Oyamada, Nathaniel; Randell, Scott; Matsumoto, Akiko; Thompson, David C.; Lin, Yong; Vasiliou, Vasilis; Tesfaigzi, Yohannes; Nyunoya, Toru

    2014-01-01

    Aldehyde dehydrogenase 3A1 (ALDH3A1), an ALDH superfamily member, catalyzes the oxidation of reactive aldehydes, highly toxic components of cigarette smoke (CS). Even so, the role of ALDH3A1 in CS-induced cytotoxicity and DNA damage has not been examined. Among all of the ALDH superfamily members, ALDH3A1 mRNA levels showed the greatest induction in response to CS extract (CSE) exposure of primary human bronchial epithelial cells (HBECs). ALDH3A1 protein accumulation was accompanied by increased ALDH enzymatic activity in CSE-exposed immortalized HBECs. The effects of overexpression or suppression of ALDH3A1 on CSE-induced cytotoxicity and DNA damage (?H2AX) were evaluated in cultured immortalized HBECs. Enforced expression of ALDH3A1 attenuated cytotoxicity and downregulated ?H2AX. siRNA-mediated suppression of ALDH3A1 blocked ALDH enzymatic activity and augmented cytotoxicity in CSE-exposed cells. Our results suggest that the availability of ALDH3A1 is important for cell survival against CSE in HBECs. PMID:24316006

  8. Laser induced nanoparticles and crystals and their characterization

    NASA Astrophysics Data System (ADS)

    Rezaee, Mohammadreza; Compton, Robert

    2014-03-01

    Intense nanosecond lasers are used to fabricate nanoparticles by direct laser solid interactions as well as laser produced shock wave induced crystallization in saturated solutions. In particular, laser graphite interactions under liquid nitrogen results in variety of interesting new carbon nanoclusters. In particular, exfoliation of graphite to produce graphene is considered. Laser produced shock wave in unsaturated salt (e.g. NaCl, NaClO3) solution immediately produces thousands of tiny crystals. These nonmaterials are examined using Raman spectroscopy under liquid nitrogen, RUN), laser induced fluorescence, plasma spectroscopy, UV-Vis spectroscopy as well as conventional characterization methods such as SEM and HRTEM imaging.

  9. Evaluation of antioxidative, protective effect against H 2O 2 induced cytotoxicity, and cytotoxic activities of three different Quercus species

    Microsoft Academic Search

    Didem ?öhreto?lu; Suna Sabuncuo?lu; Ü. ?ebnem Harput

    Quercus species are used as antidiarrheic, for the treatment of hemorrhoid, oral and anal mucosa inflammation. These tree species have been of interest to researchers because of their usage in folk medicine, consumption as food, beverage and especially usage of oak woods for construction in wine barrels. The DPPH, SO and NO radical scavenging activities, protective effect against H2O2 induced

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

    PubMed

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

    2011-07-01

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

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

    PubMed

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

    2006-04-01

    The chemopreventive and cytotoxic effect of ethanol extract of Bauhinia variegata (EBV) was evaluated in N-nitrosodiethylamine (DEN, 200 mg/kg) induced experimental liver tumor in rats and human cancer cell lines. Oral administration of ethanol extract of Bauhinia variegata (250 mg/kg) effectively suppressed liver tumor induced by DEN as revealed by decrease in DEN induced elevated levels of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO), glutathione peroxidase (GPx) and glutathione S-transferase (GST). The extract produced an increase in enzymatic antioxidant (superoxide dismutase and catalase) levels and total proteins when compared to those in liver tumor bearing rats. The histopathological changes of liver samples were compared with respective controls. EBV was found to be cytotoxic against human epithelial larynx cancer (HEp2) and human breast cancer (HBL-100) cells. These results show a significant chemopreventive and cytotoxic effect of ethanol extract of Bauhinia variegata against DEN induced liver tumor and human cancer cell lines. PMID:16257158

  12. Clostridium perfringens Phospholipase C Induced ROS Production and Cytotoxicity Require PKC, MEK1 and NF?B Activation

    PubMed Central

    Monturiol-Gross, Laura; Flores-Díaz, Marietta; Pineda-Padilla, Maria Jose; Castro-Castro, Ana Cristina; Alape-Giron, Alberto

    2014-01-01

    Clostridium perfringens phospholipase C (CpPLC), also called ?-toxin, is the most toxic extracellular enzyme produced by this bacteria and is essential for virulence in gas gangrene. At lytic concentrations, CpPLC causes membrane disruption, whereas at sublytic concentrations this toxin causes oxidative stress and activates the MEK/ERK pathway, which contributes to its cytotoxic and myotoxic effects. In the present work, the role of PKC, ERK 1/2 and NF?B signalling pathways in ROS generation induced by CpPLC and their contribution to CpPLC-induced cytotoxicity was evaluated. The results demonstrate that CpPLC induces ROS production through PKC, MEK/ERK and NF?B pathways, the latter being activated by the MEK/ERK signalling cascade. Inhibition of either of these signalling pathways prevents CpPLC's cytotoxic effect. In addition, it was demonstrated that NF?B inhibition leads to a significant reduction in the myotoxicity induced by intramuscular injection of CpPLC in mice. Understanding the role of these signalling pathways could lead towards developing rational therapeutic strategies aimed to reduce cell death during a clostridialmyonecrosis. PMID:24466113

  13. Dissecting the Mechanisms of Doxorubicin and Oxidative Stress-Induced Cytotoxicity: The Involvement of Actin Cytoskeleton and ROCK1

    PubMed Central

    Wei, Lei; Surma, Michelle; Gough, Gina; Shi, Stephanie; Lambert-Cheatham, Nathan; Chang, Jiang; Shi, Jianjian

    2015-01-01

    We have recently reported that ROCK1 deficiency in mouse embryonic fibroblasts (MEF) has superior anti-apoptotic and pro-survival effects than antioxidants against doxorubicin, a chemotherapeutic drug. Although oxidative stress is the most widely accepted mechanism, our studies suggest that ROCK1-dependent actin cytoskeleton remodeling plays a more important role in mediating doxorubicin cytotoxicity on MEFs. To further explore the contributions of ROCK1-dependent actin cytoskeleton remodeling in response to stress, this study investigates the mechanistic differences between the cytotoxic effects of doxorubicin versus hydrogen peroxide (H2O2), with a focus on cytoskeleton alterations, apoptosis and necrosis induction. We found that both types of stress induce caspase activation but with different temporal patterns and magnitudes in MEFs: H2O2 induces the maximal levels (2 to 4-fold) of activation of caspases 3, 8, and 9 within 4 h, while doxorubicin induces much higher maximal levels (15 to 25-fold) of caspases activation at later time points (16–24 h). In addition, necrosis induced by H2O2 reaches maximal levels within 4 h while doxorubicin-induced necrosis largely occurs at 16–24 h secondary to apoptosis. Moreover, both types of stress induce actin cytoskeleton remodeling but with different characteristics: H2O2 induces disruption of stress fibers associated with cytosolic translocation of phosphorylated myosin light chain (p-MLC) from stress fibers, while doxorubicin induces cortical F-actin formation associated with cortical translocation of p-MLC from central stress fibers. Furthermore, N-acetylcysteine (an antioxidant) is a potent suppressor for H2O2-induced cytotoxic effects including caspase activation, necrosis, and cell detachment, but shows a much reduced inhibition on doxorubicin-induced changes. On the other hand, ROCK1 deficiency is a more potent suppressor for the cytotoxic effects induced by doxorubicin than by H2O2. These results support the notion that doxorubicin induces caspase activation, necrosis, and actin cytoskeleton alterations largely through ROCK1-dependent and oxidative stress-independent pathways. PMID:26134406

  14. Template-Induced Structure Transition in Sub-10 nm Self-Assembling Nanoparticles

    E-print Network

    Cao, Jianshu

    Template-Induced Structure Transition in Sub-10 nm Self- Assembling Nanoparticles Mohamed Asbahi-assembly of sub-10 nm gold nanoparticles confined within a template comprising channels of gradually varying widths. When the colloidal lattice parameter is mismatched with the channel width, the nanoparticles

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

    PubMed

    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

    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

  16. Depletion-induced shape and size selection of gold nanoparticles.

    PubMed

    Park, Kyoungweon; Koerner, Hilmar; Vaia, Richard A

    2010-04-14

    For nanoparticle-based technologies, efficient and rapid approaches that yield particles of high purity with a specific shape and size are critical to optimize the nanostructure-dependent optical, electrical, and magnetic properties, and not bias conclusions due to the existence of impurities. Notwithstanding the continual improvement of chemical methods for shaped nanoparticle synthesis, byproducts are inevitable. Separation of these impurities may be achieved, albeit inefficiently, through repeated centrifugation steps only when the sedimentation coefficient of the species shows sufficient contrast. We demonstrate a robust and efficient procedure of shape and size selection of Au nanoparticles (NPs) through the formation of reversible flocculates by surfactant micelle induced depletion interaction. Au NP flocculates form at a critical surfactant micelle molar concentration, C(m)* where the number of surfactant micelles is sufficient to induce an attractive potential energy between the Au NPs. Since the magnitude of this potential depends on the interparticle contact area of Au NPs, separation is achieved even for the NPs of the same mass with different shape by tuning the surfactant concentration and extracting flocculates from the sediment by centrifugation or gravitational sedimentation. The refined NPs are redispersed by subsequently decreasing the surfactant concentration to reduce the effective attractive potential. These concepts provide a robust method to improve the quality of large scale synthetic approaches of a diverse array of NPs, as well as fine-tune interparticle interactions for directed assembly, both crucial challenges to the continual realization of the broad technological potential of monodispersed NPs. PMID:20349972

  17. Naturally produced citral can significantly inhibit normal physiology and induce cytotoxicity on Magnaporthe grisea.

    PubMed

    Li, Rong-Yu; Wu, Xiao-Mao; Yin, Xian-Hui; Long, You-Hua; Li, Ming

    2015-02-01

    Given the importance of finding alternatives to synthetic fungicides, the antifungal effects of natural product citral on six plant pathogenic fungi (Magnaporthe grisea, Gibberella zeae, Fusarium oxysporum, Valsa mali, Botrytis cinerea, and Rhizoctonia solani) were determined. Mycelial growth rate results showed that citral possessed high antifungal activities on those test fungi with EC50 values ranging from 39.52 to 193.00?µg/mL, which had the highest inhibition rates against M. grisea. Further action mechanism of citral on M. grisea was carried out. Citral treatment was found to alter the morphology of M. grisea hyphae by causing a loss of cytoplasm and distortion of mycelia. Moreover, citral was able to induce an increase in chitinase activity in M. grisea, indicating disruption of the cell wall. These results indicate that citral may act by disrupting cell wall integrity and membrane permeability, thus resulting in physiology changes and causing cytotoxicity. Importantly, the inhibitory effect of citral on M. grisea appears to be associated with its effects on mycelia reducing sugar, soluble protein, chitinase activity, pyruvate content, and malondialdehyde content. PMID:25752425

  18. Isoflavone lupiwighteone induces cytotoxic, apoptotic, and antiangiogenic activities in DU-145 prostate cancer cells.

    PubMed

    Ren, Jie; Huang, Qianhui; Xu, Yuanyuan; Yang, Meng; Yang, Jie; Hu, Kun

    2015-07-01

    Isoflavones constitute a large series of compounds found in many plants. They make up an important part of the diet and have a broad spectrum of biological activities such as cytotoxic and antitumor effects. Lupiwighteone (Lup) is an isoflavone-type compound. It is distributed widely in wild-growing plants such as Glycyrrhiza glabra, Lupinus, and Lotus pedunculatus. On the basis of existing research, Lup shows antioxidant and antimicrobial effects, but its antitumor activity has not been reported as yet. This study aimed to examine the antitumor activity of Lup, explore its antitumor mechanism in a human prostate carcinoma cell line (DU-145), and evaluate its antiangiogenetic activity in the human umbilical vein endothelial cell line (HUVEC). The results showed that Lup could inhibit the growth of DU-145 and HUVEC cells in a concentration-dependent and time-dependent manner by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis indicated that Lup could induce cell cycle arrest, cells apoptosis, mitochondrial membrane potential loss, and an increase in intracellular reactive oxygen species of DU-145 cells. Upregulation of Bax, cytochrome c, caspase-3, and PARP-1 protein expressions and downregulation of Bcl-2, procaspase-9, and p-Akt protein expressions were observed by western blot after the treatment of Lup. Furthermore, the effects of Lup on the cellular behavior of HUVECs were also investigated. Altogether, our data proved the anticancer and antiangiogenesis potential of Lup. PMID:25734831

  19. Multi-Walled Carbon Nanotubes Induce Cytotoxicity, Genotoxicity And Apoptosis In Normal Human Dermal Fibroblast Cells

    PubMed Central

    Knighten, Brionna; Tchounwou, Paul

    2010-01-01

    Multi walled carbon nanotubes [MWCNT's] have won enormous popularity in nanotechnology. Due to their unusual one dimensional, hollow nanostructure and unique physicochemical properties they are highly desirable for use within the commercial, environmental and medical sectors. Despite their wide application, there is a lack of information concerning their impact on human health and the environment. While nanotechnology looms large with commercial promise and potential benefit, an equally large issue is the evaluation of potential effects on humans and other biological systems. Our research is focused on cellular response to purified MWCNT in normal human dermal fibroblast cells (NHDF). Three doses (40, 200, 400 ?g/ml) of MWCNT and control (tween-80 + 0.9% saline) were used in this study. Following exposure to MWCNT, cytotoxicity, genotoxicity and apoptosis assays were performed using standard protocols. Our results demonstrated a dose-dependent toxicity with MWCNT. It was found to be toxic and induced massive loss of cell viability through DNA damage and programmed cell-death of all doses compared to control. Our results demonstrate that carbon nanotubes indeed can be very toxic at sufficiently high concentrations and that careful monitoring of toxicity studies is essential for risk assessment. PMID:20521388

  20. Multigenerational Study of Chemically Induced Cytotoxicity and Proliferation in Cultures of Human Proximal Tubular Cells

    PubMed Central

    Lash, Lawrence H.; Putt, David A.; Benipal, Bavneet

    2014-01-01

    Primary cultures of human proximal tubular (hPT) cells are a useful experimental model to study transport, metabolism, cytotoxicity, and effects on gene expression of a diverse array of drugs and environmental chemicals because they are derived directly from the in vivo human kidney. To extend the model to investigate longer-term processes, primary cultures (P0) were passaged for up to four generations (P1–P4). hPT cells retained epithelial morphology and stained positively for cytokeratins through P4, although cell growth and proliferation successively slowed with each passage. Necrotic cell death due to the model oxidants tert-butyl hydroperoxide (tBH) and methyl vinyl ketone (MVK) increased with increasing passage number, whereas that due to the selective nephrotoxicant S-(1,2-dichlorovinyl)-l-cysteine (DCVC) was modest and did not change with passage number. Mitochondrial activity was lower in P2–P4 cells than in either P0 or P1 cells. P1 and P2 cells were most sensitive to DCVC-induced apoptosis. DCVC also increased cell proliferation most prominently in P1 and P2 cells. Modest differences with respect to passage number and response to DCVC exposure were observed in expression of three key proteins (Hsp27, GADD153, p53) involved in stress response. Hence, although there are some modest differences in function with passage, these results support the use of multiple generations of hPT cells as an experimental model. PMID:25411799

  1. Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death.

    PubMed

    Armstrong, Jane L; Hill, David S; McKee, Christopher S; Hernandez-Tiedra, Sonia; Lorente, Mar; Lopez-Valero, Israel; Eleni Anagnostou, Maria; Babatunde, Fiyinfoluwa; Corazzari, Marco; Redfern, Christopher P F; Velasco, Guillermo; Lovat, Penny E

    2015-06-01

    Although the global incidence of cutaneous melanoma is increasing, survival rates for patients with metastatic disease remain <10%. Novel treatment strategies are therefore urgently required, particularly for patients bearing BRAF/NRAS wild-type tumors. Targeting autophagy is a means to promote cancer cell death in chemotherapy-resistant tumors, and the aim of this study was to test the hypothesis that cannabinoids promote autophagy-dependent apoptosis in melanoma. Treatment with ?(9)-Tetrahydrocannabinol (THC) resulted in the activation of autophagy, loss of cell viability, and activation of apoptosis, whereas cotreatment with chloroquine or knockdown of Atg7, but not Beclin-1 or Ambra1, prevented THC-induced autophagy and cell death in vitro. Administration of Sativex-like (a laboratory preparation comprising equal amounts of THC and cannabidiol (CBD)) to mice bearing BRAF wild-type melanoma xenografts substantially inhibited melanoma viability, proliferation, and tumor growth paralleled by an increase in autophagy and apoptosis compared with standard single-agent temozolomide. Collectively, our findings suggest that THC activates noncanonical autophagy-mediated apoptosis of melanoma cells, suggesting that cytotoxic autophagy induction with Sativex warrants clinical evaluation for metastatic disease. PMID:25674907

  2. Reactive oxygen species-mediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells

    Microsoft Academic Search

    Qiong Wang; Xue-lian Zheng; Lan Yang; Fang Shi; Lin-bo Gao; Ying-jia Zhong; Hong Sun; Fan He; Yong Lin; Xia Wang

    2010-01-01

    BACKGROUND: Saikosaponin-a and -d, two naturally occurring compounds derived from Bupleurum radix, have been shown to exert anti-cancer activity in several cancer cell lines. However, the effect of combination of saikosaponins with chemotherapeutic drugs has never been addressed. Thus, we investigated whether these two saikosaponins have chemosensitization effect on cisplatin-induced cancer cell cytotoxicity. METHODS: Two cervical cancer cell lines, HeLa

  3. Inhibition of nuclear factor-kappa B activation attenuates hydrogen peroxide-induced cytotoxicity in human lens epithelial cells

    Microsoft Academic Search

    Xue-Hai Jin; Kazuhiro Ohgami; Kenji Shiratori; Yoshikazu Koyama; Kazuhiko Yoshida; Satoru Kase; Shigeaki Ohno

    2007-01-01

    Aims: Hydrogen peroxide (H2O2) is the major oxidant involved in cataract formation. Lens epithelial cells have been suggested to be the first site of oxidative damage. The authors investigated the relationship between H2O2-induced cytotoxicity and activation of nuclear factor kappa B (NF-?B) in human lens epithelial (HLE) cells.Methods: HLE B-3 cells were stimulated by various concentrations of H2O2 in the

  4. Evaluation of 51Cr release for detecting cell-mediated cytotoxic responses to solid chemically induced rat tumours

    Microsoft Academic Search

    M Zöller; M R Price; R W Baldwin

    1977-01-01

    A 51Cr-release test was developed for the detection of cell-mediated cytotoxicity against transplanted solid chemically induced rat tumours, and the findings were compared with those obtained in parallel tests using a microcytotoxicity assay. It was necessary to incorporate several modifications of the original Brunner assay (Brunner et al., 1968) in order to increase the sensitivity of the test as applied

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

    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.

  6. Spongean alkaloids protect rat kidney cells against cisplatin-induced cytotoxicity.

    PubMed

    Funk, Florian; Krüger, Katharina; Henninger, Christian; Wätjen, Wim; Proksch, Peter; Thomale, Jürgen; Fritz, Gerhard

    2014-09-01

    Nephrotoxicity is the major dose-limiting adverse effect of cisplatin (CisPt) and results from CisPt-induced damage of tubular cells. Nephroprotective strategies are preferential to improve supportive care in cancer. We investigated a subset of purified substances originating from various plants or from marine sponges as to their potency to protect rat renal tubular cells (NRK-52E) against the cytotoxic and genotoxic effects of cisplatin. Cotreatment with a substance pool containing five purified substances originating from marine sponges increased the viability of NRK-52E cells following cisplatin treatment. Cytoprotection was accompanied by a reduced level of DNA damage as indicated by a lower amount of S139 phosphorylated histone H2AX (?H2AX) 24 h after treatment. Cytoprotection and genoprotection by the sponge substance pool did not comprise the anthracycline derivative doxorubicin. The spongean alkaloid aaptamine was identified as major bioactive compound that mediates cisplatin resistance. Aeroplysinin-1 was less cytoprotective than aaptamine. Notably, aaptamine preferentially conferred resistance to cisplatin, but not to oxaliplatin. Cytoprotection by aaptamine was also observed in rat glomerular endothelial cells, but not in RT-112 bladder cancer cells. Protection by aaptamine does not rest on a reduced formation of DNA damage caused by cisplatin treatment. Aaptamine and aeroplysinin-1 affected cisplatin-stimulated DDR as reflected on the level of S15-phosphorlyated p53 and S345-phosphorylated checkpoint kinase-1. Summarizing, the spongean alkaloid aaptamine alleviates cisplatin-induced damage in tubular and glomerular rat kidney cells. Therefore, we hypothesize that aaptamine might be useful to widen the therapeutic window of a cisplatin-based therapeutic regimen. PMID:24820908

  7. Urethane dimethacrylate induces cytotoxicity and regulates cyclooxygenase-2, hemeoxygenase and carboxylesterase expression in human dental pulp cells.

    PubMed

    Chang, Hsiao-Hua; Chang, Mei-Chi; Wang, Hsin-Hui; Huang, Guay-Fen; Lee, Yuan-Ling; Wang, Yin-Lin; Chan, Chiu-Po; Yeung, Sin-Yuet; Tseng, Shuei-Kuen; Jeng, Jiiang-Huei

    2014-02-01

    The toxic effect of urethane dimethacrylate (UDMA), a major dental resin monomer, on human dental pulp is not fully clear. In this study, we investigated the influence of UDMA on the cytotoxicity, cell cycle distribution, apoptosis and related gene expression of dental pulp cells. The role of reactive oxygen species, hemeoxygenase-1 (HO-1) and carboxylesterase (CES) in UDMA cytotoxicity, was evaluated. UDMA induced morphological changes of pulp cells and decreased cell viability by 29-49% at concentrations of 0.1-0.35 mM. UDMA induced G0/G1, G2/M cell cycle arrest and apoptosis. The expression of cdc2, cyclinB1 and cdc25C was inhibited by UDMA. Moreover, UDMA stimulated COX-2, HO-1 and CES2 mRNA expression of pulp cells. The cytotoxicity of UDMA was attenuated by N-acetyl-l-cysteine, catalase and esterase, but was enhanced by Zn-protoporphyrin (HO-1 inhibitor), BNPP (CES inhibitor) and loperamide (CES2 inhibitor). Exposure of UDMA may potentially induce the inflammation and toxicity of dental pulp. These findings are important for understanding the clinical response of human pulp to resin monomers after operative restoration and pulp capping, and also provide clues for improvement of dental materials. PMID:24140606

  8. Cytotoxicity of ZnO Nanoparticles Can Be Tailored by Modifying Their Surface Structure: A Green Chemistry Approach for Safer Nanomaterials.

    PubMed

    Punnoose, Alex; Dodge, Kelsey; Rasmussen, John W; Chess, Jordan; Wingett, Denise; Anders, Catherine

    2014-07-01

    ZnO nanoparticles (NP) are extensively used in numerous nanotechnology applications; however, they also happen to be one of the most toxic nanomaterials. This raises significant environmental and health concerns and calls for the need to develop new synthetic approaches to produce safer ZnO NP, while preserving their attractive optical, electronic, and structural properties. In this work, we demonstrate that the cytotoxicity of ZnO NP can be tailored by modifying their surface-bound chemical groups, while maintaining the core ZnO structure and related properties. Two equally sized (9.26 ± 0.11 nm) ZnO NP samples were synthesized from the same zinc acetate precursor using a forced hydrolysis process, and their surface chemical structures were modified by using different reaction solvents. X-ray diffraction and optical studies showed that the lattice parameters, optical properties, and band gap (3.44 eV) of the two ZnO NP samples were similar. However, FTIR spectroscopy showed significant differences in the surface structures and surface-bound chemical groups. This led to major differences in the zeta potential, hydrodynamic size, photocatalytic rate constant, and more importantly, their cytotoxic effects on Hut-78 cancer cells. The ZnO NP sample with the higher zeta potential and catalytic activity displayed a 1.5-fold stronger cytotoxic effect on cancer cells. These results suggest that by modifying the synthesis parameters/conditions and the surface chemical structures of the nanocrystals, their surface charge density, catalytic activity, and cytotoxicity can be tailored. This provides a green chemistry approach to produce safer ZnO NP. PMID:25068096

  9. Cytotoxicity of ZnO Nanoparticles Can Be Tailored by Modifying Their Surface Structure: A Green Chemistry Approach for Safer Nanomaterials

    PubMed Central

    2015-01-01

    ZnO nanoparticles (NP) are extensively used in numerous nanotechnology applications; however, they also happen to be one of the most toxic nanomaterials. This raises significant environmental and health concerns and calls for the need to develop new synthetic approaches to produce safer ZnO NP, while preserving their attractive optical, electronic, and structural properties. In this work, we demonstrate that the cytotoxicity of ZnO NP can be tailored by modifying their surface-bound chemical groups, while maintaining the core ZnO structure and related properties. Two equally sized (9.26 ± 0.11 nm) ZnO NP samples were synthesized from the same zinc acetate precursor using a forced hydrolysis process, and their surface chemical structures were modified by using different reaction solvents. X-ray diffraction and optical studies showed that the lattice parameters, optical properties, and band gap (3.44 eV) of the two ZnO NP samples were similar. However, FTIR spectroscopy showed significant differences in the surface structures and surface-bound chemical groups. This led to major differences in the zeta potential, hydrodynamic size, photocatalytic rate constant, and more importantly, their cytotoxic effects on Hut-78 cancer cells. The ZnO NP sample with the higher zeta potential and catalytic activity displayed a 1.5-fold stronger cytotoxic effect on cancer cells. These results suggest that by modifying the synthesis parameters/conditions and the surface chemical structures of the nanocrystals, their surface charge density, catalytic activity, and cytotoxicity can be tailored. This provides a green chemistry approach to produce safer ZnO NP. PMID:25068096

  10. Pentoxifylline: a potent inhibitor of IL-2 and IFN-gamma biosynthesis and BCG-induced cytotoxicity.

    PubMed Central

    Thanhäuser, A; Reiling, N; Böhle, A; Toellner, K M; Duchrow, M; Scheel, D; Schlüter, C; Ernst, M; Flad, H D; Ulmer, A J

    1993-01-01

    In the present study we investigated the influence of pentoxifylline (POF) on bacillus Calmette-Guérin (BCG)- and phytohaemagglutinin (PHA)-induced DNA synthesis and cytokine release, and BCG-induced cytotoxicity of human peripheral blood mononuclear cells (PBMC). DNA synthesis of PBMC stimulated with either BCG or PHA was inhibited by POF. We also demonstrated that the addition of POF led to a POF dose-dependent decrease of the release of the cytokines interleukin (IL)-2, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). The release of IL-6 remained unaffected. With respect to the inhibition of BCG-induced IL-2 and IFN-gamma release POF is active at the transcriptional (mRNA) level, as found by polymerase chain reaction (PCR). However, PHA-induced mRNA expression of these lymphokines is not affected by POF. Thus, the existence of a post-transcriptional regulation of PHA-induced cytokine release by POF can be assumed. The observed inhibition of cytokine release is correlated with a potent inhibitory effect of POF on BCG-induced cytotoxicity against bladder tumour cell lines. This effect is reversible. Images Figure 3 Figure 4 PMID:8244458

  11. Pentoxifylline: a potent inhibitor of IL-2 and IFN-gamma biosynthesis and BCG-induced cytotoxicity.

    PubMed

    Thanhäuser, A; Reiling, N; Böhle, A; Toellner, K M; Duchrow, M; Scheel, D; Schlüter, C; Ernst, M; Flad, H D; Ulmer, A J

    1993-09-01

    In the present study we investigated the influence of pentoxifylline (POF) on bacillus Calmette-Guérin (BCG)- and phytohaemagglutinin (PHA)-induced DNA synthesis and cytokine release, and BCG-induced cytotoxicity of human peripheral blood mononuclear cells (PBMC). DNA synthesis of PBMC stimulated with either BCG or PHA was inhibited by POF. We also demonstrated that the addition of POF led to a POF dose-dependent decrease of the release of the cytokines interleukin (IL)-2, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). The release of IL-6 remained unaffected. With respect to the inhibition of BCG-induced IL-2 and IFN-gamma release POF is active at the transcriptional (mRNA) level, as found by polymerase chain reaction (PCR). However, PHA-induced mRNA expression of these lymphokines is not affected by POF. Thus, the existence of a post-transcriptional regulation of PHA-induced cytokine release by POF can be assumed. The observed inhibition of cytokine release is correlated with a potent inhibitory effect of POF on BCG-induced cytotoxicity against bladder tumour cell lines. This effect is reversible. PMID:8244458

  12. Lindane-induced cytotoxicity and the role of vitamin E in Chinese Hamster Ovary (CHO-K1) cells.

    PubMed

    Kmetic, Ivana; Radosevi?, Kristina; Murati, Teuta; Simi?, Branimir; Kniewald, Zlatko; Kniewald, Jasna

    2009-10-01

    Lindane, a toxic insecticide from the persistent organic pollutants (POP's) group, may act as an endocrine disrupter affecting crucial tissues of reproductive system. In this study a Chinese Hamster Ovary cell line (CHO-K1) was applied to assess the potential of lindane cytotoxicity at the cellular level. The methods of Trypan blue exclusion, MTT and Kenacid blue assays were used to assess cytotoxicity and confirmed a decrease in the number of viable CHO-K1 cells at 34.4-344 microM lindane during 24, 48 and 72 hours of exposure. The cell proliferation tests showed significant inhibition (p < 0.025-0.001 vs control) and a progressive increase in toxicity with increasing lindane concentrations. Corresponding IC(50) values were determined with each applied method. After 72 h of lindane exposure, IC(50) values were 184 microM according to the Trypan blue method and 272 and 256 microM with the Kenacid blue and MTT assays, respectively. Morphological changes induced by the cytotoxicity of lindane were followed by the fluorescence microscopy and only necrotic cells were detected. Vitamin E (25 and 50 microg/mL) was used for protection of ovarian cells against lidane-induced oxidative stress damage, and lipid peroxidation was postulated as a possible mechanism of lindane toxicity. The viability of cells pre-incubated with vitamin E was significantly enhanced (up to p < 0.025) compared to the results observed in cells exposed to lindane only, but vitamin E treatment could not prevent complete lindane-induced cytotoxicity. Results suggest that vitamin E may exert a slightly protective role in cell defense against lipophilic pro-oxidant xenobiotics such as lindane. PMID:19788352

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

    PubMed Central

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

    2012-01-01

    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. PMID:22514708

  14. In vivo and cytotoxicity evaluation of repaglinide-loaded binary solid lipid nanoparticles after oral administration to rats.

