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Sample records for nanoparticles induced cytotoxicity

  1. Copper Nanoparticle Induced Cytotoxicity to Nitrifying Bacteria ...

    EPA Pesticide Factsheets

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

  2. Silver nanoparticles-induced cytotoxicity requires ERK activation in human bladder carcinoma cells.

    PubMed

    Castiglioni, Sara; Cazzaniga, Alessandra; Perrotta, Cristiana; Maier, Jeanette A M

    2015-09-17

    Silver nanoparticles are toxic both in vitro and in vivo. We have investigated the possibility to exploit the cytotoxic potential of silver nanoparticles in T24 bladder carcinoma cells using both bare and PolyVinylPyrrolidone-coated silver nanoparticles. We show that the two types of silver nanoparticles promote morphological changes and cytoskeletal disorganization, are cytotoxic and induce cell death. These effects are due to the increased production of reactive oxygen species which are responsible, at least in part, for the sustained activation of ERK1/2. Indeed, both cytotoxicity and ERK1/2 activation are prevented by exposing the cells to the anti-oxidant N-acetylcysteine. Also blocking the ERK1/2 pathway with the MEK inhibitor PD98059 protects the cells from nanoparticles' cytotoxicity. Our findings suggest that ERK activation plays a role in silver nanoparticle-mediated cytotoxicity in T24 cells.

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

    SciTech Connect

    De Berardis, Barbara; Civitelli, Gabriele; Condello, Maria; Lista, Pasquale; Pozzi, Roberta; Arancia, Giuseppe; Meschini, Stefania

    2010-08-01

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

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

    PubMed Central

    2011-01-01

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

  5. Cytotoxicity and genotoxicity in liver cells induced by cobalt nanoparticles and ions

    PubMed Central

    Liu, Y. K.; Deng, X. X.

    2016-01-01

    Objectives The cytotoxicity induced by cobalt ions (Co2+) and cobalt nanoparticles (Co-NPs) which released following the insertion of a total hip prosthesis, has been reported. However, little is known about the underlying mechanisms. In this study, we investigate the toxic effect of Co2+ and Co-NPs on liver cells, and explain further the potential mechanisms. Methods Co-NPs were characterised for size, shape, elemental analysis, and hydrodynamic diameter, and were assessed by Transmission Electron Microscope, Scanning Electron Microscope, Energy Dispersive X-ray Spectroscopy and Dynamic Light Scattering. BRL-3A cells were used in this study. Cytotoxicity was evaluated by MTT and lactate dehydrogenase release assay. In order to clarify the potential mechanisms, reactive oxygen species, Bax/Bcl-2 mRNA expression, IL-8 mRNA expression and DNA damage were assessed on BRL-3A cells after Co2+ or Co-NPs treatment. Results Results showed cytotoxic effects of Co2+ and Co-NPs were dependent upon time and dosage, and the cytotoxicity of Co-NPs was greater than that of Co2+. In addition, Co-NPs elicited a significant (p < 0.05) reduction in cell viability with a concomitant increase in lactic dehydrogenase release, reactive oxygen species generation, IL-8 mRNA expression, Bax/Bcl-2 mRNA expression and DNA damage after 24 hours of exposure. Conclusion Co-NPs induced greater cytotoxicity and genotoxicity in BRL-3A cells than Co2+. Cell membrane damage, oxidative stress, immune inflammation and DNA damage may play an important role in the effects of Co-NPs on liver cells. Cite this article: Y. K. Liu, X. X. Deng, H.L. Yang. Cytotoxicity and genotoxicity in liver cells induced by cobalt nanoparticles and ions. Bone Joint Res 2016;5:461–469. DOI: 10.1302/2046-3758.510.BJR-2016-0016.R1. PMID:27754833

  6. Importance of the HIF pathway in cobalt nanoparticle-induced cytotoxicity and inflammation in human macrophages.

    PubMed

    Nyga, Agata; Hart, Alister; Tetley, Teresa D

    2015-01-01

    Recent, unexpected high failure rates of metal-on-metal hip implants have reintroduced the issue of cobalt toxicity. An adverse reaction to cobalt ions and cobalt-induced lung injury occurs during environmental exposure and is now strictly controlled. Currently adverse reaction occurs to cobalt nanoparticles during wear and tear of metal-on-metal hip implants of which the underlying mechanism is not fully understood. The putative role of the hypoxia-inducible factor (HIF) pathway in the mechanism of cobalt nanoparticle (Co-NPs) toxicity was examined using the U937 cell line, human alveolar macrophages and monocyte-derived macrophages. Co-NPs (5-20 μg/ml)-induced cytotoxicity (viability ranged from 75% to <20% of control, respectively) and reactive oxygen species (ROS), whereas a comparable concentration of cobalt ions (Co(II); up to 350 μM) did not. Co-NPs induced HIF-1α stabilization. Addition of ascorbic acid (100 µM) and glutathione (1 mM) both prevented the increased ROS. However, only treatment with ascorbic acid reduced HIF-1α levels and prevented cell death, indicating that a ROS-independent pathway is involved in Co-NPs-induced cytotoxicity. Replenishing intracellular ascorbate, which is crucial in preventing HIF pathway activation, modified Co-induced HIF target gene expression and the inflammatory response, by decreasing interleukin-1 beta (IL-1β) mRNA and protein expression. Addition of glutathione had no effect on Co-NPs-induced HIF target gene expression or inflammatory response. Thus, Co-NPs induce the HIF pathway by depleting intracellular ascorbate, leading to HIF stabilization and pathway activation. This suggests a strong, ROS-independent role for HIF activation in Co-NPs-induced cytotoxicity and a possible role for HIF in metal-on-metal hip implant pathology.

  7. Pathway of cytotoxicity induced by folic acid modified selenium nanoparticles in MCF-7 cells.

    PubMed

    Pi, Jiang; Jin, Hua; Liu, Ruiying; Song, Bing; Wu, Qing; Liu, Li; Jiang, Jinhuan; Yang, Fen; Cai, Huaihong; Cai, Jiye

    2013-02-01

    Selenium nanoparticles (Se NPs) have been recognized as promising materials for biomedical applications. To prepare Se NPs which contained cancer targeting methods and to clarify the cellular localization and cytotoxicity mechanisms of these Se NPs against cancer cells, folic acid protected/modified selenium nanoparticles (FA-Se NPs) were first prepared by a one-step method. Some morphologic and spectroscopic methods were obtained to prove the successfully formation of FA-Se NPs while free folate competitive inhibition assay, microscope, and several biological methods were used to determine the in vitro uptake, subcellular localization, and cytotoxicity mechanism of FA-Se NPs in MCF-7 cells. The results indicated that the 70-nm FA-Se NPs were internalized by MCF-7 cells through folate receptor-mediated endocytosis and targeted to mitochondria located regions through endocytic vesicles transporting. Then, the FA-Se NPs entered into mitochondria; triggered the mitochondria-dependent apoptosis of MCF-7 cells which involved oxidative stress, Ca(2)+ stress changes, and mitochondrial dysfunction; and finally caused the damage of mitochondria. FA-Se NPs released from broken mitochondria were transported into nucleus and further into nucleolus which then induced MCF-7 cell cycle arrest. In addition, FA-Se NPs could induce cytoskeleton disorganization and induce MCF-7 cell membrane morphology alterations. These results collectively suggested that FA-Se NPs could be served as potential therapeutic agents and organelle-targeted drug carriers in cancer therapy.

  8. Gold Nanoparticles Cytotoxicity

    NASA Astrophysics Data System (ADS)

    Mironava, Tatsiana

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

  9. Reduction of polyethylenimine-coated iron oxide nanoparticles induced autophagy and cytotoxicity by lactosylation

    PubMed Central

    Du, Jiuju; Zhu, Wencheng; Yang, Li; Wu, Changqiang; Lin, Bingbing; Wu, Jun; Jin, Rongrong; Shen, Taipeng; Ai, Hua

    2016-01-01

    Superparamagnetic iron oxide (SPIO) nanoparticles are excellent magnetic resonance contrast agents and surface engineering can expand their applications. When covered with amphiphilic alkyl-polyethyleneimine (PEI), the modified SPIO nanoparticles can be used as MRI visible gene/drug delivery carriers and cell tracking probes. However, the positively charged amines of PEI can also cause cytotoxicity and restricts their further applications. In this study, we used lactose to modify amphiphilic low molecular weight polyethylenimine (C12-PEI2K) at different lactosylation degree. It was found that the N-alkyl-PEI-lactobionic acid wrapped SPIO nanocomposites show better cell viability without compromising their labelling efficacy as well as MR imaging capability in RAW 264.7 cells, comparing to the unsubstituted ones. Besides, we found the PEI induced cell autophagy can be reduced via lactose modification, indicating the increased cell viability might rely on down-regulating autophagy. Thus, our findings provide a new approach to overcome the toxicity of PEI wrapped SPIO nanocomposites by lactose modification. PMID:27482464

  10. Copper ferrite nanoparticle-induced cytotoxicity and oxidative stress in human breast cancer MCF-7 cells.

    PubMed

    Ahamed, Maqusood; Akhtar, Mohd Javed; Alhadlaq, Hisham A; Alshamsan, Aws

    2016-06-01

    Copper ferrite (CuFe2O4) nanoparticles (NPs) are important magnetic materials currently under research due to their applicability in nanomedicine. However, information concerning the biological interaction of copper ferrite NPs is largely lacking. In this study, we investigated the cellular response of copper ferrite NPs in human breast cancer (MCF-7) cells. Copper ferrite NPs were prepared by co-precipitation technique with the thermal effect. Prepared NPs were characterized by X-ray diffraction (XRD), field emission transmission electron microscopy (FETEM) and dynamic light scattering (DLS). Characterization data showed that copper ferrite NPs were crystalline, spherical with smooth surfaces and average diameter of 15nm. Biochemical studies showed that copper ferrite NPs induce cell viability reduction and membrane damage in MCF-7 cells and degree of induction was dose- and time-dependent. High SubG1 cell population during cell cycle progression and MMP loss with a concomitant up-regulation of caspase-3 and caspase-9 genes suggested that copper ferrite NP-induced cell death through mitochondrial pathway. Copper ferrite NP was also found to induce oxidative stress in MCF-7 cells as indicated by reactive oxygen species (ROS) generation and glutathione depletion. Cytotoxicity due to copper ferrite NPs exposure was effectively abrogated by N-acetyl-cysteine (ROS scavenger) suggesting that oxidative stress could be the plausible mechanism of copper ferrite NPs toxicity. Further studies are underway to explore the toxicity mechanisms of copper ferrite NPs in different types of human cells. This study warrants further generation of extensive biointeraction data before their application in nanomedicine.