    PubMed

    Rawat, Manoj K; Jain, Achint; Singh, Sanjay

    2011-06-01

    The purpose of this work was to develop prolonged release binary lipid matrix-based solid lipid nanoparticles (SLN) of repaglinide (RG) for oral intestinal delivery and to improve the bioavailability of RG. SLN were designed by using glycerol monostearate and tristearin as lipid core materials and Pluronic-F68 as stabilizer. SLN were characterised by their particle size, zeta potential, entrapment efficiency, solid-state studies, in vitro drug release, particle surface and storage stability at 30 °C/65% relative humidity for 3 months. Pharmacodynamic (PD) and pharmacokinetic (PK) studies were also performed in diabetes-induced rat. Moreover, an in vitro toxicity study was performed in rat macrophage cells to establish the safety of the prepared SLN. It was observed that binary lipid matrix-based SLN had better drug entrapment, desired release characteristics, spherical shape and maximum storage stability. Pharmacodynamic study indicated that RG delivered through binary SLN significantly reduces blood glucose, blood cholesterol and blood triglycerides level. The area under the curves after oral administration of optimised RG-SLN formulation and RG control were 113.36 ± 3.01 and 08.08 ± 1.98 h/(ng · mL), respectively. The relative bioavailability of RG was enhanced with optimised SLN formulation when compared with RG control. There was a direct correlation found between the plasma drug level (drug concentration) and the peak response (% blood glucose inhibition) in optimised RG-SLN batch. The in vitro toxicity study indicated that the SLN were well tolerated. PMID:21491451

  15. A Vault Nanoparticle Vaccine Induces Protective Mucosal Immunity

    PubMed Central

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

    2009-01-01

    Background Generation of robust cell-mediated immune responses at mucosal surfaces while reducing overall inflammation is a primary goal for vaccination. Here we report the use of a recombinant nanoparticle as a vaccine delivery platform against mucosal infections requiring T cell-mediated immunity for eradication. Methodology/Principal Findings We encapsulated an immunogenic protein, the major outer membrane protein (MOMP) of Chlamydia muridarum, within hollow, vault nanocapsules (MOMP-vaults) that were engineered to bind IgG for enhanced immunity. Intranasal immunization (i.n) with MOMP-vaults induced anti-chlamydial immunity plus significantly attenuated bacterial burden following challenge infection. Vault immunization induced anti-chlamydial immune responses and inflammasome formation but did not activate toll-like receptors. Moreover, MOMP-vault immunization enhanced microbial eradication without the inflammation usually associated with adjuvants. Conclusions/Significance Vault nanoparticles containing immunogenic proteins delivered to the respiratory tract by the i.n. route can act as “smart adjuvants” for inducing protective immunity at distant mucosal surfaces while avoiding destructive inflammation. PMID:19404403

  16. Aralin, a new cytotoxic protein from Aralia elata, inducing apoptosis in human cancer cells

    Microsoft Academic Search

    Makoto Tomatsu; Mayumi Ohnishi-Kameyama; Norio Shibamoto

    2003-01-01

    In this study, we purified a novel cytotoxic protein, aralin, from the shoots of Aralia elata. Aralin is composed of two subunits, A and B chains whose molecular weights are 29,100 and 32,200, respectively. In the assay using a normal human lung fibroblast cells (WI-38) and its SV40-transformed cells (VA-13), aralin demonstrated selective cytotoxicity against the virus-transformed cell line; the

  17. Gold nanoparticle sensor for homocysteine thiolactone-induced protein modification.

    PubMed

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

    2008-04-15

    Homocysteine thiolactone-induced protein modification (HTPM) is a unique post-translational protein modification that is recognized as an emergent biomarker for cardiovascular disease. HTPM involves the site-specific acylation of proteins at lysine residues by homocysteine thiolactone (HTL) to produce protein homocystamide, which has been found at elevated levels in patients with coronary heart disease. Herein, we report the development of a novel gold nanoparticle (GNP) biochemical sensor for detection of protein homocystamide in an in vitro serum protein-based model system. Human serum albumin (HSA) and human sera were subjected to HTPM in vitro to produce HSA-homocystamide or serum protein homocystamide, respectively, which was subsequently treated with citrate-capped GNPs. This GNP sensor typically provided instantaneous visual confirmation of HTPM in the protein model systems. Transmission electron microscopy images of the GNPs in the presence of HSA-homocystamide suggest that modification-directed nanoparticle assembly is the mechanism by which the biochemical sensor produces a colorimetric signal. The resultant nanoparticle-protein assembly exhibited excellent thermal and dilutional stability, which is expected for a system stabilized by chemisorption and intermolecular disulfide bonding. The sensor typically provided a linear response for modified human sera concentrations greater than approximately 5 mg/mL. The calculated limit of detection and calibration sensitivity for the method in human sera were 5.2 mg/mL and 13.6 AU . (microg/mL)-1, respectively. PMID:18324853

  18. Cytotoxicity, oxidative stress and genotoxicity induced by glass fibers on human alveolar epithelial cell line A549.

    PubMed

    Rapisarda, Venerando; Loreto, Carla; Ledda, Caterina; Musumeci, Giuseppe; Bracci, Massimo; Santarelli, Lory; Renis, Marcella; Ferrante, Margherita; Cardile, Venera

    2015-04-01

    Man-made vitreous fibers have been widely used as insulation material as asbestos substitutes; however their morphology and composition raises concerns. In 1988 the International Agency for Research on Cancer classified fiberglass, rock wool, slag wool, and ceramic fibers as Group 2B, i.e. possibly carcinogenic to humans. In 2002 it reassigned fiberglass, rock and slag wool, and continuous glass filaments to Group 3, not classifiable as carcinogenic to humans. The aim of this study was to verify the cytotoxic and genotoxic effects and oxidative stress production induced by in vitro exposure of human alveolar epithelial cells A549 to glass fibers with a predominant diameter <3 ?m (97%) and length >5 ?m (93%). A549 cells were incubated with 5, 50, or 100 ?g/ml (2.1, 21, and 42 ?g/cm(2), respectively) of glass fibers for 72 h. Cytotoxicity and DNA damage were tested by the MTT and the Comet assay, respectively. Oxidative stress was determined by measuring inducible nitric oxide synthase (iNOS) expression by Western blotting, production of nitric oxide (NO) with Griess reagent, and concentration of reactive oxygen species by fluorescent quantitative analysis with 2',7'-dichlorofluorescein-diacetate (DCFH-DA). The results showed that glass fiber exposure significantly reduced cell viability and increased DNA damage and oxidative stress production in a concentration-dependent manner, demonstrating that glass fibers exert cytotoxic and genotoxic effects related to increased oxidative stress on the human alveolar cell line A549. PMID:25620604

  19. A NEW POLYMER-LIPID HYBRID NANOPARTICLE SYSTEM INCREASES CYTOTOXICITY OF DOXORUBICIN AGAINST MULTIDRUG-RESISTANT HUMAN BREAST CANCER CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This work is intended to develop and evaluate a new polymer-lipid hybrid nanoparticle system that can efficiently load and release water-soluble anticancer drug doxorubicin hydrochloride (Dox) and enhance Dox toxicity against multidrug-resistant (MDR) cancer cells. Dox loaded nanoparticles (Dox-SLN...

  20. Analysis of laser-induced breakdown images measuring the sizes of mixed aquatic nanoparticles

    Microsoft Academic Search

    J. W. Kim; J. A. Son; J. I. Yun; E. C. Jung; S. H. Park; J. G. Choi

    2008-01-01

    Sizes of aquatic colloidal nanoparticles are determined by utilizing the laser-induced breakdown detection technique. Specifically, the number of breakdown events is measured as a function of area in laser-induced plasma images, generated from a mixture of two different size nanoparticles in aqueous solution, by minimizing the energy of the incident laser irradiation to generate the plasma. We find that the

  1. Alloantigen-induced cytotoxicity against syngeneic tumor cells: analysis at the clonal level.

    PubMed

    Sensi, M; Orosz, C G; Bach, F H

    1984-06-01

    It has been shown that peritoneal exudate cells (PEC) from BALB/c mice immunized with minor histocompatibility antigens presented by DBA/2 or B10.D2 spleen cells are capable of lysing syngeneic YC8 tumor cells in a 4-hr 51Cr-release assay. In this study, we employed limiting dilution analysis to determine the frequency of CTL precursors (CTL-P) reactive against both the specific DBA/2 (or P815) target and the syngeneic tumor YC8. The mean frequency of anti-DBA/2 CTL-P in PEC from BALB/c mice immunized with DBA/2 was 1/302. Between one-third and one-fifth of limiting dilution microcultures that exhibited lytic activity against DBA/2 lymphoblasts (or P815) were also able to lyse YC8. No lysis of YC8 was observed in the absence of a parallel lysis on DBA/2 lymphoblasts or P815 target cells. T cell clones, derived by micromanipulation from microcultures selected for cytotoxic activity against YC8 and/or P815, maintained either the specific anti-allogeneic or the doubly reactive ( antiallogeneic plus anti-syngeneic tumor) phenotype. Fourteen clones (six specific and eight doubly reactive) were tested for cytotoxic activity on a panel of target cells with different haplotypes. All showed H-2-restricted specificity for minor histocompatibility antigens shared by DBA/2 and B10.D2. The restriction element for some of the clones mapped in the K region of the H-2 complex, whereas for other clones the restriction element mapped in the D region; both K- and D-restricted clones were able to lyse YC8. When the clones that exhibited lysis on YC8 were tested on two other BALB/c tumor targets, LSTRA, a Moloney virus induced lymphoma, and RL male-1, a radiation induced lymphoma, two of seven were found to lyse all three syngeneic tumor targets equally well, but not syngeneic BALB/c blasts. These clones were functionally categorized as conventional CTL because they were unable to proliferate when cultured with antigen in the absence of exogenous lymphokines, and were unable to produce lymphokine with IL 2 activity when stimulated by the appropriate splenocytes. When tested in vivo in a Winn assay, a strong anti-tumor activity against YC8 was exerted by the anti-DBA/2 clones DY4 -3 and DY16 -3. These clones lysed both YC8 and the immunizing target cells in vitro. No in vivo effect in neutralizing YC8 tumor growth was observed with clone D2-1, a clone that lysed DBA/2 targets but not YC8 in vitro. PMID:6202778

  2. Natural plant extract tubeimoside I induces cytotoxicity via the mitochondrial pathway in human normal liver cells.

    PubMed

    Wang, Yashu; Deng, Linhong; Wang, Yajie; Zhong, Hongzhe; Jiang, Xuemei; Chen, Jun

    2011-01-01

    Tubeimoside I (TBMS I) is a natural compound extracted from Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae), a traditional Chinese herbal medicine widely used for the treatment of inflammation. Recently, it has been suggested that TBMS I may be a potent anticancer agent for a variety of human cancers. However, TBMS I is known to distribute preferentially in the liver, and thus may harm normal liver cells if it is delivered systemically for cancer treatment. This safety concern warrants careful evaluation of the hepatotoxicity of TBMS I to normal liver cells, which to date has not been carried out. Here, we report the cytotoxic effects of TBMS I on one type of normal liver cells (L-02 cells), and the associated molecular events as underlying mechanisms. Cultured human normal liver L-02 cells were treated with TBMS I at concentrations of 0, 15 and 30 µM for 24, 48 and 72 h, respectively. Subsequently, the cell survival rate was evaluated by the MTT dye method, and several key molecular events associated with apoptosis were assayed, including mitochondrial depolarization, release of cytochrome c (cyt-c), activation of caspases, and the balance between Bax and Bcl-2 protein expression. Our results indicate that TBMS I inhibited the proliferation of L-02 cells in a dose- and time-dependent manner. The TBMS I-induced growth inhibition of L-02 cells was accompanied by the collapse of mitochondrial membrane potential, release of cyt-c from the mitochondria to the cytosol, activation of caspase-9 and -3, decrease of anti-apoptotic protein Bcl-2 levels and increase of the pro-apoptotic protein Bax levels, all indicative of apoptosis through the mitochondrial pathway. Taken together, these results confirm that TBMS I has a significant apoptotic effect on normal liver L-02 cells, which may be significant to its clinical applications. PMID:21537846

  3. Occupational Styrene Exposure Induces Stress-Responsive Genes Involved in Cytoprotective and Cytotoxic Activities

    PubMed Central

    Strafella, Elisabetta; Bracci, Massimo; Staffolani, Sara; Manzella, Nicola; Giantomasi, Daniele; Valentino, Matteo; Amati, Monica; Tomasetti, Marco; Santarelli, Lory

    2013-01-01

    Objective The aim of this study was to evaluate the expression of a panel of genes involved in toxicology in response to styrene exposure at levels below the occupational standard setting. Methods Workers in a fiber glass boat industry were evaluated for a panel of stress- and toxicity-related genes and associated with biochemical parameters related to hepatic injury. Urinary styrene metabolites (MA+PGA) of subjects and environmental sampling data collected for air at workplace were used to estimate styrene exposure. Results Expression array analysis revealed massive upregulation of genes encoding stress-responsive proteins (HSPA1L, EGR1, IL-6, IL-1?, TNSF10 and TNF?) in the styrene-exposed group; the levels of cytokines released were further confirmed in serum. The exposed workers were then stratified by styrene exposure levels. EGR1 gene upregulation paralleled the expression and transcriptional protein levels of IL-6, TNSF10 and TNF? in styrene exposed workers, even at low level. The activation of the EGR1 pathway observed at low-styrene exposure was associated with a slight increase of hepatic markers found in highly exposed subjects, even though they were within normal range. The ALT and AST levels were not affected by alcohol consumption, and positively correlated with urinary styrene metabolites as evaluated by multiple regression analysis. Conclusion The pro-inflammatory cytokines IL-6 and TNF? are the primary mediators of processes involved in the hepatic injury response and regeneration. Here, we show that styrene induced stress responsive genes involved in cytoprotection and cytotoxicity at low-exposure, that proceed to a mild subclinical hepatic toxicity at high-styrene exposure. PMID:24086524

  4. Combined TLR2/4-activated dendritic/tumor cell fusions induce augmented cytotoxic T lymphocytes.

    PubMed

    Koido, Shigeo; Homma, Sadamu; Okamoto, Masato; Namiki, Yoshihisa; Takakura, Kazuki; Takahara, Akitaka; Odahara, Shunichi; Tsukinaga, Shintaro; Yukawa, Toyokazu; Mitobe, Jimi; Matsudaira, Hiroshi; Nagatsuma, Keisuke; Uchiyama, Kan; Kajihara, Mikio; Arihiro, Seiji; Imazu, Hiroo; Arakawa, Hiroshi; Kan, Shin; Komita, Hideo; Ito, Masaki; Ohkusa, Toshifumi; Gong, Jianlin; Tajiri, Hisao

    2013-01-01

    Induction of antitumor immunity by dendritic cell (DC)-tumor fusion cells (DC/tumor) can be modulated by their activation status. In this study, to address optimal status of DC/tumor to induce efficient antigen-specific cytotoxic T lymphocytes (CTLs), we have created various types of DC/tumor: 1) un-activated DC/tumor; 2) penicillin-killed Streptococcus pyogenes (OK-432; TLR4 agonist)-activated DC/tumor; 3) protein-bound polysaccharides isolated from Coriolus versicolor (PSK; TLR2 agonist)-activated DC/tumor; and 4) Combined OK-432- and PSK-activated DC/tumor. Moreover, we assessed the effects of TGF-?1 derived from DC/tumor on the induction of MUC1-specific CTLs. Combined TLR2- and TLR4-activated DC/tumor overcame immune-suppressive effect of TGF-?1 in comparison to those single activated or un-activated DC/tumor as demonstrated by: 1) up-regulation of MHC class II and CD86 expression on DC/tumor; 2) increased fusion efficiency; 3) increased production of fusions derived IL-12p70; 4) activation of CD4(+) and CD8(+) T cells that produce high levels of IFN-?; 5) augmented induction of CTL activity specific for MUC1; and 6) superior efficacy in inhibiting CD4(+)CD25(+)Foxp3(+) T cell generation. However, DC/tumor-derived TGF-?1 reduced the efficacy of DC/tumor vaccine in vitro. Incorporating combined TLRs-activation and TGF-?1-blockade of DC/tumor may enhance the effectiveness of DC/tumor-based cancer vaccines and have the potential applicability to the field of adoptive immunotherapy. PMID:23555011

  5. Metalloproteins and phytochelatin synthase may confer protection against zinc oxide nanoparticle induced toxicity in Caenorhabditis elegans.

    PubMed

    Polak, Natasa; Read, Daniel S; Jurkschat, Kerstin; Matzke, Marianne; Kelly, Frank J; Spurgeon, David J; Stürzenbaum, Stephen R

    2014-03-01

    Zinc oxide nanoparticles (ZnONPs) are used in large quantities by the cosmetic, food and textile industries. Here we exposed Caenorhabditis elegans wild-type and a metal sensitive triple knockout mutant (mtl-1;mtl-2;pcs-1) to ZnONPs (0-50mg/L) to study strain and exposure specific effects on transcription, reactive oxygen species generation, the biomolecular phenotype (measured by Raman microspectroscopy) and key endpoints of the nematode life cycle (growth, reproduction and lifespan). A significant dissolution effect was observed, where dissolved ZnO constituted over 50% of total Zn within a two day exposure to the test medium, suggesting that the nominal exposure to pure ZnONPs represents in vivo, at best, a mixture exposure of ionic zinc and nanoparticles. Nevertheless, the analyses provided evidence that the metallothioneins (mtl-1 and mtl-2), the phytochelatin synthase (pcs-1) and an apoptotic marker (cep-1) were transcriptionally activated. In addition, the DCFH-DA assay provided in vitro evidence of the oxidative potential of ZnONPs in the metal exposure sensitive triple mutant. Raman spectroscopy highlighted that the biomolecular phenotype changes significantly in the mtl-1;mtl-2;pcs-1 triple knockout worm upon ZnONP exposure, suggesting that these metalloproteins are instrumental in the protection against cytotoxic damage. Finally, ZnONP exposure was shown to decrease growth and development, reproductive capacity and lifespan, effects which were amplified in the triple knockout. By combining diverse toxicological strategies, we identified that individuals (genotypes) housing mutations in key metalloproteins and phytochelatin synthase are more susceptible to ZnONP exposure, which underlines their importance to minimize ZnONP induced toxicity. PMID:24333255

  6. Ion beam induced effects on the ferromagnetism in Pd nanoparticles

    SciTech Connect

    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

    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.

  7. Ion beam induced effects on the ferromagnetism in Pd nanoparticles

    NASA Astrophysics Data System (ADS)

    Kulriya, P. K.; Mehta, B. R.; Agarwal, D. C.; Agarwal, Kanika; Kumar, Praveen; Shivaprasad, S. M.; Avasthi, D. K.

    2012-06-01

    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.

  8. TiO2 Nanoparticles Induced Hippocampal Neuroinflammation in Mice

    PubMed Central

    Ze, Xiao; Yu, Xiaohong; Pan, Xiaoyu; Lin, Anan; Zhao, Yue; Zhang, Chi; Zhou, Qiuping; Wang, Ling; Hong, Fashui

    2014-01-01

    Titanium dioxide nanoparticles (TiO2 NPs) have been used in various medical and industrial areas. However, the impacts of these nanoparticles on neuroinflammation in the brain are poorly understood. In this study, mice were exposed to 2.5, 5, or 10 mg/kg body weight TiO2 NPs for 90 consecutive days, and the TLRs/TNF-?/NF-?B signaling pathway associated with the hippocampal neuroinflammation was investigated. Our findings showed titanium accumulation in the hippocampus, neuroinflammation and impairment of spatial memory in mice following exposure to TiO2 NPs. Furthermore, TiO2 NPs significantly activated the expression of Toll-like receptors (TLR2, TLR4), tumor necrosis factor-?, nucleic I?B kinase, NF-?B-inducible kinase, nucleic factor–?B, NF-?B2(p52), RelA(p65), and significantly suppressed the expression of I?B and interleukin-2. These findings suggest that neuroinflammation may be involved in TiO2 NP-induced alterations of cytokine expression in mouse hippocampus. Therefore, more attention should be focused on the application of TiO2 NPs in the food industry and their long-term exposure effects, especially in the human central nervous system. PMID:24658543

  9. Salvianic acid A protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity.

    PubMed

    Wang, Xin-Jian; Xu, Jian-Xing

    2005-02-01

    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 with elevation of intracellular reactive oxygen species (ROS) level and apoptotic death. Salvianic acid A (SA), isolated from the Chinese herbal medicine Salvia miltiorrhiza, is capable of protecting diverse kinds of cells from damage caused by a variety of toxic stimuli. In the present study, we investigated the protective effects of SA on MPP(+)-induced cytotoxicity in human neuroblastoma SH-SY5Y cells, as well as the underlying mechanism. Treatment of SH-SY5Y cells with MPP(+) caused the loss of cell viability, and condensation and fragmentation of nuclei, which was associated with the elevation of ROS level, the increase in Bax/Bcl-2 ratio, and the activation of caspase-3. MPP(+) induced mitochondria dysfunction characterized by mitochondrial membrane potential loss and cytochrome c release. These phenotypes induced by MPP(+) were reversed by SA. Our results suggested that the protective effects of SA on MPP(+)-induced cytotoxicity may be ascribed to its antioxidative properties and anti-apoptotic activity via regulating the expression of Bcl-2 and Bax. These data indicated that SA might provide a useful therapeutic strategy for the treatment of progressive neurodegenerative disease such as Parkinson's disease. PMID:15681030

  10. NiO nanoparticles induce apoptosis through repressing SIRT1 in human bronchial epithelial cells.

    PubMed

    Duan, Wei-Xia; He, Min-Di; Mao, Lin; Qian, Feng-Hua; Li, Yu-Ming; Pi, Hui-Feng; Liu, Chuan; Chen, Chun-Hai; Lu, Yong-Hui; Cao, Zheng-Wang; Zhang, Lei; Yu, Zheng-Ping; Zhou, Zhou

    2015-07-15

    With application of nano-sized nickel-containing particles (Nano-Ni) expanding, the health concerns about their adverse effects on the pulmonary system are increasing. However, the mechanisms for the pulmonary toxicity of these materials remain unclear. In the present study, we focused on the impacts of NiO nanoparticles (NiONPs) on sirtuin1 (SIRT1), a NAD-dependent deacetylase, and investigated whether SIRT1 was involved in NiONPs-induced apoptosis. Although the NiONPs tended to agglomerate in fluid medium, they still entered into the human bronchial epithelial cells (BEAS-2B) and released Ni(2+) inside the cells. NiONPs at doses of 5, 10, and 20?g/cm(2) inhibited the cell viability. NiONPs' produced cytotoxicity was demonstrated through an apoptotic process, indicated by increased numbers of Annexin V positive cells and caspase-3 activation. The expression of SIRT1 was markedly down-regulated by the NiONPs, accompanied by the hyperacetylation of p53 (tumor protein 53) and overexpression of Bax (Bcl-2-associated X protein). However, overexpression of SIRT1 through resveratrol treatment or transfection clearly attenuated the NiONPs-induced apoptosis and activation of p53 and Bax. Our results suggest that the repression of SIRT1 may underlie the NiONPs-induced apoptosis via p53 hyperacetylation and subsequent Bax activation. Because SIRT1 participates in multiple biologic processes by deacetylation of dozens of substrates, this knowledge of the impact of NiONPs on SIRT1 may lead to an improved understanding of the toxic mechanisms of Nano-Ni and provide a molecular target to antagonize Nano-Ni toxicity. PMID:25840356

  11. Ptaquiloside-induced cytotoxicity in Crandall feline kidney and HGC-27 cells

    PubMed Central

    YURDAKOK, BEGUM; KISMALI, GORKEM; OZEN, DOGUKAN

    2014-01-01

    Ptaquiloside (PTA) is a potent genotoxic carcinogenic compound, which is found in bracken ferns and predominantly causes gastric tumors in humans, as well as bladder tumors and chronic enzootic hematuria in cattle. The underlying molecular mechanisms of PTA remain a topic for interdisciplinary investigation. The aim of the present study was to determine the possible cytotoxic effect of 24 h of PTA exposure in Crandall feline kidney (CrFK) and human gastric cells (the HGC-27 cell line) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactose dehydrogenase (LDH) analysis. The cytotoxic effects of PTA (0.0005–500 ?g/ml) were found to increase in a dose-dependent manner, whereby the half maximal inhibitory concentration values were 11.17 and 11.86 ?g/ml in the CrFK cells, and 2.03 and 2.56 ?g/ml in the HGC-27 cells, by LDH and MTT assay, respectively. The results of the present study are consistent with those of previous studies associated with the cytotoxicity of PTA; however, cytotoxicity was identified to occur at significantly lower doses. This cytotoxic effect in vitro at particularly high doses may be linked to the initiation of carcinogenesis as a result of oxidative stress. PMID:25202422

  12. Synergistic Cytotoxic Effect of Gold Nanoparticles and 5-Aminolevulinic Acid-Mediated Photodynamic Therapy against Skin Cancer Cells

    PubMed Central

    Hadizadeh, Mahnaz; Fateh, Mohsen

    2014-01-01

    Background: Photodynamic therapy (PDT) is a promising therapeutic modality for the treatment of cancer and other diseases. In this study, the epidermoid carcinoma cell line A431 and the normal fibroblasts were used to investigate whether gold nanoparticles (GNPs) can induce an increase in cell death during PDT using 5-aminolevulinic acid (5-ALA) as a photosensitizer. Methods: Human fibroblast and A431 cells were grown in 96-well plates. The effect of GNPs on the efficacy of 5-ALA-mediated PDT (5-ALA-PDT) was evaluated by comparing the effect of 5-ALA with GNPs to the effect of 5-ALA alone. Cell viability was determined by the methyl- tetrazolium assay. Results: Dark toxicity experiments showed that 5-ALA at concentrations 0.5, 1 and 2 mM had no significant effect on cell viability of both cell lines. However, treatment of cells with 5-ALA (0.5 to 2 mM) and light dose of 25 Jcm-2 led to 5-10% and 31-42% decrease in cell viability of fibroblast and A431 cells respectively. The data also shows that GNPs in both the absence and the presence of light, results in a dose-dependent decrease in cell viability of both cell lines. However, the sensitivity of cancer cells to GNPs at concentrations more than 24 ?g/ml was approximately 2.5- to 4-fold greater than healthy cells. Furthermore, data indicates that 5-ALA in combination with GNPs results in a synergistic reduction in viability of A431 cells. Conclusion: In summary, the findings of this study suggest that concomitant treatment with 5-ALA and GNPs may be useful in enhancing the effect of 5-ALA-PDT. PMID:25242844

  13. Mechanisms of Nanoparticle-Induced Oxidative Stress and Toxicity

    PubMed Central

    Wang, Liying

    2013-01-01

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

  14. Silver nanoparticles induce degradation of the endoplasmic reticulum stress sensor activating transcription factor-6 leading to activation of the NLRP-3 inflammasome.

    PubMed

    Simard, Jean-Christophe; Vallieres, Francis; de Liz, Rafael; Lavastre, Valerie; Girard, Denis

    2015-02-27

    In the past decade, the increasing amount of nanoparticles (NP) and nanomaterials used in multiple applications led the scientific community to investigate the potential toxicity of NP. Many studies highlighted the cytotoxic effects of various NP, including titanium dioxide, zinc oxide, and silver nanoparticles (AgNP). In a few studies, endoplasmic reticulum (ER) stress was found to be associated with NP cytotoxicity leading to apoptosis in different cell types. In this study, we report for the first time that silver nanoparticles of 15 nm (AgNP15), depending on the concentration, induced different signature ER stress markers in human THP-1 monocytes leading to a rapid ER stress response with degradation of the ATF-6 sensor. Also, AgNP15 induced pyroptosis and activation of the NLRP-3 inflammasome as demonstrated by the processing and increased activity of caspase-1 and secretion of IL-1? and ASC (apoptosis-associated speck-like protein containing a CARD domain) pyroptosome formation. Transfection of THP-1 cells with siRNA targeting NLRP-3 decreased the AgNP15-induced IL-1? production. The absence of caspase-4 expression resulted in a significant reduction of pro-IL-1?. However, caspase-1 activity was significantly higher in caspase-4-deficient cells when compared with WT cells. Inhibition of AgNP15-induced ATF-6 degradation with Site-2 protease inhibitors completely blocked the effect of AgNP15 on pyroptosis and secretion of IL-1?, indicating that ATF-6 is crucial for the induction of this type of cell death. We conclude that AgNP15 induce degradation of the ER stress sensor ATF-6, leading to activation of the NLRP-3 inflammasome regulated by caspase-4 in human monocytes. PMID:25593314

  15. Structural responses of cells to intracellular magnetic force induced by superparamagnetic iron oxide nanoparticles

    PubMed Central

    Shen, Han; Tong, Sheng; Bao, Gang; Wang, Biao

    2014-01-01

    In this paper, we study the effects of intracellular force on human umbilical vein endothelial cells. We generated intracellular force on endothelial cells under different magnetic fields using the cell uptake of superparamagnetic iron oxide nanoparticles. Cell responses to intracellular force were observed using fluorescent microscopy. Our results indicated that nanoparticles were taken up by the cell by endocytosis and were deposited in lysosomes. Nanoparticles and lysosomes inside the cell could be relocated by the application of a magnetic force. The intracellular magnetic force could also be used to accelerate cell migration by adjusting the magnetic fields and giving the cell free culture space. No cytotoxicity of nanoparticles was found in our experiments. By comparing intracellular relocalization with migration of the whole cell, we obtained a better understanding of the self-defence mechanisms of cells based on their mechanical properties. Based on the promising mechanical properties and low cytotoxicity of our magnetic nanoparticles, their potential applications in cytomechanics and cell patterning are discussed. PMID:24336693

  16. Comparative Cytotoxicity Study of Silver Nanoparticles (AgNPs) in a Variety of Rainbow Trout Cell Lines (RTL-W1, RTH-149, RTG-2) and Primary Hepatocytes.

    PubMed

    Connolly, Mona; Fernandez-Cruz, Maria-Luisa; Quesada-Garcia, Alba; Alte, Luis; Segner, Helmut; Navas, Jose M

    2015-01-01

    Among all classes of nanomaterials, silver nanoparticles (AgNPs) have potentially an important ecotoxicological impact, especially in freshwater environments. Fish are particularly susceptible to the toxic effects of silver ions and, with knowledge gaps regarding the contribution of dissolution and unique particle effects to AgNP toxicity, they represent a group of vulnerable organisms. Using cell lines (RTL-W1, RTH-149, RTG-2) and primary hepatocytes of rainbow trout (Oncorhynchus mykiss) as in vitro test systems, we assessed the cytotoxicity of the representative AgNP, NM-300K, and AgNO3 as an Ag+ ion source. Lack of AgNP interference with the cytotoxicity assays (AlamarBlue, CFDA-AM, NRU assay) and their simultaneous application point to the compatibility and usefulness of such a battery of assays. The RTH-149 and RTL-W1 liver cell lines exhibited similar sensitivity as primary hepatocytes towards AgNP toxicity. Leibovitz's L-15 culture medium composition (high amino acid content) had an important influence on the behaviour and toxicity of AgNPs towards the RTL-W1 cell line. The obtained results demonstrate that, with careful consideration, such an in vitro approach can provide valuable toxicological data to be used in an integrated testing strategy for NM-300K risk assessment. PMID:26006119

  17. Comparative Cytotoxicity Study of Silver Nanoparticles (AgNPs) in a Variety of Rainbow Trout Cell Lines (RTL-W1, RTH-149, RTG-2) and Primary Hepatocytes

    PubMed Central

    Connolly, Mona; Fernandez-Cruz, Maria-Luisa; Quesada-Garcia, Alba; Alte, Luis; Segner, Helmut; Navas, Jose M.

    2015-01-01

    Among all classes of nanomaterials, silver nanoparticles (AgNPs) have potentially an important ecotoxicological impact, especially in freshwater environments. Fish are particularly susceptible to the toxic effects of silver ions and, with knowledge gaps regarding the contribution of dissolution and unique particle effects to AgNP toxicity, they represent a group of vulnerable organisms. Using cell lines (RTL-W1, RTH-149, RTG-2) and primary hepatocytes of rainbow trout (Oncorhynchus mykiss) as in vitro test systems, we assessed the cytotoxicity of the representative AgNP, NM-300K, and AgNO3 as an Ag+ ion source. Lack of AgNP interference with the cytotoxicity assays (AlamarBlue, CFDA-AM, NRU assay) and their simultaneous application point to the compatibility and usefulness of such a battery of assays. The RTH-149 and RTL-W1 liver cell lines exhibited similar sensitivity as primary hepatocytes towards AgNP toxicity. Leibovitz’s L-15 culture medium composition (high amino acid content) had an important influence on the behaviour and toxicity of AgNPs towards the RTL-W1 cell line. The obtained results demonstrate that, with careful consideration, such an in vitro approach can provide valuable toxicological data to be used in an integrated testing strategy for NM-300K risk assessment. PMID:26006119

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

    NASA Astrophysics Data System (ADS)

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

    2011-02-01

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

  19. Nonlethal dose of silver nanoparticles attenuates TNF-?-induced hepatic epithelial cell death through HSP70 overexpression.

    PubMed

    Tsai, Tsen-Ni; Lee, Tzu-Ying; Liu, Maw-Shung; Ho, Jia-Jing; Huang, Li-Ju; Liu, Chia-Jen; Chen, Tsan-Ju; Yang, Rei-Cheng

    2015-06-15

    Silver nanoparticles (Ag-nps) have been widely used in various biomedical products. Compared with its hazardous effects extensively being studied, rare attention has been paid to the potential protective effect of Ag-nps to human health. The present study was designed to evaluate the protective effects of Ag-nps and heat shock treatment on tumor necrosis factor-? (TNF-?)-induced cell damage in Clone 9 cells. Clone 9 cells were pretreated with nonlethal concentration of Ag-nps (1 ?g/ml) or heat shock, and then cell damages were induced by TNF-? (1 ng/ml). Protective effects of Ag-nps administration or heat shock treatment were determined by examining the TNF-?-induced changes in cell viabilities. The results showed that the intensity of cytotoxicity produced by TNF-? was alleviated upon treatment with nonlethal concentration of Ag-nps (1 ?g/ml). Similar protective effects were also found upon heat shock treatment. These data demonstrate that Ag-nps and heat shock treatment were equally capable of inducing heat shock protein 70 (HSP70) protein expression in Clone 9 cells. The results suggest that clinically Ag-nps administration is a viable strategy to induce endogenous HSP70 expression instead of applying heat shock. In conclusion, our study for the first time provides evidence that Ag-nps may act as a viable alternative for HSP70 induction clinically. PMID:25877698

  20. In Salvia miltiorrhiza, phenolic acids possess protective properties against amyloid ?-induced cytotoxicity, and tanshinones act as acetylcholinesterase inhibitors.

    PubMed

    Zhou, Yongqiang; Li, Weize; Xu, Lei; Chen, Lvyi

    2011-05-01

    Radix Salvia miltiorrhiza (RSM), a traditional Chinese medicinal herb, has been alleged to possess therapeutic effects against senile dementia, also known as Alzheimer's disease (AD). However, the effects of the major components in RSM on cytotoxicity induced by amyloid-? peptide (A?) and on acetylcholinesterase activity have not been studied in depth to date. In this report, the effects of RSM aqueous/ethanol extracts, total polyphenols, total tanshinones and 3 phenolic compounds against toxicity mediated by A?(25-35) were tested with PC-12 cells. The results showed that A?(25-35)-induced cytotoxicity was revised by RSM aqueous/ethanol extracts and total polyphenols and that danshensu and salvianolic acid B could protect PC-12 cells by blocking A?(25-35)-induced Ca(2+)-intake, lactate dehydrogenase release, cell viability decrease and apoptosis. In addition, the activities of RSM extracts and relevant constituents in their inhibition of acetylcholinesterase were investigated using rat brain homogenates as an enzyme resource. Galanthamine hydrobromide, an accepted acetylcholinesterase inhibitor, was employed as a positive control agent. Our preliminary studies demonstrated that RSM ethanol extract, total tanshinones, tanshinone I and dihydrotanshinone I had remarkable inhibition effects on acetylcholinesterase in vitro. These findings suggest that both tanshinones and polyphenols in RSM are the active constituents responsible for the beneficial effects of this herb in AD treatment. PMID:21787715

  1. Effect of glutathione-modulating compounds on hydrogen-peroxide-induced cytotoxicity in human glioblastoma and glioma cell lines

    Microsoft Academic Search

    Masataka Iida; Shigeki Sunaga; Nobuo Hirota; Nobuyuki Kuribayashi; Hiroshi Sakagami; Minoru Takeda; Kiyoshi Matsumoto

    1997-01-01

    The relation between the intracellular glutathione (GSH) concentration and hydrogen-peroxide(H2O2)-induced cytotoxicity was investigated. The intracellular GSH concentration in human glioblastoma (T98G, U87MG) and glioma\\u000a (KG1C) cell lines was one or two orders of magnitude higher than that in a human myelogenous leukemic cell line (HL-60), which\\u000a showed higher sensitivity to H2O2. Pretreatment of these cell lines with l-buthionine-[S,R]-sulfoximine, which significantly

  2. A mechanism for nano-titanium dioxide-induced cytotoxicity in HaCaT cells under UVA irradiation.

    PubMed

    Xue, Chengbin; Luo, Wen; Yang, Xiang Liang

    2015-08-01

    Nano-TiO2 has been reported to be an efficient photocatalyst, which is able to produce reactive oxygen species (ROS) under UVA irradiation. In this study, we investigated the effects of nano-TiO2 on the cytotoxicity, induction of apoptosis, and the putative pathways of its actions in HaCaT cells. We show that nano-TiO2 is a potent inducer of apoptosis and that it transduces the apoptotic signal via ROS generation, thereby inducing mitochondrial permeability transition (MPT) and activating Caspase-3 from HaCaT cells. ROS production, mitochondrial alteration, and subsequent apoptotic cell death in nano-TiO2-treated cells were blocked by the MPT pore-blocker cyclosporin A. Taken together, our data indicate that nano-TiO2 induces the ROS-mediated MPT and resultant Caspase-3 activation. PMID:25822594

  3. Increasing the cytotoxicity of doxorubicin in breast cancer MCF-7 cells with multidrug resistance using a mesoporous silica nanoparticle drug delivery system

    PubMed Central

    Wang, Xin; Teng, Zhaogang; Wang, Haiyan; Wang, Chunyan; Liu, Ying; Tang, Yuxia; Wu, Jiang; Sun, Jin; Wang, Hai; Wang, Jiandong; Lu, Guangming

    2014-01-01

    Resistance to cytotoxic chemotherapy is the main cause of therapeutic failure and death in women with breast cancer. Overexpression of various members of the superfamily of adenosine triphosphate binding cassette (ABC)-transporters has been shown to be associated with multidrug resistance (MDR) phenotype in breast cancer cells. MDR1 protein promotes the intracellular efflux of drugs. A novel approach to address cancer drug resistance is to take advantage of the ability of nanocarriers to sidestep drug resistance mechanisms by endosomal delivery of chemotherapeutic agents. Doxorubicin (DOX) is an anthracycline antibiotic commonly used in breast cancer chemotherapy and a substrate for ABC-mediated drug efflux. In the present study, we developed breast cancer MCF-7 cells with overexpression of MDR1 and designed mesoporous silica nanoparticles (MSNs) which were used as a drug delivery system. We tested the efficacy of DOX in the breast cancer cell line MCF-7/MDR1 and in a MCF-7/MDR1 xenograft nude mouse model using the MSNs drug delivery system. Our data show that drug resistance in the human breast cancer cell line MCF-7/MDR1 can be overcome by treatment with DOX encapsulated within mesoporous silica nanoparticles. PMID:24817930

  4. Taraxacum officinale induces cytotoxicity through TNF-? and IL1? secretion in Hep G2 cells

    Microsoft Academic Search

    Hyun-Na Koo; Seung-Heon Hong; Bong-Keun Song; Cheorl-Ho Kim; Young-Hyun Yoo; Hyung-Min Kim

    2004-01-01

    Taraxacum officinale (TO) has been frequently used as a remedy for women's disease (e.g. breast and uterus cancer) and disorders of the liver and gallbladder. Several earlier studies have indicated that TO exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we investigated the effect of TO on the cytotoxicity and production of cytokines in human

  5. Real-time monitoring of copper ions-induced cytotoxicity by EIS cell chips

    Microsoft Academic Search

    Elisabetta Primiceri; Maria Serena Chiriacň; Eliana D’Amone; Emanuela Urso; Rodica Elena Ionescu; Antonia Rizzello; Michele Maffia; Roberto Cingolani; Ross Rinaldi; Giuseppe Maruccio

    2010-01-01

    An important goal of biomedical research is the development of tools for high-throughput evaluation of drug effects and cytotoxicity tests. Here we demonstrate EIS cell chips able to monitor cell growth, morphology, adhesion and their changes as a consequence of treatment with drugs or toxic compounds. As a case study, we investigate the uptake of copper ions and its effect

  6. The detergent Triton X-100 induces a death pattern in human carcinoma cell lines that resembles cytotoxic lymphocyte-induced apoptosis.

    PubMed

    Borner, M M; Schneider, E; Pirnia, F; Sartor, O; Trepel, J B; Myers, C E

    1994-10-17

    The detergent Triton X-100 (TX100) was used with the intention to establish a model for necrotic cell death. However, TX100 was found to induce apoptotic and necrotic death in prostate and colon cancer cell lines. Apoptosis was characterized by the typical morphological features and internucleosomal DNA fragmentation. The rapid onset within 60 min and the lack of inhibition by cycloheximide indicated that apoptosis induced by TX100 was not dependent on protein synthesis. Removal of extracellular calcium blocked internucleosomal DNA fragmentation. This pattern of cell death shows a striking similarity to the effect of cytotoxic lymphocytes on their target cells. PMID:7926036

  7. Gravity-induced swirl of nanoparticles in microfluidics.

    PubMed

    Zhao, Chao; Oztekin, Alparslan; Cheng, Xuanhong

    2013-04-01

    Parallel flows of two fluids in microfluidic devices are used for miniaturized chemistry, physics, biology and bioengineering studies, and the streams are often considered to remain parallel. However, as the two fluids do not always have the same density, interface reorientation induced by density stratification is unavoidable. In this paper, flow characteristics of an aqueous polystyrene nanofluid and a sucrose-densified aqueous solution flowing parallel in microchannels are examined. Nanoparticles 100 nm in diameter are used in the study. The motion of the nanoparticles is simulated using the Lagrangian description and directly observed by a confocal microscope. Matched results are obtained from computational and empirical analysis. Although solution density homogenizes rapidly resulting from a fast diffusion of sucrose in water, the nanofluid is observed to rotate for an extended period. Angular displacement of the nanofluid depends on the ratio of gravitational force to viscous force, Re/Fr (2), where Re is the Reynolds number and Fr is the Froude number. In the developing region at the steady state, the angular displacement is related to y/D h, the ratio between distance from the inlet and the hydraulic diameter of the microfluidic channel. The development of nanofluid flow feature also depends on h/w, the ratio of microfluidic channel's height to width. The quantitative description of the angular displacement of nanofluid will aid rational designs of microfluidic devices utilizing multistream, multiphase flows. PMID:24563612

  8. Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes

    PubMed Central

    Hussain, Salik; Al-Nsour, Faris; Rice, Annette B; Marshburn, Jamie; Ji, Zhaoxia; Zink, Jeffery I; Yingling, Brenda; Walker, Nigel J; Garantziotis, Stavros

    2012-01-01

    Background Cerium dioxide (CeO2) nanoparticles have potential therapeutic applications and are widely used for industrial purposes. However, the effects of these nanoparticles on primary human cells are largely unknown. The ability of nanoparticles to exacerbate pre-existing inflammatory disorders is not well documented for engineered nanoparticles, and is certainly lacking for CeO2 nanoparticles. We investigated the inflammation-modulating effects of CeO2 nanoparticles at noncytotoxic concentrations in human peripheral blood monocytes. Methods CD14+ cells were isolated from peripheral blood samples of human volunteers. Cells were exposed to either 0.5 or 1 ?g/mL of CeO2 nanoparticles over a period of 24 or 48 hours with or without lipopolysaccharide (10 ng/mL) prestimulation. Modulation of the inflammatory response was studied by measuring secreted tumor necrosis factor-alpha, interleukin-1beta, macrophage chemotactic protein-1, interferon-gamma, and interferon gamma-induced protein 10. Results CeO2 nanoparticle suspensions were thoroughly characterized using dynamic light scattering analysis (194 nm hydrodynamic diameter), zeta potential analysis (?14 mV), and transmission electron microscopy (irregular-shaped particles). Transmission electron microscopy of CD14+ cells exposed to CeO2 nanoparticles revealed that these nanoparticles were efficiently internalized by monocytes and were found either in vesicles or free in the cytoplasm. However, no significant differences in secreted cytokine profiles were observed between CeO2 nanoparticle-treated cells and control cells at noncytotoxic doses. No significant effects of CeO2 nanoparticle exposure subsequent to lipopolysaccharide priming was observed on cytokine secretion. Moreover, no significant difference in lipopolysaccharide-induced cytokine production was observed after exposure to CeO2 nanoparticles followed by lipopolysaccharide exposure. Conclusion CeO2 nanoparticles at noncytotoxic concentrations neither modulate pre-existing inflammation nor prime for subsequent exposure to lipopolysaccharides in human monocytes from healthy subjects. PMID:22457596

  9. Laser-induced growth and reformation of gold and silver nanoparticles

    Microsoft Academic Search

    Seol Ji Kim; Chil Seong Ah; Du-Jeon Jang

    2009-01-01

    The sizes, shapes, and growth rates of gold and silver nanoparticles stabilized with polyvinylpyrrolidone in water can be\\u000a controlled by using picosecond laser pulses. The nucleation of small metal clusters formed with NaBH4 addition to produce nanoparticles takes two months with aging but 30 min with laser irradiation. Laser pulses can also induce\\u000a nanoparticles to have narrow size and shape distribution

  10. Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish

    SciTech Connect

    Christen, Verena [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Capelle, Martinus [Crucell, P.O. Box 2048, NL-2301 Leiden (Netherlands); Fent, Karl, E-mail: karl.fent@fhnw.ch [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Swiss Federal Institute of Technology Zürich, Department of Environmental Systems Science, CH-8092 Zürich (Switzerland)

    2013-10-15

    Silver nanoparticles (AgNPs) find increasing applications, and therefore humans and the environment are increasingly exposed to them. However, potential toxicological implications are not sufficiently known. Here we investigate effects of AgNPs (average size 120 nm) on zebrafish in vitro and in vivo, and compare them to human hepatoma cells (Huh7). AgNPs are incorporated in zebrafish liver cells (ZFL) and Huh7, and in zebrafish embryos. In ZFL cells AgNPs lead to induction of reactive oxygen species (ROS), endoplasmatic reticulum (ER) stress response, and TNF-?. Transcriptional alterations also occur in pro-apoptotic genes p53 and Bax. The transcriptional profile differed in ZFL and Huh7 cells. In ZFL cells, the ER stress marker BiP is induced, concomitant with the ER stress marker ATF-6 and spliced XBP-1 after 6 h and 24 h exposure to 0.5 g/L and 0.05 g/L AgNPs, respectively. This indicates the induction of different pathways of the ER stress response. Moreover, AgNPs induce TNF-?. In zebrafish embryos exposed to 0.01, 0.1, 1 and 5 mg/L AgNPs hatching was affected and morphological defects occurred at high concentrations. ER stress related gene transcripts BiP and Synv are significantly up-regulated after 24 h at 0.1 and 5 mg/L AgNPs. Furthermore, transcriptional alterations occurred in the pro-apoptotic genes Noxa and p21. The ER stress response was strong in ZFL cells and occurred in zebrafish embryos as well. Our data demonstrate for the first time that AgNPs lead to induction of ER stress in zebrafish. The induction of ER stress can have several consequences including the activation of apoptotic and inflammatory pathways. - Highlights: • Effects of silver nanoparticles (120 nm AgNPs) are investigated in zebrafish. • AgNPs induce all ER stress reponses in vitro in zebrafish liver cells. • AgNPs induce weak ER stress in zebrafish embryos. • AgNPs induce oxidative stress and transcripts of pro-apoptosis genes.

  11. A New Polymer–Lipid Hybrid Nanoparticle System Increases Cytotoxicity of Doxorubicin Against Multidrug-Resistant Human Breast Cancer Cells

    Microsoft Academic Search

    Ho Lun Wong; Andrew M. Rauth; Reina Bendayan; Janet L. Manias; Manisha Ramaswamy; Zengshe Liu; Sevim Z. Erhan; Xiao Yu Wu

    2006-01-01

    \\u000a Purpose  This work is intended to develop and evaluate a new polymer–lipid hybrid nanoparticle system that can efficiently load and\\u000a release water-soluble anticancer drug doxorubicin hydrochloride (Dox) and enhance Dox toxicity against multidrug-resistant\\u000a (MDR) cancer cells.\\u000a \\u000a \\u000a \\u000a Methods  Cationic Dox was complexed with a new soybean-oil-based anionic polymer and dispersed together with a lipid in water to form\\u000a Dox-loaded solid lipid nanoparticles (Dox–SLNs).

  12. Insights into the Distinguishing Stress-induced Cytotoxicity of Chiral Gold Nanoclusters and the Relationship with GSTP1

    PubMed Central

    Zhang, Chunlei; Zhou, Zhijun; Zhi, Xiao; Ma, Yue; Wang, Kan; Wang, Yuxia; Zhang, Yingge; Fu, Hualin; Jin, Weilin; Pan, Fei; Cui, Daxiang

    2015-01-01

    Chiral gold nanoclusters (Au NCs) exhibit attracting properties owing to their unique physical and chemical properties. Herein we report for the first time chiral gold nanoclusters' cytotoxicity and potential molecular mechanism. The L-glutathione (i.e. L-GSH) and D-glutathione (i.e. D-GSH)-capped Au NCs were prepared and characterized by HRTEM, UV-vis, photoluminescence and circular dichroism (CD) spectroscopy. Results showed that the CD spectra of L-glutathione (i.e. L-GSH) and D-glutathione (i.e. D-GSH)-capped Au NCs exhibited multiple bands which were identically mirror-imaged, demonstrating that the chirality of GSH-capped NCs had contributions from both the metal core and the ligand. The effects of AuNCs@L-GSH and AuNCs@D-GSH on cells were similar based on the cell physiology related cytotoxicity, although the effects became more prominent in AuNCs@D-GSH treated cells, including ROS generation, mitochondrial membrane depolarization, cell cycle arrest and apoptosis. Global gene expression and pathway analysis displayed that both AuNCs@L-GSH and AuNCs@D-GSH caused the up-regulation of genes involved in cellular rescue and stress response, while AuNCs@D-GSH individually induced up-regulation of transcripts involved in some metabolic- and biosynthetic-related response. MGC-803 cells were more sensitive to the oxidative stress damage induced by chiral Au NCs than GES-1 cells, which was associated with GSTP1 hypermethylation. In conclusion, chiral gold nanoclusters exhibit this chirality-associated regulation of cytotoxicity, different gene expression profiling and epigenetic changes should be responsible for observed phenomena. Our study highlights the importance of the interplays between chiral materials and biological system at sub-nano level. PMID:25553104

  13. Cytotoxicity, oxidative stress, and apoptosis in HepG2 cells induced by ionic liquid 1-methyl-3-octylimidazolium bromide.

    PubMed

    Li, Xiaoyu; Ma, Junguo; Wang, Jianji

    2015-10-01

    The present study aimed to determine the cytotoxicity of 1-methyl-3-octylimidazolium bromide ([C8mim]Br) on the human hepatocellular carcinoma (HepG2) cells in order to elucidate the biochemical and molecular mechanism of [C8mim]Br-cytotoxicity. For this purpose, cell viability, oxidative stress, apoptosis, caspase activity, and apoptosis-related gene expression in HepG2 cells following [C8mim]Br-exposure were evaluated. The results showed that viability of HepG2 cells was decreased by [C8mim]Br-exposure in a concentration-dependent pattern. Moreover, biochemical assays reveal that [C8mim]Br-exposure can induce apoptosis, cause overproduction of reactive oxygen species (ROS), inhibit superoxide dismutase and catalase, reduce glutathione content, and increase the cellular malondialdehyde level of HepG2 cells. The transcriptions of p53 and bax were markedly up-regulated while bcl-2 was significantly down-regulated in HepG2 cells after [C8mim]Br-exposure, suggesting that p53 and bcl-2 family may be involved in the cytotoxicity and apoptosis of HepG2 cells caused by [C8mim]Br. In addition, we also found that caspase-3, caspase-8, and caspase-9 were significantly activated in HepG2 cells following [C8mim]Br-exposure. Our results suggest that ROS may be a key early signal of [C8mim]Br-induced apoptosis and caspases play a key role in the initiation and execution of apoptosis of HepG2 cells. PMID:26099465

  14. Microcystin-LR-induced cytotoxicity and apoptosis in human embryonic kidney and human kidney adenocarcinoma cell lines.

    PubMed

    Piyathilaka, M A P C; Pathmalal, M M; Tennekoon, K H; De Silva, B G D N K; Samarakoon, S R; Chanthirika, S

    2015-04-01

    Microcystin-LR (MC-LR) is a potent hepatotoxin, and increasing evidence suggests that it might also induce kidney injury. The aim of the present work was to evaluate the cytotoxicity and possible apoptotic effects of MC-LR on a human embryonic kidney cell line (HEK-293) and human kidney adenocarcinoma cell line (ACHN). Cells were exposed for 24 h to pure MC-LR (1.0-200 µM) and the cytotoxic effects were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulphorhodamine B (SRB) cell viability assays. Cell viability in both cell lines was significantly decreased after treatment with MC-LR at 50 µM for 24 h (P<0.001). Moreover, MC-LR-treated ACHN and HEK-293 cells exhibited a marked dose-dependent loss of confluence as judged by phase-contrast microscopy. Similarly, fluorescence microscopic observations following acridine orange-ethidium bromide (AO/EB) staining confirmed that both cell types were undergoing apoptosis after treatment with MC-LR for 24 h. Expression of three apoptosis-related genes, Bax, Survivin and p53, was analysed by quantitative reverse transcriptase PCR analysis. Both Bax and p53 functioned as promoters of MC-LR-mediated apoptosis in ACHN and HEK-293 cells. The Survivin gene acted as a suppressor of apoptosis at lower MC-LR concentration (1 µM) and the gene was upregulated at higher MC-LR concentration (10 µM) (P<0.001). Significant increases of caspase 3 (P<0.0001) and caspase 9 (P<0.0001) activity were detected in both cell lines after exposure to MC-LR for 24 h, indicating the MC-LR induces cytotoxicity and a marked apoptosis in both ACHN and HEK-293 kidney cell lines. PMID:25635275

  15. Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides:

    NASA Astrophysics Data System (ADS)

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

    2006-11-01

    Photoreceptor cells are incessantly bombarded with photons of light, which, along with the cells' high rate of oxygen metabolism, continuously exposes them to elevated levels of toxic reactive oxygen intermediates (ROIs). Vacancy-engineered mixed-valence-state cerium oxide nanoparticles (nanoceria particles) scavenge ROIs. Our data show that nanoceria particles prevent increases in the intracellular concentrations of ROIs in primary cell cultures of rat retina and, in vivo, prevent loss of vision due to light-induced degeneration of photoreceptor cells. These data indicate that the nanoceria particles may be effective in inhibiting the progression of ROI-induced cell death, which is thought to be involved in macular degeneration, retinitis pigmentosa and other blinding diseases, as well as the ROI-induced death of other cell types in diabetes, Alzheimer's disease, atherosclerosis, stroke and so on. The use of nanoceria particles as a direct therapy for multiple diseases represents a novel strategy and suggests that they may represent a unique platform technology.

  16. Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides.

    PubMed

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

    2006-11-01

    Photoreceptor cells are incessantly bombarded with photons of light, which, along with the cells' high rate of oxygen metabolism, continuously exposes them to elevated levels of toxic reactive oxygen intermediates (ROIs). Vacancy-engineered mixed-valence-state cerium oxide nanoparticles (nanoceria particles) scavenge ROIs. Our data show that nanoceria particles prevent increases in the intracellular concentrations of ROIs in primary cell cultures of rat retina and, in vivo, prevent loss of vision due to light-induced degeneration of photoreceptor cells. These data indicate that the nanoceria particles may be effective in inhibiting the progression of ROI-induced cell death, which is thought to be involved in macular degeneration, retinitis pigmentosa and other blinding diseases, as well as the ROI-induced death of other cell types in diabetes, Alzheimer's disease, atherosclerosis, stroke and so on. The use of nanoceria particles as a direct therapy for multiple diseases represents a novel strategy and suggests that they may represent a unique platform technology. PMID:18654167

  17. NANO EXPRESS Open Access H2-induced copper and silver nanoparticle

    E-print Network

    Paris-Sud XI, Université de

    NANO EXPRESS Open Access H2-induced copper and silver nanoparticle precipitation inside sol nanoparticles with diameters in the range of 3 to 6 nm and nano-rods were obtained. Keywords: copper Bernard, Christophe Kinowski, Mohamed Bouazaoui* and Bruno Capoen Abstract Ionic copper- or silver

  18. Implication of limonene and linalyl acetate in cytotoxicity induced by bergamot essential oil in human neuroblastoma cells.

    PubMed

    Russo, Rossella; Ciociaro, Antonella; Berliocchi, Laura; Cassiano, Maria Gilda Valentina; Rombolŕ, Laura; Ragusa, Salvatore; Bagetta, Giacinto; Blandini, Fabio; Corasaniti, Maria Tiziana

    2013-09-01

    Bergamot (Citrus bergamia, Risso et Poiteau) essential oil (BEO) is a widely used plant extract showing anxiolytic, analgesic and neuroprotective effects in rodents; also, BEO activates multiple death pathways in cancer cells. Despite detailed knowledge of its chemical composition, the constituent/s responsible for these pharmacological activities remain largely unknown. Aim of the present study was to identify the components of BEO implicated in cell death. To this end, limonene, linalyl acetate, linalool, ?-terpinene, ?-pinene and bergapten were individually tested in human SH-SY5Y neuroblastoma cultures at concentrations comparable with those found in cytotoxic dilutions of BEO. None of the tested compounds elicited cell death. However, significant cytotoxicity was observed when cells were cotreated with limonene and linalyl acetate whereas no other associations were effective. Only cotreatment, but not the single exposure to limonene and linalyl acetate, replicated distinctive morphological and biochemical changes induced by BEO, including caspase-3 activation, PARP cleavage, DNA fragmentation, cell shrinkage, cytoskeletal alterations, together with necrotic and apoptotic cell death. Collectively, our findings suggest a major role for a combined action of these monoterpenes in cancer cell death induced by BEO. PMID:23707744

  19. BSA modification to reduce CTAB induced nonspecificity and cytotoxicity of aptamer-conjugated gold nanorods.

    PubMed

    Yasun, Emir; Li, Chunmei; Barut, Inci; Janvier, Denisse; Qiu, Liping; Cui, Cheng; Tan, Weihong

    2015-06-14

    Aptamer-conjugated gold nanorods (AuNRs) are excellent candidates for targeted hyperthermia therapy of cancer cells. However, in high concentrations of AuNRs, aptamer conjugation alone fails to result in highly cell-specific AuNRs due to the presence of positively charged cetyltrimethylammonium bromide (CTAB) as a templating surfactant. Besides causing nonspecific electrostatic interactions with the cell surfaces, CTAB can also be cytotoxic, leading to uncontrolled cell death. To avoid the nonspecific interactions and cytotoxicity triggered by CTAB, we report the further biologically inspired modification of aptamer-conjugated AuNRs with bovine serum albumin (BSA) protein. Following this modification, interaction between CTAB and the cell surface was efficiently blocked, thereby dramatically reducing the side effects of CTAB. This approach may provide a general and simple method to avoid one of the most serious issues in biomedical applications of nanomaterials: nonspecific binding of the nanomaterials with biological cells. PMID:25990591

  20. BSA modification to reduce CTAB induced nonspecificity and cytotoxicity of aptamer-conjugated gold nanorods

    NASA Astrophysics Data System (ADS)

    Yasun, Emir; Li, Chunmei; Barut, Inci; Janvier, Denisse; Qiu, Liping; Cui, Cheng; Tan, Weihong

    2015-05-01

    Aptamer-conjugated gold nanorods (AuNRs) are excellent candidates for targeted hyperthermia therapy of cancer cells. However, in high concentrations of AuNRs, aptamer conjugation alone fails to result in highly cell-specific AuNRs due to the presence of positively charged cetyltrimethylammonium bromide (CTAB) as a templating surfactant. Besides causing nonspecific electrostatic interactions with the cell surfaces, CTAB can also be cytotoxic, leading to uncontrolled cell death. To avoid the nonspecific interactions and cytotoxicity triggered by CTAB, we report the further biologically inspired modification of aptamer-conjugated AuNRs with bovine serum albumin (BSA) protein. Following this modification, interaction between CTAB and the cell surface was efficiently blocked, thereby dramatically reducing the side effects of CTAB. This approach may provide a general and simple method to avoid one of the most serious issues in biomedical applications of nanomaterials: nonspecific binding of the nanomaterials with biological cells.Aptamer-conjugated gold nanorods (AuNRs) are excellent candidates for targeted hyperthermia therapy of cancer cells. However, in high concentrations of AuNRs, aptamer conjugation alone fails to result in highly cell-specific AuNRs due to the presence of positively charged cetyltrimethylammonium bromide (CTAB) as a templating surfactant. Besides causing nonspecific electrostatic interactions with the cell surfaces, CTAB can also be cytotoxic, leading to uncontrolled cell death. To avoid the nonspecific interactions and cytotoxicity triggered by CTAB, we report the further biologically inspired modification of aptamer-conjugated AuNRs with bovine serum albumin (BSA) protein. Following this modification, interaction between CTAB and the cell surface was efficiently blocked, thereby dramatically reducing the side effects of CTAB. This approach may provide a general and simple method to avoid one of the most serious issues in biomedical applications of nanomaterials: nonspecific binding of the nanomaterials with biological cells. Electronic supplementary information (ESI) available: Fig. S-1 to S-6 are included. See DOI: 10.1039/c5nr01704a

  1. Cytotoxic and genotoxic effects induced by stannous chloride associated to nuclear medicine kits

    Microsoft Academic Search

    Anderson P. Guedes; Valbert N. Cardoso; Jose C. P. De Mattos; Flavio J. S. Dantas; Vanessa C. Matos; Josiane C. F. Silva; Roberto J. A. C. Bezerra; Adriano Caldeira-de-Araujo

    2006-01-01

    At present, more than 75% of routine nuclear medicine diagnostic procedures use technetium-99m (99mTc). The binding between 99mTc and the drug to obtain the radiopharmaceutical needs a reducing agent, with stannous chloride (SnCl2) being one of the most used. There are controversies about the cytotoxic, genotoxic and mutagenic effects of SnCl2 in the literature. Thus, the approaches below were used

  2. Mycalamide A Shows Cytotoxic Properties and Prevents EGF-Induced Neoplastic Transformation through Inhibition of Nuclear Factors

    PubMed Central

    Dyshlovoy, Sergey A.; Fedorov, Sergey N.; Kalinovsky, Anatoly I.; Shubina, Larisa K.; Bokemeyer, Carsten; Stonik, Valentin A.; Honecker, Friedemann

    2012-01-01

    Mycalamide A, a marine natural compound previously isolated from sponges, is known as a protein synthesis inhibitor with potent antitumor activity. However, the ability of this compound to prevent malignant transformation of cells has never been examined before. Here, for the first time, we report the isolation of mycalamide A from ascidian Polysincraton sp. as well as investigation of its cancer preventive properties. In murine JB6 Cl41 P+ cells, mycalamide A inhibited epidermal growth factor (EGF)-induced neoplastic transformation, and induced apoptosis at subnanomolar or nanomolar concentrations. The compound inhibited transcriptional activity of the oncogenic nuclear factors AP-1 and NF-?B, a potential mechanism of its cancer preventive properties. Induction of phosphorylation of the kinases MAPK p38, JNK, and ERK was also observed at high concentrations of mycalamide A. The drug shows promising potential for both cancer-prevention and cytotoxic therapy and should be further developed. PMID:22822368

  3. Disulfiram-induced cytotoxicity and endo-lysosomal sequestration of zinc in breast cancer cells

    PubMed Central

    Wiggins, Helen L.; Wymant, Jennifer M.; Solfa, Francesca; Hiscox, Stephen E.; Taylor, Kathryn M.; Westwell, Andrew D.; Jones, Arwyn T.

    2015-01-01

    Disulfiram, a clinically used alcohol-deterrent has gained prominence as a potential anti-cancer agent due to its impact on copper-dependent processes. Few studies have investigated zinc effects on disulfiram action, despite it having high affinity for this metal. Here we studied the cytotoxic effects of disulfiram in breast cancer cells, and its relationship with both intra and extracellular zinc. MCF-7 and BT474 cancer cell lines gave a striking time-dependent biphasic cytotoxic response between 0.01 and 10 ?M disulfiram. Co-incubation of disulfiram with low-level zinc removed this effect, suggesting that availability of extracellular zinc significantly influences disulfiram efficacy. Live-cell confocal microscopy using fluorescent endocytic probes and the zinc dye Fluozin-3 revealed that disulfiram selectively and rapidly increased zinc levels in endo-lysosomes. Disulfiram also caused spatial disorganization of late endosomes and lysosomes, suggesting they are novel targets for this drug. This relationship between disulfiram toxicity and ionophore activity was consolidated via synthesis of a new disulfiram analog and overall we demonstrate a novel mechanism of disulfiram-cytotoxicity with significant clinical implications for future use as a cancer therapeutic. PMID:25557293

  4. Cytotoxicity induced by ochratoxin A, zearalenone, and ?-zearalenol: effects of individual and combined treatment.

    PubMed

    Wang, H W; Wang, J Q; Zheng, B Q; Li, S L; Zhang, Y D; Li, F D; Zheng, N

    2014-09-01

    This study investigated the cytotoxicity of combined mycotoxins of ochratoxin A (OTA), zearalenone (ZEA), and/or ?-zearalenol (?-ZOL). The cytotoxicity of two mycotoxin combinations (two two-toxin combinations and one three-toxin combination) on human Hep G2 cells was evaluated using a tetrazolium salt (MTT) assay and isobologram analysis. Our results demonstrated significant cytotoxic effects of the two-toxin combination and the three-toxin combination on Hep G2 cells in a time- and concentration-dependent manner. The combination indexes (CI) were 2.73-7.67 for the OTA+ZEA combination and 1.23-17.82 for the OTA+?-ZOL combination after 24 h, 48 h, and 72 h of exposure at all inhibit concentration (IC) levels (IC10-IC90), indicating an antagonism. The CIs of the ZEA+?-ZOL combination were 1.29-2.55 after 24 h and 72 h of exposure (IC10-IC90), indicating an antagonism. The CIs of the ZEA+?-ZOL combination were 0.74-1.68 after 48 h of exposure, indicating synergism (IC80-IC90), additive effects (IC50-IC70), or antagonism (IC10-IC40). For the OTA+ZEA+?-ZOL combination, the CIs were 1.41-14.65 after 24 h, 48 h, and 72 h of exposure (IC10-IC90), indicating an antagonism. PMID:24952310

  5. Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects

    EPA Science Inventory

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe res...

  6. Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines

    PubMed Central

    Lanone, Sophie; Rogerieux, Françoise; Geys, Jorina; Dupont, Aurélie; Maillot-Marechal, Emmanuelle; Boczkowski, Jorge; Lacroix, Ghislaine; Hoet, Peter

    2009-01-01

    Background A critical issue with nanomaterials is the clear understanding of their potential toxicity. We evaluated the toxic effect of 24 nanoparticles of similar equivalent spherical diameter and various elemental compositions on 2 human pulmonary cell lines: A549 and THP-1. A secondary aim was to elaborate a generic experimental set-up that would allow the rapid screening of cytotoxic effect of nanoparticles. We therefore compared 2 cytotoxicity assays (MTT and Neutral Red) and analyzed 2 time points (3 and 24 hours) for each cell type and nanoparticle. When possible, TC50 (Toxic Concentration 50 i.e. nanoparticle concentration inducing 50% cell mortality) was calculated. Results The use of MTT assay on THP-1 cells exposed for 24 hours appears to be the most sensitive experimental design to assess the cytotoxic effect of one nanoparticle. With this experimental set-up, Copper- and Zinc-based nanoparticles appear to be the most toxic. Titania, Alumina, Ceria and Zirconia-based nanoparticles show moderate toxicity, and no toxicity was observed for Tungsten Carbide. No correlation between cytotoxicity and equivalent spherical diameter or specific surface area was found. Conclusion Our study clearly highlights the difference of sensitivity between cell types and cytotoxicity assays that has to be carefully taken into account when assessing nanoparticles toxicity. PMID:19405955

  7. Effects of surface-modifying ligands on the colloidal stability of ZnO nanoparticle dispersions in in vitro cytotoxicity test media

    PubMed Central

    Kwon, Dongwook; Park, Jonghoon; Park, Jaehong; Choi, Seo Yeon; Yoon, Tae Hyun

    2014-01-01

    The extrinsic physicochemical properties of nanoparticles (NPs), such as hydrodynamic size, surface charge, surface functional group, and colloidal stabilities, in toxicity testing media are known to have a significant influence on in vitro toxicity assessments. Therefore, interpretation of nanotoxicity test results should be based on reliable characterization of the NPs’ extrinsic properties in actual toxicity testing media. Here, we present a set of physicochemical characterization results for commercially available ZnO NPs, including core diameter, hydrodynamic diameter, surface charges, and colloidal stabilities, in two in vitro toxicity testing media (Roswell Park Memorial Institute [RPMI] and Dulbecco’s Modified Eagle’s Medium [DMEM]), as well as simple cell viability assay results for selected ZnO NPs. Four commercially available and manufactured ZnO NPs, with different core sizes, were used in this study, and their surface charge was modified with five different surface coating materials (sodium citrate, tris(2-aminoethyl)amine, poly(acrylic acid), poly(allylamine hydrochloride), and poly-L-lysine hydrochloride). The results showed that ZnO NPs were better dispersed in cell culture media via surface modification with positively or negatively charged molecules. Moreover, in the presence of fetal bovine serum (FBS) in RPMI and DMEM media, ZnO NPs were found even better dispersed for a longer period (at least 48 hours). For the HeLa cells exposed to ZnO NPs in DMEM media without FBS, surface charge-dependent cytotoxicity trends were observed, while these trends were not observed for those cells cultured in FBS-containing media. This confirmed the important roles of surface-modifying compounds and of surface charge on the resultant cytotoxicities of NPs. PMID:25565826

  8. Cytotoxicity of TiO2 nanoparticles to mussel hemocytes and gill cells in vitro: Influence of synthesis method, crystalline structure, size and additive.