  11. Copper Nanoparticles and Copper Sulphate Induced Cytotoxicity in Hepatocyte Primary Cultures of Epinephelus coioides

    PubMed Central

    Wang, Tao; Chen, Xiaoyan; Long, Xiaohua; Liu, Zhaopu; Yan, Shaohua

    2016-01-01

    Copper nanoparticles (Cu-NPs) were widely used in various industrial and commercial applications. The aim of this study was to analyze the cytotoxicity of Cu-NPs on primary hepatocytes of E.coioides compared with copper sulphate (CuSO4). Cultured cells were exposed to 0 or 2.4 mg Cu L-1 as CuSO4or Cu-NPs for 24-h. Results showed either form of Cu caused a dramatic loss in cell viability, more so in the CuSO4 than Cu-NPs treatment. Compared to control, either CuSO4 or Cu-NPs significantly increased reactive oxygen species(ROS) and malondialdehyde(MDA) concentration in hepatocytes by overwhelming total superoxide dismutase (T-SOD) activity, catalase(CAT) activity and glutathione(GSH) concentration. In addition, the antioxidative-related genes [SOD (Cu/Zn), SOD (Mn), CAT, GPx4] were also down-regulated. The apoptosis and necrosis percentage was significantly higher after the CuSO4 or Cu-NPs treatment than the control. The apoptosis was induced by the increased cytochrome c concentration in the cytosol and elevated caspase-3, caspase-8 and caspase-9 activities. Additionally, the apoptosis-related genes (p53, p38β and TNF-α) and protein (p53 protein) were up-regulated after the CuSO4 or Cu-NPs treatment, with CuSO4 exposure having a greater effect than Cu-NPs. In conclusion, Cu-NPs had similar types of toxic effects as CuSO4 on primary hepatocytes of E.coioides, but toxicity of CuSO4 was more severe than that of Cu-NPs. PMID:26890000

  12. Copper Nanoparticles and Copper Sulphate Induced Cytotoxicity in Hepatocyte Primary Cultures of Epinephelus coioides.

    PubMed

    Wang, Tao; Chen, Xiaoyan; Long, Xiaohua; Liu, Zhaopu; Yan, Shaohua

    2016-01-01

    Copper nanoparticles (Cu-NPs) were widely used in various industrial and commercial applications. The aim of this study was to analyze the cytotoxicity of Cu-NPs on primary hepatocytes of E.coioides compared with copper sulphate (CuSO4). Cultured cells were exposed to 0 or 2.4 mg Cu L-1 as CuSO4or Cu-NPs for 24-h. Results showed either form of Cu caused a dramatic loss in cell viability, more so in the CuSO4 than Cu-NPs treatment. Compared to control, either CuSO4 or Cu-NPs significantly increased reactive oxygen species(ROS) and malondialdehyde(MDA) concentration in hepatocytes by overwhelming total superoxide dismutase (T-SOD) activity, catalase(CAT) activity and glutathione(GSH) concentration. In addition, the antioxidative-related genes [SOD (Cu/Zn), SOD (Mn), CAT, GPx4] were also down-regulated. The apoptosis and necrosis percentage was significantly higher after the CuSO4 or Cu-NPs treatment than the control. The apoptosis was induced by the increased cytochrome c concentration in the cytosol and elevated caspase-3, caspase-8 and caspase-9 activities. Additionally, the apoptosis-related genes (p53, p38β and TNF-α) and protein (p53 protein) were up-regulated after the CuSO4 or Cu-NPs treatment, with CuSO4 exposure having a greater effect than Cu-NPs. In conclusion, Cu-NPs had similar types of toxic effects as CuSO4 on primary hepatocytes of E.coioides, but toxicity of CuSO4 was more severe than that of Cu-NPs.

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

    PubMed Central

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

    2009-01-01

    Background During the last years engineered nanoparticles (NPs) have been extensively used in different technologies and consequently many questions have arisen about the risk and the impact on human health following exposure to nanoparticles. Nevertheless, at present knowledge about the cytotoxicity induced by NPs is still largely incomplete. In this context, we have investigated the cytotoxicity induced by gold nanoparticles (AuNPs), which differed in size and purification grade (presence or absence of sodium citrate residues on the particle surface) in vitro, in the human alveolar type-II (ATII)-like cell lines A549 and NCIH441. Results We found that the presence of sodium citrate residues on AuNPs impaired the viability of the ATII-like cell lines A549 and NCIH441. Interestingly, the presence of an excess of sodium citrate on the surface of NPs not only reduced the in vitro viability of the cell lines A549 and NCIH441, as shown by MTT assay, but also affected cellular proliferation and increased the release of lactate dehydrogenase (LDH), as demonstrated by Ki-67 and LDH-release assays respectively. Furthermore, we investigated the internalization of AuNPs by transmission electron microscopy (TEM) and we observed that particles were internalized by active endocytosis in the cell lines A549 and NCIH441 within 3 hr. In addition, gold particles accumulated in membrane-bound vesicles and were not found freely dispersed in the cytoplasm. Conclusion Our data suggest that the presence of contaminants, such as sodium citrate, on the surface of gold nanoparticles might play a pivotal role in inducing cytotoxicity in vitro, but does not influence the uptake of the particles in human ATII-like cell lines. PMID:19545423

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

    To date, considerable effort has been devoted to determine the potential toxicity of nanoparticles to cells and organisms. However, determining the mechanism of cytotoxicity induced by different types of nanoparticles remains challenging. Herein, typically low toxicity nanomaterials were used as a model to investigate the mechanism of cytotoxicity induced by low toxicity nanomaterials. We studied the effect of nano-TiO2, nano-Al2O3 and nano-SiO2 deposition films on the ion concentration on a cell-free system simulating the cell membrane. The results showed that the ion concentration of K+, Ca2+, Na+, Mg2+ and SO42- decreased significantly following filtration of the prepared deposition films. More specifically, at a high nano-TiO2 concentration (200 mg L-1) and a long nano-TiO2 deposition time (48 h), the concentration of Na+ decreased from 2958.01 to 2775.72, 2749.86, 2757.36, and 2719.82 mg L-1, respectively, for the four types of nano-TiO2 studied. Likewise, the concentration of SO42- decreased from 38.83 to 35.00, 35.80, 35.40, and 35.27 mg L-1, respectively. The other two kinds of typical low toxicity nanomaterials (nano-Al2O3 and nano-SiO2) have a similar impact on the ion concentration change trend. Adsorption of ions on nanoparticles and the hydrated shell around the ions strongly hindered the ions through the nanoparticle films. The endocytosed nanoparticles could be released from the cells without inducing cytotoxicity. Hindering the ion exchange and disrupting the exocytosis process are the main factors that induce cytotoxicity in the presence of excess nano-TiO2 on the cell surface. The current findings may offer a universal principle for understanding the mechanism of cytotoxicity induced by low toxicity nanomaterials.To date, considerable effort has been devoted to determine the potential toxicity of nanoparticles to cells and organisms. However, determining the mechanism of cytotoxicity induced by different types of nanoparticles remains challenging

  15. Cytotoxicity, oxidative stress and inflammation induced by ZnO nanoparticles in endothelial cells: interaction with palmitate or lipopolysaccharide.

    PubMed

    Gong, Yu; Ji, Yuejia; Liu, Fang; Li, Juan; Cao, Yi

    2016-11-15

    Recent studies showed that ZnO nanoparticles (NPs) might induce the toxicity to human endothelial cells. However, little is known about the interaction between ZnO NPs and circulatory components, which is likely to occur when NPs enter the blood. In this study, we evaluated ZnO NP-induced cytotoxicity, oxidative stress and inflammation in human umbilical vein endothelial cells (HUVECs), with the emphasis on the interaction with palmitate (PA) or lipopolysaccharide (LPS), because PA and LPS are normal components in human blood that increase in metabolic diseases. Overall, ZnO NPs induced cytotoxicity and intracellular reactive oxygen species (ROS) at a concentration of 32 μg ml(-1) , but did not significantly affect the release of inflammatory cytokines or adhesion of THP-1 monocytes to HUVECs. In addition, exposure to ZnO NPs dose-dependently promoted intracellular Zn ions in HUVECs. PA and LPS have different effects. Two hundred μm PA significantly induced cytotoxicity and THP-1 monocyte adhesion, but did not affect ROS or release of inflammatory cytokines. In contrast, 1 μg ml(-1) LPS significantly induced ROS, release of inflammatory cytokines and THP-1 monocyte adhesion, but not cytotoxicity. The presence of ZnO NPs did not significantly affect the toxicity induced by PA or LPS. In addition, the accumulation of Zn ions after ZnO NP exposure was not significantly affected by the presence of PA or LPS. We concluded that there was no interaction between ZnO NPs and PA or LPS on toxicity to HUVECs in vitro. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Titanium dioxide nanoparticles induce cytotoxicity and reduce mitotic index in human amniotic fluid-derived cells.

    PubMed

    Acar, M S; Bulut, Z B; Ateş, A; Nami, B; Koçak, N; Yıldız, B

    2015-01-01

    Titanium dioxide (TiO2) nanoparticles (NPs) are commonly used materials present in many consumables for which most people are exposed to. The biological hazards of the NPs on human health have been demonstrated previously. In this study, we aimed to assess the cytotoxicity potency of TiO2 NPs on the primary human amniotic fluid cells. The cells derived from amniotic fluid were treated with different dosages of TiO2 NPs for some periods. Cell adhesion status was assessed using a light microscopic observation. Cell proliferation and cell death rates were determined using trypan blue staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Also, mitotic index was determined using fluorescence in situ hybridization with chromosome 8 centromer-specific DNA probe. Disrupted cell adhesion, decreased proliferation, and increased mortality rates were detected in the cells that were treated with TiO2 NPs depending on the dosage (p < 0.001). Also, reduced mitotic index was determined in the cells depending on the time and TiO2 dosage when compared with the controls (p < 0.0001). These results showed that TiO2 NPs have high cytotoxicity for amniotic fluid-derived cells. Therefore, different products containing TiO2 NPs should be used with care, especially for pregnant women.

  17. Strain-rate Dependence of Elastic Modulus Reveals Silver Nanoparticle Induced Cytotoxicity.

    PubMed

    Caporizzo, Matthew Alexander; Roco, Charles M; Ferrer, Maria Carme Coll; Grady, Martha E; Parrish, Emmabeth; Eckmann, David M; Composto, Russell John

    Force-displacement measurements are taken at different rates with an atomic force microscope to assess the correlation between cell health and cell viscoelasticity in THP-1 cells that have been treated with a novel drug carrier. A variable indentation-rate viscoelastic analysis, VIVA, is employed to identify the relaxation time of the cells that are known to exhibit a frequency dependent stiffness. The VIVA agrees with a fluorescent viability assay. This indicates that dextran-lysozyme drug carriers are biocompatible and deliver concentrated toxic material (rhodamine or silver nanoparticles) to the cytoplasm of THP-1 cells. By modelling the frequency dependence of the elastic modulus, the VIVA provides three metrics of cytoplasmic viscoelasticity: a low frequency modulus, a high frequency modulus and viscosity. The signature of cytotoxicity by rhodamine or silver exposure is a frequency independent twofold increase in the elastic modulus and cytoplasmic viscosity, while the cytoskeletal relaxation time remains unchanged. This is consistent with the known toxic mechanism of silver nanoparticles, where metabolic stress causes an increase in the rigidity of the cytoplasm. A variable indentation-rate viscoelastic analysis is presented as a straightforward method to promote the self-consistent comparison between cells. This is paramount to the development of early diagnosis and treatment of disease.