    PubMed

    Katsumiti, Alberto; Berhanu, Deborah; Howard, Kieren T; Arostegui, Inmaculada; Oron, Miriam; Reip, Paul; Valsami-Jones, Eugenia; Cajaraville, Miren P

    2015-08-01

    Increasing the production and applications of TiO2 nanoparticles (NPs) has led to grow concerns about the consequences for the environment. In this study, we investigated the effects of a set of TiO2 NPs on the viability of mussel hemocytes and gill cells using neutral red and thiazolyl tetrazolium bromide assays. For this, we compared the cytotoxicity of TiO2 NPs (0.1-100?mg Ti/L) produced by different techniques: rutile NPs (60?nm) produced by milling and containing disodium laureth sulfosuccinate (DSLS), rutile NPs (10, 40 and 60?nm) produced by wet chemistry and anatase/rutile NPs (?100?nm) produced by plasma synthesis. The commercially available P25 anatase/rutile NPs (10-20?nm) were also tested. Exposures were performed in parallel with their respective bulk forms and the cytotoxicity of the additive DSLS was also tested. Z potential values in distilled water indicated different stabilities depending on the NP type and all NPs tested formed agglomerates/aggregates in cell culture media. In general, TiO2 NPs showed a relatively low and dose-dependent toxicity for both cell models with the two assays tested. NPs produced by milling showed the highest effects, probably due to the toxicity of DSLS. Size-dependent toxicity was found for NPs produced by wet chemistry (10?nm?>?40?nm and 60?nm). All TiO2 NPs tested were more toxic than bulk forms excepting for plasma produced ones, which were the least toxic TiO2 tested. The mixture bulk anatase/rutile TiO2 was more toxic than bulk rutile TiO2. In conclusion, the toxicity of TiO2 NPs varied with the mode of synthesis, crystalline structure and size of NPs and can also be influenced by the presence of additives in the suspensions. PMID:25188678

  9. The endoplasmic reticulum is a target organelle for trivalent dimethylarsinic acid (DMA{sup III})-induced cytotoxicity

    SciTech Connect

    Naranmandura, Hua, E-mail: narenman@zju.edu.cn [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China)] [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Xu, Shi [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China)] [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Koike, Shota [Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan)] [Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan); Pan, Li Qiang [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China)] [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Chen, Bin [Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China)] [Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Wang, Yan Wei; Rehman, Kanwal; Wu, Bin [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China)] [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Chen, Zhe [Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou (China)] [Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou (China); Suzuki, Noriyuki, E-mail: n-suzuki@p.chiba-u.ac.jp [Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan)] [Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan)

    2012-05-01

    The purpose of present study was to characterize the endoplasmic reticulum stress and generation of ROS in rat liver RLC-16 cells by exposing to trivalent dimethylarsinous acid (DMA{sup III}) and compared with that of trivalent arsenite (iAs{sup III}) and monomethylarsonous acid (MMA{sup III}). Protein kinase-like endoplasmic reticulum kinase (PERK) phosphorylation was significantly induced in cells exposed to DMA{sup III}, while there was no change in phosphorylated PERK (P-PERK) detected in cells after exposure to iAs{sup III} or MMA{sup III}. The generation of reactive oxygen species (ROS) after DMA{sup III} exposure was found to take place specifically in the endoplasmic reticulum (ER), while previous reports showed that ROS was generated in mitochondria following exposure to MMA{sup III}. Meanwhile, cycloheximide (CHX) which is an inhibitor of protein biosynthesis strongly inhibited the DMA{sup III}-induced intracellular ROS generation in the ER and the phosphorylation of PERK, suggesting the induction of ER stress probably occurs through the inhibition of the protein folding process. Activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) mRNA were induced by all three arsenic species, however, evidence suggested that they might be induced by different pathways in the case of iAs{sup III} and MMA{sup III}. In addition, ER resident molecular chaperone glucose-regulated protein78 (GRP78) was not affected by trivalent arsenicals, while it was induced in positive control only at high concentration (Thapsigargin;Tg), suggesting the GRP78 is less sensitive to low levels of ER stress. In summary, our findings demonstrate that the endoplasmic reticulum is a target organelle for DMA{sup III}-induced cytotoxicity. Highlights: ?ER is a target organelle for trivalent DMA{sup III}-induced cytotoxicity. ?Generation of ROS in ER can be induced specially by trivalent DMA{sup III}. ?ER-stress and generation of ROS are caused by the increase in unfolded proteins.

  10. Strong antibody responses induced by protein antigens conjugated onto the surface of lecithin-based nanoparticles.

    PubMed

    Sloat, Brian R; Sandoval, Michael A; Hau, Andrew M; He, Yongqun; Cui, Zhengrong

    2010-01-01

    An accumulation of research over the years has demonstrated the utility of nanoparticles as antigen carriers with adjuvant activity. Herein we defined the adjuvanticity of a novel lecithin-based nanoparticle engineered from emulsions. The nanoparticles were spheres of around 200nm. Model protein antigens, bovine serum albumin (BSA) or Bacillus anthracis protective antigen (PA) protein, were covalently conjugated onto the nanoparticles. Mice immunized with the BSA-conjugated nanoparticles developed strong anti-BSA antibody responses comparable to that induced by BSA adjuvanted with incomplete Freund's adjuvant and 6.5-fold stronger than that induced by BSA adsorbed onto aluminum hydroxide. Immunization of mice with the PA-conjugated nanoparticles elicited a quick, strong, and durable anti-PA antibody response that afforded protection of the mice against a lethal dose of anthrax lethal toxin challenge. The potent adjuvanticity of the nanoparticles was likely due to their ability to move the antigens into local draining lymph nodes, to enhance the uptake of the antigens by antigen-presenting cells (APCs), and to activate APCs. This novel nanoparticle system has the potential to serve as a universal protein-based vaccine carrier capable of inducing strong immune responses. PMID:19729045

  11. Radio frequency radiation-induced hyperthermia using Si nanoparticle-based sensitizers for mild cancer therapy

    NASA Astrophysics Data System (ADS)

    Tamarov, Konstantin P.; Osminkina, Liubov A.; Zinovyev, Sergey V.; Maximova, Ksenia A.; Kargina, Julia V.; Gongalsky, Maxim B.; Ryabchikov, Yury; Al-Kattan, Ahmed; Sviridov, Andrey P.; Sentis, Marc; Ivanov, Andrey V.; Nikiforov, Vladimir N.; Kabashin, Andrei V.; Timoshenko, Victor Yu

    2014-11-01

    Offering mild, non-invasive and deep cancer therapy modality, radio frequency (RF) radiation-induced hyperthermia lacks for efficient biodegradable RF sensitizers to selectively target cancer cells and thus avoid side effects. Here, we assess crystalline silicon (Si) based nanomaterials as sensitizers for the RF-induced therapy. Using nanoparticles produced by mechanical grinding of porous silicon and ultraclean laser-ablative synthesis, we report efficient RF-induced heating of aqueous suspensions of the nanoparticles to temperatures above 45-50°C under relatively low nanoparticle concentrations (<1 mg/mL) and RF radiation intensities (1-5 W/cm2). For both types of nanoparticles the heating rate was linearly dependent on nanoparticle concentration, while laser-ablated nanoparticles demonstrated a remarkably higher heating rate than porous silicon-based ones for the whole range of the used concentrations from 0.01 to 0.4 mg/mL. The observed effect is explained by the Joule heating due to the generation of electrical currents at the nanoparticle/water interface. Profiting from the nanoparticle-based hyperthermia, we demonstrate an efficient treatment of Lewis lung carcinoma in vivo. Combined with the possibility of involvement of parallel imaging and treatment channels based on unique optical properties of Si-based nanomaterials, the proposed method promises a new landmark in the development of new modalities for mild cancer therapy.

  12. Strong Antibody Responses Induced by Protein Antigens Conjugated onto the Surface of Lecithin-Based Nanoparticles

    PubMed Central

    Sloat, Brian R.; Sandoval, Michael A.; Hau, Andrew M.; He, Yongqun; Cui, Zhengrong

    2009-01-01

    An accumulation of research over the years has demonstrated the utility of nanoparticles as antigen carriers with adjuvant activity. Herein we defined the adjuvanticity of a novel lecithin-based nanoparticle engineered from emulsions. The nanoparticles were spheres of around 200 nm. Model protein antigens, bovine serum albumin (BSA) or Bacillus anthracis protective antigen (PA) protein, were covalently conjugated onto the nanoparticles. Mice immunized with the BSA-conjugated nanoparticles developed strong anti-BSA antibody responses comparable to that induced by BSA adjuvanted with incomplete Freund's adjuvant and 6.5-fold stronger than that induced by BSA adsorbed onto aluminum hydroxide. Immunization of mice with the PA-conjugated nanoparticles elicited a quick, strong, and durable anti-PA antibody response that afforded protection of the mice against a lethal dose of anthrax lethal toxin challenge. The potent adjuvanticity of the nanoparticles was likely due to their ability to move the antigens into local draining lymph nodes, to enhance the uptake of the antigens by antigen-presenting cells (APCs), and to activate APCs. This novel nanoparticle system has the potential to serve as a universal protein-based vaccine carrier capable of inducing strong immune responses. PMID:19729045

  13. Evaluation of antibacterial property induced by surface-modified titanium dioxide nanoparticles

    Microsoft Academic Search

    Weijie Wan; John T. W. Yeow

    2011-01-01

    In this paper, we evaluate excellent antibacterial effect induced by poly(quaternary ammonium) functionalized titanium dioxide nanoparticles without external excitations. The idea originates from the excellent antimicrobial property of quaternary ammonium salts. The effects of poly(quaternary ammonium) and polyacrylate sodium functional groups as nanoparticle surfactants are compared to show that poly(quaternary ammonium) functional groups are responsible for the induced antibacterial effect.

  14. Plasmon-induced Hot Carriers in Metallic Nanoparticles

    NASA Astrophysics Data System (ADS)

    Liu, Jun; Manjavacas, Alejandro; Kulkarni, Vikram; Nordlander, Peter; LANP Team

    2015-03-01

    Plasmon-induced hot carrier formation is attracting an increasing research interest due to its potential for applications in photocatalysis, photodetection and solar energy harvesting. Here we develop a theoretical model for the plasmon-induced hot carrier process and apply it to spherical silver nanoparticles and nanoshells. We show that the inclusion of many-body interactions has only a minor influence on the results. Using the model we calculate the rate of hot carrier generation, finding that it closely follows the spectral profile of the plasmon. Our analysis reveals that particle size and hot carrier lifetime play a central role in determining both the production rate and the energy distribution of the hot carriers. We characterize the efficiency of the hot carrier generation process by introducing a figure of merit that measures the number of high energy carriers generated per plasmon. Furthermore, we analyze the spatial distribution and directionality of these excitations. A. M. acknowledges financial support from the Welch foundation through the J. Evans Attwell-Welch Postdoctoral Fellowship Program of the Smalley Institute of Rice University (Grant No. L-C-004).

  15. Self-assembled and fluorescence enhancement of semiconductor nanoparticles induced by surfactant adsorption

    NASA Astrophysics Data System (ADS)

    Quintana, M.; Pérez, E.

    2007-04-01

    When semiconductor colloidal CdS nanoparticles and nonylphenol are mixed together in dimethyl sulfoxide at room temperature, a self-assembling process is induced. In the course, the size tunable properties of CdS nanoparticles are amplified. A blue shift in the emission spectrum and a strong photoluminescence enhancement are observed without significant change in the absorption features of the colloidal nanoparticles. These results are attributed to the adsorption of nonylphenol onto the nanoparticles surface and to the association process of the surfactant molecules. The surfactant adsorption process provides a nanoparticle surface passivation and induces an associative phase that enlarges the photoluminescence stability. This strategy opens the possibility to improve simultaneously physicochemical and photoluminescence properties of nanocrystals in solution as well as to control their deposition on two-dimensional surfaces.

  16. Protective effect of kombucha tea against tertiary butyl hydroperoxide induced cytotoxicity and cell death in murine hepatocytes.

    PubMed

    Bhattacharya, Semantee; Manna, Prasenjit; Gachhui, Ratan; Sil, Parames C

    2011-07-01

    Kombucha (KT), a fermented black tea (BT), is known to have many beneficial properties. In the present study, antioxidant property of KT has been investigated against tertiary butyl hydroperoxide (TBHP) induced cytotoxicity using murine hepatocytes. TBHP, a reactive oxygen species inducer, causes oxidative stress resulting in organ pathophysiology. Exposure to TBHP caused a reduction in cell viability, increased membrane leakage and disturbed the intra-cellular antioxidant machineries in hepatocytes. TBHP exposure disrupted mitochondrial membrane potential and induced apoptosis as evidenced by flow cytometric analyses. KT treatment, however, counteracted the changes in mitochondrial membrane potential and prevented apoptotic cell death of the hepatocytes. BT treatment also reverted TBHP induced hepatotoxicity, however KT was found to be more efficient. This may be due to the formation of antioxidant molecules like D-saccharic acid-1,4-lactone (DSL) during fermentation process and are absent in BT. Moreover, the radical scavenging activities of KT were found to be higher than BT. Results of the study showed that KT has the potential to ameliorate TBHP induced oxidative insult and cell death in murine hepatocytes more effectively than BT. PMID:21800502

  17. A novel immunogenic CS1-specific peptide inducing antigen-specific cytotoxic T lymphocytes targeting multiple myeloma

    PubMed Central

    Bae, Jooeun; Song, Weihua; Smith, Robert; Daley, John; Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.

    2013-01-01

    The CS1 antigen provides a unique target for the development of an immunotherapeutic strategy to treat patients with multiple myeloma (MM). This study aimed to identify HLA-A2+ immunogenic peptides from the CS1 antigen, which induce peptide-specific cytotoxic T lymphocytes (CTL) against HLA-A2+ MM cells. We identified a novel immunogenic HLA-A2-specific CS1239–247 (SLFVLGLFL) peptide, which induced CS1-specific CTL (CS1-CTL) to MM cells. The CS1-CTL showed a distinct phenotype, with an increased percentage of effector memory and activated CTL and a decreased percentage of naive CTL. CS1239–247 peptide-specific CD8+ T cells were detected by DimerX analyses and demonstrated functional activities specific to the peptide. The CTL displayed HLA-A2-restricted and antigen-specific cytotoxicity, proliferation, degranulation and ?-interferon (IFN-?)production against both primary MM cells and MM cell lines. In addition, the effector memory cells subset (CD45RO?CCR7?/CD3+CD8+) within CS1-CTL showed a higher level of CD107a degranulation and IFN-?production as compared to effector cells (CD45RO?CCR7?/CD3+CD8+) against HLA-A2+ primary MM cells or MM cell lines. In conclusion, this study introduced a novel immunogenic HLA-A2-specific CS1239–247 peptide capable of inducing antigen-specific CTL against MM cells that will provide a framework for its application as a novel MM immunotherapy. PMID:22533610

  18. A novel immunogenic CS1-specific peptide inducing antigen-specific cytotoxic T lymphocytes targeting multiple myeloma.

    PubMed

    Bae, Jooeun; Song, Weihua; Smith, Robert; Daley, John; Tai, Yu-Tzu; Anderson, Kenneth C; Munshi, Nikhil C

    2012-06-01

    The CS1 antigen provides a unique target for the development of an immunotherapeutic strategy to treat patients with multiple myeloma (MM). This study aimed to identify HLA-A2(+) immunogenic peptides from the CS1 antigen, which induce peptide-specific cytotoxic T lymphocytes (CTL) against HLA-A2(+) MM cells. We identified a novel immunogenic HLA-A2-specific CS1(239-247) (SLFVLGLFL) peptide, which induced CS1-specific CTL (CS1-CTL) to MM cells. The CS1-CTL showed a distinct phenotype, with an increased percentage of effector memory and activated CTL and a decreased percentage of naďve CTL. CS1(239-247) peptide-specific CD8(+) T cells were detected by DimerX analyses and demonstrated functional activities specific to the peptide. The CTL displayed HLA-A2-restricted and antigen-specific cytotoxicity, proliferation, degranulation and ?-interferon (IFN-?) production against both primary MM cells and MM cell lines. In addition, the effector memory cells subset (CD45RO(+) CCR7(-) /CD3(+) CD8(+) ) within CS1-CTL showed a higher level of CD107a degranulation and IFN-? production as compared to effector cells (CD45RO(-) CCR7(-) /CD3(+) CD8(+) ) against HLA-A2(+) primary MM cells or MM cell lines. In conclusion, this study introduced a novel immunogenic HLA-A2-specific CS1(239-247) peptide capable of inducing antigen-specific CTL against MM cells that will provide a framework for its application as a novel MM immunotherapy. PMID:22533610

  19. Cerium dioxide nanoparticles induce apoptosis and autophagy in human peripheral blood monocytes.

    PubMed

    Hussain, Salik; Al-Nsour, Faris; Rice, Annette B; Marshburn, Jamie; Yingling, Brenda; Ji, Zhaoxia; Zink, Jeffrey I; Walker, Nigel J; Garantziotis, Stavros

    2012-07-24

    Cerium dioxide nanoparticles (CeO(2) NPs) have diversified industrial uses, and novel therapeutic applications are actively being pursued. There is a lack of mechanistic data concerning the effects of CeO(2) NPs on primary human cells. We aimed at characterizing the cytotoxic effects of CeO(2) NPs in human peripheral blood monocytes. CeO(2) NPs and their suspensions were thoroughly characterized, including using transmission electron microscopy (TEM), dynamic light scattering, and zeta potential analysis. Blood from healthy human volunteers was drawn through phlebotomy, and CD14+ cells were isolated. Cells were exposed to CeO(2) NPs (0.5-10 ?g/mL) for 20 or 40 h, and mechanisms of cell injury were studied. TEM revealed that CeO(2) NPs are internalized by monocytes and are found either in vesicles or free in the cytoplasm. CeO(2) NP exposure leads to decrease in cell viability, and treated cells exhibit characteristic hallmarks of apoptosis (activation of Bax, loss of mitochondrial membrane potential, DNA fragmentation). CeO(2) NP toxicity is caused by mitochondrial damage and overexpression of apoptosis inducing factor, but is not due to caspase activation or reactive oxygen species production. Moreover, CeO(2) NP exposure leads to autophagy, which is further increased after pharmacological inhibition of tumor suppressor protein p53. Inhibition of autophagy partially reverses cell death by CeO(2) NPs. It is concluded that CeO(2) NPs are toxic to primary human monocytes at relatively low doses. PMID:22717232

  20. Preparation and evaluation of charged solid lipid nanoparticles of tetrandrine for ocular drug delivery system: pharmacokinetics, cytotoxicity and cellular uptake studies.

    PubMed

    Li, Jiawei; Guo, Xiujun; Liu, Zhidong; Okeke, Chukwunweike Ikechukwu; Li, Nan; Zhao, Hainan; Aggrey, Mike Okweesi; Pan, Weisan; Wu, Tao

    2014-07-01

    In this study, tetrandrine-loaded cationic solid lipid nanoparticles (TET-CNP) and solid lipid nanoparticles (TET-NP) were prepared by the emulsion evaporation-solidification at low temperature method. The particle size, zeta potential, and entrapment efficiency of TET-CNP and TET-NP were characterized. The results showed that the TET-CNP and TET-NP had average diameters of (15.29?±?1.34) nm and (18.77?±?1.23) nm with zeta potentials of (5.11?±?1.03) mV and (-8.71?±?-1.23) mV and entrapment efficiencies of (94.1?±?2.37)% and (95.6?±?2.43)%, respectively. In vitro release studies indicated that the TET-CNP and TET-NP retained the drug entity better than tetrandrine ophthalmic solutions (TET-SOL). In the pharmacokinetics studies, the AUC values of TET-CNP and TET-NP were 1.96-fold and 2.00-fold higher than that of TET-SOL (?p?Cytotoxicity study showed that TET-CNP and TET-NP had no significant toxicity at low concentrations. Flow cytometry studies and confocal microscopy analysis demonstrated that calcein labeled NP (CA-NP) uptake by SRA 01/04 cells was much higher than those of calcein labeled CNP (CA-CNP) and calcein solution (CA-SOL). PMID:23662696

  1. Arginine-assisted immobilization of silver nanoparticles on ZnO nanorods: an enhanced and reusable antibacterial substrate without human cell cytotoxicity.

    PubMed

    Agnihotri, Shekhar; Bajaj, Geetika; Mukherji, Suparna; Mukherji, Soumyo

    2015-04-28

    Silver-based hybrid nanomaterials are gaining interest as potential alternatives for conventional antimicrobial agents. Herein, we present a simple, facile and eco-friendly approach for the deposition of silver nanoparticles (AgNPs) on ZnO nanorods, which act as a nanoreactor for in situ synthesis and as an immobilizing template in the presence of arginine. The presence of arginine enhanced the stability of ZnO deposition on the glass substrate by hindering the dissolution of zinc under alkaline conditions. Various Ag/ZnO hybrid nanorod (HNR) samples were screened to obtain a high amount of silver immobilization on the ZnO substrate. Ag/ZnO HNRs displayed potent antibacterial ability and could achieve 100% kill for both Escherichia coli and Bacillus subtilis strains under various test conditions. The hybrid material mediated its dual mode of antibacterial action through direct contact-killing and release of silver ions/nanoparticles and showed superior bactericidal performance compared to pure ZnO nanorods and colloidal AgNPs. No significant decline in antibacterial efficacy was observed even after the same substrate was repeatedly reused multiple times. Interestingly, the amount of Ag and Zn release was much below their maximal limit in drinking water, thus preventing potential health hazards. Immobilized AgNPs showed no cytotoxic effects on the human hepatocarcinoma cell line (HepG2). Moreover, treating cells with the antibacterial substrate for 24 hours did not lead to significant generation of reactive oxygen species (ROS). The good biocompatibility and bactericidal efficacy would thus make it feasible to utilize this immobilization strategy for preparing new-generation antibacterial coatings. PMID:25830178

  2. The p53-inducible gene 3 involved in flavonoid-induced cytotoxicity through the reactive oxygen species-mediated mitochondrial apoptotic pathway in human hepatoma cells.

    PubMed

    Zhang, Qiang; Cheng, Guangdong; Qiu, Hongbin; Zhu, Liling; Ren, Zhongjuan; Zhao, Wei; Zhang, Tao; Liu, Lei

    2015-05-13

    Flavonoids have been reported to exhibit prooxidant cytotoxicity against cancer cells, but the underlying mechanism is still poorly understood. Here we investigated the potential mechanism that p53-inducible gene 3 (PIG3), a NADPH:quinone oxidoreductase, mediated the prooxidant cytotoxicity of flavonoids on human hepatoma HepG2 cells. The results showed that flavonoids (apigenin, luteolin, kaempferol, and quercetin) inhibited the growth of HepG2 cells in a dosage- and time-dependent manner, and induced the morphological changes characteristic of apoptosis in HepG2 cells. We also found that expression of PIG3 was increased markedly in HepG2 cells treated with flavonoids at both mRNA and protein levels, which was accompanied by increased intracellular ROS production and a decreased mitochondrial membrane potential (??m). All these effects were largely reversed through knockdown of the PIG3 gene in HepG2 cells. Western blotting indicated that flavonoids increased cytochrome c release, upregulated the ratio of Bax/Bcl-2, and activated the caspases-9 and -3. Moreover, knockdown of PIG3 could reverse the changes of these apoptotic-related proteins. These results suggest that PIG3 plays an important role in regulating the prooxidant activity and apoptosis-inducing action of flavonoids on HepG2 cells though the ROS-triggered mitochondrial apoptotic pathway. PMID:25820747

  3. Triphenyltin acetate-induced cytotoxicity and CD4(+) and CD8(+) depletion in mouse thymocyte primary cultures.

    PubMed

    Dacasto, M; Cornaglia, E; Nebbia, C; Bollo, E

    2001-12-28

    Organotin compounds (OTs) find application worldwide as catalysts, stabilizers and biocides. Triphenyltin derivatives (TPs), including the fungicide triphenyltin acetate (TPTA), are OTs mostly used in our country. Some OTs were proved to be immunotoxic and in this paper the cytotoxicity, the possible selective activity upon definite lymphocyte subsets as well as the antiproliferative effect of TPTA was investigated in vitro by using primary cultures of mouse thymocytes. TPTA (5, 10 and 25 microM) was cytotoxic to these cells, as demonstrated by the significant (P<0.05) reduction of the cell viability percentage (trypan blue dye exclusion test), the neutral red uptake and the reduction of tetrazolium salts to formazan products (MTT assay). These overt effects were already noticed after 4 h of exposure to TPTA. The fungicide otherwise significantly reduced, after 24 h of incubation, the percentage of mature single positive thymocytes, particularly the CD4(+)/CD8(-) one. Finally, a significative dose-dependent inhibition of the T-cell mitogen-induced cell proliferation was observed in thymocytes exposed to 1 and 8 microM TPTA. These results are indicative of the TPTA immunotoxic properties, according to previous published reports concerning the in vitro and in vivo toxicity of some di- and triorganotin compounds. PMID:11718962

  4. Extracts of Artemisia ciniformis Protect Cytotoxicity Induced by Hydrogen Peroxide in H9c2 Cardiac Muscle Cells through the Inhibition of Reactive Oxygen Species.

    PubMed

    Mojarrab, Mahdi; Jamshidi, Maryam; Ahmadi, Farahnaz; Alizadeh, Ellahe; Hosseinzadeh, Leila

    2013-01-01

    Objective. Artemisia ciniformis (Asteraceae) and A. biennis are two of 34 Artemisia species growing naturally in Iran. In this study we investigated whether different extracts of A. ciniformis and A. biennis have protective effect against hydrogen peroxide-induced cytotoxicity in rat cardiomyoblast cells (H9c2). Method. The dried and ground aerial parts of these two species were extracted successively using petroleum ether (40-60), dichloromethane, ethyl acetate (EA), ethanol (EtOH) and ethanol?:?water (1?:?1) by maceration method. To evaluate whether different extracts of A. ciniformis and A. biennis protect cardiomyoblast H9c2 cells from H2O2 cytotoxicity, we examined the direct cytotoxic effect of H2O2 on H9c2 cells in the presence and absence of different extracts. After then, cell viability was measured by MTT assay. Results. H2O2 induced cytotoxicity in a concentration dependent manner. The IC50 value was 62.5? ? M for 24?h exposure. However, pretreatment of cells with various concentrations of EA, EtOH, and EtOH/wt extract of A. ciniformis protected cells from H2O2-induced cytotoxicity. Moreover, pretreatment with EA, EtOH and EtOH/wt extracts of A. ciniformis lead to a decrease in the reactive oxygen species (ROS) generation. Taken together our observation indicated that nontoxic concentration of different extracts of A. ciniformis has protective effect on H2O2-induced cytotoxicity in H9c2 cells. PMID:24381586

  5. Communication: Nanosize-induced restructuring of Sn nanoparticles

    SciTech Connect

    Sabet, Sareh [Institute of Materials Science, Technical University of Darmstadt, Alarich-Weiss-Strasse 2, 64287 Darmstadt (Germany); Kaghazchi, Payam, E-mail: payam.kaghazchi@fu-berlin.de [Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin (Germany)

    2014-05-21

    Stabilities and structures of ?- and ?-Sn nanoparticles are studied using density functional theory. Results show that ?-Sn nanoparticles are more stable. For both phases of Sn, nanoparticles smaller than 1 nm (?48 atoms) are amorphous and have a band gap between 0.4 and 0.7 eV. The formation of band gap is found to be due to amorphization. By increasing the size of Sn nanoparticles (1–2.4 nm), the degree of crystallization increases and the band gap decreases. In these cases, structures of the core of nanoparticles are bulk-like, but structures of surfaces on the faces undergo reconstruction. This study suggests a strong size dependence of electronic and atomic structures for Sn nanoparticle anodes in Li-ion batteries.

  6. A Comparison between Cytotoxicity Induced by Two Resin Based Sealers (2Seal and AH Plus) in Saos-2 and MG-63 Cell Lines

    PubMed Central

    Ehsani, Maryam; Zabihi, Ebrahim; Gharouee, Hamed

    2012-01-01

    The aim of this study was to evaluate and compare the cytotoxicity induced by two resin-based sealers, 2Seal and AH Plus, in two osteoblast-like cell lines, MG-63 and Saos-2. Using sterile discs of both sealers in complete media, 24- and 72-h extracts were prepared. The extracts were exchanged with Saos-2 or MG-63 cell culture media at 75% confluence, and after 24 h incubation, cell viability tests were performed for each extract and cell line using MTT and trypan blue dye exclusion assays. Corresponding incubated media were used as negative control groups. For both extracts and sealers, cytotoxicity was observed in both cell lines. For Saos-2, there was no statistical difference in toxicity between the sealers for either extract (p > 0.05). For MG-63, the 2Seal 24-h extract and the AH Plus 72-h extract had greater cytotoxicity than the other extracts (p < 0.05(. Both AH Plus and 2Seal demonstrated significant cytotoxicity in these two cell lines. In contrast to 2Seal, the cytotoxicity of AH Plus in the MG-63 cell line increased with extraction time from 24 to 72 h. The AH Plus and 2Seal 24-h extracts showed different levels of cytotoxicity in the MG-63 cell line, while in the Saos-2 cell line there were no detectable differences. This may reflect higher sensitivity of the MG-63 cell line compared to Saos-2 toward cytotoxicity induced by these two sealers, or different kinetics of toxicant release from the sealers. PMID:24551778

  7. Mitophagy induced by nanoparticle-peptide conjugates enabling an alternative intracellular trafficking route.

    PubMed

    Zhang, Zhaolei; Zhou, Lei; Zhou, Yanqing; Liu, Jinyin; Xing, Xiaoyun; Zhong, Jun; Xu, Guoqiang; Kang, Zhenhui; Liu, Jian

    2015-10-01

    The intracellular behaviors of nanoparticles are fundamentally important for the evaluation of their biosafety and the designs of nano carrier-assisted drug delivery with high therapeutic efficacy. It is still in a great need to discover how functionalized nanoparticles are transported inside the cells, for instance, in a complicated fashion of translocation between different types of cell organelles. Here we report a new understanding of the interactions between nanoparticles and cells by the development of polyoxometalates nanoparticle-peptide conjugates and investigation of their intracellular trafficking behaviors. The as-prepared nanoparticles are featured with a unique combination of fluorescence and high contrast for synchrotron X-ray-based imaging. Functional surface modification with peptides facilitates effective delivery of the nanoparticles onto the target organelle (mitochondria) and subsequent intracellular trafficking in a dynamic mode. Interestingly, our experimental results have revealed that autophagy of mitochondria (mitophagy) can be induced by NP-peptide as a cellular response for recycling the damaged organelles, through molecular mediation associated with the change of mitochondrial membrane potential. The biological effects induced by NP-peptide reciprocally affect the distribution patterns and fates of nanoparticles in the cell metabolism by providing an alternative route of intracellular trafficking. The new understanding of the mutual activities between nanoparticles and cells will enrich our approaches in the development of nanobiotechnology and nano-medicine for disease treatments. PMID:26142776

  8. In vitro cytotoxicity tests of ZnO?Bi{sub 2}O{sub 3}?Mn{sub 2}O{sub 3}-based varistor fabricated from ZnO micro and nanoparticle powders on L929 mouse cells

    SciTech Connect

    Sendi, Rabab Khalid, E-mail: last-name3@hotmail.com, E-mail: shahromx@hotmail.com, E-mail: ameerah7@hotmail.com; Mahmud, Shahrom, E-mail: last-name3@hotmail.com, E-mail: shahromx@hotmail.com, E-mail: ameerah7@hotmail.com; Munshi, Ayman, E-mail: last-name3@hotmail.com, E-mail: shahromx@hotmail.com, E-mail: ameerah7@hotmail.com [Nano-optoelectronics Research and Technology Laboratory (N.O.R.), School of Physics, Universiti Sains Malaysia, 11800, Penang (Malaysia); Seeni, Azman, E-mail: azanseeni@gmail.com [Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, 13200, Bertam, Pulau Pinang (Malaysia)

    2014-10-24

    The present study investigated the cytotoxicity of ZnO?Bi{sub 2}O{sub 3}?Mn{sub 2}O{sub 3}-varistors. To this effect, ZnO?Bi{sub 2}O{sub 3}?Mn{sub 2}O{sub 3} varistors fabricated from ZnO micro-and nanoparticle powders are prepared via conventional ceramic processing method. The effects of ZnO particle size on the properties of ZnO varistors are also investigated. The strong solid-state reaction during sintering may be attributed to the high surface area of the 20 nm ZnO nanoparticles that promote strong surface reaction. The intensity of XRD peaks reflected the high degree of crystallinity of the ZnO nanoparticles. However, the width of the peaks in case of ZnO nanoparticles has increased due to the quantum size effect. The cytotoxicity evaluation of ZnO varistor was conducted on mouse connective tissue fibroblast cells (L929) using Trypan Blue Exclusion Assay analysis. The results show that the four types of varistor samples lead to cellular mitochondrial dysfunction, morphological modifications and apoptosis at the various concentration range and the toxic effects are obviously displayed in high concentration samples. 20nm-VDR is the most toxic materials followed by 40nm-VDR, P8-VDR, and W4-VDR in a descending order.

  9. Electron-induced adhesion and patterning of gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Torchinsky, I.; Amdursky, N.; Inberg, A.; Rosenman, G.

    2010-03-01

    Self assembly of ligand-covered gold nanoparticles from water colloid solution on silicon dioxide substrate, modified, and patterned by low energy electron beam, has been observed. High selective adhesion of Au-nanoparticles on hydrophobic regions of wettability patterning was discovered and has been explained within the framework of the classical thermodynamic theory of particle adhesion on a substrate immersed into the colloid solution. The Au-nanoparticles patterns were imaged using confocal microscopy. Our results indicate that the developed technique may be considered as high resolution and environmentally clean technology for nanoparticles adhesion for metal nanoelectrode deposition, development of biosensor arrays, and nanophotonic devices.

  10. Evolution of light-induced vapor generation at a liquid-immersed metallic nanoparticle

    PubMed Central

    Zhen, Yu-Rong; Neumann, Oara; Polman, Albert; García de Abajo, F. Javier

    2013-01-01

    When an Au nanoparticle in a liquid medium is illuminated with resonant light of sufficient intensity, a nanometer scale envelope of vapor -a “nanobubble”- surrounding the particle, is formed. This is the nanoscale onset of the well-known process of liquid boiling, occurring at a single nanoparticle nucleation site, resulting from the photothermal response of the nanoparticle. Here we examine bubble formation at an individual metallic nanoparticle in detail. Incipient nanobubble formation is observed by monitoring the plasmon resonance shift of an individual, illuminated Au nanoparticle, when its local environment changes from liquid to vapor. The temperature on the nanoparticle surface is monitored during this process, where a dramatic temperature jump is observed as the nanoscale vapor layer thermally decouples the nanoparticle from the surrounding liquid. By increasing the intensity of the incident light or decreasing the interparticle separation, we observe the formation of micron sized bubbles resulting from the coalescence of nanoparticle-“bound” vapor envelopes. These studies provide the first direct and quantitative analysis of the evolution of light-induced steam generation by nanoparticles from the nanoscale to the macroscale, a process that is of fundamental interest for a growing number of applications. PMID:23517407

  11. ACTX-8, a cytotoxic l-amino acid oxidase isolated from Agkistrodon acutus snake venom, induces apoptosis in Hela cervical cancer cells

    Microsoft Academic Search

    Liang Zhang; Li-Jun Wei

    2007-01-01

    ACTX-8 is a protein isolated from Agkistrodon acutus snake venom in our laboratory. It demonstrates cytotoxic activity on various carcinoma cell lines in vitro. However, the mechanism by which ACTX-8 inhibits cell proliferation remains poorly understood. In this study the influence of ACTX-8 on the activation of apoptotic pathway in Hela cells was investigated. We demonstrated that cell death induced

  12. Further characterization of suppressor lymphocytes induced by fetal calf serum in murine lymphoid cell cultures: comparison with in vitro-generated cytotoxic lymphocytes. [X Radiation

    Microsoft Academic Search

    E. Kedar; M. Schwartzach

    1979-01-01

    Nonspecific suppressor cell (SPC) activity has been induced in vitro by preculturing splenocytes from normal mice in the presence of fetal calf serum (FCS) for 3 days or more. In adoptive transfer experiments in vivo, these precultured SPC were shown to reduce the humoral response of mice to SRBC and the cell-mediated cytotoxic (CMC) response to allogeneic tumor cells. In

  13. The Effect of Seal Oil on Paclitaxel Induced Cytotoxicity and Apoptosis in Breast Carcinoma MCF7 and MDA-MB-231 Cell Lines

    Microsoft Academic Search

    Zheyu Wang; Krista Butt; Lili Wang; Hu Liu

    2007-01-01

    Some studies have suggested that ?-3 polyunsaturated fatty acids (PUFAs) have an inhibitory effect on the growth of cancer cells and therefore have the potential to increase the efficacy of cancer chemotherapeutic drugs. Considering that ?-3 PUFAs are present abundantly in harp seal oil, we investigated the effect of seal oil on the cytotoxicity and apoptosis induced by paclitaxel in

  14. Cytotoxicity of aluminum oxide nanoparticles on Allium cepa root tip-effects of oxidative stress generation and biouptake.

    PubMed

    Rajeshwari, A; Kavitha, S; Alex, Sruthi Ann; Kumar, Deepak; Mukherjee, Anita; Chandrasekaran, Natarajan; Mukherjee, Amitava

    2015-07-01

    The commercial usage of Al2O3 nanoparticles (Al2O3 NPs) has gone up significantly in the recent times, enhancing the risk of environmental contamination with these agents and their consequent adverse effects on living systems. The current study has been designed to evaluate the cytogenetic potential of Al2O3 NPs in Allium cepa (root tip cells) at a range of exposure concentrations (0.01, 0.1, 1, 10, and 100 ?g/mL), their uptake/internalization profile, and the oxidative stress generated. We noted a dose-dependent decrease in the mitotic index (42 to 28 %) and an increase in the number of chromosomal aberrations. Various chromosomal aberrations, e.g. sticky, multipolar and laggard chromosomes, chromosomal breaks, and the formation of binucleate cells, were observed by optical, fluorescence, and confocal laser scanning microscopy. FT-IR analysis demonstrated the surface chemical interaction between the nanoparticles and root tip cells. The biouptake of Al2O3 in particulate form led to reactive oxygen species generation, which in turn probably contributed to the induction of chromosomal aberrations. PMID:25794585

  15. Protective effects of aloe-emodin on scopolamine-induced memory impairment in mice and H?O?-induced cytotoxicity in PC12 cells.

    PubMed

    Tao, Li; Xie, Jianmei; Wang, Yuting; Wang, Shi; Wu, Shuangchan; Wang, Qiman; Ding, Hong

    2014-12-01

    Aloe-emodin (AE) is one of the most important active components of Rheum officinale Baill. The present study aimed to investigate that AE could attenuate scopolamine-induced cognitive deficits via inhibiting acetylcholinesterase (AChE) activity and modulating oxidative stress. Kunming (KM) mice were received intraperitoneal injection of scopolamine (2 mg/kg) to induce cognitive impairment. Learning and memory performance were assessed in the Morris water maze (MWM). After behavioral testing, the mice were sacrificed and their hippocampi were removed for biochemical assays (superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), AChE and acetylcholine (ACh)). In vitro, we also performed the AChE activity assay and H?O?-induced PC12 cells toxicity assay. After 2 h exposure to 200 ?M H?O? in PC12 cells, the cytotoxicity were evaluated by cell viability (MTT), nitric oxide (NO)/lactate dehydrogenase (LDH) release and intracellular reactive oxygen species (ROS) production. Our results confirmed that AE showed significant improvement in cognitive deficit in scopolamine-induced amnesia animal model. Besides, it increased SOD, GPx activities and ACh content, while decreased the level of MDA and AChE activity in AE treated mice. In addition, AE was found to inhibit AChE activity (IC?? = 18.37 ?g/ml) in a dose-dependent manner. Furthermore, preincubation of PC12 cells with AE could prevent cytotoxicity induced by H?O? and reduce significantly extracellular release of NO, LDH and intracellular accumulation of ROS. The study indicated that AE could have neuroprotective effects against Alzheimer's disease (AD) via inhibiting the activity of AChE and modulating oxidative stress. PMID:25453793

  16. Characterizing the mechanism for ginsenoside-induced cytotoxicity in cultured leukemia (THP-1) cells.

    PubMed

    Kitts, David D; Popovich, David G; Hu, Chun

    2007-11-01

    Pure ginsenoside standards (saponins Rh2, PD, and PT), along with an Rh2-enhanced North American ginseng (Panax quinquefolius) leaf extract (LFRh2), were tested for cytotoxic activity in cultured THP-1 leukemia cells. Thermal treatment of ginseng leaf resulted in production of both Rh2 and Rg3 content that was confirmed by liquid chromatography - mass spectrometry (LC-MS). Flow cytometry of cells stained with annexin V - fluorescein isothiocyanate and propidium iodide showed that the LFRh2 significantly (p < or = 0.05) increased apoptosis (18% +/- 0.4%) after 23 h at a concentration that inhibited cell viability by 50% (LC50 (72 h) = 52 microg/mL. In comparison, a similar significant (p < or = 0.05) increase in apoptotic cell numbers occurred at 41 h of exposure for pure ginsenoside standards, PD (LC50 (72 h) = 13 microg/mL), PT (LC50 (72 h) = 19 microg/mL), and Rh2 (LC50 (72 h) = 15 microg/mL). Although no further increase in apoptosis was observed in THP-1 cells after exposure to increasing concentrations of LFRh2 and pure Rh2, PD, and PT standards, a significant (p < 0.05) increase in the percentage of necrotic cells did occur after exposure of cells to different ginsenosides at elevated concentrations. THP-1 caspase-3 activity was greatest (p cytotoxicity and reduced cell proliferation of different ginsenosides in cultured THP-1 cells. Moreover, thermal treatment of North American ginseng leaf produced a marked transformation of ginsenoside, largely attributable to an increase in Rh2 content. This change was associated with cytotoxic properties in THP-1 cell that were related to alterations in cell membrane properties, which were also obtained with the pure ginsenosides PD, PT, and Rh2. PMID:18066119

  17. Formation of silicon nanoparticles by a pressure induced nucleation mechanism.

    PubMed

    Kang, Myung-Koo; Kim, Si Joon; Kim, Hyun Jae

    2013-04-21

    Formation of silicon nanoparticles (SiNPs) was achieved using excimer laser crystallization of an amorphous Si (a-Si) thin film using a SiO2 capping layer (C/L) with improved thin-film transistor (TFT) performance due to the enlarged grain size of polycrystalline Si (poly-Si). After laser irradiation of an a-Si thin film covered with C/L, fluctuation in the surface morphology of the C/L was observed above the critical laser energy density (Ecr) with the formation of SiNPs. The grain size of the poly-Si layer after crystallization increased abruptly at the same time. A non-uniform pressure distribution beneath the SiO2 C/L was proposed for the initiation of nucleation, which is named pressure induced nucleation (PIN) mechanism. Following nucleation, the release of latent heat made it difficult for the remnant liquid Si to solidify and the volume increased due to the density difference between the liquid and solid Si. Consequently, the pressure on the liquid Si caused SiNPs to sprout through the SiO2 C/L as grains grew from the low temperature to high temperature point. This study offers not only a simple method to fabricate SiNPs with controllable size/density but also larger grain size with lower laser energy density, which leads to higher TFT performance. PMID:23467641

  18. Dynamics of laser induced metal nanoparticle and pattern formation

    NASA Astrophysics Data System (ADS)

    Peláez, R. J.; Kuhn, T.; Rodríguez, C. E.; Afonso, C. N.

    2015-02-01

    Discontinuous metal films are converted into either almost round, isolated, and randomly distributed nanoparticles (NPs) or fringed patterns of alternate non transformed film and NPs by exposure to single pulses (20 ns pulse duration and 193 nm wavelength) of homogeneous or modulated laser beam intensity. The dynamics of NPs and pattern formation is studied by measuring in real time the transmission and reflectivity of the sample upon homogeneous beam exposure and the intensity of the diffraction orders 0 and 1 in transmission configuration upon modulated beam exposure. The results show that laser irradiation induces melting of the metal either completely or at regions around intensity maxima sites for homogeneous and modulated beam exposure, respectively, within ?10 ns. The aggregation and/or coalescence of the initially irregular metal nanostructures is triggered upon melting and continues after solidification (estimated to occur at ?80 ns) for more than 1 ?s. The present results demonstrate that real time transmission rather than reflectivity measurements is a valuable and easy-to-use tool for following the dynamics of NPs and pattern formation. They provide insights on the heat-driven processes occurring both in liquid and solid phases and allow controlling in-situ the process through the fluence. They also evidence that there is negligible lateral heat release in discontinuous films upon laser irradiation.

  19. Sensitization of TNF-induced cytotoxicity in lung cancer cells by concurrent suppression of the NF-{kappa}B and Akt pathways

    SciTech Connect

    Wang Xia [Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108 (United States); Chen Wenshu [Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108 (United States); Lin Yong [Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108 (United States)]. E-mail: ylin@lrri.org

    2007-04-13

    Blockage of either nuclear factor-{kappa}B (NF-{kappa}B) or Akt sensitizes cancer cells to TNF-induced apoptosis. In this study, we investigated the undetermined effect of concurrent blockage of these two survival pathways on TNF-induced cytotoxicity in lung cancer cells. The results show that Akt contributes to TNF-induced NF-{kappa}B activation in lung cancer cells through regulating phosphorylation of the p65/RelA subunit of NF-{kappa}B. Although individually blocking IKK or Akt partially suppressed TNF-induced NF-{kappa}B activation, concurrent suppression of these pathways completely inhibited TNF-induced NF-{kappa}B activation and downstream anti-apoptotic gene expression, and synergistically potentiated TNF-induced cytotoxicity. Moreover, suppression of Akt inhibited the Akt-mediated anti-apoptotic pathway through dephosphorylation of BAD. These results indicate that concurrent suppression of NF-{kappa}B and Akt synergistically sensitizes TNF-induced cytotoxicity through blockage of distinct survival pathways downstream of NF-{kappa}B and Akt, which may be applied in lung cancer therapy.

  20. Induced Resistance to Ofatumumab Mediated Cell Clearance Mechanisms, Including Complement Dependent Cytotoxicity, in Chronic Lymphocytic Leukemia

    PubMed Central

    Baig, Nisar A.; Taylor, Ronald P.; Lindorfer, Margaret A.; Church, Amy K.; LaPlant, Betsy R.; Pettinger, Adam M.; Shanafelt, Tait D.; Nowakowski, Grzegorz S.; Zent, Clive S.

    2014-01-01

    Ofatumumab (OFA), a human CD20 targeting mAb, kills B-lymphocytes utilizing the innate immune system including complement dependent cytotoxicity (CDC). The efficacy of OFA in patients with chronic lymphocytic leukemia (CLL) is limited by drug resistance, which is not well characterized. To better understand mechanisms of resistance, we prospectively studied CLL cells isolated from blood samples collected before and after in vivo exposure to the initial dose of OFA therapy in 25 patients undergoing their first treatment for progressive CLL. As previously reported, OFA therapy rapidly decreased the absolute lymphocyte count, CD20 expression by CLL cells, and serum complement levels. We now show that after administration of the first dose of OFA, there was a modest rebound in the absolute lymphocyte count and serum complement levels, but substantial ongoing loss of CD20 expression by CLL cells. These post-OFA treatment CLL cells were highly resistant to OFA-mediated CDC but retained sensitivity to alemtuzumab-mediated CDC in vitro. Post-therapy serum OFA levels correlated inversely with both the amount of pre-treatment circulating cell bound CD20 and with the decrease in this value following treatment. In vitro OFA-mediated CDC did not predict clinical responses and the patients with “first dose” reactions to OFA did not have markers of increased complement activation in vivo. We propose that optimal efficacy of CD20 targeted therapy for CLL requires determining a mAb dose size and frequency that optimizes CLL killing without exceeding the capacity of the cytotoxic mechanisms and thus minimizes loss of CD20 expression in the surviving CLL cells. PMID:24431228

  1. Yeast DEL Assay Detects Protection against Radiation-Induced Cytotoxicity and Genotoxicity: Adaptation of a Microtiter Plate Version

    PubMed Central

    Hafer, Kurt; Rivina, Yelena; Schiestl, Robert H.

    2010-01-01

    The DEL assay in yeast detects DNA deletions that are inducible by many carcinogens. Here we use the colorimetric agent MTS to adapt the yeast DEL assay for microwell plate measurement of ionizing radiation-induced cell killing and DNA deletions. Using the microwell-based DEL assay, cell killing and genotoxic DNA deletions both increased with radiation dose between 0 and 2000 Gy. We used the microwell-based DEL assay to assess the effectiveness of varying concentrations of five different radioprotectors, N-acetyl-l-cysteine, l-ascorbic acid, DMSO, Tempol and Amifostine, and one radiosensitizer, 5-bromo-2-deoxyuridine. The microwell format of the DEL assay was able to successfully detect protection against and sensitization to both radiation-induced cytotoxicity and genotoxicity. Such radioprotection and sensitization detected by the micro-well-based DEL assay was validated and compared with similar measurements made using the traditional agar-based assay format. The yeast DEL assay in microwell format is an effective tool for rapidly detecting chemical protectors and sensitizers to ionizing radiation and is automatable for chemical high-throughput screening purposes. PMID:21128795

  2. Yeast DEL assay detects protection against radiation-induced cytotoxicity and genotoxicity: adaptation of a microtiter plate version.

    PubMed

    Hafer, Kurt; Rivina, Yelena; Schiestl, Robert H

    2010-12-01

    The DEL assay in yeast detects DNA deletions that are inducible by many carcinogens. Here we use the colorimetric agent MTS to adapt the yeast DEL assay for microwell plate measurement of ionizing radiation-induced cell killing and DNA deletions. Using the microwell-based DEL assay, cell killing and genotoxic DNA deletions both increased with radiation dose between 0 and 2000 Gy. We used the microwell-based DEL assay to assess the effectiveness of varying concentrations of five different radioprotectors, N-acetyl-l-cysteine, l-ascorbic acid, DMSO, Tempol and Amifostine, and one radiosensitizer, 5-bromo-2-deoxyuridine. The microwell format of the DEL assay was able to successfully detect protection against and sensitization to both radiation-induced cytotoxicity and genotoxicity. Such radioprotection and sensitization detected by the microwell-based DEL assay was validated and compared with similar measurements made using the traditional agar-based assay format. The yeast DEL assay in microwell format is an effective tool for rapidly detecting chemical protectors and sensitizers to ionizing radiation and is automatable for chemical high-throughput screening purposes. PMID:21128795

  3. Temperature induced phase separation of luminescent silica nanoparticles in Triton X-100 solutions.

    PubMed

    Mustafina, Asiya R; Elistratova, Julia G; Bochkova, Olga D; Burilov, Vladimir A; Fedorenko, Svetlana V; Konovalov, Alexander I; Soloveva, Svetlana Ye

    2011-02-15

    The aggregation and cloud point behavior of Tb(III)-doped silica nanoparticles has been studied in Triton X-100 (TX-100) solutions at various concentration conditions by fluorimetry, dynamic light scattering, electrophoresis and transmission electron microscopy methods. The temperature responsive behavior of nanoparticles is observed at definite concentration of TX-100, where the aggregation of TX-100 at the silica/water interface is evident from the increased size of the silica nanoparticles. The reversible dehydration of TX-100 aggregates at the silica/water interface should be assumed as the main reason of the temperature induced phase separation of silica nanoparticles. The distribution of nanoparticles between aqueous and surfactant rich phases at the phase separation conditions can be modified by the effect of additives. PMID:21163490

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

    PubMed Central

    2013-01-01

    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. PMID:24225302

  5. Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studies

    NASA Astrophysics Data System (ADS)

    Sanna, Vanna; Roggio, Anna Maria; Posadino, Anna Maria; Cossu, Annalisa; Marceddu, Salvatore; Mariani, Alberto; Alzari, Valeria; Uzzau, Sergio; Pintus, Gianfranco; Sechi, Mario

    2011-12-01

    Docetaxel (Dtx) chemotherapy is the optional treatment in patients with hormone-refractory metastatic prostate cancer, and Dtx-loaded polymeric nanoparticles (NPs) have the potential to induce durable clinical responses. However, alternative formulations are needed to overcome the serious side effects, also due to the adjuvant used, and to improve the clinical efficacy of the drug. In the present study, two novel biodegradable block-copolymers, poly(lactide-co-caprolactone) (PLA-PCL) and poly(lactide-co-caprolactone-co-glycolide) (PLGA-PCL), were explored for the formulation of Dtx-loaded NPs and compared with PLA- and PLGA-NPs. The nanosystems were prepared by an original nanoprecipitation method, using Pluronic F-127 as surfactant agent, and were characterized in terms of morphology, size distribution, encapsulation efficiency, crystalline structure, and in vitro release. To evaluate the potential anticancer efficacy of a nanoparticulate system, in vitro cytotoxicity studies on human prostate cancer cell line (PC3) were carried out. NPs were found to be of spherical shape with an average diameter in the range of 100 to 200 nm and a unimodal particle size distribution. Dtx was incorporated into the PLGA-PCL NPs with higher ( p < 0.05) encapsulation efficiency than that of other polymers. Differential scanning calorimetry suggested that Dtx was molecularly dispersed in the polymeric matrices. In vitro drug release study showed that release profiles of Dtx varied on the bases of characteristics of polymers used for formulation. PLA-PCL and PLGA-PCL drug loaded NPs shared an overlapping release profiles, and are able to release about 90% of drug within 6 h, when compared with PLA- and PLGA-NPs. Moreover, cytotoxicity studies demonstrated advantages of the Dtx-loaded PLGA-PCL NPs over pure Dtx in both time- and concentration-dependent manner. In particular, an increase of 20% of PC3 growth inhibition was determined by PLGA-PCL NPs with respect to free drug after 72 h incubation and at all tested Dtx concentration. In summary, PLGA-PCL copolymer may be considered as an attractive and promising polymeric material for the formulation of Dtx NPs as delivery system for prostate cancer treatment, and can also be pursued as a validated system in a more large context.

  6. Size and alloying induced shift in core and valence bands of Pd-Ag and Pd-Cu nanoparticles

    SciTech Connect

    Sengar, Saurabh K.; Mehta, B. R., E-mail: brmehta@physics.iitd.ac.in [Thin Film Laboratory, Department of Physics, Indian Institute of Technology Delhi, New Delhi 110016 (India); Govind [Surface Physics Group, National Physical Laboratory (CSIR), New Delhi 110012 (India)

    2014-03-28

    In this report, X-ray photoelectron spectroscopy studies have been carried out on Pd, Ag, Cu, Pd-Ag, and Pd-Cu nanoparticles having identical sizes corresponding to mobility equivalent diameters of 60, 40, and 20?nm. The nanoparticles were prepared by the gas phase synthesis method. The effect of size on valence and core levels in metal and alloy nanoparticles has been studied by comparing the values to those with the 60?nm nanoparticles. The effect of alloying has been investigated by comparing the valence and core level binding energies of Pd-Cu and Pd-Ag alloy nanoparticles with the corresponding values for Pd, Ag, and Cu nanoparticles of identical sizes. These effects have been explained in terms of size induced lattice contractions, alloying induced charge transfer, and hybridization effects. The observation of alloying and size induced binding energy shifts in bimetallic nanoparticles is important from the point of view of hydrogen reactivity.

  7. Protective effect of Porphyra yezoensis glycoprotein on D-galactosamine?induced cytotoxicity in Hepa 1c1c7 cells.

    PubMed

    Choi, Jeong-Wook; Kim, Young-Min; Park, Su-Jin; Kim, In-Hye; Nam, Taek-Jeong

    2015-05-01

    The present study aimed to examine the signaling pathways and enzyme activity associated with the protective effect of Porphyra yezoensis glycoprotein (PYGP) on D?galactosamine (D?GaIN)?induced cytotoxicity in Hepa 1c1c7 cells. D?GaIN is commonly used to induce hepatic injury models in vivo as well as in vitro. PYGP was extracted from Porphyra yezoensis, a red algae distributed along the coasts of Republic of Korea, China and Japan. In the present study, Hepa 1c1c7 cells were pre?treated with PYGP (20 and 40 µg/ml) for 24 h and then the media was replaced with D?GaIN (20 mM) and PYGP (20 and 40 µg/ml). The results demonstrated that D?GaIN induced Hepa 1c1c7 cell death and pretreatment with PYGP was found to attenuate D?GaIN toxicity. In addition, D?GaIN decreased the antioxidant activity and increased lipid peroxidation processes; however, pre?treatment with PYGP reduced the generation of lipid peroxidation products, such as thiobarbituric acid reactive substances, as well as increased the activity of antioxidant enzymes, including superoxide dismutase, catalase and glutathione?s?transferase (GST). PYGP was shown to suppress the overexpression of extracellular signal?regulated kinase, c?jun N?terminal kinase and p38 mitogen?activated protein kinase (MAPK) phosphorylation induced by D?GaIN. Furthermore, PYGP increased the protein expression of nuclear factor erythroid 2?related factor 2 (Nrf2), quinine oxidoreductase 1, GST and heme oxygenase 1 protein expression. These results suggested that PYGP had cytoprotective effects against D?GaIN?induced cell damage, which may be associated with MAPKs and the Nrf2 signaling pathway. PMID:25626067

  8. The SUV39H1 inhibitor chaetocin induces differentiation and shows synergistic cytotoxicity with other epigenetic drugs in acute myeloid leukemia cells

    PubMed Central

    Lai, Y-S; Chen, J-Y; Tsai, H-J; Chen, T-Y; Hung, W-C

    2015-01-01

    Epigenetic modifying enzymes have a crucial role in the pathogenesis of acute myeloid leukemia (AML). Methylation of lysine 9 on histone H3 by the methyltransferase G9a and SUV39H1 is associated with inhibition of tumor suppressor genes. We studied the effect of G9a and SUV39H1 inhibitors on viability and differentiation of AML cells and tested the cytotoxicity induced by combination of G9a and SUV39H1 inhibitors and various epigenetic drugs. The SUV39H1 inhibitor (chaetocin) and the G9a inhibitor (UNC0638) caused cell death in AML cells at high concentrations. However, only chaetocin-induced CD11b expression and differentiation of AML cells at non-cytotoxic concentration. HL-60 and KG-1a cells were more sensitive to chaetocin than U937 cells. Long-term incubation of chaetocin led to downregulation of SUV39H1 and reduction of H3K9 tri-methylation in HL-60 and KG-1a cells. Combination of chaetocin with suberoylanilide hydroxamic acid (SAHA, a histone deacetylase inhibitor) or JQ (a BET (bromodomain extra terminal) bromodomain inhibitor) showed synergistic cytotoxicity. Conversely, no synergism was found by combining chaetocin and UNC0638. More importantly, chaetocin-induced differentiation and combined cytotoxicity were also found in the primary cells of AML patients. Collectively, the SUV39H1 inhibitor chaetocin alone or in combination with other epigenetic drugs may be effective for the treatment of AML. PMID:25978433

  9. Strain-induced matrix-dependent deformation of GaAs nanoparticles.

    PubMed

    Yuan, Cailei; Jiang, Zixiong; Ye, Shuangli

    2014-01-21

    The influence of compressive strain on the deformation of GaAs nanoparticles embedded in different host matrices is investigated. The simulation results indicate that it can be easier to deform GaAs nanoparticles grown in an Al2O3 film than those in an SiO2 film. The deformation induced by the applied compressive strain has significant influence on the shape, size and microstructure of GaAs nanoparticles. Most significantly, these simulated results have a good agreement with HRTEM experimental results. PMID:24296681

  10. Electric-Field-Induced Alignment of Block Copolymer/Nanoparticle Blends

    SciTech Connect

    Liedel, Clemens [RWTH Aachen University] [RWTH Aachen University; Schindler, Kerstin [RWTH Aachen University] [RWTH Aachen University; Pavan, Mariela J. [Hebrew University of Jerusalem] [Hebrew University of Jerusalem; Lewin, Christian [RWTH Aachen University] [RWTH Aachen University; Pester, Christian W [ORNL] [ORNL; Ruppel, Markus A [ORNL] [ORNL; Urban, Volker S [ORNL] [ORNL; Shenhar, Roy [Hebrew University of Jerusalem] [Hebrew University of Jerusalem; Boker, Alexander [RWTH Aachen University] [RWTH Aachen University

    2013-01-01

    External electric fi elds readily align birefringent block-copolymer mesophases. In this study the effect of gold nanoparticles on the electric-fi eld-induced alignment of a lamellae-forming polystyrene- block -poly(2-vinylpyridine) copolymer is assessed. Nanoparticles are homogeneously dispersed in the styrenic phase and promote the quantitative alignment of lamellar domains by substantially lowering the critical field strength above which alignment proceeds. The results suggest that the electric-fi eldassisted alignment of nanostructured block copolymer/nanoparticle composites may offer a simple way to greatly mitigate structural and orientational defects of such fi lms under benign experimental conditions.

  11. Rapamycin enhances docetaxel-induced cytotoxicity in a androgen-independent prostate cancer xenograft model by survivin downregulation

    SciTech Connect

    Morikawa, Yasuyuki, E-mail: yasu-m@med.gunma-u.ac.jp [Department of Urology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maeabshi, Gunma 3718511 (Japan)] [Department of Urology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maeabshi, Gunma 3718511 (Japan); Koike, Hidekazu; Sekine, Yoshitaka; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Suzuki, Kazuhiro [Department of Urology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maeabshi, Gunma 3718511 (Japan)] [Department of Urology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maeabshi, Gunma 3718511 (Japan)

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer Rapamycin (RPM) enhances the susceptibility of PC3 cells to docetaxel. Black-Right-Pointing-Pointer Low-dosage of docetaxel (DTX) did not reduce survivin expression levels in PC3 cells. Black-Right-Pointing-Pointer Combination treatment of RPM with DTX suppressed the expression of surviving. Black-Right-Pointing-Pointer SiRNA against survivin enhanced the susceptibility of PC3 cells to DTX. Black-Right-Pointing-Pointer RPM and DTX cotreatment inhibited PC3 cell growth and decreased surviving in vivo. -- Abstract: Background: Docetaxel is a first-line treatment choice in castration-resistant prostate cancer (CRPC). However, the management of CRPC remains an important challenge in oncology. There have been many reports on the effects of rapamycin, which is an inhibitor of the mammalian target of rapamycin (mTOR), in the treatment of carcinogenesis. We assessed the cytotoxic effects of the combination treatment of docetaxel and rapamycin in prostate cancer cells. Furthermore, we examined the relationship between these treatments and survivin, which is a member of the inhibitory apoptosis family. Methods: Prostate cancer cells were cultured and treated with docetaxel and rapamycin. The effects on proliferation were evaluated with the MTS assay. In addition, we evaluated the effect on proliferation of the combination treatment induced knockdown of survivin expression by small interfering RNA transfection and docetaxel. Protein expression levels were assayed using western blotting. PC3 cells and xenograft growth in nude mice were used to evaluate the in vivo efficacy of docetaxel and its combination with rapamycin. Results: In vitro and in vivo, the combination of rapamycin with docetaxel resulted in a greater inhibition of proliferation than treatment with rapamycin or docetaxel alone. In addition, in vitro and in vivo, rapamycin decreased basal surviving levels, and cotreatment with docetaxel further decreased these levels. Transfection siRNA against survivin enhanced the cytotoxicity of docetaxel in PC3 cells. Conclusion: The rapamycin-dependent enhancement of the cytotoxic effects of docetaxel was associated with the downregulation of survivin expression. Our results suggest that the combination of docetaxel and rapamycin is a candidate for the improved treatment of advanced prostate cancer.

  12. The influence of repair pathways on the cytotoxicity and mutagenicity induced by the pyridyloxobutylation pathway of tobacco specific nitrosamines

    PubMed Central

    Li, Li; Perdigao, Joana; Pegg, Anthony E.; Lao, Yanbin; Hecht, Stephen S.; Lindgren, Bruce R.; Reardon, Joyce T.; Sancar, Aziz; Wattenberg, Elizabeth V.

    2009-01-01

    Tobacco-specific nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N?-nitrosonornicotine (NNN), are considered to be human carcinogens. Both compounds are metabolized to pyridyloxobutylating intermediates that react with DNA to form adducts such as 7-[4-(3-pyridyl)-4-oxobut-1-yl]-guanine (7-pobG), O2-[4-(3-pyridyl)-4-oxobut-1-yl]-cytosine (O2-pobC), O2-[4-(3-pyridyl)-4-oxobut-1-yl]-2?-deoxythymidine (O2-pobdT), O6-[4-(3-pyridyl)-4-oxobut-1-yl]-2?-deoxyguanosine (O6-pobdG) and 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing adducts. The role of specific DNA adducts in the overall genotoxic activity of the pyridyloxobutylation pathway is not known. One adduct, O6-pobdG, is mutagenic. To characterize the mutagenic and cytotoxic properties of pyridyloxobutyl DNA adducts, the impact of DNA repair pathways on the cytotoxic and mutagenic properties of the model pyridyloxobutylating agent, 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc) was investigated in Chinese hamster ovary (CHO) cell lines proficient or deficient in O6-alkylguanine DNA alkyltransferase (AGT), deficient in both AGT and base excision repair (BER), or deficient in both AGT and nucleotide excision repair (NER). The repair of the four pyridyloxobutyl DNA adducts was determined in the same cell lines via sensitive LC-MS/MS methods. NNKOAc was more cytotoxic in the cell lines lacking AGT, BER and NER repair pathways. It also induced more mutations in the hprt gene in the BER and NER deficient cell lines. However, AGT expression did not influence NNKOAc’s mutagenicity despite efficient repair of O6-pobdG. Analysis of the hprt mutational spectra indicated that NNKOAc primarily caused point mutations at AT base pairs. GC to AT transition mutations were a minor contributor to the overall mutation spectrum, providing a rationale for the observation that AGT does not protect against the overall mutagenic properties of NNKOAc in this model system. The only adduct affected by the absence of effective NER was O2-pobdT. Slower repair of O2-pobdT in NER deficient cells was associated with increased AT to TA transversion mutations, supporting the hypothesis that these mutations are caused by O2-pobdT. Together, these data support a hypothesis that the pyridyloxobutylation pathway generates multiple mutagenic and toxic adducts. PMID:19601657

  13. Optical detection of target molecule induced aggregation of nanoparticles by means of high-Q resonators.

    PubMed

    Witzens, Jeremy; Hochberg, Michael

    2011-04-11

    We theoretically investigate a novel scheme to detect target molecule induced, or suppressed, aggregation of nanoparticles. High-Q optical resonators are used to both optically trap gold nanoparticle clusters and to detect their presence via a shift in the resonance wavelength. The well depth of the optical trap is chosen to be relatively low compared to the thermal energy of the nanoparticles, so that trapping of single nanoparticles is marginal and results in a comparatively small wavelength shift. Aggregation of functionalized gold nanoparticles is mediated or suppressed via binding to a target molecule. The well depth for the resulting nanoparticle clusters scales much more favorably relative to Brownian motion, resulting in large nanoparticle concentration enhancements in the evanescent field region of the resonator. We predict a target molecule sensitivity in the tens of fM range. In order to predict the resonator response, a complete theory of time resolved nanoparticle cluster trapping dynamics is derived. In particular, the formalism of Kramers' escape time is adapted to 2D (silicon wire) and 3D (ring resonator) optical traps. PMID:21503017

  14. Swift heavy-ion irradiation-induced shape and structural transformation in cobalt nanoparticles

    SciTech Connect

    Sprouster, D.J.; Giulian, R.; Araujo, L.L.; Kluth, P.; Johannessen, B.; Cookson, D.J.; Ridgway, M.C. (Aust. Synch.); (ANU)

    2012-02-07

    The shape and structural evolution of Co nanoparticles embedded in SiO{sub 2} and subjected to swift heavy-ion irradiation have been investigated over a wide energy and fluence range. Modifications of the nanoparticle size and shape were characterized with transmission electron microscopy and small-angle x-ray scattering. Nanoparticles below a threshold diameter remained spherical in shape and progressively decreased in size under irradiation due to dissolution. Nanoparticles above the threshold diameter transformed into nanorods with their major dimension parallel to the incident ion direction. Modifications of the atomic-scale structure of the Co nanoparticles were identified with x-ray absorption spectroscopy. Analysis of the x-ray absorption near-edge spectra showed that prior to irradiation all Co atoms were in a metallic state, while after irradiation Co atoms were in both oxidized and metallic environments, the former consistent with dissolution. The evolution of the nanoparticle short-range order was determined from extended x-ray absorption fine structure spectroscopy. Structural changes in the Co nanoparticles as a function of ion fluence included an increase in disorder and asymmetric deviation from a Gaussian interatomic distance distribution coupled with a decrease in bondlength. Such changes resulted from the irradiation-induced decrease in nanoparticle size and subsequent dissolution.