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

    PubMed Central

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

    2013-01-01

    Background Cobalt oxide nanoparticles (Co3O4NPs) are increasingly recognized for their utility in biological applications, magnetic resonance imaging, and drug delivery. However, little is known about the toxicity of Co3O4NPs in human cells. Methods We investigated the possible mechanisms of genotoxicity induced by Co3O4NPs in human hepatocarcinoma (HepG2) cells. Cell viability, reactive oxygen species (ROS), glutathione, thiobarbituric acid reactive substance, apoptosis, and DNA damage were assessed in HepG2 cells after Co3O4NPs and Co2+ exposure. Results Co3O4NPs elicited a significant (P < 0.01) reduction in glutathione with a concomitant increase in lipid hydroperoxide, ROS generation, superoxide dismutase, and catalase activity after 24- and 48-hour exposure. Co3O4NPs had a mild cytotoxic effect in HepG2 cells; however, it induced ROS and oxidative stress, leading to DNA damage, a probable mechanism of genotoxicity. The comet assay showed a statistically significant (P < 0.01) dose- and time-related increase in DNA damage for Co3O4NPs, whereas Co2+ induced less change than Co3O4NPs but significantly more than control. Conclusion Our results demonstrated that Co3O4NPs induced cytotoxicity and genotoxicity in HepG2 cells through ROS and oxidative stress. PMID:23326189

  19. Activation of Erk and p53 regulates copper oxide nanoparticle-induced cytotoxicity in keratinocytes and fibroblasts

    PubMed Central

    Luo, Cheng; Li, Yan; Yang, Liang; Zheng, Yan; Long, Jiangang; Jia, Jinjing; Xiao, Shengxiang; Liu, Jiankang

    2014-01-01

    Copper oxide nanoparticles (CuONP) have attracted increasing attention due to their unique properties and have been extensively utilized in industrial and commercial applications. For example, their antimicrobial capability endows CuONP with applications in dressings and textiles against bacterial infections. Along with the wide applications, concerns about the possible effects of CuONP on humans are also increasing. It is crucial to evaluate the safety and impact of CuONP on humans, and especially the skin, prior to their practical application. The potential toxicity of CuONP to skin keratinocytes has been reported recently. However, the underlying mechanism of toxicity in skin cells has remained unclear. In the present work, we explored the possible mechanism of the cytotoxicity of CuONP in HaCaT human keratinocytes and mouse embryonic fibroblasts (MEF). CuONP exposure induced viability loss, migration inhibition, and G2/M phase cycle arrest in both cell types. CuONP significantly induced mitogen-activated protein kinase (extracellular signal-regulated kinase [Erk], p38, and c-Jun N-terminal kinase [JNK]) activation in dose- and time-dependent manners. U0126 (an inhibitor of Erk), but not SB 239063 (an inhibitor of p38) or SP600125 (an inhibitor of JNK), enhanced CuONP-induced viability loss. CuONP also induced decreases in p53 and p-p53 levels in both cell types. Cyclic pifithrin-α, an inhibitor of p53 transcriptional activity, enhanced CuONP-induced viability loss. Nutlin-3α, a p53 stabilizer, prevented CuONP-induced viability loss in HaCaT cells, but not in MEF cells, due to the inherent toxicity of nutlin-3α to MEF. Moreover, the experiments on primary keratinocytes are in accordance with the conclusions acquired from HaCaT and MEF cells. These data demonstrate that the activation of Erk and p53 plays an important role in CuONP-induced cytotoxicity, and agents that preserve Erk or p53 activation may prevent CuONP-induced cytotoxicity. PMID:25336953

  20. Size-dependent cytotoxicity of Fe3O4 nanoparticles induced by biphasic regulation of oxidative stress in different human hepatoma cells.

    PubMed

    Xie, Yuexia; Liu, Dejun; Cai, Chenlei; Chen, Xiaojing; Zhou, Yan; Wu, Liangliang; Sun, Yongwei; Dai, Huili; Kong, Xianming; Liu, Peifeng

    2016-01-01

    The application of Fe3O4 nanoparticles (NPs) has made great progress in the diagnosis of disease and in the drug delivery system for cancer therapy, but the relative mechanisms of potential toxicity induced by Fe3O4 have not kept pace with its development in the application, which has hampered its further clinical application. In this article, we used two kinds of human hepatoma cell lines, SK-Hep-1 and Hep3B, to investigate the cytotoxic effects and the involved mechanisms of small Fe3O4 NPs with different diameters (6 nm, 9 nm, and 14 nm). Results showed that the size of NPs effectively influences the cytotoxicity of hepatoma cells: 6 nm Fe3O4 NPs exhibited negligible cytotoxicity and 9 nm Fe3O4 NPs affected cytotoxicity via cellular mitochondrial dysfunction and by inducing necrosis mediated through the mitochondria-dependent intracellular reactive oxygen species generation. Meanwhile, 14 nm Fe3O4 NPs induced cytotoxicity by impairing the integrity of plasma membrane and promoting massive lactate dehydrogenase leakage. These results explain the detailed mechanism of different diameters of small Fe3O4 NPs-induced cytotoxicity. We anticipate that this study will provide different insights into the cytotoxicity mechanism of Fe3O4 NPs, so as to make them safer to use in clinical application.

  1. Size-dependent cytotoxicity of Fe3O4 nanoparticles induced by biphasic regulation of oxidative stress in different human hepatoma cells

    PubMed Central

    Xie, Yuexia; Liu, Dejun; Cai, Chenlei; Chen, Xiaojing; Zhou, Yan; Wu, Liangliang; Sun, Yongwei; Dai, Huili; Kong, Xianming; Liu, Peifeng

    2016-01-01

    The application of Fe3O4 nanoparticles (NPs) has made great progress in the diagnosis of disease and in the drug delivery system for cancer therapy, but the relative mechanisms of potential toxicity induced by Fe3O4 have not kept pace with its development in the application, which has hampered its further clinical application. In this article, we used two kinds of human hepatoma cell lines, SK-Hep-1 and Hep3B, to investigate the cytotoxic effects and the involved mechanisms of small Fe3O4 NPs with different diameters (6 nm, 9 nm, and 14 nm). Results showed that the size of NPs effectively influences the cytotoxicity of hepatoma cells: 6 nm Fe3O4 NPs exhibited negligible cytotoxicity and 9 nm Fe3O4 NPs affected cytotoxicity via cellular mitochondrial dysfunction and by inducing necrosis mediated through the mitochondria-dependent intracellular reactive oxygen species generation. Meanwhile, 14 nm Fe3O4 NPs induced cytotoxicity by impairing the integrity of plasma membrane and promoting massive lactate dehydrogenase leakage. These results explain the detailed mechanism of different diameters of small Fe3O4 NPs-induced cytotoxicity. We anticipate that this study will provide different insights into the cytotoxicity mechanism of Fe3O4 NPs, so as to make them safer to use in clinical application. PMID:27536098

  2. 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.

  3. Cytotoxic Potential of Silver Nanoparticles

    PubMed Central

    Zhang, Tianlu; Wang, Liming

    2014-01-01

    Silver nanoparticles (AgNPs) have been widely used in industrial, household, and healthcare-related products due to their excellent antimicrobial activity. With increased exposure of AgNPs to human beings, the risk of safety has attracted much attention from the public and scientists. In review of recent studies, we discuss the potential impact of AgNPs on individuals at the cell level. In detail, we highlight the main effects mediated by AgNPs on the cell, such as cell uptake and intracellular distribution, cytotoxicity, genotoxicity, and immunological responses, as well as some of the major factors that influence these effects in vivo and in vivo, such as dose, time, size, shape, surface chemistry, and cell type. At the end, we summarize the main influences on the cell and indicate the challenges in this field, which may be helpful for assessing the risk of AgNPs in future. PMID:24532494

  4. 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

  5. Laser-induced modifications of gold nanoparticles and their cytotoxic effect.

    PubMed

    Abdelhamid, Shimaa; Saleh, Hazem; Abdelhamid, Mahmoud; Gohar, Adel; Youssef, Tareq

    2012-06-01

    As nanotechnology continues to develop, an assessment of nanoparticles' toxicity becomes very crucial for biomedical applications. The current study examines the deleterious effects of pre-irradiated gold nanoparticles (GNPs) solutions on primary rat kidney cells (PRKCs). Spectroscopic and transmission electron microscopic studies demonstrated that exposure of 15 nm GNPs in size to pulsed laser caused a reduction both in optical density and mean particle diameter. GNPs showed an aggregation when added to the cell culture medium (DMEM). This aggregation was markedly decreased upon adding serum to the medium. Under our experimental conditions, trypan blue and MTT assays revealed no significant changes in cell viability when PRKCs were incubated with non-irradiated GNPs over a period of 72 h and up to 4 nM GNPs concentration. On the contrary, when cells were incubated with irradiated GNPs a significant reduction in PRKCs viability was revealed.

  6. Silver nanoparticle induced cytotoxicity, oxidative stress, and DNA damage in CHO cells

    NASA Astrophysics Data System (ADS)

    Awasthi, Kumud Kant; Awasthi, Anjali; Kumar, Narender; Roy, Partha; Awasthi, Kamlendra; John, P. J.

    2013-09-01

    Silver nanoparticles (Ag NPs) are being used increasingly in wound dressings, catheters, and in various household products due to their antimicrobial activity. The present study reports the toxicity evaluation of synthesized and well characterized Ag NPs using Chinese hamster ovary (CHO) cells. The UV-Vis spectroscopy reveals the formation of silver nanoparticles by exhibiting the typical surface plasmon absorption maxima at 408-410 nm. Transmission electron microscopy (TEM) reveals that the average diameter of silver nanoparticles is about 5.0 ± 1.0 nm and that they have spherical shape. Cell visibility and cell viability percentage show dose-dependent cellular toxicity of Ag NPs. The half maximal inhibitory concentration (IC50) for CHO cells is 68.0 ± 2.65 μg/ml after 24 h Ag NPs exposure. Toxicity evaluations, including cellular morphology, mitochondrial function (MTT assay), reactive oxygen species (ROS), and DNA fragmentation assay (Ladder pattern) were assessed in unexposed CHO cells (control) and the cells exposed to Ag NPs concentrations of 15, 30, and 60 μg/ml for 24 h. The findings may assist in the designing of Ag NPs for various applications and provide insights into their toxicity.

  7. 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

  8. Negligible cytotoxicity induced by different titanium dioxide nanoparticles in fish cell lines.

    PubMed

    Bermejo-Nogales, Azucena; Connolly, Mona; Rosenkranz, Philipp; Fernández-Cruz, María-Luisa; Navas, José M

    2017-04-01

    Titanium dioxide nanoparticles (TiO2-NPs) have a wide number of applications in cosmetic, solar and paint industries due to their photocatalyst and ultraviolet blocking properties. The continuous increase in the production of TiO2-NPs enhances the risk for this manufactured nanomaterial to enter water bodies through treated effluents or agricultural amendments. TiO2-NPs have shown very low toxicity in a number of aquatic organisms. However, there are no conclusive data about their deleterious effects and on their possible mechanisms of toxic action. At this level, in vitro cell culture systems are a useful tool to gain insight about processes underlying the toxicity of a wide variety of substances, including nanomaterials. Differences in the physiology of different taxa make advisable the use of cells coming from the taxon of interest, but collecting data from a variety of cellular types allows a better understanding of the studied processes. Taking all this into account, the aim of the present study was to assess the toxicity of three types of TiO2-NP, rutile hydrophobic (NM-103), rutile hydrophilic (NM-104) and rutile-anatase (NM-105), obtained from the EU Joint Research Centre (JRC) repository, using various fish cell lines (RTG-2, PLHC-1, RTH-149, RTL-W1) and rainbow trout primary hepatocytes. For comparative purposes, the effect of different dispersion protocols, end-point assays and extended exposure time was studied in a fish cell line (RTG-2) and in the rat hepatoma cell line (H4IIE). TiO2-NPs dispersions showed a variable degree of aggregation in cell culture media. Disruption of mitochondrial metabolic activity, plasma membrane integrity and lysosome function was not detected in any cell line after exposure to TiO2-NPs at any time and concentration ranges tested. These results are indicative of a low toxicity of the TiO2-NPs tested and show the usefulness of fish cells maintained in vitro as high throughput screening methods that can facilitate further

  9. Molybdenum nanoparticles-induced cytotoxicity, oxidative stress, G2/M arrest, and DNA damage in mouse skin fibroblast cells (L929).