  15. 5-AZA-2'-DEOXYCYTIDINE INDUCED CYTOTOXICITY AND LONG BONE REDUCTION DEFECTS IN THE MURINE LIMB

    EPA Science Inventory

    The antineoplastic drug 5-aza-2'-deoxycytidine (dAZA) is a DNA hypomethylating agent that can be used to induce hind limb phocomelia in the offspring of CD-1 Swiss Webster mice. Previously, our laboratory investigated the possibility that dAZA induced alterations in gene express...

  16. The combination 5-fluorouracil/levamisole induces enhanced rat Kupffer cell-mediated cytotoxicity in vitro against the syngeneic colon adenocarcinoma cell line CC531.

    PubMed

    Schuurman, B; Sirovich, I; Heuff, G; van der Wilt, C L; Peters, G J; Beelen, R H; Meyer, S

    1995-11-01

    The mode of action of the combination treatment 5-fluorouracil (5-FU) and levamisole in colorectal cancer patients is unknown. It is postulated that the beneficial effect may be explained by an immunomodulatory effect on Kupffer cell (KC) cytotoxicity. We evaluated the effect of levamisole (200 micrograms/ml) and 5-FU (10 microM) on rat KC cytotoxicity against syngeneic CC531 tumor cells. Viability of KCs was unaffected by 5-FU and/or levamisole. The combination did not enhance growth inhibition of CC531 compared to 5-FU alone. A significant increase in KC cytotoxicity was observed after 24-hr incubation with 5-FU/levamisole especially at an effector/target ratio of 10 (P < 0.05). 5-FU alone had no effect on KC cytotoxicity, while levamisole induced only a slight increase. Our in vitro data suggest that the additive effect of the combination 5-FU/levamisole on KC cytotoxicity may attribute to the beneficial effect of the adjuvant treatment in colorectal cancer patients. PMID:7475068

  17. Laser-induced incandescence diagnostic for in situ monitoring of nanoparticle synthesis in an atmospheric plasma

    NASA Astrophysics Data System (ADS)

    Mitrani, James; Patel, Shane; Shneider, Mikhail; Stratton, Brent; Raitses, Yevgeny

    2014-10-01

    A DC arc discharge with a consumed graphite electrode is commonly used for synthesis of carbon nanoaparticles in a low temperature (0.1-1 eV), atmospheric pressure plasma. The formation of nanoparticles in this plasma is poorly understood; it is not clear where nanoparticles nucleate and grow in the arc discharge. Therefore, a laser-induced incandescence (LII) diagnostic for in situ monitoring of the nanoparticles' spatial distribution in the plasma is currently being constructed. The LII diagnostic involves heating the particles with a short-pulsed laser, and measuring the induced spatiotemporal incandescence profiles on longer timescales. By appropriately modeling the induced spatiotemporal incandescence profiles, one can measure particle diameters and volume fraction. LII diagnostics have been extensively used to study soot particles in flames. However, they have never been applied in a strongly coupled plasma background. Even though the spatial dimensions for soot and nanoparticles are similar, great care is needed in developing an LII diagnostic for monitoring nanoparticles in a plasma background. Therefore, we will calibrate our LII diagnostic by measuring spatiotemporal incandescence profiles of known, research grade soot and nanoparticles. This work was supported by DOE Contract DE-AC02-09CH11466.

  18. Cerium oxide nanoparticles attenuate monocrotaline induced right ventricular hypertrophy following pulmonary arterial hypertension.

    PubMed

    Kolli, Madhukar B; Manne, Nandini D P K; Para, Radhakrishna; Nalabotu, Siva K; Nandyala, Geeta; Shokuhfar, Tolou; He, Kun; Hamlekhan, Azhang; Ma, Jane Y; Wehner, Paulette S; Dornon, Lucy; Arvapalli, Ravikumar; Rice, Kevin M; Blough, Eric R

    2014-12-01

    Cerium oxide (CeO2) nanoparticles have been posited to exhibit potent anti-oxidant activity which may allow for the use of these materials in biomedical applications. Herein, we investigate whether CeO2 nanoparticle administration can diminish right ventricular (RV) hypertrophy following four weeks of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male Sprague Dawley rats were randomly divided into three groups: control, MCT only (60 mg/kg), or MCT + CeO2 nanoparticle treatment (60 mg/kg; 0.1 mg/kg). Compared to the control group, the RV weight to body weight ratio was 45% and 22% higher in the MCT and MCT + CeO2 groups, respectively (p < 0.05). Doppler echocardiography demonstrated that CeO2 nanoparticle treatment attenuated monocrotaline-induced changes in pulmonary flow and RV wall thickness. Paralleling these changes in cardiac function, CeO2 nanoparticle treatment also diminished MCT-induced increases in right ventricular (RV) cardiomyocyte cross sectional area, ?-myosin heavy chain, fibronectin expression, protein nitrosylation, protein carbonylation and cardiac superoxide levels. These changes with treatment were accompanied by a decrease in the ratio of Bax/Bcl2, diminished caspase-3 activation and reduction in serum inflammatory markers. Taken together, these data suggest that CeO2 nanoparticle administration may attenuate the hypertrophic response of the heart following PAH. PMID:25224369

  19. Parthenolide induces apoptosis and lytic cytotoxicity in Epstein-Barr virus-positive Burkitt lymphoma.

    PubMed

    Li, Yuan; Zhang, Yongli; Fu, Mingming; Yao, Qin; Zhuo, Huiqin; Lu, Quanyi; Niu, Xiaoqing; Zhang, Peng; Pei, Yihua; Zhang, Kejie

    2012-09-01

    Burkitt lymphoma (BL) has been reported to be strongly associated with Epstein-Barr virus (EBV) infection. The fact that EBV is generally present in cancer cells but rarely found in healthy cells represents an opportunity for targeted cancer therapy. One approach is to activate the lytic replication cycle of the latent EBV. Nuclear factor (NF)-?B is thought to play an essential role in EBV lytic infection. Elevated NF-?B levels inhibit EBV lytic replication. Parthenolide (PN) is a sesquiterpene lactone found in medicinal plants, particularly in feverfew (Tanacetum parthenium). The aim of the present study was to analyze the effect of PN on the survival of Raji EBV-positive lymphoma cells. Raji cells were treated with 0, 4 or 6 µmol/l PN for 48 h. MTT assay and western blot analysis were performed to evaluate the findings. Results showd that PN suppressed the growth of the EBV-positive BL cell line, Raji, and activated the transcription of BZLF1 and BRLF1 by inhibiting NF-?B activity. Most notably, when PN was used in combination with ganciclovir (GCV), the cytotoxic effect of PN was amplified. These data suggest that the induction of lytic EBV infection with PN in combination with GCV may be a viral?targeted therapy for EBV-associated BL. PMID:22735892

  20. Co-activation of AMPK and mTORC1 Induces Cytotoxicity in Acute Myeloid Leukemia.

    PubMed

    Sujobert, Pierre; Poulain, Laury; Paubelle, Etienne; Zylbersztejn, Florence; Grenier, Adrien; Lambert, Mireille; Townsend, Elizabeth C; Brusq, Jean-Marie; Nicodeme, Edwige; Decrooqc, Justine; Nepstad, Ina; Green, Alexa S; Mondesir, Johanna; Hospital, Marie-Anne; Jacque, Nathalie; Christodoulou, Alexandra; Desouza, Tiffany A; Hermine, Olivier; Foretz, Marc; Viollet, Benoit; Lacombe, Catherine; Mayeux, Patrick; Weinstock, David M; Moura, Ivan C; Bouscary, Didier; Tamburini, Jerome

    2015-06-01

    AMPK is a master regulator of cellular metabolism that exerts either oncogenic or tumor suppressor activity depending on context. Here, we report that the specific AMPK agonist GSK621 selectively kills acute myeloid leukemia (AML) cells but spares normal hematopoietic progenitors. This differential sensitivity results from a unique synthetic lethal interaction involving concurrent activation of AMPK and mTORC1. Strikingly, the lethality of GSK621 in primary AML cells and AML cell lines is abrogated by chemical or genetic ablation of mTORC1 signaling. The same synthetic lethality between AMPK and mTORC1 activation is established in CD34-positive hematopoietic progenitors by constitutive activation of AKT or enhanced in AML cells by deletion of TSC2. Finally, cytotoxicity in AML cells from GSK621 involves the eIF2?/ATF4 signaling pathway that specifically results from mTORC1 activation. AMPK activation may represent a therapeutic opportunity in mTORC1-overactivated cancers. PMID:26004183

  1. Programmed death-1 blockade enhances the antitumor effects of peptide vaccine-induced peptide-specific cytotoxic T lymphocytes

    PubMed Central

    SAWADA, YU; YOSHIKAWA, TOSHIAKI; SHIMOMURA, MANAMI; IWAMA, TATSUAKI; ENDO, ITARU; NAKATSURA, TETSUYA

    2015-01-01

    Novel treatment modalities are required urgently in patients with hepatocellular carcinoma (HCC). A vaccine that induces cytotoxic T lymphocytes (CTLs) is an ideal strategy for cancer, and glypican-3 (GPC3) is a potential option for HCC. Blocking the programmed death-1 (PD-1)/PD-L1 pathway is a rational strategy to overcome tumor escape and tolerance toward CTLs. In the present study, we investigated whether anti-PD-1 blocking antibodies (?PD-1 Ab) enhanced the number of vaccine-induced peptide-specific CTLs in peripheral blood mononuclear cells (PBMCs) following the administration of GPC3 peptide vaccine to both patients and in a mouse model. The inhibitory receptor PD-1 was highly expressed in ex vivo GPC3-specific CTLs isolated from the PBMCs of vaccinated HCC patients. In vitro, interferon-? induced PD-L1 expression in liver cancer cell lines. In addition, PD-1 blockade increased the number of GPC3-specific CTLs, which degranulate against liver cancer cell lines. In vivo experiments using tumor-bearing mouse models showed that the combination therapy of peptide vaccine and ?PD-1 Ab suppressed tumor growth synergistically. PD-1 blockade increased the number of peptide-specific tumor-infiltrating T cells (TILs) and decreased the expression of inhibitory receptors on TILs. This study demonstrated that PD-1/PD-L1 blockade augmented the antitumor effects of a peptide vaccine by increasing the immune response of vaccine-induced CTLs, and provided a foundation for the clinical development of a combination therapy using a GPC3 peptide vaccine and ?PD-1 Ab. PMID:25354479

  2. Hepatoprotective potential of Lavandula coronopifolia extracts against ethanol induced oxidative stress-mediated cytotoxicity in HepG2 cells.

    PubMed

    Farshori, Nida Nayyar; Al-Sheddi, Ebtsam S; Al-Oqail, Mai M; Hassan, Wafaa H B; Al-Khedhairy, Abdulaziz A; Musarrat, Javed; Siddiqui, Maqsood A

    2013-03-28

    The present investigations were carried out to study the protective potential of four extracts (namely petroleum ether extract (LCR), chloroform extract (LCM), ethyl acetate extract (LCE), and alcoholic extract (LCL)) of Lavandula coronopifolia on oxidative stress-mediated cell death induced by ethanol, a known hepatotoxin in human hapatocellular carcinoma (HepG2) cells. Cells were pretreated with LCR, LCM, LCE, and LCL extracts (10-50 ?g/ml) of L. coronopifolia for 24 h and then ethanol was added and incubated further for 24 h. After the exposure, cell viability using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red uptake assays and morphological changes in HepG2 cells were studied. Pretreatment with various extracts of L. coronpifolia was found to be significantly effective in countering the cytotoxic responses of ethanol. Antioxidant properties of these L. coronopifolia extracts against reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and glutathione (GSH) levels induced by ethanol were investigated. Results show that pretreatment with these extracts for 24 h significantly inhibited ROS generation and LPO induced and increased the GSH levels reduced by ethanol. The data from the study suggests that LCR, LCM, LCE, and LCL extracts of L. coronopifolia showed hepatoprotective activity against ethanol-induced damage in HepG2 cells. However, a comparative study revealed that the LCE extract was found to be the most effective and LCL the least effective. The hepatoprotective effects observed in the study could be associated with the antioxidant properties of these extracts of L. coronopifolia. PMID:23546397

  3. Airborne quinones induce cytotoxicity and DNA damage in human lung epithelial A549 cells: the role of reactive oxygen species.

    PubMed

    Shang, Yu; Zhang, Ling; Jiang, Yuting; Li, Yi; Lu, Ping

    2014-04-01

    Ambient particulate matter (PM) is associated with adverse health effects. Quinones present in PM are hypothesized to contribute to these harmful effects through the generation of reactive oxygen species (ROS). However, whether the ROS induced by quinones is involved in mediating DNA damage as well as other biological responses in pulmonary cells is less well known. In this study, the toxic effects of five typical airborne quinones, including 1,2-naphthoquinone, 2-methylanthraquinone, 9,10-phenanthrenequinone, 2-methyl-1,4-naphthoquinone, and acenaphthenequinone, on cytotoxicity, DNA damage, intracellular calcium homeostasis, and ROS generation, were studied in human lung epithelial A549 cells. An antioxidant N-acetylcysteine (NAC) was used to examine the involvement of ROS in adverse biological responses induced by quinones. The quinones caused a concentration-dependent viability decrease, cellular LDH release, DNA damage, and ROS production in A549 cells. 1,2-Naphthoquinone, but not the other four quinones, increased intracellular calcium (Ca(2+)) levels in a dose-dependent manner. These toxic effects were abolished by administration of NAC, suggesting that ROS played a key role in the observed toxic effects of quinones in A549 cells. These results emphasize the importance of quinones in PM on the adverse health effects of PMs, which has been underestimated in the past few years, and highlight the need, when evaluating the effects on health and exposure management, to always consider their qualitative chemical compositions in addition to the size and concentration of PMs. PMID:24480427

  4. The MDM2 Inhibitor AMG 232 Demonstrates Robust Antitumor Efficacy and Potentiates the Activity of p53-Inducing Cytotoxic Agents.

    PubMed

    Canon, Jude; Osgood, Tao; Olson, Steven H; Saiki, Anne Y; Robertson, Rebecca; Yu, Dongyin; Eksterowicz, John; Ye, Qiuping; Jin, Lixia; Chen, Ada; Zhou, Jing; Cordover, David; Kaufman, Stephen; Kendall, Richard; Oliner, Jonathan D; Coxon, Angela; Radinsky, Robert

    2015-03-01

    p53 is a critical tumor suppressor and is the most frequently inactivated gene in human cancer. Inhibition of the interaction of p53 with its negative regulator MDM2 represents a promising clinical strategy to treat p53 wild-type tumors. AMG 232 is a potential best-in-class inhibitor of the MDM2-p53 interaction and is currently in clinical trials. We characterized the activity of AMG 232 and its effect on p53 signaling in several preclinical tumor models. AMG 232 binds the MDM2 protein with picomolar affinity and robustly induces p53 activity, leading to cell-cycle arrest and inhibition of tumor cell proliferation. AMG 232 treatment inhibited the in vivo growth of several tumor xenografts and led to complete and durable regression of MDM2-amplified SJSA-1 tumors via growth arrest and induction of apoptosis. Therapeutic combination studies of AMG 232 with chemotherapies that induce DNA damage and p53 activity resulted in significantly superior antitumor efficacy and regression, and markedly increased activation of p53 signaling in tumors. These preclinical data support the further evaluation of AMG 232 in clinical trials as both a monotherapy and in combination with standard-of-care cytotoxics. Mol Cancer Ther; 14(3); 649-58. ©2015 AACR. PMID:25567130

  5. Skin Dendritic Cell Targeting via Microneedle Arrays Laden with Antigen-Encapsulated Poly-d,l-lactide-co-Glycolide Nanoparticles Induces Efficient Antitumor and Antiviral Immune Responses

    PubMed Central

    2013-01-01

    The efficacious delivery of antigens to antigen-presenting cells (APCs), in particular, to dendritic cells (DCs), and their subsequent activation remains a significant challenge in the development of effective vaccines. This study highlights the potential of dissolving microneedle (MN) arrays laden with nanoencapsulated antigen to increase vaccine immunogenicity by targeting antigen specifically to contiguous DC networks within the skin. Following in situ uptake, skin-resident DCs were able to deliver antigen-encapsulated poly-d,l-lactide-co-glycolide (PGLA) nanoparticles to cutaneous draining lymph nodes where they subsequently induced significant expansion of antigen-specific T cells. Moreover, we show that antigen-encapsulated nanoparticle vaccination via microneedles generated robust antigen-specific cellular immune responses in mice. This approach provided complete protection in vivo against both the development of antigen-expressing B16 melanoma tumors and a murine model of para-influenza, through the activation of antigen-specific cytotoxic CD8+ T cells that resulted in efficient clearance of tumors and virus, respectively. In addition, we show promising findings that nanoencapsulation facilitates antigen retention into skin layers and provides antigen stability in microneedles. Therefore, the use of biodegradable polymeric nanoparticles for selective targeting of antigen to skin DC subsets through dissolvable MNs provides a promising technology for improved vaccination efficacy, compliance, and coverage. PMID:23373658

  6. IRON OXIDE NANOPARTICLE-INDUCED OXIDATIVE STRESS AND INFLAMMATION

    EPA Science Inventory

    Nanoparticle Physicochemical Characterizations We first focused on creating NP systems that could be used to test our hypotheses and assessing their stability in aqueous media. The iron oxide NP systems were not stable in cell culture medium o...

  7. Single Stranded DNA Induced Assembly of Gold Nanoparticles

    E-print Network

    Yang, Jun

    The binding affinity of single stranded DNA (ssDNA) for gold nanoparticle surface is studied in this work. The data indicate that the strength of interaction between ssDNA and Au particle surface is closely related to the ...

  8. Ionic liquid-induced synthesis of selenium nanoparticles

    SciTech Connect

    Langi, Bhushan [Changu Kana Thakur Research Centre, New Panvel 410 206 (India)] [Changu Kana Thakur Research Centre, New Panvel 410 206 (India); Shah, Chetan; Singh, Krishankant [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)] [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Chaskar, Atul, E-mail: achaskar@rediffmail.com [Changu Kana Thakur Research Centre, New Panvel 410 206 (India)] [Changu Kana Thakur Research Centre, New Panvel 410 206 (India); Kumar, Manmohan; Bajaj, Parma N. [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)] [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    2010-06-15

    A simple wet chemical method has been used to synthesize selenium nanoparticles by the reaction of ionic liquid with sodium selenosulphate, a selenium precursor, in the presence of polyvinyl alcohol stabilizer, in aqueous medium. The method is capable of producing spherical selenium nanoparticles in the size range of 76-150 nm under ambient conditions. This is a first report on the production of nano-selenium assisted by an ionic liquid. The synthesized nanoparticles can be separated easily from the aqueous sol by a high-speed centrifuge machine, and can be re-dispersed in an aqueous medium. The synthesized selenium nanoparticles have been characterized by X-ray diffraction, energy dispersive X-ray analysis, differential scanning calorimetry and transmission electron microscopy techniques.

  9. Rosiglitazone protects human neuroblastoma SH-SY5Y cells against acetaldehyde-induced cytotoxicity

    SciTech Connect

    Jung, Tae Woo [Brain Korea 21 Project for Medical Science, Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Ji Young [Brain Korea 21 Project for Medical Science, Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Shim, Wan Sub [Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kang, Eun Seok [Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Soo Kyung [Brain Korea 21 Project for Medical Science, Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Internal Medicine, Pochon CHA University College of Medicine, Sungnam (Korea, Republic of); Ahn, Chul Woo [Brain Korea 21 Project for Medical Science, Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Hyun Chul [Brain Korea 21 Project for Medical Science, Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cha, Bong Soo [Brain Korea 21 Project for Medical Science, Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of) and Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of)]. E-mail: bscha@yumc.yonsei.ac.kr

    2006-02-03

    Acetaldehyde, an inhibitor of mitochondrial function, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with elevation of the intracellular reactive oxygen species level and apoptosis. Rosiglitazone, a peroxisome proliferator-activated receptor-{gamma} agonist, has been known to show various non-hypoglycemic effects, including anti-inflammatory, anti-atherogenic, and anti-apoptotic. In this study, we investigated the protective effects of rosiglitazone on acetaldehyde-induced apoptosis in human neuroblastoma SH-SY5Y cells and attempted to examine its mechanism. Acetaldehyde-induced apoptosis was moderately reversed by rosiglitazone treatment. Our results suggest that the protective effects of rosiglitazone on acetaldehyde-induced apoptosis may be ascribed to ability to induce the expression of anti-oxidant enzymes and to regulate Bcl-2 and Bax expression. These data indicate that rosiglitazone may provide a useful therapeutic strategy for the prevention of progressive neurodegenerative disease such as Parkinson's disease.

  10. Doxorubicin-induced acute changes in cytotoxic aldehydes, antioxidant status and cardiac function in the rat

    Microsoft Academic Search

    Xiaoping Luo; Yovan Evrovsky; David Cole; Jean Trines; Lee N. Benson; Denis C. Lehotay

    1997-01-01

    Doxorubicin (DOX)-induced cardiotoxicity is thought to be caused by free radical-mediated mechanisms. An in vivo rat model was developed to investigate the DOX-induced cascade of early biochemical changes focusing on the central role of the aldehydic lipid peroxidation products. Antioxidant status was evaluated by glutathione measurements. Creatine Kinase (CK) activity was measured as an index of cardiac injury. Development of

  11. Cerium and yttrium oxide nanoparticles against lead-induced oxidative stress and apoptosis in rat hippocampus.

    PubMed

    Hosseini, Asieh; Sharifi, Ali Mohammad; Abdollahi, Mohammad; Najafi, Rezvan; Baeeri, Maryam; Rayegan, Samira; Cheshmehnour, Jamshid; Hassani, Shokoufeh; Bayrami, Zahra; Safa, Majid

    2015-03-01

    Due to numerous industrial applications, lead has caused widespread pollution in the environment; it seems that the central nervous system (CNS) is the main target for lead in the human body. Oxidative stress and programmed cell death in the CNS have been assumed as two mechanisms related to neurotoxicity of lead. Cerium oxide (CeO2) and yttrium oxide (Y2O3) nanoparticles have recently shown antioxidant effects, particularly when used together, through scavenging the amount of reactive oxygen species (ROS) required for cell apoptosis. We looked into the neuroprotective effects of the combinations of these nanoparticles against acute lead-induced neurotoxicity in rat hippocampus. We used five groups in this study: control, lead, CeO2 nanoparticles + lead, Y2O3 nanoparticles + lead, and CeO2 and Y2O3 nanoparticles + lead. Nanoparticles of CeO2 (1000 mg/kg) and Y2O3 (230 mg/kg) were administered intraperitoneally during 2 days prior to intraperitoneal injection of the lead (25 mg/kg for 3 days). At the end of the treatments, oxidative stress markers, antioxidant enzymes activity, and apoptosis indexes were investigated. The results demonstrated that pretreatments with CeO2 and/or Y2O3 nanoparticles recovered lead-caused oxidative stress markers (ROS, lipid peroxidation, and total thiol molecules) and apoptosis indexes (Bax/Bcl-2 and caspase-3 protein expression). Besides, these nanoparticles reduced the activities of lead-induced superoxide dismutase and catalase as well as the ADP/ATP ratio. Interestingly, the best recovery resulted from the compound of these nanoparticles. Based on these outcomes, it appears that this combination may potentially be beneficial for protection against lead-caused acute toxicity in the brain through improving the oxidative stress-mediated programmed cell death pathway. PMID:25516117

  12. Factors affecting T cell responses induced by fully synthetic glyco-gold-nanoparticles

    NASA Astrophysics Data System (ADS)

    Fallarini, Silvia; Paoletti, Tiziana; Battaglini, Carolina Orsi; Ronchi, Paolo; Lay, Luigi; Bonomi, Renato; Jha, Satadru; Mancin, Fabrizio; Scrimin, Paolo; Lombardi, Grazia

    2012-12-01

    We have synthesized and characterized nearly monodisperse and highly pure gold nanoparticles (2 and 5 nm) coated with non-immunoactive mono- and disaccharides, modelled after the capsular polysaccharide of serogroup A of the Neisseria meningitidis bacterium. We have used them to test their ability to induce immune cell responses as a consequence of their multivalency. The results indicate that they are indeed immunoactive and that immunoactivity is strongly dependent on size, and larger, 5 nm nanoparticles perform far better than smaller, 2 nm ones. Immune response (activation of macrophages) initiates with the whole nanoparticle recognition by the surface of antigen-presenting cells, independent of the saccharide oligomerization (or charge) on the nanoparticle surface. The induction of T cell proliferation and the increase of IL-2 levels, a consequence of the expression of MHC II involved in antigen presentation, require the presence of a disaccharide on the nanoparticle, not just a monosaccharide. A possible explanation is that, at this stage, the saccharides are detached from the gold surface. These results may provide leads for designing new saccharide-based, nanoparticle-conjugate vaccines.We have synthesized and characterized nearly monodisperse and highly pure gold nanoparticles (2 and 5 nm) coated with non-immunoactive mono- and disaccharides, modelled after the capsular polysaccharide of serogroup A of the Neisseria meningitidis bacterium. We have used them to test their ability to induce immune cell responses as a consequence of their multivalency. The results indicate that they are indeed immunoactive and that immunoactivity is strongly dependent on size, and larger, 5 nm nanoparticles perform far better than smaller, 2 nm ones. Immune response (activation of macrophages) initiates with the whole nanoparticle recognition by the surface of antigen-presenting cells, independent of the saccharide oligomerization (or charge) on the nanoparticle surface. The induction of T cell proliferation and the increase of IL-2 levels, a consequence of the expression of MHC II involved in antigen presentation, require the presence of a disaccharide on the nanoparticle, not just a monosaccharide. A possible explanation is that, at this stage, the saccharides are detached from the gold surface. These results may provide leads for designing new saccharide-based, nanoparticle-conjugate vaccines. Electronic supplementary information (ESI) available: Fig. S1-S10 mentioned in the text related to the syntheses of nanosystems, nanoparticle characterization, and biological tests. See DOI: 10.1039/c2nr32338a

  13. Influence of 50-nm polystyrene particles in inducing cytotoxicity in mice co-injected with carbon tetrachloride, cisplatin, or paraquat.

    PubMed

    Shimizu, Y; Isoda, K; Tezuka, E; Yufu, T; Nagai, Y; Ishida, I; Tezuka, M

    2012-08-01

    The toxicity of nanomaterials has yet to be fully investigated. In particular, the interactions between nanomaterials and therapeutic drugs require further study. We investigated whether nano-sized polystyrene particles affect drug-induced toxicity. The particles, which are widely used industrially, had diameters of 50 (NPP50), 200 (NPP200) or 1000 (NPP1000) nm. The toxic chemicals tested were carbon tetrachloride, cisplatin (a popular anti-tumor agent), and a widely used herbicide, paraquat. Mice were treated intraperitoneally with either carbon tetrachloride (0.01 ml/kg), cisplatin (100 micromol/kg) or paraquat (50 mg/kg), with or without intravenous administration of polystyrene particles. All treatments in the absence of the nanoparticles were non-lethal and did not result in severe toxicity. However, when mice were injected with paraquat or cisplatin together with polystyrene particles, synergistic, enhanced toxicity was observed in mice injected with NPP50. These synergic effects were not observed in mice co-injected with NPP200 or NPP1000. These findings suggest that further evaluation of the interactions between polystyrene nano-particles and drugs is a critical prerequisite to the pharmaceutical application of nanotechnology. PMID:22957437

  14. Evaluation of cellular influences of platinum nanoparticles by stable medium dispersion.

    PubMed

    Horie, Masanori; Kato, Haruhisa; Endoh, Shigehisa; Fujita, Katsuhide; Nishio, Keiko; Komaba, Lilian Kaede; Fukui, Hiroko; Nakamura, Ayako; Miyauchi, Arisa; Nakazato, Tetsuya; Kinugasa, Shinichi; Yoshida, Yasukazu; Hagihara, Yoshihisa; Morimoto, Yasuo; Iwahashi, Hitoshi

    2011-11-01

    Platinum nanoparticles have industrial application, for example in catalysis, and are used in consumer products such as cosmetics and supplements. Therefore, among the many nanoparticles, platinum is one of the more accessible nanoparticles for consumers. Most platinum nanoparticles that are used in cosmetics and supplements which have an anti-oxidant activity are modified particles. However, the cellular influences of pristine platinum nanoparticles are still unclear, although it has been reported that platinum nanoparticles induce oxidative stress. In this study, we investigated the cellular influences induced by pure pristine platinum nanoparticles. Platinum nanoparticles of 100% purity were dispersed in a cell culture medium and stable medium dispersion was obtained. The platinum nanoparticle medium dispersion was applied to two kinds of cultured cells, A549 and HaCaT cells, and the cellular influences were examined. Cell viability (MTT assay), cell proliferation (clonogenic assay), apoptosis induction (caspase-3 activity), intracellular ROS level (DCFH assay), and lipid peroxidation level (DPPP assay) were measured as markers of cellular influences. Transmission electron microscope observation showed cellular uptake of platinum nanoparticles. However, the platinum nanoparticles did not drive any markers. It is known that some metal oxide nanoparticles such as NiO and CuO show severe cytotoxicity via metal ion release. Compared with these toxic nanoparticles, the platinum nanoparticles used in this study did not release platinum ions into the culture media. These results suggest that the physically and chemically inactive cellular influences of platinum nanoparticles are small. PMID:21804981

  15. AG490 Influences UCN-01-Induced Cytotoxicity in Glioma Cells in a p53-Dependent Fashion, Correlating with Effects on BAX Cleavage and BAD Phosphorylation

    PubMed Central

    Jane, Esther P.; Premkumar, Daniel R.; Pollack, Ian F.

    2007-01-01

    We determined the cytotoxicity of AG490 as a single agent and in combination with 7-OH-hydroxystaurosporine (UCN-01) in a panel of malignant human glioma cell lines. Because p53 has important roles in cell cycle checkpoints, it has been anticipated that modulation of checkpoint pathways should sensitize p53-defective cells while sparing the normal cells. Cell proliferation was determined from dose-response curves. AG490 was effective as a cytotoxic agent alone regardless of p53 status. Combining the Chk1 inhibitor UCN-01 dramatically enhanced the response to AG490 in p53 mutated or deleted glioma cells. An opposite effect was noted in p53 wild-type cells, in which UCN-01 and AG490 had antagonist effects on cell proliferation and viability. We found that AG490 enhanced BAD phosphorylation in p53 wild type glioma cells, which appeared to protect against UCN-01 induced cytotoxicity, whereas AG490 enhances UCN-01-induced cytotoxicity in p53-defective cell lines by suppression of BAD phosphorylation, and induction of BAX and PARP cleavage. These observations highlight the potential for genotype-dependent factors to strongly influence response to signaling-targeted therapies in malignant gliomas and the importance of considering such factors in correlative response analyses for these agents. PMID:17900801

  16. Electron-irradiation-induced phase separation in GaSb nanoparticles

    NASA Astrophysics Data System (ADS)

    Yasuda, H.; Mori, H.; Lee, J. G.

    2004-12-01

    Electron irradiation effects in GaSb compound nanoparticles have been studied by transmission electron microscopy, in order to examine structural stability under electron irradiation in a nanometer-sized system. It is revealed that when 75 keV electron irradiation was carried out in approximately (10-25)-nm-sized GaSb particles kept at 423 K, a phase separation of the GaSb compound was induced to form a two-phase structure consisting of a crystalline antimony core and a liquid gallium shell. The phase separation was induced neither by 75 keV electron irradiation in GaSb nanoparticles kept at more than 443 K or less than 363 K nor by 200 keV electron irradiation in particles kept from 363 to 443 K. It is suggested that the phase separation in GaSb nanoparticles may be induced by electronic excitations rather than knock-on displacements.