    PubMed

    Siddiqui, Maqsood A; Saquib, Quaiser; Ahamed, Maqusood; Farshori, Nida N; Ahmad, Javed; Wahab, Rizwan; Khan, Shams T; Alhadlaq, Hisham A; Musarrat, Javed; Al-Khedhairy, Abdulaziz A; Pant, Aditya B

    2015-01-01

    The present investigation was aimed to study the cytotoxicity, oxidative stress, and genotoxicity induced by molybdenum nanoparticles (Mo-NPs) in mouse skin fibroblast cells (L929). Cells were exposed to different concentrations (1-100 μg/ml) of Mo-NPs (size 40 nm) for 24 and 48 h. After the exposure, different cytotoxicity assays (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide, MTT; neutral red uptake, NRU; and cellular morphology) and oxidative stress markers (lipid peroxidation, LPO; glutathione, GSH; and catalase) were studied. Further, Mo-NPs-induced intracellular reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), cell cycle arrest, and DNA damage were also studied. L929 cells treated with Mo-NPs showed a concentration- and time-dependent decrease in cell viability and a loss of the normal cell morphology. The percentage cell viability was recorded as 25%, 42%, and 58% by MTT assay and 24%, 46%, and 56% by NRU assay at 25, 50, and 100 μg/ml of Mo-NPs, respectively after 48 h exposure. Furthermore, the cells showed a significant induction of oxidative stress. This was confirmed by the increase in LPO and ROS generation, as well as the decrease in the GSH and catalase levels. The decrease in MMP also confirms the impaired mitochondrial membrane. The cell cycle analysis and comet assay data revealed that Mo-NPs induced G2/M arrest and DNA damage in a concentration-dependent manner. Our results demonstrated, for the first time, Mo-NPs induced cytotoxicity, oxidative stress and genotoxicity in L929 cells. Thus, data suggest the potential hazardous nature of Mo-NPs.

  10. Cobalt iron oxide nanoparticles induce cytotoxicity and regulate the apoptotic genes through ROS in human liver cells (HepG2).

    PubMed

    Ahamed, Maqusood; Akhtar, Mohd Javed; Khan, M A Majeed; Alhadlaq, Hisham A; Alshamsan, Aws

    2016-12-01

    Cobalt iron oxide (CoFe2O4) nanoparticles (CIO NPs) have been one of the most widely explored magnetic NPs because of their excellent chemical stability, mechanical hardness and heat generating potential. However, there is limited information concerning the interaction of CIO NPs with biological systems. In this study, we investigated the reactive oxygen species (ROS) mediated cytotoxicity and apoptotic response of CIO NPs in human liver cells (HepG2). Diameter of crystalline CIO NPs was found to be 23nm with a band gap of 1.97eV. CIO NPs induced cell viability reduction and membrane damage, and degree of induction was dose- and time-dependent. CIO NPs were also found to induce oxidative stress revealed by induction of ROS, depletion of glutathione and lower activity of superoxide dismutase enzyme. Real-time PCR data has shown that mRNA level of tumor suppressor gene p53 and apoptotic genes (bax, CASP3 and CASP9) were higher, while the expression level of anti-apoptotic gene bcl-2 was lower in cells following exposure to CIO NPs. Activity of caspase-3 and caspase-9 enzymes was also higher in CIO NPs exposed cells. Furthermore, co-exposure of N-acetyl-cysteine (ROS scavenger) efficiently abrogated the modulation of apoptotic genes along with the prevention of cytotoxicity caused by CIO NPs. Overall, we observed that CIO NPs induced cytotoxicity and apoptosis in HepG2 cells through ROS via p53 pathway. This study suggests that toxicity mechanisms of CIO NPs should be further investigated in animal models.

  11. 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 μg/mL with no significant differences of response in 5 and 10 μg/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 μg/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 μg/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.

  12. CuO nanoparticles induce cytotoxicity and apoptosis in human K562 cancer cell line via mitochondrial pathway, through reactive oxygen species and P53

    PubMed Central

    Shafagh, Maryam; Rahmani, Fatemeh; Delirezh, Norouz

    2015-01-01

    Objective(s): This study focused on determining cytotoxic effects of copper oxide nanoparticles (CuO NPs) on chronic myeloid leukemia (CML) K562 cell line in a cell-specific manner and its possible mechanism of cell death. We investigated the cytotoxicity of CuO NPs against K562 cell line (cancerous cell) and peripheral blood mononuclear cell (normal cell). Materials and Methods: The toxicity was evaluated using cell viability, oxidative stress and apoptosis detection. In addition, the expression levels of P53, Caspase 3, Bcl-2, and Bax genes in K562 cells were studied by reverse transcription polymerase chain reaction (RT-PCR) analysis. Results: CuO NPs exerted distinct effects on cell viability via selective killing of cancer cells in a dose-dependent manner while not impacting normal cells in MTT assay. The dose-dependent cytotoxicity of CuO NPs against K562 cells was shown through reactive oxygen species (ROS) generation. The CuO NPs induced apoptosis was confirmed through acridine orange and propidium iodide double staining. Tumor suppressor gene P53 was up regulated due to CuO NPs exposure, and increase in Bax/Bcl-2 ratio suggested mitochondria-mediated pathway is involved in CuO NPs induced apoptosis. We also observed that Caspase 3 gene expression remained unchanged up to 24 hr exposure. Conclusion: These molecular alterations provide an insight into CuO NPs-caused inhibition of growth, generation of ROS, and apoptotic death of K562 cells. PMID:26730334

  13. In vitro cytotoxicity of surface modified bismuth nanoparticles.

    PubMed

    Luo, Yang; Wang, Chaoming; Qiao, Yong; Hossain, Mainul; Ma, Liyuan; Su, Ming

    2012-10-01

    This paper describes in vitro cytotoxicity of bismuth nanoparticles revealed by three complementary assays (MTT, G6PD, and calcein AM/EthD-1). The results show that bismuth nanoparticles are more toxic than most previously reported bismuth compounds. Concentration dependent cytotoxicities have been observed for bismuth nanoparticles and surface modified bismuth nanoparticles. The bismuth nanoparticles are non-toxic at concentration of 0.5 nM. Nanoparticles at high concentration (50 nM) kill 45, 52, 41, 34 % HeLa cells for bare nanoparticles, amine terminated bismuth nanoparticles, silica coated bismuth nanoparticles, and polyethylene glycol (PEG) modified bismuth nanoparticles, respectively; which indicates cytotoxicity in terms of cell viability is in the descending order of amine terminated bismuth nanoparticles, bare bismuth nanoparticles, silica coated bismuth nanoparticles, and PEG modified bismuth nanoparticles. HeLa cells are more susceptible to toxicity from bismuth nanoparticles than MG-63 cells. The simultaneous use of three toxicity assays provides information on how nanoparticles interact with cells. Silica coated bismuth nanoparticles can damage cellular membrane yet keep mitochondria less influenced; while amine terminated bismuth nanoparticles can affect the metabolic functions of cells. The findings have important implications for caution of nanoparticle exposure and evaluating toxicity of bismuth nanoparticles.

  14. Silver nanoparticles inhibit the function of hypoxia-inducible factor-1 and target genes: insight into the cytotoxicity and antiangiogenesis.

    PubMed

    Yang, Tieshan; Yao, Qian; Cao, Fei; Liu, Qianqian; Liu, Binlei; Wang, Xiu-Hong

    Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that is activated upon exposure to hypoxic stress. It modulates a number of cellular responses including proliferation, apoptosis, angiogenesis, and metabolism by activating a panel of target genes in response to hypoxia. The HIF-1 level is often upregulated in the hypoxic microenvironment of solid tumors, which contributes to cancer treatment failure. Here we report that silver nanoparticles (AgNPs), which are widely used as an antimicrobial agent, are an effective inhibitor of HIF-1. AgNPs inhibited the activation of a HIF-dependent reporter construct after the cells were exposed to hypoxic conditions or treated with cobalt chloride, a hypoxia mimetic agent. The AgNPs also interfered with the accumulation of HIF-1α protein and the induction of the endogenous HIF target genes, VEGF-A and GLUT1. Since both HIF-1 and vascular endothelial growth factor-A play an important role in angiogenesis, AgNPs also inhibited angiogenesis in vitro. Our data reveal a new mechanism of how AgNPs act on cellular function, that is, they disrupt HIF signaling pathway. This finding provides a novel insight into how AgNPs can inhibit cancer cell growth and angiogenesis.

  15. Silver nanoparticles inhibit the function of hypoxia-inducible factor-1 and target genes: insight into the cytotoxicity and antiangiogenesis

    PubMed Central

    Yang, Tieshan; Yao, Qian; Cao, Fei; Liu, Qianqian; Liu, Binlei; Wang, Xiu-Hong

    2016-01-01

    Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that is activated upon exposure to hypoxic stress. It modulates a number of cellular responses including proliferation, apoptosis, angiogenesis, and metabolism by activating a panel of target genes in response to hypoxia. The HIF-1 level is often upregulated in the hypoxic microenvironment of solid tumors, which contributes to cancer treatment failure. Here we report that silver nanoparticles (AgNPs), which are widely used as an antimicrobial agent, are an effective inhibitor of HIF-1. AgNPs inhibited the activation of a HIF-dependent reporter construct after the cells were exposed to hypoxic conditions or treated with cobalt chloride, a hypoxia mimetic agent. The AgNPs also interfered with the accumulation of HIF-1α protein and the induction of the endogenous HIF target genes, VEGF-A and GLUT1. Since both HIF-1 and vascular endothelial growth factor-A play an important role in angiogenesis, AgNPs also inhibited angiogenesis in vitro. Our data reveal a new mechanism of how AgNPs act on cellular function, that is, they disrupt HIF signaling pathway. This finding provides a novel insight into how AgNPs can inhibit cancer cell growth and angiogenesis. PMID:27994464

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

  17. ApoE3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin: study of enhanced activity of curcumin against beta amyloid induced cytotoxicity using in vitro cell culture model.