  17. Drug-loaded nanoparticles induce gene expression in human pluripotent stem cell derivatives

    PubMed Central

    Gajbhiye, Virendra; Escalante, Leah; Chen, Guojun; Laperle, Alex; Zheng, Qifeng; Steyer, Benjamin; Gong, Shaoqin; Saha, Krishanu

    2014-01-01

    Tissue engineering and advanced manufacturing of human stem cells requires a suite of tools to control gene expression spatiotemporally in culture. Inducible gene expression systems offer cell-extrinsic control, typically through addition of small molecules, but small molecule inducers typically contain few functional groups for further chemical modification. Doxycycline (DXC), a potent small molecule inducer of tetracycline (Tet) transgene systems, was conjugated to a hyperbranched dendritic polymer (Boltorn H40) and subsequently reacted with polyethylene glycol (PEG). The resulting PEG-H40-DXC nanoparticle exhibited pH-sensitive drug release behavior and successfully controlled gene expression in stem-cell-derived fibroblasts with a Tet-On system. While free DXC inhibited fibroblast proliferation and matrix metalloproteinase (MMP) activity, PEG-H40-DXC nanoparticles maintained higher fibroblast proliferation levels and MMP activity. The results demonstrate that the PEG-H40-DXC nanoparticle system provides an effective tool to controlling gene expression in human stem cell derivatives. PMID:24232694

  18. Histologic and apoptotic changes induced by titanium dioxide nanoparticles in the livers of rats

    PubMed Central

    Alarifi, Saud; Ali, Daoud; Al-Doaiss, Amin A; Ali, Bahy A; Ahmed, Mukhtar; Al-Khedhairy, Abdulaziz A

    2013-01-01

    Titanium dioxide (TiO2) nanoparticles are among the top five nanoparticles used in consumer products, paints, and pharmaceutical preparations. Given that exposure to such nanoparticles is mainly via the skin and inhalation, the present study was conducted in male Wistar albino rats (Rattus norvegicus). Our aim was to investigate the effect of TiO2 nanoparticles on hepatic tissue in an attempt to understand their toxicity and the potential effect of their therapeutic and diagnostic use. To investigate the effects of TiO2 nanoparticles on liver tissue, 30 healthy male Wistar albino rats were exposed to TiO2 nanoparticles at doses of 63 mg, 126 mg, and 252 mg per animal for 24 and 48 hours. Serum glutamate oxaloacetate transaminase and alkaline phosphatase activity was altered. Changes in hepatocytes can be summarized as hydropic degeneration, cloudy swelling, fatty degeneration, portal and lobular infiltration by chronic inflammatory cells, and congested dilated central veins. The histologic alterations observed might be an indication of hepatocyte injury due to the toxicity of TiO2 nanoparticles, resulting in an inability to deal with accumulated residues from the metabolic and structural disturbances caused by these nanoparticles. The appearance of cytoplasmic degeneration and destruction of nuclei in hepatocytes suggests that TiO2 nanoparticles interact with proteins and enzymes in hepatic tissue, interfering with antioxidant defense mechanisms and leading to generation of reactive oxygen species which, in turn, may induce stress in hepatocytes, promoting atrophy, apoptosis, and necrosis. More immunohistochemical and ultrastructural investigations are needed in relation to TiO2 nanoparticles and their potential effects when used as therapeutic and diagnostic tools. PMID:24143098

  19. Surface modification of silica nanoparticles by UV-induced graft polymerization of methyl methacrylate

    Microsoft Academic Search

    Sooyeon Kim; Eunhye Kim; Sungsoo Kim; Woosik Kim

    2005-01-01

    In this study we modified the surface of silica nanoparticles with methyl methacrylate by UV-induced graft polymerization. It is a surface-initiated polymerization reaction induced by ultraviolet irradiation. The resulting organic–inorganic nanocomposites were near-monodisperse and fabricated without homopolymerization of the monomer. Substantial increase in mean particle size was observed by SEM image analysis after UV-induced grafting of methyl methacrylate onto pure

  20. Probing cytotoxicity of gadolinium hydroxide nanostructures.

    PubMed

    Hemmer, Eva; Kohl, Yvonne; Colquhoun, Victoria; Thielecke, Hagen; Soga, Kohei; Mathur, Sanjay

    2010-04-01

    Gadolinium hydroxide, Gd(OH)(3), nanostructures were examined for their possible use in imaging and tracking of cells and tissues by investigating their cellular interactions and cytotoxic behaviors. For this purpose, Gd(OH)(3) nanorods (length, several hundred nanometers; diameter, approximately 40 nm) and spherical nanoparticles (average diameter, <10 nm) were synthesized by solvothermal decomposition of gadolinium containing molecular precursors. After comprehensive characterization of material properties, human colon adenocarcinoma (Caco2) and human lung epithelial (A549) cells were incubated with Gd(OH)(3) nanostructures in concentrations up to 900 microg/mL to perform cytotoxicity assays (BrdU (5-bromo-2'-deoxyuridine), WST-1 (4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzol-disulfonate)) and living/dead staining. As observed in all in vitro assays, the investigated Gd(OH)(3) nanostructures do not induce any significant cytotoxic effect, making them promising candidates for a new class of contrast agents, which may overcome the limitations of organic stains such as photobleaching and single usage. PMID:20218658

  1. Neutral endopeptidase 24.11 in neutrophils modulates protective effects of natriuretic peptides against neutrophils-induced endothelial cytotoxity.

    PubMed Central

    Matsumura, T; Kugiyama, K; Sugiyama, S; Ohgushi, M; Amanaka, K; Suzuki, M; Yasue, H

    1996-01-01

    This study was performed to determine effects of atrial and brain natriuretic peptides (ANP, BNP) on neutrophils-induced endothelial injury which is known to play a role in the pathophysiology of ischemia/reperfusion myocardial injury and to examine whether the effects of ANP and BNP on neutrophils are modulated by neutral endopeptidase 24.11 (NEP) in neutrophils themselves. The incubation of human neutrophils with ANP and BNP inhibited the neutrophils-induced detachment of cultured human endothelial cells (HEC). The inhibitory effect of ANP and BNP was associated with the suppressions of the neutrophils adhesiveness to HEC, CD18 expression on the neutrophils and elastase release from the neutrophils. Coincubation with UK73967 or phosphoramidon, inhibitors of NEP, potentiated all of the effects of ANP and BNP on the neutrophil functions, and the NEP inhibitors protected degradation of ANP and BNP by the neutrophils. NEP enzymatic activity in the particulate fractions and immunoreactive NEP expression were found to increase in the neutrophils from patients with early phase of acute myocardial infarction (AMI) by 5.2- and by 4.2-fold of the neutrophils from patients with late phase of AMI, respectively. In an in vivo canine model of myocardial ischemia/reperfusion, the intravenous administration of UK73967 suppressed the neutrophil adherence to endothelium and the neutrophil accumulation in the ischemic/reperfused myocardium. The results indicate that ANP and BNP, which are known to increase in AMI, modulate the neutrophil functions and exert protective effects against the neutrophils-induced endothelial cytotoxity. But the effects are suppressed due to their degradation by the neutrophil own NEP. Thus, neutrophil NEP, which also increases in AMI, may play a role in the pathophysiology of neutrophils-mediated ischemia/reperfusion endothelial and myocardial injury. PMID:8636398

  2. Mitochondrial Vulnerability and Increased Susceptibility to Nutrient-Induced Cytotoxicity in Fibroblasts from Leigh Syndrome French Canadian Patients

    PubMed Central

    Burelle, Yan; Thompson Legault, Julie; Boucher, Gabrielle; Morin, Charles; Coderre, Lise; Des Rosiers, Christine

    2015-01-01

    Mutations in LRPPRC are responsible for the French Canadian variant of Leigh Syndrome (LSFC), a severe disorder characterized biochemically by a tissue-specific deficiency of cytochrome c oxidase (COX) and clinically by the occurrence of severe and deadly acidotic crises. Factors that precipitate these crises remain unclear. To better understand the physiopathology and identify potential treatments, we performed a comprehensive analysis of mitochondrial function in LSFC and control fibroblasts. Furthermore, we have used this cell-based model to screen for conditions that promote premature cell death in LSFC cells and test the protective effect of ten interventions targeting well-defined aspects of mitochondrial function. We show that, despite maintaining normal ATP levels, LSFC fibroblasts present several mitochondrial functional abnormalities under normal baseline conditions, which likely impair their capacity to respond to stress. This includes mitochondrial network fragmentation, impaired oxidative phosphorylation capacity, lower membrane potential, increased sensitivity to Ca2+-induced permeability transition, but no changes in reactive oxygen species production. We also show that LSFC fibroblasts display enhanced susceptibility to cell death when exposed to palmitate, an effect that is potentiated by high lactate, while high glucose or acidosis alone or in combination were neutral. Furthermore, we demonstrate that compounds that are known to promote flux through the electron transport chain independent of phosphorylation (methylene blue, dinitrophenol), or modulate fatty acid (L-carnitine) or Krebs cycle metabolism (propionate) are protective, while antioxidants (idebenone, N-acetyl cysteine, resveratrol) exacerbate palmitate plus lactate-induced cell death. Collectively, beyond highlighting multiple alterations in mitochondrial function and increased susceptibility to nutrient-induced cytotoxicity in LSFC fibroblasts, these results raise questions about the nature of the diets, particularly excess fat intake, as well as on the use of antioxidants in patients with LSFC and, possibly, other COX defects. PMID:25835550

  3. KIR/HLA interactions negatively affect rituximab- but not GA101 (obinutuzumab)-induced antibody-dependent cellular cytotoxicity.

    PubMed

    Terszowski, Grzegorz; Klein, Christian; Stern, Martin

    2014-06-15

    Ab-dependent cellular cytotoxicity (ADCC) mediated by NK cells is regulated by inhibitory killer cell Ig-like receptors (KIRs), which interact with target cell HLA class I. We analyzed how KIR/HLA interactions influence ADCC induced by rituximab and by GA101, a novel type II CD20 Ab glycoengineered for increased FcgRIII binding and ADCC capacity. We found that KIR/HLA interactions strongly and selectively inhibit rituximab-induced in vitro ADCC toward target cells expressing cognate HLA KIR ligands. NK cells of donors carrying all three ligands to inhibitory KIR showed weak activation and target cell depletion capacity when incubated with rituximab and KIR-ligand matched target B cells. In contrast, NK cells from individuals missing one or more KIR ligands activated more strongly and depleted KIR ligand-matched target B cells more efficiently in the presence of rituximab. NK cells expressing a KIR for which the ligand was absent were the main effectors of ADCC in these donors. Notably, the influence of KIR/HLA interactions on NK cell activation was synergistic with the effect of the V158F FCGR3A single nucleotide polymorphism. In contrast, GA101 induced activation of NK cells irrespective of inhibitory KIR expression, and efficiency of target cell depletion was not negatively affected by KIR/HLA interactions. These data show that modification of the Fc fragment to enhance ADCC can be an effective strategy to augment the efficacy of therapeutic mAbs by recruiting NK cells irrespective of their inhibitory KIR expression. PMID:24795454

  4. Oligomeric proanthocyanidins alleviate hexabromocyclododecane-induced cytotoxicity in HepG2 cells through regulation on ROS formation and mitochondrial pathway.

    PubMed

    An, Jing; Chen, Cen; Wang, Xiu; Zhong, Yufang; Zhang, Xinyu; Yu, Yingxin; Yu, Zhiqiang

    2014-03-01

    Hexabromocyclododecane (HBCD), a type of brominated flame retardants (BFR), has become ubiquitous organic contaminants in recent years. However, studies on HBCD toxicity and the related molecular mechanisms are so far limited. The objective of the present study was to investigate the effects of oligomeric proanthocyanidins (OPCs) on cytotoxicity induced by HBCD and the underlying molecular mechanisms. HepG2 cells were treated with HBCD and/or OPCs at different concentrations, and cell viability, cell apoptosis, reactive oxygen species (ROS) production, cellular Ca(2+) level, mitochondrial membrane potential (??), cytochrome C (Cyt-c) release, and nuclear factor-erythroid 2-related factor 2 (Nrf2) proteins expression were evaluated. Results showed that HBCD induced toxic effects in HepG2 cells in a concentration-dependent manner. HBCD at high concentrations (40 and 60?M) caused a significant decrease of cell viability and led to elevated cell apoptosis ratio, intracellular Ca(2+) level, cytoplasmic Cyt-c level, and ROS production, together with a loss of ?? and mobilization of Nrf2. Pretreatment with OPCs effectively attenuated the cytotoxic effects and ROS production, as well as mitochondrial responses induced by HBCD. Thus, OPCs could alleviate cytotoxicity in HepG2 cells induced by HBCD through regulation on intracellular Ca(2+) level and ROS formation in a mitochondrial pathway. PMID:24291159

  5. Comparative study of cytotoxic and genotoxic effects induced by herbicide S-metolachlor and its commercial formulation Twin Pack Gold® in human hepatoma (HepG2) cells.

    PubMed

    Nikoloff, Noelia; Escobar, Luciana; Soloneski, Sonia; Larramendy, Marcelo L

    2013-12-01

    The in vitro effects of S-metolachlor and its formulation Twin Pack Gold(®) (96% a.i.) were evaluated in human hepatoma (HepG2) cells. Cytokinesis-blocked micronucleus cytome (CBMN-cyt) and MTT assays as well as Neutral Red uptake were employed for genotoxicity and cytotoxicity evaluation. Activities were tested within the concentration range of 0.25-15 ?g/ml S-metolachlor for 24h of exposure. Both compounds rendered a minor reduction in the NDI although not reaching statistical significance. Results demonstrated that the S-metolachlor was not able to induce MNs. On the other hand, 0.5-6 ?g/ml Twin Pack Gold(®) increased the frequency of MNs. When cytotoxicity was estimated, S-metolachlor was not able to induce either a reduction of lysosomal or mitochondrial activity. Contrarily, whereas 1-15 ?g/ml Twin Pack Gold(®) induced a significant reduction of mitochondrial activity, all tested concentrations of the formulated product induced a significant decrease of lysosomal performance as a function of the concentration of the S-metolachlor-based formulation titrated into cultures. Genotoxicity and cytotoxicity differences obtained with pure S-metolachlor and the commercial S-metolachlor-based formulation indicate that the latter may contain additional unsafe xenobiotics and support the concept of the importance of evaluating not only the active principle but also the commercial formulation when estimating the real hazard from agrochemicals. PMID:24144947

  6. Biosynthesis of Se nanoparticles and its effect on UV-induced DNA damage.

    PubMed

    Prasad, Kumar Suranjit; Patel, Hirnee; Patel, Tirtha; Patel, Khusbu; Selvaraj, Kaliaperumal

    2013-03-01

    This paper reports, an environmentally benign procedure of synthesis and characterizations of selenium nanoparticles and their protective effect against UV-induced DNA damage activities. An aqueous leaf extract of lemon plant was used as a precursor for synthesis of colloidal selenium nanoparticles. Resulting nanoparticles were characterized using UV-vis spectrophotometer, photoluminescence, TEM, EDAX, FT-IR and XRD, respectively. Selenium colloidal solution exhibited an absorption maximum at 395 nm and produced an emission maximum at 525 nm. Transmission electron microscopy followed by selected area electron diffraction pattern analysis indicated the formation of spherical, polydispersed, crystalline, selenium nanoparticles of diameter ranging from (?60 to 80 nm). X-ray diffraction studies showed the formation of 111, 200 and 220 planes of face-centered cubic (fcc) selenium. EDAX analysis confirmed the presence of selenium in nanosphere. Fourier transformed infrared spectroscopic investigation reveled the involvement of carboxyl (?C=O), hydroxyl (?OH), amine (?NH) functional group of lemon plant extract in preparation of selenium nanoparticles. MTT assay as well single cell gel electrophoresis assay or comet assay revealed that synthesized selenium nanoparticles, caused less cell death of lymphocytes and prevented DNA damage, when cells were exposed to UVB. The fluorescent property of selenium nanoparticles can be used as diagnostic agent. Further, their anti DNA damaging property can be investigated as a chemotherapeutic agent in cancer therapy. PMID:23201746

  7. Far-red/near-infrared fluorescent bioprobes based on biocompatible nanoparticles with aggregation-induced emission characteristics for bioimaging applications

    NASA Astrophysics Data System (ADS)

    Qin, Wei; Ding, Dan; Liu, Bin; Tang, Ben Zhong

    2013-09-01

    Light emission of 2-(2,6-bis((E)-4-(diphenylamino)styryl]-4H-pyran-4-ylidene}malononitrile (TPA-DCM) is weakened by aggregate formation. Attaching tetraphenylethene (TPE) units as terminals to TPA-DCM dramatically changes its emission behavior: the resulting fluorogen 2-(2,6-bis((E)-4-(phenyl(4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl]-4- yl)amino)styryl)-4H-pyran-4-ylidene)malononitrile (TPE-TPA-DCM) is more emissive in the aggregate state, showing a novel phenomenon of aggregation-induced emission (AIE). Formulation of TPE-TPA-DCM using bovine serum albumin (BSA) as the polymer matrix yields uniformly sized protein nanoparticles (NPs) with high brightness and low cytotoxicity. Applications of the fluorogen-loaded BSA NPs for in vitro and in vivo far-red/near-infrared (FR/NIR) bioimaging are successfully demonstrated using MCF-7 breast cancer cells and a murine hepatoma-22 (H22) tumorbearing mice model, respectively. The AIE-active fluorogen-loaded BSA NPs show excellent cancer cell uptake and prominent tumor targeting ability in vivo due to the enhanced permeability and retention effect.

  8. Cerium Oxide Nanoparticles Induced Toxicity in Human Lung Cells: Role of ROS Mediated DNA Damage and Apoptosis

    PubMed Central

    Pandey, Alok K.

    2014-01-01

    Cerium oxide nanoparticles (CeO2 NPs) have promising industrial and biomedical applications. In spite of their applications, the toxicity of these NPs in biological/physiological environment is a major concern. Present study aimed to understand the molecular mechanism underlying the toxicity of CeO2 NPs on lung adenocarcinoma (A549) cells. After internalization, CeO2 NPs caused significant cytotoxicity and morphological changes in A549 cells. Further, the cell death was found to be apoptotic as shown by loss in mitochondrial membrane potential and increase in annexin-V positive cells and confirmed by immunoblot analysis of BAX, BCl-2, Cyt C, AIF, caspase-3, and caspase-9. A significant increase in oxidative DNA damage was found which was confirmed by phosphorylation of p53 gene and presence of cleaved poly ADP ribose polymerase (PARP). This damage could be attributed to increased production of reactive oxygen species (ROS) with concomitant decrease in antioxidant “glutathione (GSH)” level. DNA damage and cell death were attenuated by the application of ROS and apoptosis inhibitors N-acetyl-L- cysteine (NAC) and Z-DEVD-fmk, respectively. Our study concludes that ROS mediated DNA damage and cell cycle arrest play a major role in CeO2 NPs induced apoptotic cell death in A549 cells. Apart from beneficial applications, these NPs also impart potential harmful effects which should be properly evaluated prior to their use. PMID:24987704

  9. X-ray CT and pneumonia inhibition properties of gold-silver nanoparticles for targeting MRSA induced pneumonia.

    PubMed

    Huo, Da; Ding, Jing; Cui, Yi X; Xia, Lu Y; Li, Hui; He, Jian; Zhou, Zheng Y; Wang, Hong W; Hu, Yong

    2014-08-01

    Non-invasive assay for the early stage diagnosis of methicillin resistant Staphylococcus aureus (MRSA) related pneumonia is of great clinical importance and still a great challenge. In this paper, we reported a novel kind of Au@Ag core-shell theranostic nanoparticles (NPs) conjugated with MRSA specific antibody on their surface. Compared with the raw Au@Ag NPs, these antibody modified NPs (AAMA NPs) showed 10.66 fold enhancement targeting to the MRSA in vitro. In vivo target efficacy was measured with rats bearing pneumonia induced by different pathogens. Computed tomography (CT) results revealed that these AAMA NPs had higher CT contrast enhancement (498 HU), than those of raw Au@Ag and Omnipaque (oth <100 HU). In addition, lesions labeled by AAMA NPs could be distinguished from lung parenchyma by taking advantage of spectra CT. Bio-distribution analysis confirmed that these AAMA NPs accumulated in the MRSA rich site. Both BAL and Elisa assays indicated that these AAMA NPs greatly alleviated the inflammation reaction by reducing bacterial proliferation and cytokine production. Pathological study showed that these NPs exerted negligible long term cytotoxicity in vivo. PMID:24836950

  10. Aldose reductase mediates endotoxin-induced production of nitric oxide and cytotoxicity in murine macrophages

    Microsoft Academic Search

    Kota V. Ramana; Aramati B. M. Reddy; Ravinder Tammali; Satish K. Srivastava

    2007-01-01

    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

  11. Cytotoxicity, DNA Cross-Linking, and Single Strand Breaks Induced by Activated Cyclophosphamide and Acrolein in Human Leukemia Cells

    Microsoft Academic Search

    Tim R. Crook; Robert L. Souhami; E. M. McLean

    1986-01-01

    The in vitro cytotoxicity and mechanism of action of Cyclophosphamide (CP) were studied in a dual cell culture system, using rat hepatocytes and K562 human chronic myeloid leukemia cells. Cytotoxicity and DNA damage were measurable in KS62 cells using CP concentrations that are clinically attainable. Alkaline elution analysis of cellular DNA demon strated the presence of concentration- and time-dependent DNA

  12. Virus inhibition induced by polyvalent nanoparticles of different sizes.

    PubMed

    Vonnemann, Jonathan; Sieben, Christian; Wolff, Christopher; Ludwig, Kai; Böttcher, Christoph; Herrmann, Andreas; Haag, Rainer

    2014-02-21

    The development of antiviral agents is one of the major challenges in medical science. So far, small monovalent molecular drugs that inhibit the late steps in the viral replication cycle, i.e., virus budding, have not worked well which emphasizes the need for alternative approaches. Polyvalently presented viral receptors, however, show potential as good inhibitors of virus-cell binding, which is the first step in the viral infection cycle. By gradually increasing the size of ligand functionalized gold nanoparticles, up to virus-like dimensions, we are now able to quantify the polyvalent enhancement of virus-cell binding inhibition and to identify varying mechanisms of virus inhibition with different efficacies: by employing a new binding assay we found that surface area-normalized polysulfated gold nanoparticles of diameters equal to and larger than the virus diameter (>50 nm) more efficiently inhibit the binding of vesicular stomatitis virus (VSV) to cells than smaller particles. On a per particle basis, larger sized gold nanoparticles were surprisingly shown to inhibit the viral infection up to two orders of magnitude more efficiently than smaller particles, which suggests different mechanisms of virus inhibition. Based on complementary electron microscopic data, we noticed that larger gold nanoparticles act as efficient cross-linkers between virions, whereas smaller gold nanoparticles decorate the surface of individual virus particles. Our systematic study accentuates the need for the design of biodegradable, virus-sized inhibitors capitalizing on polyvalent binding. PMID:24430614

  13. Direct patterning of Cu microstructures using femtosecond laser-induced CuO nanoparticle reduction

    NASA Astrophysics Data System (ADS)

    Arakane, Shun; Mizoshiri, Mizue; Hata, Seiichi

    2015-06-01

    Cu-based microstructures were directly patterned using femtosecond laser-induced CuO nanoparticle reduction. CuO nanoparticle-based solution, consisting CuO nanoparticles, ethylene glycol, and polyvinylpyrrolidone, was spin-coated on glass substrates. Microstructures were formed by irradiating focused femtosecond laser pulses. Cu and Cu2O peak intensities were observed in the X-ray diffraction (XRD) spectra of the microstructures. Compared to single scan, the Cu peak intensities increased by double scan. This result suggests that double scan is effective for increasing the amount of Cu from CuO nanoparticle solution. Cu- and Cu2O-rich microstructures were formed selectively by controlling laser irradiation conditions. The resistivity of the Cu-rich microstructures was estimated by 528 µ? m which was 104 times and 10 times larger than the values of Cu and Cu2O, respectively. This large resistivity could be applied for microheaters.

  14. Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response

    NASA Astrophysics Data System (ADS)

    Li, Haiyan; Li, Yuhuan; Jiao, Jun; Hu, Hong-Ming

    2011-10-01

    Therapeutic cancer vaccination is an attractive strategy because it induces T cells of the immune system to recognize and kill tumour cells in cancer patients. However, it remains difficult to generate large numbers of T cells that can recognize the antigens on cancer cells using conventional vaccine carrier systems. Here we show that ?-Al2O3 nanoparticles can act as an antigen carrier to reduce the amount of antigen required to activate T cells in vitro and in vivo. We found that ?-Al2O3 nanoparticles delivered antigens to autophagosomes in dendritic cells, which then presented the antigens to T cells through autophagy. Immunization of mice with ?-Al2O3 nanoparticles that are conjugated to either a model tumour antigen or autophagosomes derived from tumour cells resulted in tumour regression. These results suggest that ?-Al2O3 nanoparticles may be a promising adjuvant in the development of therapeutic cancer vaccines.

  15. Photo-induced electric polarizability of Fe3O4 nanoparticles in weak optical fields

    PubMed Central

    2013-01-01

    Using a developed co-precipitation method, we synthesized spherical Fe3O4 nanoparticles with a wide nonlinear absorption band of visible radiation. Optical properties of the synthesized nanoparticles dispersed in an optically transparent copolymer of methyl methacrylate with styrene were studied by optical spectroscopy and z-scan techniques. We found that the electric polarizability of Fe3O4 nanoparticles is altered by low-intensity visible radiation (I ? 0.2 kW/cm2; ? = 442 and 561 nm) and reaches a value of 107 Ĺ3. The change in polarizability is induced by the intraband phototransition of charge carriers. This optical effect may be employed to improve the drug uptake properties of Fe3O4 nanoparticles. PACS 33.15.Kr 78.67.Bf 42.70.Nq PMID:23837726

  16. Protective effects of mangosteen extract on H2O2-induced cytotoxicity in SK-N-SH cells and scopolamine-induced memory impairment in mice.

    PubMed

    Sattayasai, Jintana; Chaonapan, Pongsatorn; Arkaravichie, Tarinee; Soi-Ampornkul, Rungtip; Junnu, Sarawut; Charoensilp, Patcharakajee; Samer, Jutima; Jantaravinid, Jiraporn; Masaratana, Patarabutr; Suktitipat, Bhoom; Manissorn, Juthatip; Thongboonkerd, Visith; Neungton, Neelobol; Moongkarndi, Primchanien

    2013-01-01

    Mangosteen extracts (ME) contain high levels of polyphenolic compounds and antioxidant activity. Protective effects of ME against ?-amyloid peptide (A?), induced cytotoxicity have been reported. Here, we further studied the protective effects of ME against oxidative stress induced by hydrogen peroxide (H2O2) and polychlorinated biphenyls (PCBs), and demonstrated the protection against memory impairment in mice. The cytoprotective effects of ME were measured as cell viability and the reduction in ROS activity. In SK-N-SH cell cultures, 200 ?g/ml ME could partially antagonize the effects of 150 or 300 µM H2O2 on cell viability, ROS level and caspase-3 activity. At 200, 400 or 800 µg/ml, ME reduced AChE activity of SK-N-SH cells to about 60% of the control. In vivo study, Morris water maze and passive avoidance tests were used to assess the memory of the animals. ME, especially at 100 mg/kg body weight, could improve the animal's memory and also antagonize the effect of scopolamine on memory. The increase in ROS level and caspase-3 activity in the brain of scopolamine-treated mice were antagonized by the ME treatment. The study demonstrated cytoprotective effects of ME against H2O2 and PCB-52 toxicity and having AChE inhibitory effect in cell culture. ME treatment in mice could attenuate scopolamine-induced memory deficit and oxidative stress in brain. PMID:24386444

  17. Protective Effects of Mangosteen Extract on H2O2-Induced Cytotoxicity in SK-N-SH Cells and Scopolamine-Induced Memory Impairment in Mice

    PubMed Central

    Sattayasai, Jintana; Chaonapan, Pongsatorn; Arkaravichie, Tarinee; Soi-ampornkul, Rungtip; Junnu, Sarawut; Charoensilp, Patcharakajee; Samer, Jutima; Jantaravinid, Jiraporn; Masaratana, Patarabutr; Suktitipat, Bhoom; Manissorn, Juthatip; Thongboonkerd, Visith; Neungton, Neelobol; Moongkarndi, Primchanien

    2013-01-01

    Mangosteen extracts (ME) contain high levels of polyphenolic compounds and antioxidant activity. Protective effects of ME against ?-amyloid peptide (A?), induced cytotoxicity have been reported. Here, we further studied the protective effects of ME against oxidative stress induced by hydrogen peroxide (H2O2) and polychlorinated biphenyls (PCBs), and demonstrated the protection against memory impairment in mice. The cytoprotective effects of ME were measured as cell viability and the reduction in ROS activity. In SK-N-SH cell cultures, 200 ?g/ml ME could partially antagonize the effects of 150 or 300 µM H2O2 on cell viability, ROS level and caspase-3 activity. At 200, 400 or 800 µg/ml, ME reduced AChE activity of SK-N-SH cells to about 60% of the control. In vivo study, Morris water maze and passive avoidance tests were used to assess the memory of the animals. ME, especially at 100 mg/kg body weight, could improve the animal’s memory and also antagonize the effect of scopolamine on memory. The increase in ROS level and caspase-3 activity in the brain of scopolamine-treated mice were antagonized by the ME treatment. The study demonstrated cytoprotective effects of ME against H2O2 and PCB-52 toxicity and having AChE inhibitory effect in cell culture. ME treatment in mice could attenuate scopolamine-induced memory deficit and oxidative stress in brain. PMID:24386444

  18. Evaluation of DNA damage and cytotoxicity induced by three commonly used organophosphate pesticides individually and in mixture, in rat tissues.

    PubMed

    Ojha, Anupama; Yaduvanshi, Santosh Kumar; Pant, Satish Chnadra; Lomash, Vinay; Srivastava, Nalini

    2013-10-01

    Organophosphate pesticides are among the most widely used synthetic chemicals for controlling a wide variety of pests. Chlorpyrifos (CPF), methyl parathion (MPT), and malathion (MLT) are among the most extensively used organophosphate (OP) pesticides. The main target of action of OP compounds is the central and peripheral nervous system, although it has also been postulated that these compounds in both acute and chronic intoxication, disturb the redox processes and thus induce oxidative stress. The excessive generation of reactive oxygen species (ROS) causes damage to all vital macromolecules including lipids, proteins, and DNA. This study was aimed to investigate the genotoxicity and cytotoxicity of CPF, MPT, and MLT when given singly or in combination. The DNA damage was measured by alkaline single-cell gel electrophoresis or comet assay and expressed as DNA damage index. The results showed that both acute and chronic exposure with CPF, MPT, and MLT, caused significantly marked DNA damage in rat tissues namely, liver, brain, kidney, and spleen, when measured 24 hour posttreatment. It was also observed that MPT caused highest level of DNA damage and brain was maximally affected by these OP compounds. When these pesticides were given in mixture, the damage was not the sum of damage caused by individual pesticide, confirming that these pesticides do not potentiate the toxicity of each other. When the DNA damage was measured 48 and 72 hour posttreatment, the damage was partially repaired. Pesticide exposure also caused histopathological changes in rat tissues. PMID:21786386

  19. Carbamates: A study on genotoxic, cytotoxic, and apoptotic effects induced in Chinese hamster ovary (CHO-K1) cells.

    PubMed

    Soloneski, Sonia; Kujawski, Maciej; Scuto, Anna; Larramendy, Marcelo L

    2015-08-01

    In vitro effects of the carbamates pirimicarb and zineb and their formulations Aficida® (50% pirimicarb) and Azzurro® (70% zineb), respectively, were evaluated in Chinese hamster ovary (CHO-K1) cells. Whereas the cytokinesis-blocked micronucleus cytome assay was employed to test for genotoxicity, MTT, neutral red (NR), and apoptosis evaluation were used as tests for estimating cell viability and succinic dehydrogenase activity, respectively. Concentrations tested were 10-300?g/ml for pirimicarb and Aficida®, and 1-50?g/ml for zineb and Azzurro®. All compounds were able to increase the frequency of micronuclei. A marked reduction in the nuclear division index was observed after treatment with 5?g/ml of zineb and Azzurro® and 10?g/ml of Azzurro®. Alterations in the cellular morphology not allowing the recognition of binucleated cells exposed to 300?g/ml pirimicarb and Aficida® as well as 10-50?g/ml zineb and Azzurro®. All four compounds induced inhibition of both cell viability and succinic dehydrogenase activity and trigger apoptosis in CHO-K1 cells, at least when exposed for 24h. The data herein demonstrate the genotoxic and cytotoxic effects exerted by these carbamates and reveal the potential risk factor of these pesticides, still extensively used worldwide, for both human health and the environment. PMID:25820133

  20. Vitamin C Derivative Ascorbyl Palmitate Promotes Ultraviolet-B-Induced Lipid Peroxidation and Cytotoxicity in Keratinocytes

    Microsoft Academic Search

    Alexander Meves; Sibylle N Stock; Astrid Beyerle; Mark R Pittelkow; Dominik Peus

    2002-01-01

    Among the preventative and protective strategies against the harmful effects of ultraviolet radiation to the skin is the application of antioxidants. Ascorbic acid has been shown to protect against sunburn, delay the onset of skin tumors, and reduce ultraviolet-B-radiation-induced skin wrinkling. In this work, we sought to determine the antioxidative properties of a lipid-soluble derivative of ascorbic acid, ascorbic acid-6-palmitate.

  1. PLGA-Loaded Gold-Nanoparticles Precipitated with Quercetin Downregulate HDAC-Akt Activities Controlling Proliferation and Activate p53-ROS Crosstalk to Induce Apoptosis in Hepatocarcinoma Cells.