    PubMed

    Mulik, Rohit S; Mönkkönen, Jukka; Juvonen, Risto O; Mahadik, Kakasaheb R; Paradkar, Anant R

    2010-06-07

    Beta amyloid plays a main role in the pathophysiology of Alzheimer's disease by inducing oxidative stress in the brain. Curcumin, a natural antioxidant, is known to inhibit beta amyloid and beta amyloid induced oxidative stress. However, low bioavailability and photodegradation are the major concerns for the use of curcumin. In the present study, we have formulated apolipoprotein E3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin (ApoE3-C-PBCA) to provide photostability and enhanced cell uptake of curcumin by targeting. Prepared nanoparticles were characterized for particle size, zeta potential, entrapment efficiency and in vitro drug release. The entrapment of curcumin inside the nanoparticles was confirmed by X-ray diffraction analysis. Physicochemical characterization confirmed the suitability of the method of preparation. The photostability of curcumin was increased significantly in nanoparticles compared to plain curcumin. In vitro cell culture study showed enhanced therapeutic efficacy of ApoE3-C-PBCA against beta amyloid induced cytotoxicity in SH-SY5Y neuroblastoma cells compared to plain curcumin solution. Beta amyloid is known to induce apoptosis in neuronal cells, therefore antiapoptotic activity of curcumin was studied using flow cytometry assays. From all the experiments, it was found that the activity of curcumin was enhanced with ApoE3-C-PBCA compared to plain curcumin solution suggesting enhanced cell uptake and a sustained drug release effect. The synergistic effect of ApoE3 and curcumin was also studied, since ApoE3 also possesses both antioxidant and antiamyloidogenic activity. It was found that ApoE3 did indeed have activity against beta amyloid induced cytotoxicity along with curcumin. Hence, ApoE3-C-PBCA offers great advantage in the treatment of beta amyloid induced cytotoxicity in Alzheimer's disease.

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

    PubMed Central

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

    2012-01-01

    Background This follow-up study aims to determine the physical parameters which govern the differential radiosensitization capacity of two tumor cell lines and one immortalized normal cell line to 1.9 nm gold nanoparticles. In addition to comparing the uptake potential, localization, and cytotoxicity of 1.9 nm gold nanoparticles, the current study also draws on comparisons between nanoparticle size and total nanoparticle uptake based on previously published data. Methods We quantified gold nanoparticle uptake using atomic emission spectroscopy and imaged intracellular localization by transmission electron microscopy. Cell growth delay and clonogenic assays were used to determine cytotoxicity and radiosensitization potential, respectively. Mechanistic data were obtained by Western blot, flow cytometry, and assays for reactive oxygen species. Results Gold nanoparticle uptake was preferentially observed in tumor cells, resulting in an increased expression of cleaved caspase proteins and an accumulation of cells in sub G1 phase. Despite this, gold nanoparticle cytotoxicity remained low, with immortalized normal cells exhibiting an LD50 concentration approximately 14 times higher than tumor cells. The surviving fraction for gold nanoparticle-treated cells at 3 Gy compared with that of untreated control cells indicated a strong dependence on cell type in respect to radiosensitization potential. Conclusion Gold nanoparticles were most avidly endocytosed and localized within cytoplasmic vesicles during the first 6 hours of exposure. The lack of significant cytotoxicity in the absence of radiation, and the generation of gold nanoparticle-induced reactive oxygen species provide a potential mechanism for previously reported radiosensitization at megavoltage energies. PMID:22701316

  19. Differential cytotoxicity of copper ferrite nanoparticles in different human cells.

    PubMed

    Ahmad, Javed; Alhadlaq, Hisham A; Alshamsan, Aws; Siddiqui, Maqsood A; Saquib, Quaiser; Khan, Shams T; Wahab, Rizwan; Al-Khedhairy, Abdulaziz A; Musarrat, Javed; Akhtar, Mohd Javed; Ahamed, Maqusood

    2016-10-01

    Copper ferrite nanoparticles (NPs) have the potential to be applied in biomedical fields such as cell labeling and hyperthermia. However, there is a lack of information concerning the toxicity of copper ferrite NPs. We explored the cytotoxic potential of copper ferrite NPs in human lung (A549) and liver (HepG2) cells. Copper ferrite NPs were crystalline and almost spherically shaped with an average diameter of 35 nm. Copper ferrite NPs induced dose-dependent cytotoxicity in both types of cells, evident by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide and neutral red uptake assays. However, we observed a quite different susceptibility in the two kinds of cells regarding toxicity of copper ferrite NPs. Particularly, A549 cells showed higher susceptibility against copper ferrite NP exposure than those of HepG2 cells. Loss of mitochondrial membrane potential due to copper ferrite NP exposure was observed. The mRNA level as well as activity of caspase-3 enzyme was higher in cells exposed to copper ferrite NPs. Cellular redox status was disturbed as indicated by induction of reactive oxygen species (oxidant) generation and depletion of the glutathione (antioxidant) level. Moreover, cytotoxicity induced by copper ferrite NPs was efficiently prevented by N-acetylcysteine treatment, which suggests that reactive oxygen species generation might be one of the possible mechanisms of cytotoxicity caused by copper ferrite NPs. To the best of our knowledge, this is the first report showing the cytotoxic potential of copper ferrite NPs in human cells. This study warrants further investigation to explore the mechanisms of differential toxicity of copper ferrite NPs in different types of cells. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Cytotoxicity of titanium and silicon dioxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Wagner, Stefanie; Münzer, Simon; Behrens, Peter; Scheper, Thomas; Bahnemann, Detlef; Kasper, Cornelia

    2009-05-01

    Different TiO2 and SiO2 nanoparticles have been tested concerning their toxicity on selected mammalian cell lines. Various powders and suspensions, all of which consist of titanium or silicon dioxide nanoparticles have been examined. These particles differ in the crystal structure, the size and the BET-surface area. There was also a classification in fixed particles and in particles easily accessible in solution. With focus on the possible adsorption of the nanoparticles into the human organism, via skin and via respiratory tract, the effects on fibroblasts (NIH-3T3) and on a human lung adenocarcinoma epithelial cell line were examined. Additionally, the particles were tested with HEP-G2 cells, which are often used as model cell line for biocompatibility tests, and PC-12 cells, a rat adrenal pheochromocytoma cell line. The viability of the cells was examined by the MTT-test. The viability results were found to partly depend on the type of cells used. The experimental results show that the adhesion of the cells on the different powders strongly depends on the type of cell lines as well as on the type of powder. It was found that the lower viability of some cells on the powder coatings is not only caused by a cytotoxicity effect of the powders, but is also due to a lower adhesion of the cells on the particle surfaces. Furthermore, it could be shown that the physical properties of the powders cannot be easily correlated to any observed biological effect. While some powders show a significant suppression of the cell growth, others with similar physical properties indicate no toxic effect.

  1. Improved cytotoxicity and preserved level of cell death induced in colon cancer cells by doxorubicin after its conjugation with iron-oxide magnetic nanoparticles.

    PubMed

    Augustin, Ewa; Czubek, Bartłomiej; Nowicka, Anna M; Kowalczyk, Agata; Stojek, Zbigniew; Mazerska, Zofia

    2016-06-01

    A promising strategy for overcoming the problem of limited efficacy in antitumor drug delivery and in drug release is the use of a nanoparticle-conjugated drug. Doxorubicin (Dox) anticancer chemotherapeutics has been widely studied in this respect, because of severe cardiotoxic side effects. Here, we investigated the cytotoxic effects, the uptake process, the changes in cell cycle progression and the cell death processes in the presence of iron-oxide magnetic nanoparticles (Nps) and doxorubicin conjugates (Dox-Nps) in human colon HT29 cells. The amount of Dox participated in biological action of Dox-Nps was determined by cyclic voltammetry and thermogravimetric measurements. The cytotoxicity of Dox-Nps was shown to be two/three times higher than free Dox, whereas Nps alone did not inhibit cell proliferation. Dox-Nps penetrated cancer cells with higher efficacy than free Dox, what could be a consequence of Dox-Nps aggregation with proteins in culture medium and/or with cell surface. The treatment of HT29 cells with Dox-Nps and Dox at IC50 concentration resulted in G2/M arrest followed by late apoptosis and necrosis. Summing up, the application of iron-oxide magnetic nanoparticles improved Dox-Nps cell penetration compared to free Dox and achieved the cellular response to Dox-Nps conjugates similar to that of Dox alone.

  2. The role of reactive oxygen species in silicon dioxide nanoparticle-induced cytotoxicity and DNA damage in HaCaT cells.

    PubMed

    Gong, Chunmei; Tao, Gonghua; Yang, Linqing; Liu, Jianjun; He, Haowei; Zhuang, Zhixiong

    2012-04-01

    The increasing applications of silicon dioxide (SiO(2)) nanomaterials have been widely concerned over their biological effects and potential hazard to human health. In this study, we explored the effects of SiO(2) nanoparticles (15, 30, and 100 nm) and their micro-sized counterpart on cultured human epidermal Keratinocyte (HaCaT) cells. Cell viability, cell morphology, reactive oxygen species (ROS), DNA damage (8-OHdG, γH2AX and comet assay) and apoptosis were assessed under control and SiO(2) nanoparticles exposed conditions. As observed in the Cell Counting Kit-8 (CCK-8) assay, exposure to 15, 30 or 100 nm SiO(2) nanoparticles at dosage levels between 0 and 100 μg/ml decreased cell viability in a concentration- and size dependent manner and the IC50 of 24 hour exposure was 19.4 ± 1.3, 27.7 ± 1.5 and 35.9 ± 1.6 μg/ml for 15, 30 and 100 nm SiO(2) nanoparticles, respectively. Morphological examination revealed cell shrinkage and cell wall missing after SiO(2) nanoparticle exposure. Increase in intracellular ROS level and DNA damage as well as apoptosis were also observed in SiO(2) nanoparticle-exposed HaCaT cells. Exposure to SiO(2) nanoparticles results in a concentration- and size-dependent cytotoxicity and DNA damage in cultural HaCaT cells which is closely correlated to increased oxidative stress.

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

    PubMed

    Hatipoglu, Manolya Kukut; Keleştemur, 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.

  4. Source of cytotoxicity in a colloidal silver nanoparticle suspension

    NASA Astrophysics Data System (ADS)

    Kukut Hatipoglu, Manolya; Keleştemur, Seda; Altunbek, Mine; Culha, Mustafa

    2015-05-01

    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.

  5. Cytotoxicity and proliferative capacity impairment induced on human brain cell cultures after short- and long-term exposure to magnetite nanoparticles.

    PubMed

    Coccini, Teresa; Caloni, Francesca; Ramírez Cando, Lenin Javier; De Simone, Uliana

    2017-03-01

    Since magnetic iron oxide nanoparticles (IONP) as magnetite (Fe3 O4 NPs) have potential applications in life sciences, industrial fields and biomedical care, the risks for occupational, general population and patients rises correspondingly. Excessive IONP accumulation in central nervous system (CNS) cells can lead to a disruption of normal iron metabolism/homeostasis, which is a characteristic hallmark resembling that of several neurodegenerative disorders. Fe3 O4 NPs- versus Fe3 O4 bulk-induced toxic effects have been assessed in two human CNS cells namely astrocytes (D384) and neurons (SH-SY5Y) after short-term exposure (4-24-48 h) to 1-100 μg ml(-1) , and long-term exposure to lower concentrations. Short-term Fe3 O4 NPs induced significant concentration- and time-dependent alterations of mitochondrial function in D384 (25-75% cell viability decrease): effects started at 25 μg ml(-1) after 4 h, and 1 μg ml(-1) after 48 h. SH-SY5Y were less susceptible: cytotoxicity occurred after 48  h only with 35-45% mortality (10-100 μg ml(-1) ). Accordingly, a more marked intracellular iron accumulation was observed in astrocytes than neurons. Membrane integrity was unaltered in both CNS cell types. Lowering Fe3 O4 NP concentrations (0.05-10 μg ml(-1) ) and prolonging the exposure time (up to 10 days), D384 toxicity was again observed (colony number decrease at ≥0.05 μg ml(-1) , morphology alterations and colony size reduction at ≥0.5 μg ml(-1) ). Effects on SH-SY5Y appeared at the highest concentration only. Fe3 O4 bulk was always remarkably toxic toward both cells. In summary, human cultured astrocytes were susceptible to both Fe3 O4 NP and bulk forms following short-term and extended exposure to low concentrations, while neurons were more resistant to NPs. Cellular iron overload may trigger adverse responses by releasing iron ions (particularly in astrocytes) thus compromising the normal functions of CNS. Copyright © 2016

  6. Reducing the cytotoxicity of inhalable engineered nanoparticles via in situ passivation with biocompatible materials.

    PubMed

    Byeon, Jeong Hoon; Park, Jae Hong; Peters, Thomas M; Roberts, Jeffrey T

    2015-07-15

    The cytotoxicity of model welding nanoparticles was modulated through in situ passivation with soluble biocompatible materials. A passivation process consisting of a spark discharge particle generator coupled to a collison atomizer as a co-flow or counter-flow configuration was used to incorporate the model nanoparticles with chitosan. The tested model welding nanoparticles are inhaled and that A549 cells are a human lung epithelial cell line. Measurements of in vitro cytotoxicity in A549 cells revealed that the passivated nanoparticles had a lower cytotoxicity (>65% in average cell viability, counter-flow) than the untreated model nanoparticles. Moreover, the co-flow incorporation between the nanoparticles and chitosan induced passivation of the nanoparticles, and the average cell viability increased by >80% compared to the model welding nanoparticles. As a more convenient way (additional chitosan generation and incorporation devices may not be required), other passivation strategies through a modification of the welding rod with chitosan adhesive and graphite paste did also enhance average cell viability (>58%). The approach outlined in this work is potentially generalizable as a new platform, using only biocompatible materials in situ, to treat nanoparticles before they are inhaled.

  7. Evaluation of the cytotoxic and genotoxic potential of lecithin/chitosan nanoparticles

    NASA Astrophysics Data System (ADS)

    Taner, Gökçe; Yeşilöz, Recep; Özkan Vardar, Deniz; Şenyiğit, Taner; Özer, Özgen; Degen, Gisela H.; Başaran, Nurşen

    2014-02-01

    Nanoparticles-based drug targeting delivery systems have been introduced in the treatment for various diseases because of their effective properties, although there have been conflicting results on the toxicity of nanoparticles. In the present study, the aim was to evaluate the cytotoxicity and the genotoxicity of different concentrations of lecithin/chitosan nanoparticles with and without clobetasol-17-propionate (CP) by neutral red uptake (NRU) cytotoxicity assay and single cell gel electrophoresis (Comet) and cytokinesis-blocked micronucleus assays. The IC50 values of lecithin/chitosan nanoparticles with/without CP were found as 1.9 and 1.8 %, respectively, in the NRU cytotoxicity test. High concentrations of lecithin/chitosan nanoparticles induced DNA damage in human lymphocytes as evaluated by comet assay. The micronucleus frequency was increased by the lecithin/chitosan treatment in a dose-dependent manner. Also at the two highest concentrations, a significant increase in micronucleus formation was observed. Lecithin/chitosan nanoparticles with CP did not increase the frequency of micronucleus and also did not induce additional DNA damage when compared with lecithin/chitosan nanoparticles without CP; therefore, CP itself has not found to be genotoxic at the studied concentration.

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

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

    The nanoparticles containing thermosensitive and magnetic properties were investigated for their potential use as a novel drug carrier for targeted and controlled release drug delivery system. These thermosensitive and magnetic nanoparticles were prepared by grafting thermosensitive poly ( N-isopropylacrylamide) (PNIPAM) on the surface of silica (SiO2)-coated Fe3O4 nanoparticles with the particle size of 18.8 ± 1.6 nm. Adsorption and desorption behavior of bovine serum albumin (BSA) on the surface of PNIPAM-grafted SiO2/Fe3O4 nanoparticles was studied, and the results indicated that these nanoparticles were able to absorb protein at temperature above the lower critical solution temperature (LCST) and to be desorbed below the LCST. Cytotoxicity studies conducted on Chinese hamster ovary (CHO-K1) cells using methyl tetrazolium (MTT) assays revealed that cell viability of 1 mg/mL PNIPAM-grafted nanoparticles was slightly decreased after 24 h of incubation as compared to the lower concentration of nanoparticles. Furthermore, the concentration of 0.5 mg/mL PNIPAM-grafted nanoparticles was totally biocompatible for 48 h, but had low cytotoxicity after 72 h of incubation. These PNIPAM-grafted nanoparticles did not induce morphological change in their cellularity after exposure for 24 and 108 h. These results demonstrate that PNIPAM-grafted nanoparticles are biocompatible and have potential use as drug carriers.

  9. Nanoparticle incorporation of melittin reduces sperm and vaginal epithelium cytotoxicity.

    PubMed

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

    2014-01-01

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

  10. Cytotoxicity of gold nanoparticles prepared by ultrasonic spray pyrolysis.

    PubMed

    Rudolf, R; Friedrich, B; Stopić, S; Anžel, I; Tomić, S; Čolić, M

    2012-01-01

    The aim of this work was to study the cytotoxicity of different fractions of gold nanoparticles prepared by ultrasonic spray pyrolysis from gold scrap. The target cells were rat thymocytes, as a type of nonproliferating cells, and L929 mouse fibroblasts, as a type of continuous proliferating cells. Fractions 1 and 2, composed of pure gold nanoparticles, as determined by scanning electron microscopy with a combination of energy dispersive X-ray analysis, were nontoxic for thymocytes, but reduced moderately the proliferative activity of L929 cells. The inhibitory effect of fraction 2, containing particles smaller in size than fraction 1, was stronger. Fraction 3, composed of Au and up to 3% Cu was noncytotoxic for thymocytes, but was cytotoxic for L929 cells. Fraction 4, composed of Au and Ag nanoparticles, and fraction 5, composed of Au together with Cu, Ni, Zn, Fe, and In were cytotoxic for both thymocytes and L929 cells. These results suggest that USP enables the synthesis of pure gold nanoparticles with controlled size, even from gold scrap. However, microstructural analyses and biocompatibility testing are necessary for their proper selection from more cytotoxic gold nanoparticles, contaminated with other elements of gold alloys.

  11. Imaging carbon nanoparticles and related cytotoxicity

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

  12. Cytotoxicity and therapeutic effect of irinotecan combined with selenium nanoparticles.

    PubMed

    Gao, Fuping; Yuan, Qing; Gao, Liang; Cai, Pengju; Zhu, Huarui; Liu, Ru; Wang, Yaling; Wei, Yueteng; Huang, Guodong; Liang, Jian; Gao, Xueyun

    2014-10-01

    Although chemotherapeutic drugs are widely applied for clinic tumor treatment, severe toxicity restricts their therapeutic efficacy. In this study, we reported a new form of selenium, selenium nanoparticles (Nano Se) which have significant lower toxicity and acceptable bioavailability. We investigated Nano Se as chemotherapy preventive agent to protect against toxicities of anticancer drug irinotecan and synergistically enhance the anti-tumor treatment effect in vitro and in vivo. The underlying mechanisms were also investigated. The combination of Nano Se and irinotecan showed increased cytotoxic effect with HCT-8 tumor cells likely by p53 mediated apoptosis. Nano Se inhibited growth of HCT-8 tumor cells partially through caspases mediated apoptosis. In vivo experiment showed Nano Se at a dose of 4 mg/kg/day significantly alleviated adverse effects induced by irinotecan (60 mg/kg) treatment. Nano Se alone treatment did not induce any toxic manifestations. The combination of Nano Se and irinotecan dramatically inhibited tumor growth and significantly induced apoptosis of tumor cells in HCT-8 cells xenografted tumor. Tumor inhibition rate was about 17.2%, 48.6% and 62.1% for Nano Se, irinotecan and the combination of Nano Se and irinotecan, respectively. The beneficial effects of Nano Se for tumor therapy were mainly ascribed to selectively regulating Nrf2-ARE (antioxidant responsive elements) pathway in tumor tissues and normal tissues. Our results suggest Nano Se is a promising selenium species with potential application in cancer treatment.

  13. Amphipathic silica nanoparticles induce cytotoxicity through oxidative stress mediated and p53 dependent apoptosis pathway in human liver cell line HL-7702 and rat liver cell line BRL-3A.

    PubMed

    Zuo, Daiying; Duan, Zhenfang; Jia, Yuanyuan; Chu, Tianxue; He, Qiong; Yuan, Juan; Dai, Wei; Li, Zengqiang; Xing, Liguo; Wu, Yingliang

    2016-09-01

    The aim of this study was to evaluate the potential cytotoxicity and the underlying mechanism of amphipathic silica nanoparticles (SiO2 NPs) exposure to human normal liver HL-7702 cells and rat normal liver BRL-3A cells. Prior to the cellular studies, transmission electron microscopy (TEM), dynamic light scattering (DLS), and X ray diffraction (XRD) were used to characterize SiO2 NPs, which proved the amorphous nature of SiO2 NPs with TEM diameter of 19.8±2.7nm. Further studies proved that exposure to SiO2 NPs dose-dependently induced cytotoxicity as revealed by cell counting kit (CCK-8) and lactate dehydrogenase (LDH) assays, with more severe cytotoxicity in HL-7702 cells than BRL-3A cells. Reactive oxygen species (ROS) and glutathione (GSH) assays showed elevated oxidative stress in both cells. Morphological studies by microscopic observation, Hochest 33258 and AO/EB staining indicated significant apoptotic changes after the cells being exposed to SiO2 NPs. Further studies by western blot indicated that SiO2 NPs exposure to both cells up-regulated p53, Bax and cleaved caspase-3 expression and down-regulated Bcl-2 and caspase-3 levels. Activated caspase-3 activity detected by colorimetric assay kit and caspase-3/7 activity detected by fluorescent real-time detection kit were significantly increased by SiO2 NPs exposure. In addition, antioxidant vitamin C significantly attenuated SiO2 NPs-induced caspase-3 activation, which indicated that SiO2 NPs-induced oxidative stress was involved in the process of HL-7702 and BRL-3A cell apoptosis. Taken together, these results suggested that SiO2 NPs-induced cytotoxicity in HL-7702 and BRL-3A cells was through oxidative stress mediated and p53, caspase-3 and Bax/Bcl-2 dependent pathway and HL-7702 cells were more sensitive to SiO2 NPs-induced cytotoxicity than BRL-3A cells.

  14. Toxicity of nanoparticle surface coating agents: Structure-cytotoxicity relationship.

    PubMed

    Zhang, Ying; Li, Xiaoping; Yu, Hongtao

    2016-07-02

    Surface coating agents for metal nanoparticles, cationic alkyl ammonium bromides, and anionic alkyl sulfates were tested against human skin keratinocytes (HaCaT) and blood T lymphocytes (TIB-152). The surfactants of short chain (C8) are not cytotoxic, but as chain length increases, their cytotoxicity increases and levels off at C12 for cationic surfactants against both cell lines and for anionic surfactants against the TIB-152, but C14 for anionic surfactants against HaCaT. The cationic surfactants are more toxic than the anionic surfactants for HaCaT; while with similar cytotoxicity for TIB-152 cells. di- and tetra-Alkyl ammonium salts are more cytotoxic than the mono-substituted.

  15. The mechanism of asbestos-induced cytotoxicity

    SciTech Connect

    Goodglick, L.A.