    PubMed

    Bishayee, Kausik; Khuda-Bukhsh, Anisur Rahman; Huh, Sung-Oh

    2015-06-30

    Controlled release of medications remains the most convenient way to deliver drugs. In this study, we precipitated gold nanoparticles with quercetin. We loaded gold-quercetin into poly(DL-lactide-co-glycolide) nanoparticles (NQ) and tested the biological activity of NQ on HepG2 hepatocarcinoma cells to acquire the sustained release property. We determined by circular dichroism spectroscopy that NQ effectively caused conformational changes in DNA and modulated different proteins related to epigenetic modifications and c ell cycle control. The mitochondrial membrane potential (MMP), reactive oxygen species (ROS), cell cycle, apoptosis, DNA damage, and caspase 3 activity were analyzed by flow cytometry, and the expression profiles of different anti- and pro-apoptotic as well as epigenetic signals were studied by immunoblotting. A cytotoxicity assay indicated that NQ preferentially killed cancer cells, compared to normal cells. NQ interacted with HepG2 cell DNA and reduced histone deacetylases to control cell proliferation and arrest the cell cycle at the sub-G stage. Activities of cell cycle-related proteins, such as p21(WAF), cdk1, and pAkt, were modulated. NQ induced apoptosis in HepG2 cells by activating p53-ROS crosstalk and induces epigenetic modifications leading to inhibited proliferation and cell cycle arrest. PMID:25947292

  2. PLGA-Loaded Gold-Nanoparticles Precipitated with Quercetin Downregulate HDAC-Akt Activities Controlling Proliferation and Activate p53-ROS Crosstalk to Induce Apoptosis in Hepatocarcinoma Cells

    PubMed Central

    Bishayee, Kausik; Khuda-Bukhsh, Anisur Rahman; Huh, Sung-Oh

    2015-01-01

    Controlled release of medications remains the most convenient way to deliver drugs. In this study, we precipitated gold nanoparticles with quercetin. We loaded gold-quercetin into poly(DL-lactide-co-glycolide) nanoparticles (NQ) and tested the biological activity of NQ on HepG2 hepatocarcinoma cells to acquire the sustained release property. We determined by circular dichroism spectroscopy that NQ effectively caused conformational changes in DNA and modulated different proteins related to epigenetic modifications and c ell cycle control. The mitochondrial membrane potential (MMP), reactive oxygen species (ROS), cell cycle, apoptosis, DNA damage, and caspase 3 activity were analyzed by flow cytometry, and the expression profiles of different anti- and pro-apoptotic as well as epigenetic signals were studied by immunoblotting. A cytotoxicity assay indicated that NQ preferentially killed cancer cells, compared to normal cells. NQ interacted with HepG2 cell DNA and reduced histone deacetylases to control cell proliferation and arrest the cell cycle at the sub-G stage. Activities of cell cycle-related proteins, such as p21WAF, cdk1, and pAkt, were modulated. NQ induced apoptosis in HepG2 cells by activating p53-ROS crosstalk and induces epigenetic modifications leading to inhibited proliferation and cell cycle arrest. PMID:25947292

  3. Role of autophagy in high linear energy transfer radiation-induced cytotoxicity to tumor cells.

    PubMed

    Jin, Xiaodong; Liu, Yan; Ye, Fei; Liu, Xiongxiong; Furusawa, Yoshiya; Wu, Qingfeng; Li, Feifei; Zheng, Xiaogang; Dai, Zhongying; Li, Qiang

    2014-07-01

    Heavy-ion radiotherapy has a potential advantage over conventional radiotherapy due to improved dose distribution and a higher biological effectiveness in cancer therapy. However, there is a little information currently available on the cellular and molecular basis for heavy-ion irradiation-induced cell death. Autophagy, as a novel important target to improve anticancer therapy, has recently attracted considerable attention. In this study, the effect of autophagy induced by high linear energy transfer (LET) carbon ions was examined in various tumor cell lines. To our knowledge, our study is the first to reveal that high-LET carbon ions could induce autophagy in various tumor cells effectively, and the autophagic level in the irradiated cells increased in a dose- and LET-dependent manner. The ability of carbon ions to inhibit the activation of the PI3K/Akt pathway rose with increasing their LET. Moreover, modulation of autophagy in tumor cells could modify their sensitivity to high-LET radiation, and inhibiting autophagy accelerated apoptotic cell death, resulting in an increase in radiosensitivity. Our data imply that targeting autophagy might enhance the effectiveness of heavy-ion radiotherapy. PMID:24731006

  4. All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity.

    PubMed

    Sanchez-Martínez, Diego; Krzywinska, Ewelina; Rathore, Moeez G; Saumet, Anne; Cornillon, Amelie; Lopez-Royuela, Nuria; Martínez-Lostao, Luis; Ramirez-Labrada, Ariel; Lu, Zhao-Yang; Rossi, Jean-François; Fernández-Orth, Dietmar; Escorza, Sergio; Anel, Alberto; Lecellier, Charles-Henri; Pardo, Julian; Villalba, Martin

    2014-04-01

    NK cell is an innate immune system lymphocyte lineage with natural cytotoxicity. Its optimal use in the clinic requires in vitro expansion and activation. Cytokines and encounter with target cells activate NK cells and induce proliferation, and this could depend on the presence of other immune cells. Here we activated PBMCs during 5 days with IL-2, with IL-2 plus the tumor cell line K562 and with the lymphoblastoid cell line R69 and perform integrated analyses of microRNA and mRNA expression profiles of purified NK cells. The samples cluster depending on the stimuli and not on the donor, indicating that the pattern of NK cell stimulation is acutely well conserved between individuals. Regulation of mRNA expression is tighter than that of miRNA expression. All stimuli induce a common preserved genetic remodeling. In addition, encounter with target cells mainly activates pathways related to metabolism. Different target cells induce different NK cell remodeling which affects cytokine response and cytotoxicity, supporting the notion that encounter with different target cells significantly changing the activation pattern. We validate our analysis by showing that activation down regulates miR-23a, which is a negative regulator of cathepsin C (CTSC) mRNA, a gene up regulated by all stimuli. The peptidase CTSC activates the granzymes, the main effector proteases involved in NK cell cytotoxicity. All-trans retinoic acid (ATRA), which induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity in an in vivo mouse model. PMID:24440757

  5. Humic acid mediates iron release from ferritin and promotes lipid peroxidation in vitro: a possible mechanism for humic acid-induced cytotoxicity

    Microsoft Academic Search

    Kuo-Jang Ho; Tsung-Kwei Liu; Tien-Shang Huang; Fung-Jou Lu

    2003-01-01

    Humic acid (HA) has been shown to be a toxic factor for many mammalian cells, however the specific mechanism of the cytotoxicity induced by HA remains unclear. From the assessment of its redox properties, HA has been shown to be capable of reducing iron(III) to iron(II) in aqueous conditions over a broad range of pH values (from 4.0 to 9.0).

  6. DNA-damaging activity and mutagenicity of 16 newly synthesized thiazolo[5,4- a]acridine derivatives with high photo-inducible cytotoxicity

    Microsoft Academic Search

    Carole Di Giorgio; Anna Nikoyan; Laetitia Decome; Céline Botta; Maxime Robin; Jean-Pierre Reboul; Anne-Sophie Sabatier; Alain Matta; Michel De Méo

    2008-01-01

    The discovery of the potent anticancer properties of natural alkaloids in the pyrido-thiazolo-acridine series has suggested that thiazolo-acridine derivatives could be of great interest. In a continuous attempt to develop DNA-binding molecules and DNA photo-cleavers, 16 new thiazolo[5,4-a]acridines were synthesized and studied for their photo-inducible DNA-intercalative, cytotoxic and mutagenic activities, by use of the DNA methyl-green bioassay, the Alamar Blue®

  7. Innate immune agonist, dsRNA, induces apoptosis in ovarian cancer cells and enhances the potency of cytotoxic chemotherapeutics.

    PubMed

    Van, Danielle N; Roberts, Charlotte F; Marion, James D; Lépine, Sandrine; Harikumar, Kuzhuvelil B; Schreiter, Jessica; Dumur, Catherine I; Fang, Xianjun; Spiegel, Sarah; Bell, Jessica K

    2012-08-01

    Ovarian cancer is the most lethal gynecological cancer. Here we show that innate immune agonist, dsRNA, directly induces ovarian cancer cell death and identify biomarkers associated with responsiveness to this targeted treatment. Nuclear staining and MTT assays following dsRNA stimulation revealed two subpopulations, sensitive (OVCAR-3, CAOV-3; patient samples malignant 1 and 2) and resistant (DOV-13, SKOV-3). Microarray analysis identified 75 genes with differential expression that further delineated these two subpopulations. qPCR and immunoblot analyses showed increased dsRNA receptor expression after stimulation as compared to resistant and immortalized ovarian surface epithelial cells (e.g., 70-fold with malignant 2, 43-fold with OVCAR-3). Using agonists, antagonists, and shRNA-mediated knockdown of dsRNA receptors, we show that TLR3, RIG-I, and mda5 coordinated a caspase 8/9- and interferon-dependent cell death. In resistant cells, dsRNA receptor overexpression restored dsRNA sensitivity. When dsRNA was combined with carboplatin or paclitaxel, cell viability significantly decreased over individual treatments (1.5- to 7.5-fold). Isobologram analyses showed synergism in dsRNA combinations (CI=0.4-0.82) vs. an additive effect in carboplatin/paclitaxel treatment (CI=1.5-2). Our data identify a predictive marker, dsRNA receptor expression, to target dsRNA responsive populations and show that, in dsRNA-sensitive cells, dsRNA induces apoptosis and enhances the potency of cytotoxic chemotherapeutics. PMID:22532440

  8. Hepatitis C virus-specific cytotoxic T cell response restoration after treatment-induced hepatitis C virus control

    PubMed Central

    Larrubia, Juan-Ramón; Moreno-Cubero, Elia; Miquel, Joaquín; Sanz-de-Villalobos, Eduardo

    2015-01-01

    Hepatitis C virus (HCV)-specific cytotoxic T cell (CTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onset, being unable to get rid of HCV. The role of this response in contributing to sustained viral response (SVR) after anti-HCV is controversial. Recent studies show that after successful interferon-based anti-HCV treatment, HCV traces are still detectable and this correlates with a peak of HCV-specific CTL response activation, probably responsible for maintaining SVR by subsequent complete HCV clearing. Moreover, SVR patients’ serum is still able to induce HCV infection in naďve chimpanzees, suggesting that the infection could be under the control of the immune system after a successful treatment, being transmissible in absence of this adaptive response. At least theoretically, treatment-induced viral load decrease could allow an effective HCV-specific CTL response reestablishment. This effect has been recently described with anti-HCV interferon-free regimes, based on direct-acting antivirals. Nevertheless, this is to some extent controversial with interferon-based therapies, due to the detrimental immunoregulatory ?-interferon effect on T cells. Moreover, HCV-specific CTL response features during anti-HCV treatment could be a predictive factor of SVR that could have clinical implications in patient management. In this review, the recent knowledge about the role of HCV-specific CTL response in the development of SVR after anti-HCV treatment is discussed. PMID:25834312

  9. Split anergized natural killer cells halt inflammation by inducing stem cell differentiation, resistance to NK cell cytotoxicity and prevention of cytokine and chemokine secretion

    PubMed Central

    Tseng, Han-Ching; Cacalano, Nicholas; Jewett, Anahid

    2015-01-01

    The mechanism of suppression of NK cytotoxicity in cancer patients is not clearly established. In this paper we provide evidence that anergized NK cells induce differentiation of healthy Dental Pulp Stem Cells (DPSCs) or transformed Oral Squamous Cancer Stem Cells (OSCSCs) resulting in cell growth inhibition, resistance to NK cell-mediated cytotoxicity and prevention of inflammatory mediators secretion. Induction of cytotoxicity resistance in differentiated cells correlated with increased CD54 and MHC class I surface expression and mediated by the combination of IFN-? and TNF-? since antibodies to both, but not each cytokine alone, was able to inhibit resistance. In contrast, inhibition of cytokine and chemokine release was mediated by IFN-? since the addition of anti-IFN-? antibody, and not anti-TNF-?, restored secretion of inflammatory mediators in NK cell cultures with differentiated DPSCs and OSCSCs. There was a gradual and time dependent decrease in MHC class I and CD54 expression which correlated with the restoration of NK cell cytotoxicity, augmentation of cytokine secretion and increased cell growth from days 0–12 post NK removal. Continuous presence of NK cells is required for the maintenance of cell differentiation since the removal of NK cell-mediated function reverses the phenotype and function of differentiated cells to their stem-like cells. PMID:25860927

  10. Carbon and iron ion radiation-induced cytotoxicity and transformation in vitro

    PubMed Central

    Zhou, Zhaozong; Ware, Jeffrey H.; Kennedy, Ann R.

    2011-01-01

    The present study was undertaken to characterize carbon and iron ion radiation-induced adverse biological effects in terms of toxicity and transformation in vitro. HTori-3 human thyroid epithelial cells were irradiated with 0.3-GeV/n (13.6 KeV/µm) carbon ions and 1-GeV/n (150 KeV/µm) iron ions, both of which represent high-mass, high atomic number (Z) and high-energy particles known as HZE particles, as well as ?-rays. The survival of the irradiated cells was determined by a clonogenic survival assay. The yield of colonies growing in soft agar was used as a surrogate endpoint biomarker for transformation in vitro. The results showed that HZE particles and ?-ray radiations are effective in increasing the yield of anchorage-independent colonies. Based on the relative biological effectiveness (RBE) values in the clonogenic survival assays, 0.3-GeV/n carbon ions and 1-GeV/n iron ions were 2.9 and 2.4 times, respectively, as effective as ?-rays at killing the irradiated HTori-3 cells. At a dose of 200 cGy, 0.3-GeV/n carbon ions and 1-GeV/n iron ions were found to be 3.5 and 7.3 times, respectively, as effective as ?-rays at inducing anchorage-independent growth. These results suggest that the carcinogenic potential of 0.3-GeV/n carbon ions, as represented by the ability to induce anchorage-independent growth, may be lower than that of 1-GeV/n iron ions. PMID:22866150

  11. Temperature-induced phenomena in systems of magnetic nanoparticles

    Microsoft Academic Search

    Abdul Wazed Bhuiya

    2009-01-01

    Magnetic nanoparticle ensembles have received a lot of attention, stemming in part from their current and potential applications in biomedicine and in the development of high-density magnetic storage media. Key to the functionality of these systems are microscopic structures and mechanisms that make them exhibit unique properties and behave differently from their bulk counterparts. We studied microscopic structures and processes

  12. Field-Induced Microwave Absorption in Ni Ferrite Nanoparticles

    Microsoft Academic Search

    Pablo Hernandez-Gomez; J. Muoz; Manuel A. Valente

    2010-01-01

    Ferrite nanoparticles are in the last years a matter of strong interest due to the fact that nanoscale materials possess size-dependent optical, electronic, magnetic, thermal, mechanical, and chemical properties that are comparable to or superior to those of bulk material counterparts, as well as its potential applications in sensors or microwave devices. Nickel ferrites, which are well-known technological materials in

  13. Enhancement of lipopolysaccharide-induced nitric oxide and interleukin-6 production by PEGylated gold nanoparticles in RAW264.7 cells

    NASA Astrophysics Data System (ADS)

    Liu, Zhimin; Li, Wenqing; Wang, Feng; Sun, Chunyang; Wang, Lu; Wang, Jun; Sun, Fei

    2012-10-01

    While the immunogenicity and cytotoxicity of gold nanoparticles (AuNPs) are noted by many researchers, the mechanisms by which AuNPs exert these effects are poorly understood. In this study, we investigated the effects of polyethylene glycolylated AuNPs (PEG@AuNPs) on lipopolysaccharide (LPS)-induced nitric oxide (NO) and interleukin-6 (IL-6) production and the associated molecular mechanism in RAW264.7 cells. The results showed that PEG@AuNPs were internalized more quickly by LPS-activated RAW264.7 cells than unstimulated cells, and they reached saturation within 24 hours. PEG@AuNPs enhanced LPS-induced production of NO and IL-6 and inducible nitric oxide synthase (iNOS) expression in RAW264.7 cells, partially by activating p38 mitogen-activated protein kinases (p38 MAPK) and nuclear factor-kappaB pathways. In addition, the p38 MAPK inhibitor SB203580 attenuated PEG@AuNP-enhanced LPS-induced NO production and iNOS expression. Overproduction of NO and IL-6 is known to be closely correlated with the pathology of many diseases and inflammations. Thus, it is speculated that the highly biocompatible gold nanoparticles can induce immunotoxicity due to their potency to stimulate macrophages to release aberrant or excessive pro-inflammatory mediators.While the immunogenicity and cytotoxicity of gold nanoparticles (AuNPs) are noted by many researchers, the mechanisms by which AuNPs exert these effects are poorly understood. In this study, we investigated the effects of polyethylene glycolylated AuNPs (PEG@AuNPs) on lipopolysaccharide (LPS)-induced nitric oxide (NO) and interleukin-6 (IL-6) production and the associated molecular mechanism in RAW264.7 cells. The results showed that PEG@AuNPs were internalized more quickly by LPS-activated RAW264.7 cells than unstimulated cells, and they reached saturation within 24 hours. PEG@AuNPs enhanced LPS-induced production of NO and IL-6 and inducible nitric oxide synthase (iNOS) expression in RAW264.7 cells, partially by activating p38 mitogen-activated protein kinases (p38 MAPK) and nuclear factor-kappaB pathways. In addition, the p38 MAPK inhibitor SB203580 attenuated PEG@AuNP-enhanced LPS-induced NO production and iNOS expression. Overproduction of NO and IL-6 is known to be closely correlated with the pathology of many diseases and inflammations. Thus, it is speculated that the highly biocompatible gold nanoparticles can induce immunotoxicity due to their potency to stimulate macrophages to release aberrant or excessive pro-inflammatory mediators. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr31355c

  14. Polyphenols as possible bioprotectors against cytotoxicity and DNA damage induced by ochratoxin A.

    PubMed

    Cariddi, L N; Sabini, M C; Escobar, F M; Montironi, I; Mańas, F; Iglesias, D; Comini, L R; Sabini, L I; Dalcero, A M

    2015-05-01

    The present study aimed to investigate the protective effects of luteolin (L), chlorogenic acid (ChlA) and caffeic acid (CafA) against cyto-genotoxic effects caused by OTA. Vero cells and rat lymphocytes were used and viability was measured by neutral red uptake, MTT and trypan blue dye exclusion method. L (50 and 100?g/mL), ChlA (100 and 200?g/mL) and CafA (10-50?g/mL) reduced the damage induced by OTA (10?g/mL) on both cells type shown a good protective effect. The comet and micronucleus tests in Balb/c mice were performed. ChlA (10mg/kg bw) reduced OTA (0.85mg/kg bw)-induced DNA damage on blood and bone marrow cells, CafA (10mg/kg bw) showed protective effect only in blood cells and luteolin (2.5mg/kg bw) failed to protect DNA integrity on cells. In conclusion, polyphenols tested reduced the toxicity caused by OTA on different target cells with good protective effect, being ChlA the compound that showed the best effects. PMID:25867686

  15. Fetuin-A and Albumin Alter Cytotoxic Effects of Calcium Phosphate Nanoparticles on Human Vascular Smooth Muscle Cells

    PubMed Central

    Dautova, Yana; Kozlova, Diana; Skepper, Jeremy N.; Epple, Matthias; Bootman, Martin D.; Proudfoot, Diane

    2014-01-01

    Calcification is a detrimental process in vascular ageing and in diseases such as atherosclerosis and arthritis. In particular, small calcium phosphate (CaP) crystal deposits are associated with inflammation and atherosclerotic plaque de-stabilisation. We previously reported that CaP particles caused human vascular smooth muscle cell (VSMC) death and that serum reduced the toxic effects of the particles. Here, we found that the serum proteins fetuin-A and albumin (?1 µM) reduced intracellular Ca2+ elevations and cell death in VSMCs in response to CaP particles. In addition, CaP particles functionalised with fetuin-A, but not albumin, were less toxic than naked CaP particles. Electron microscopic studies revealed that CaP particles were internalised in different ways; via macropinocytosis, membrane invagination or plasma membrane damage, which occurred within 10 minutes of exposure to particles. However, cell death did not occur until approximately 30 minutes, suggesting that plasma membrane repair and survival mechanisms were activated. In the presence of fetuin-A, CaP particle-induced damage was inhibited and CaP/plasma membrane interactions and particle uptake were delayed. Fetuin-A also reduced dissolution of CaP particles under acidic conditions, which may contribute to its cytoprotective effects after CaP particle exposure to VSMCs. These studies are particularly relevant to the calcification observed in blood vessels in patients with kidney disease, where circulating levels of fetuin-A and albumin are low, and in pathological situations where CaP crystal formation outweighs calcification-inhibitory mechanisms. PMID:24849210

  16. Pearling of Lipid Vesicles Induced by Nanoparticles Yan Yu and Steve Granick*

    E-print Network

    Granick, Steve

    Pearling of Lipid Vesicles Induced by Nanoparticles Yan Yu and Steve Granick* Department transforma- tion known as pearling. It is known that bacteria without division machinery can proliferate In eukaryotic cells, tubular protrusions transform into periodic chains of "pearls" upon disrupting the actin

  17. Z. B. He et al., Nickel catalyst shape Etchant-induced shaping of nanoparticle

    E-print Network

    Boyer, Edmond

    Z. B. He et al., Nickel catalyst shape - 1 - Etchant-induced shaping of nanoparticle catalysts al., Nickel catalyst shape - 2 - Abstract Carbon nanofibres (CNFs) obtained by plasma-00525194,version1-11Oct2010 #12;Z. B. He et al., Nickel catalyst shape - 3 - 1 Introduction Vertically

  18. C - Reactive Protein Induced Rearrangement of Phosphatidylcholine on Nanoparticle Mimics of Lipoprotein Particles

    PubMed Central

    Mackiewicz, Marilyn R.; Hodges, Heather L.

    2010-01-01

    Lipid-coated metal nanoparticles are developed here as a mimic of low-density lipoprotein (LDL) particles and used to study C-reactive protein (CRP) binding to highly curved lipid membranes. A 12 nm shift in the localized surface plasmon resonance (LSPR) was observed when CRP was added to the lipid-coated gold nanoparticles. Transmission electron microscopy (TEM) revealed that CRP induced a structural change to the lipids, resulting in clusters of nanoparticles. This clustering provides a visualization of how CRP could cause the aggregation of LDL particles, which is a key step in atherosclerosis. The cluster formation and resultant LSPR shift requires the presence of both CRP and calcium. Fluorescence anisotropy, using a CRP-specific, fluorophore-labeled aptamer confirmed that CRP was bound to the lipid-coated nanoparticles. An increase in the fluorescence anisotropy (?r = +0.261 ± 0.004) of the aptamer probe occurs in the presence of CRP, PC-coated nanoparticles, and calcium. Subsequent sequestration of calcium by EDTA leads to a decrease in the anisotropy (?r = -0.233 ± 0.011), however, there is no change in the LSPR and no change to the cluster structure observed by TEM. This indicates that CRP binds to the PC membrane on the nanoparticle surface reversibly through a calcium bridging mechanism while changing the underlying membrane structure irreversibly as a result of binding. PMID:20364851

  19. Induced Clustered Nanoconfinement of Superparamagnetic Iron Oxide in Biodegradable Nanoparticles Enhances Transverse Relaxivity for Targeted Theranostics

    PubMed Central

    Ragheb, Ragy R. T.; Kim, Dongin; Bandyopadhyay, Arunima; Chahboune, Halima; Bulutoglu, Beyza; Ezaldein, Harib; Criscione, Jason M.; Fahmy, Tarek M.

    2013-01-01

    Purpose Combined therapeutic and diagnostic agents, “theranostics” are emerging valuable tools for noninvasive imaging and drug delivery. Here, we report on a solid biodegradable multifunctional nanoparticle that combines both features. Methods Poly(lactide-co-glycolide) nanoparticles were engineered to confine superparamagnetic iron oxide contrast for magnetic resonance imaging while enabling controlled drug delivery and targeting to specific cells. To achieve this dual modality, fatty acids were used as anchors for surface ligands and for encapsulated iron oxide in the polymer matrix. Results We demonstrate that fatty acid modified iron oxide prolonged retention of the contrast agent in the polymer matrix during degradative release of drug. Antibody-fatty acid surface modification facilitated cellular targeting and subsequent internalization in cells while inducing clustering of encapsulated fatty-acid modified superparamagnetic iron oxide during particle formulation. This induced clustered confinement led to an aggregation within the nanoparticle and, hence, higher transverse relaxivity, r2, (294 mM?1 s?1) compared with nanoparticles without fatty-acid ligands (160 mM?1 s?1) and higher than commercially available superparamagnetic iron oxide nanoparticles (89 mM?1 s?1). Conclusion Clustering of superparamagnetic iron oxide in poly(lactide-co-glycolide) did not affect the controlled release of encapsulated drugs such as methotrexate or clodronate and their subsequent pharmacological activity, thus highlighting the full theranostic capability of our system. PMID:23401099

  20. Parasporin-1, a novel cytotoxic protein from Bacillus thuringiensis, induces Ca2+ influx and a sustained elevation of the cytoplasmic Ca2+ concentration in toxin-sensitive cells.

    PubMed

    Katayama, Hideki; Kusaka, Yoshitomo; Yokota, Haruo; Akao, Tetsuyuki; Kojima, Masayasu; Nakamura, Osamu; Mekada, Eisuke; Mizuki, Eiich

    2007-03-01

    Parasporin-1 is a novel non-insecticidal inclusion protein from Bacillus thuringiensis that is cytotoxic to specific mammalian cells. In this study, we investigated the effects of parasporin-1 on toxin-sensitive cell lines to elucidate the cytotoxic mechanism of parasporin-1. Parasporin-1 is not a membrane pore-forming toxin as evidenced by measurements of lactate dehydrogenase release, propidium iodide penetration, and membrane potential in parasporin-1-treated cells. Parasporin-1 decreased the level of cellular protein and DNA synthesis in parasporin-1-sensitive HeLa cells. The earliest change observed in cells treated with this toxin was a rapid elevation of the intracellular free-Ca(2+) concentration; increases in the intracellular Ca(2+) levels were observed 1-3 min following parasporin-1 treatment. Using four different cell lines, we found that the degree of cellular sensitivity to parasporin-1 was positively correlated with the size of the increase in the intracellular Ca(2+) concentration. The toxin-induced elevation of the intracellular Ca(2+) concentration was markedly decreased in low-Ca(2+) buffer and was not observed in Ca(2+)-free buffer. Accordingly, the cytotoxicity of parasporin-1 decreased in the low-Ca(2+) buffer and was restored by the addition of Ca(2+) to the extracellular medium. Suramin, which inhibits trimeric G-protein signaling, suppressed both the Ca(2+) influx and the cytotoxicity of parasporin-1. In parasporin-1-treated HeLa cells, degradation of pro-caspase-3 and poly(ADP-ribose) polymerase was observed. Furthermore, synthetic caspase inhibitors blocked the cytotoxic activity of parasporin-1. These results indicate that parasporin-1 activates apoptotic signaling in these cells as a result of the increased Ca(2+) level and that the Ca(2+) influx is the first step in the pathway that underlies parasporin-1 toxicity. PMID:17204466

  1. Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: intervention of folic and folinic acid.

    PubMed

    Padmanabhan, S; Tripathi, D N; Vikram, A; Ramarao, P; Jena, G B

    2009-02-19

    Methotrexate (MTX) is an anti-metabolite widely used in the treatment of neoplastic disorders, rheumatoid arthritis and psoriasis. The basis for its therapeutic efficacy is the inhibition of dihydrofolate reductase (DHFR), a key enzyme in the folic acid (FA) metabolism. FA is a water-soluble vitamin which is involved in the synthesis of purines and pyrimidines, the essential precursors of DNA. Folinic acid (FNA) is the reduced form of FA that circumvents the inhibition of DHFR. Folate supplementation during MTX therapy for psoriasis and inflammatory arthritis reduces both toxicity and side effects without compromising the efficacy. Further, FNA supplementation reduces the common side effects of MTX in the treatment of juvenile idiopathic arthritis. FA and FNA are reported to have protective effects on MTX-induced genotoxicity in the somatic cells; however their protective effects on the germ cells have not been much explored. Previously, we evaluated the cytotoxic and genotoxic effects of MTX in the germ cells of mice. In the present study, we have intervened FA and FNA for the protection of germ cell toxicity induced by MTX in male swiss mice. The animals were pre-treated with FA at the doses of 50, 100 and 200 microg/kg for 4 consecutive days per week and on day five; MTX was administered at the dose of 20mg/kg once. FNA was administered at the doses of 2.5, 5 and 10 mg/kg, 6 h (h) after single administration of MTX at the dose of 20 mg/kg. The dosing regimen was continued up to 10 weeks. The germ cell toxicity was evaluated using testes weight (wt), sperm count, sperm head morphology, sperm comet assay, histology, TUNEL and halo assay in testis. The results clearly demonstrate that prior administration of FA and post-treatment with FNA reduces the germ cell toxicity induced by MTX as evident from the decreased sperm head abnormalities, seminiferous tubule damage, sperm DNA damage, TUNEL positive cells and increased sperm counts. In the present study, we report that FA and FNA ameliorate the germ cell toxicity of MTX in mice. PMID:19110071

  2. Molecular mechanism of curcumin induced cytotoxicity in human cervical carcinoma cells.

    PubMed

    Singh, Mayank; Singh, Neeta

    2009-05-01

    Cervical cancer is the most common cancer in Indian females and is associated with infection with high risk Human papillomaviruses (HPVs). Curcumin (Diferuloyl methane), a chemopreventive agent, is a natural compound extracted from Curcuma longa that allows suppression of carcinogenesis. The objective of this study was to identify the molecular mechanism of curcumin induced apoptosis in HPV positive cervical cancer HeLa, SiHa and Ca Ski cells. Curcumin causes distinct inhibition of human telomerase reverse transcriptase (hTERT) the catalytic core of telomerase thereby reducing proliferation of cancer cells. Curcumin mediated apoptosis in these cells appears to be due to upregulation of proapoptotic Bax, AIF, release of cytochrome c and down regulation of antiapoptotic Bcl-2, Bcl-XL in HeLa and SiHa. This was accompanied by an increase in caspase-3 and -9 activity, suggesting the role of mitochondria in curcumin mediated apoptotic cell death. Curcumin acts as an anti-inflammatory and anti-proliferative agent by causing down regulation of COX-2, iNOS and cyclin D1 in all the three cell lines but to different extent. PMID:19191010

  3. Cryptotanshinone induces inhibition of breast tumor growth by cytotoxic CD4+ T cells through the JAK2/STAT4/ perforin pathway.

    PubMed

    Zhou, Jun; Xu, Xiao-Zhen; Hu, Yao-Ren; Hu, Ai-Rong; Zhu, Cheng-Liang; Gao, Guo-Sheng

    2014-01-01

    Cryptotanshinone (CPT), is a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miotiorrhiza bunge. Numerous researchers have found that it could work as a potent antitumor agent to inhibit tumor growth in vitro, buith there has been much less emphasis on its in vivo role against breast tumors. Using a mouse tumor model of MCF7 cells, we showed that CPT strongly inhibited MCF7 cell growth in vivo with polarization of immune reactions toward Th1-type responses, stimulation of naive CD4+ T cell proliferation, and also increased IFN-? and perforin production of CD4+ T cells in response to tumor-activated splenocytes. Furthermore, data revealed that the cytotoxic activity of CD4+ T cells induced by CPT was markedly abrogated by concanamycin A(CMA), a perforin inhibitor, but not IFN-? Ab. On the other hand, after depletion of CD4+ T cells or blocked perforin with CMA in a tumor-bearing model, CPT could not effectively suppress tumor growth, but this phenomenon could be reversed by injecting naive CD4+ T cells. Thus, our results suggested that CPT mainly inhibited breast tumor growth through inducing cytotoxic CD4+ T cells to secrete perforin. We further found that CPT enhanced perforin production of CD4+ T cells by up-regulating JAK2 and STAT4 phosphorylation. These findings suggest a novel potential therapeutic role for CPT in tumor therapy, and demonstrate that CPT performs its antitumor functions through cytotoxic CD4+ T cells. PMID:24761844

  4. In vitro protective effects of Withania somnifera (L.) dunal root extract against hydrogen peroxide and ?-amyloid(1-42)-induced cytotoxicity in differentiated PC12 cells.

    PubMed

    Kumar, S; Seal, C J; Howes, M J R; Kite, G C; Okello, E J

    2010-10-01

    Withania somnifera L. Dunal (Solanaceae), also known as 'ashwagandha' in Sanskrit and as 'Indian ginseng', is used widely in Ayurvedic medicine as a nerve tonic and memory enhancer, with antiaging, antistress, immunomodulatory and antioxidant properties. There is a paucity of data on the potential neuroprotective effects of W. somnifera root, as traditionally used, against H(2)O(2)- and A?((1-42))-induced cytotoxicity which are current targets for novel approaches to treat dementia, especially dementia of the Alzheimer's type (AD). In this study, an aqueous extract prepared from the dried roots of W. somnifera was assessed for potential protective effects against H(2)O(2)- and A?((1-42))-aggregated fibril cytotoxicity by an MTT assay using a differentiated rat pheochromocytoma PC12 cell line. The results suggest that pretreatments of differentiated PC12 cells with aqueous extracts of W. somnifera root significantly protect differentiated PC12 cells against both H(2)O(2)- and A?((1-42))-induced cytotoxicity, in a concentration dependent manner. To investigate the compounds that could explain the observed effects, the W. somnifera extract was analysed by liquid chromatography-serial mass spectrometry and numerous withanolide derivatives, including withaferin A, were detected. These results demonstrate the neuroprotective properties of an aqueous extract of W. somnifera root and may provide some explanation for the putative ethnopharmacological uses of W. somnifera for cognitive and other neurodegenerative disorders that are associated with oxidative stress. PMID:20680931

  5. Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides

    Microsoft Academic Search

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

    2006-01-01

    Photoreceptor cells are incessantly bombarded with photons of light, which, along with the cells' high rate of oxygen metabolism, continuously exposes them to elevated levels of toxic reactive oxygen intermediates (ROIs). Vacancy-engineered mixed-valence-state cerium oxide nanoparticles (nanoceria particles) scavenge ROIs. Our data show that nanoceria particles prevent increases in the intracellular concentrations of ROIs in primary cell cultures of rat

  6. Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells

    PubMed Central

    Kim, Yu Ri; Ban, Jung Ok; Yoo, Hwan Soo; Lee, Yong Moon; Yoon, Yeo Pyo; Eum, So Young; Jeong, Heon Sang; Yoon, Do-young; Han, Sang Bae; Hong, Jin Tae

    2013-01-01

    High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500?mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50?mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1?, MIP-1?, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity. PMID:23935693

  7. Rese