    1988-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-12-01

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

  17. Monitoring of the Enzymatic Degradation of Protein Corona and Evaluating the Accompanying Cytotoxicity of Nanoparticles.

    PubMed

    Ma, Zhifang; Bai, Jing; Jiang, Xiue

    2015-08-19

    Established nanobio interactions face the challenge that the formation of nanoparticle-protein corona complexes shields the inherent properties of the nanoparticles and alters the manner of the interactions between nanoparticles and biological systems. Therefore, many studies have focused on protein corona-mediated nanoparticle binding, internalization, and intracellular transportation. However, there are a few studies to pay attention to if the corona encounters degradation after internalization and how the degradation of the protein corona affects cytotoxicity. To fill this gap, we prepared three types of off/on complexes based on gold nanoparticles (Au NPs) and dye-labeled serum proteins and studied the extracellular and intracellular proteolytic processes of protein coronas as well as their accompanying effects on cytotoxicity through multiple evaluation mechanisms, including cell viability, adenosine triphosphate (ATP) content, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS). The proteolytic process was confirmed by recovery of the fluorescence of the dye-labeled protein molecules that was initially quenched by Au NPs. Our results indicate that the degradation rate of protein corona is dependent on the type of the protein based on systematical evaluation of the extracellular and intracellular degradation processes of the protein coronas formed by human serum albumin (HSA), γ-globulin (HGG), and serum fibrinogen (HSF). Degradation is the fastest for HSA corona and the slowest for HSF corona. Notably, we also find that the Au NP-HSA corona complex induces lower cell viability, slower ATP production, lower MMP, and higher ROS levels. The cytotoxicity of the nanoparticle-protein corona complex may be associated with the protein corona degradation process. All of these results will enrich the database of cytotoxicity induced by nanomaterial-protein corona complexes.

  18. 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.

  19. Cytotoxic Effect of Lipophilic Bismuth Dimercaptopropanol Nanoparticles on Epithelial Cells.

    PubMed

    Rene, Hernandez-Delgadillo; Badireddy, Appala Raju; José, Martínez-Sanmiguel Juan; Francisco, Contreras-Cordero Juan; Israel, Martinez-Gonzalez Gustavo; Isela, Sánchez-Nájera Rosa; Chellam, Shankararaman; Claudio, Cabral-Romero

    2016-01-01

    Bismuth nanoparticles have many interesting properties to be applied in biomedical and medicinal sectors, however their safety in humans have not been comprehensively investigated. The objective of this research was to determine the cytotoxic effect of bismuth dimercaptopropanol nanoparticles (BisBAL NPs) on epithelial cells. The nanoparticles are composed of 18.7 nm crystallites on average and have a rhombohedral structure, agglomerating into chains-like or clusters of small nanoparticles. Based on MTT viability assay and fluorescence microscopy, cytotoxicity was not observed on monkey kidney cells after growing with 5 µM of BisBAL NPs for 24 h. Employing same techniques, identical results were obtained with human epithelial cells (HeLa), showing a not strain-dependent phenomenon. The absence of toxic effects on epithelial cells growing with BisBAL NPs was corroborated with long-time experiments (24-72 hrs.), showing no difference in comparison with growing control (cells without nanoparticles). Further, genotoxicity assays, comet assay and fluorescent microscopy and electrophoresis in bromide-stained agarose gel revealed no damage to genomic DNA of MA104 cells after 24 h. of exposition to BisBAL NPs. Finally, the effect of bismuth nanoparticles on protein synthesis was studied in cells growing with BisBAL NPs for 24 h. SDS-PAGE assays showed no difference between treated and untreated cells, suggesting that BisBAL NPs did not interfere with protein synthesis. Hence BisBAL NPs do not appear to exert cytotoxic effects suggesting their biological compatibility with epithelial cells.

  20. Induction of cytotoxicity and apoptosis in mouse blastocysts by silver nanoparticles.

    PubMed

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

    2010-08-16

    Silver nanoparticles (nanoAg) are antibacterial materials widely used in various products and medical supplies. In this report, we examined the cytotoxic effects of nanoAg on mouse embryos at the blastocyst stage, subsequent embryonic attachment and outgrowth in vitro, and in vivo implantation by embryo transfer. Blastocysts treated with 50 microM nanoAg exhibited significantly increased apoptosis and a corresponding decrease in total cell number. Importantly, the implantation success rate of blastocysts pretreated with nanoAg was lower than that of their control counterparts. Moreover, in vitro treatment with 50 microM nanoAg was associated with increased resorption of post-implantation embryos and decreased fetal weight. Our results collectively indicate that in vitro exposure to nanoAg induces apoptosis and retards early post-implantation development after transfer to host mice. However, nanoAg-stimulated embryonic cytotoxicity appeared lower than that induced by the Ag+ ion. The results collectively show that nanoAg has the potential to induce embryo cytotoxicity. Further studies are required to establish effective protection strategies against the cytotoxic effects of these nanoparticles.

  1. Optimal descriptor as a translator of eclectic data into prediction of cytotoxicity for metal oxide nanoparticles under different conditions.

    PubMed

    Toropova, Alla P; Toropov, Andrey A; Rallo, Robert; Leszczynska, Danuta; Leszczynski, Jerzy

    2015-02-01

    The Monte Carlo technique has been used to build up quantitative structure-activity relationships (QSARs) for prediction of dark cytotoxicity and photo-induced cytotoxicity of metal oxide nanoparticles to bacteria Escherichia coli (minus logarithm of lethal concentration for 50% bacteria pLC50, LC50 in mol/L). The representation of nanoparticles include (i) in the case of the dark cytotoxicity a simplified molecular input-line entry system (SMILES), and (ii) in the case of photo-induced cytotoxicity a SMILES plus symbol '^'. The predictability of the approach is checked up with six random distributions of available data into the visible training and calibration sets, and invisible validation set. The statistical characteristics of these models are correlation coefficient 0.90-0.94 (training set) and 0.73-0.98 (validation set).

  2. Synthesis and Cytotoxicity of Y2O3 Nanoparticles of Various Morphologies

    NASA Astrophysics Data System (ADS)

    Andelman, Tamar; Gordonov, Simon; Busto, Gabrielle; Moghe, Prabhas V.; Riman, Richard E.

    2010-02-01

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

  3. Cytotoxicity of semiconductor nanoparticles in A549 cells is attributable to their intrinsic oxidant activity

    NASA Astrophysics Data System (ADS)

    Escamilla-Rivera, Vicente; Uribe-Ramirez, Marisela; Gonzalez-Pozos, Sirenia; Velumani, Subramaniam; Arreola-Mendoza, Laura; De Vizcaya-Ruiz, Andrea

    2016-04-01

    Copper indium gallium diselenide (CIGS) and cadmium sulfide (CdS) nanoparticles (NP) are next generation semiconductors used in photovoltaic cells (PV). They possess high quantum efficiency, absorption coefficient, and cheaper manufacturing costs compared to silicon. Due to their potential for an industrial development and the lack of information about the risk associated in their use, we investigated the influence of the physicochemical characteristics of CIGS (9 nm) and CdS (20 nm) in relation to the induction of cytotoxicity in human alveolar A549 cells through ROS generation and mitochondrial dysfunction. CIGS induced cytotoxicity in a dose dependent manner in lower concentrations than CdS; both NP were able to induce ROS in A549. Moreover, CIGS interact directly with mitochondria inducing depolarization that leads to the induction of apoptosis compared to CdS. Antioxidant pretreatment significantly prevented the loss of mitochondrial membrane potential and cytotoxicity, suggesting ROS generation as the main cytotoxic mechanism. These results demonstrate that semiconductor characteristics of NP are crucial for the type and intensity of the cytotoxic effects. Our work provides relevant information that may help guide the production of a safer NP-based PV technologies, and would be a valuable resource on future risk assessment for a safer use of nanotechnology in the development of clean sources of renewable energy.

  4. Reducing ZnO nanoparticle cytotoxicity by surface modification

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  5. Dextran and polymer polyethylene glycol (PEG) coating reduce both 5 and 30 nm iron oxide nanoparticle cytotoxicity in 2D and 3D cell culture.

    PubMed

    Yu, Miao; Huang, Shaohui; Yu, Kevin Jun; Clyne, Alisa Morss

    2012-01-01

    Superparamagnetic iron oxide nanoparticles are widely used in biomedical applications, yet questions remain regarding the effect of nanoparticle size and coating on nanoparticle cytotoxicity. In this study, porcine aortic endothelial cells were exposed to 5 and 30 nm diameter iron oxide nanoparticles coated with either the polysaccharide, dextran, or the polymer polyethylene glycol (PEG). Nanoparticle uptake, cytotoxicity, reactive oxygen species (ROS) formation, and cell morphology changes were measured. Endothelial cells took up nanoparticles of all sizes and coatings in a dose dependent manner, and intracellular nanoparticles remained clustered in cytoplasmic vacuoles. Bare nanoparticles in both sizes induced a more than 6 fold increase in cell death at the highest concentration (0.5 mg/mL) and led to significant cell elongation, whereas cell viability and morphology remained constant with coated nanoparticles. While bare 30 nm nanoparticles induced significant ROS formation, neither 5 nm nanoparticles (bare or coated) nor 30 nm coated nanoparticles changed ROS levels. Furthermore, nanoparticles were more toxic at lower concentrations when cells were cultured within 3D gels. These results indicate that both dextran and PEG coatings reduce nanoparticle cytotoxicity, however different mechanisms may be important for different size nanoparticles.

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

    SciTech Connect

    Loh, Jing Wen; Saunders, Martin; Lim, Lee-Yong

    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.

  7. Assessment of HDACi-Induced Cytotoxicity.

    PubMed

    Marx-Blümel, Lisa; Marx, Christian; Kühne, Marie; Sonnemann, Jürgen

    2017-01-01

    The chromatin contains the genetic and the epigenetic information of a eukaryotic organism. Posttranslational modifications of histones, such as acetylation and methylation, regulate their structure and control gene expression. Histone acetyltransferases (HATs) acetylate lysine residues in histones while histone deacetylases (HDACs) remove this modification. HDAC inhibitors (HDACi) can alter gene expression patterns and induce cytotoxicity in cancer cells. Here we provide an overview of methods to determine the cytotoxic effects of HDACi treatment. Our chapter describes colorimetric methods, like trypan blue exclusion test, crystal violet staining, lactate dehydrogenase assay, MTT and Alamar Blue assays, as well as fluorogenic methods like TUNEL staining and the caspase-3/7 activity assay. Moreover, we summarize flow cytometric analysis of propidium iodide uptake, annexin V staining, cell cycle status, ROS levels, and mitochondrial membrane potential as well as detection of apoptosis by Western blot.

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

    PubMed

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

    2013-01-01

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

  9. Oxidative stress-mediated cytotoxicity of zirconia nanoparticles on PC12 and N2a cells

    NASA Astrophysics Data System (ADS)

    Asadpour, Elham; Sadeghnia, Hamid R.; Ghorbani, Ahmad; Sedaghat, Mehran; Boroushaki, Mohammad T.

    2016-01-01

    In recent years, there is a growing interest in the application of nanoparticles like zirconium dioxide (zirconia <100 nm), for many purposes. Since a comprehensive study on the toxic effects of zirconia has not been done, we decided to investigate the effects of zirconia nanoparticles on cultured PC12 and N2a cells. In this study, cytotoxic effect of different concentrations of zirconia nanoparticles at three different time intervals were evaluated using MTT and ROS (reactive oxygen species) assays. Also, Lipid peroxidation, glutathione (GSH) content changes, and DNA damage were measured. Zirconia nanoparticles caused a significant reduction in cell viability and GSH content of the cells, and induce a significant increase in intracellular ROS and MDA content of PC12 and N2a cells. Moreover, it increases the percentage of DNA tail of treated cells as compared with control group. Zirconia nanoparticles have cytotoxic and genotoxic effects in PC12 and N2a cells in a time and concentration-dependent manner in concentration more than 31 µg/mL.

  10. Bio-mediated synthesis, characterization and cytotoxicity of gold nanoparticles.

    PubMed

    Klekotko, Magdalena; Matczyszyn, Katarzyna; Siednienko, Jakub; Olesiak-Banska, Joanna; Pawlik, Krzysztof; Samoc, Marek

    2015-11-21

    We report here a "green" approach for the synthesis of gold nanoparticles (GNPs) in which the Mentha piperita extract was applied for the bioreduction of chloroauric acid and the stabilization of the formed nanostructures. The obtained GNPs were characterized by UV-Vis absorption spectroscopy and transmission electron microscopy (TEM). The reduction of gold ions with the plant extract leads to the production of nanoparticles with various shapes (spherical, triangular and hexagonal) and sizes (from 10 to 300 nm). The kinetics of the reaction was monitored and various conditions of the synthesis were investigated. As a result, we established protocols optimized towards the synthesis of nanospheres and nanoprisms of gold. The cytotoxic effect of the obtained gold nanoparticles was studied by performing MTT assay, which showed lower cytotoxicity of the biosynthesized GNPs compared to gold nanorods synthesized using the usual seed-mediated growth. The results suggest that the synthesis using plant extracts may be a useful method to produce gold nanostructures for various biological and medical applications.

  11. 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 μg/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 μg nanoparticles/mL for 6-hr exposure for confirmation purposes. Results Multiple cytokines, GM-CSF, IL-1β, IL-6, IL-8, IFNγ, MCP-1, TNF-α and VEGF, were significantly elevated in THP-1 cells in a dose-dependent manner. Gene expression analysis confirmed up-regulation of the TNF-α gene in THP-1 cells, consistent with cytokine findings. In both primary epithelial cells, cytokines IL-8, VEGF, EGF, IL-1α, TNF-α, 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

  12. Tamoxifen Induces Cytotoxic Autophagy in Glioblastoma.

    PubMed

    Graham, Christopher D; Kaza, Niroop; Klocke, Barbara J; Gillespie, G Yancey; Shevde, Lalita A; Carroll, Steven L; Roth, Kevin A

    2016-10-01

    Glioblastomas (GBMs) are the most common and aggressive primary human malignant brain tumors. 4-Hydroxy tamoxifen (OHT) is an active metabolite of the tamoxifen (TMX) prodrug and a well-established estrogen receptor (ER) and estrogen-related receptor antagonist. A recent study from our laboratory demonstrated that OHT induced ER-independent malignant peripheral nerve sheath tumor (MPNST) cell death by autophagic degradation of the prosurvival protein Kirsten rat sarcoma viral oncogene homolog. Because both MPNST and GBM are glial in cell origin, we hypothesized that OHT could mediate similar effects in GBM. OHT induced a concentration-dependent reduction in cell viability that was largely independent of caspase activation in a human GBM cell line and 2 patient-derived xenolines. Further, OHT induced both cytotoxic autophagy and a concentration-dependent decrease in epidermal growth factor receptor (EGFR) protein levels. A GBM cell line expressing EGFR variant III (EGFRvIII) was relatively resistant to OHT-induced death and EGFRvIII was refractory to OHT-induced degradation. Thus, OHT induces GBM cell death through a caspase-independent, autophagy-related mechanism and should be considered as a potential therapeutic agent in patients with GBM whose tumors express wild-type EGFR.

  13. Suppressing the cytotoxicity of CuO nanoparticles by uptake of curcumin/BSA particles

    NASA Astrophysics Data System (ADS)

    Zhang, Wenjing; Jiang, Pengfei; Chen, Ying; Luo, Peihua; Li, Guanqun; Zheng, Botuo; Chen, Wei; Mao, Zhengwei; Gao, Changyou

    2016-05-01

    The adverse effects of metal-based nanoparticles on human beings and the environment have received extensive attention recently. It is urgently required to develop a simple and effective method to suppress the toxicity of metal-based nanomaterials. In this study, a hydrophobic antioxidant and a chelation agent curcumin (CUR) were encapsulated into bovine serum albumin (BSA) particles by a simple co-precipitation method, and followed by glutaraldehyde cross-linking. The CUR/BSA particles had an average size of 300 nm in diameter with a negatively charged surface and sustained curcumin release properties. The cellular uptake and cytotoxicity of CUR/BSA particles were followed on A549 cells, HepG2 cells and RAW264.7 cells. The CUR/BSA particles had higher intracellular accumulation and lower cytotoxicity compared with the free curcumin at the same drug concentration. The CUR/BSA particles could suppress the cytotoxicity generated by CuO nanoparticles as a result of decrease of both the intracellular reactive oxygen species (ROS) level and Cu2+ concentration, while the free curcumin did not show any obvious detoxicating effect. The detoxicating effects of CUR/BSA particles were further studied in an intratracheal instillation model in vivo, demonstrating significant reduction of toxicity and inflammatory response in rat lungs induced by CuO nanoparticles. The concept-proving study demonstrates the potential of the CUR/BSA particles in suppressing cytotoxicity of metal-based nanomaterials, which is a paramount requirement for the safe application of nanotechnology.

  14. Carbon nanoparticle induced cytotoxicity in human mesenchymal stem cells through upregulation of TNF3, NFKBIA and BCL2L1 genes.

    PubMed

    Periasamy, Vaiyapuri S; Athinarayanan, Jegan; Alfawaz, Mohammed A; Alshatwi, Ali A

    2016-02-01

    Carbon based nanomaterials, including carbon nanotubes, graphene, nanodiamond and carbon nanoparticles, have emerged as potential candidates for a wide variety of applications because of their unusual electrical, mechanical, thermal and optical properties. However, our understanding of how increased usage of carbon based nanomaterials could lead to harmful effects in humans and other biological systems is inadequate. Our present investigation is focused on the cellular toxicity of carbon nanoparticles (CNPs) on human mesenchymal stem cells (hMSCs). Following exposure to CNPs, cell viability, nuclear morphological changes, apoptosis and cell cycle progression were monitored. Furthermore, the expression of genes involved in both cell death (e.g., P53, TNF3, CDKN1A, TNFRSF1A, TNFSF10, NFKBIA, BCL2L1) and cell cycle regulation (e.g., PCNA, EGR1, E2F1, CCNG1, CCND1, CCNC, CYCD3) were assessed using qPCR. Our results indicated that CNPs reduce cell viability and cause chromatin condensation and DNA fragmentation. Cell cycle analysis indicated that CNPs affect the cell cycle progression. However, the gene expression measurements confirmed that CNPs significantly upregulated the P53, TNF3, CDKNIA, and NFKBIA genes and downregulated the EGR1 gene in hMSCs. Our findings suggest that CNPs reduce cell viability by disrupting the expression of cell death genes in human mesenchymal stem cell (hMSC). The results of this investigation revealed that CNPs exhibited moderate toxicity on hMSCs.

  15. Manipulating the NF-κB pathway in macrophages using mannosylated, siRNA-delivering nanoparticles can induce immunostimulatory and tumor cytotoxic functions.

    PubMed

    Ortega, Ryan A; Barham, Whitney; Sharman, Kavya; Tikhomirov, Oleg; Giorgio, Todd D; Yull, Fiona E

    2016-01-01

    Tumor-associated macrophages (TAMs) are critically important in the context of solid tumor progression. Counterintuitively, these host immune cells can often support tumor cells along the path from primary tumor to metastatic colonization and growth. Thus, the ability to transform protumor TAMs into antitumor, immune-reactive macrophages would have significant therapeutic potential. However, in order to achieve these effects, two major hurdles would need to be overcome: development of a methodology to specifically target macrophages and increased knowledge of the optimal targets for cell-signaling modulation. This study addresses both of these obstacles and furthers the development of a therapeutic agent based on this strategy. Using ex vivo macrophages in culture, the efficacy of mannosylated nanoparticles to deliver small interfering RNA specifically to TAMs and modify signaling pathways is characterized. Then, selective small interfering RNA delivery is tested for the ability to inhibit gene targets within the canonical or alternative nuclear factor-kappaB pathways and result in antitumor phenotypes. Results confirm that the mannosylated nanoparticle approach can be used to modulate signaling within macrophages. We also identify appropriate gene targets in critical regulatory pathways. These findings represent an important advance toward the development of a novel cancer therapy that would minimize side effects because of the targeted nature of the intervention and that has rapid translational potential.

  16. Silica-encapsulated magnetic nanoparticles: enzyme immobilization and cytotoxic study.

    PubMed

    Ashtari, Khadijeh; Khajeh, Khosro; Fasihi, Javad; Ashtari, Parviz; Ramazani, Ali; Vali, Hojatollah

    2012-05-01

    Silica-encapsulated magnetic nanoparticles (MNPs) were prepared via microemulsion method. The products were characterized by high resolution transmission electron microscopy (HRTEM) and energy-dispersive X-ray spectrum (EDS). MNPs with no observed cytotoxic activity against human lung carcinoma cell and brine shrimp lethality were used as suitable support for glucose oxidase (GOD) immobilization. Binding of GOD onto the support was confirmed by the FTIR spectra. The amount of immobilized GODs was 95 mg/g. Storage stability study showed that the immobilized GOD retained 98% of its initial activity after 45 days and 90% of the activity was also remained after 12 repeated uses. Considerable enhancements in thermal stabilities were observed for the immobilized GOD at elevated temperatures up to 80°C and the activity of immobilized enzyme was less sensitive to pH changes in solution.

  17. Cytotoxic effects of MgO nanoparticles on human umbilical vein endothelial cells in vitro.

    PubMed

    Ge, S; Wang, G; Shen, Y; Zhang, Q; Jia, D; Wang, H; Dong, Q; Yin, T

    2011-06-01

    The MgO nanoparticles are widely used in many fields. However, the toxicity of these nanoparticles to cells and organs remains fairly undiscovered. In this study, the cytotoxicity of MgO nanoparticles on human umbilical vein endothelial cells (HUVECs) in vitro was examined. The morphology and size of MgO nanoparticles were analysed by the transmission electron microscope (TEM) and nanoparticle size analyser. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 h-tetrazolium bromide) assay, 4',6-diamidino-2-phenylindole (DAPI) staining analysis, NO release and total antioxidation competence (T-AOC) assay were used to evaluate the cytotoxicity of MgO nanoparticles. The results showed that most MgO nanoparticles were spherical with agglomerated state and the diameter of single particle was about 100 nm. Meanwhile, low concentration (below 200 [micro sign]g/ml) of MgO nanoparticles suspension showed no cytotoxicity by MTT assay. However, once the concentration of MgO nanoparticles was higher than 500 [micro sign]g/ml, the relative growth rate was lower than the control. The DAPI staining analysis results showed no significant difference of the cells morphology between the groups with or without MgO nanoparticles. In addition, the MgO nanoparticles significantly enhanced the NO release and T-AOC content of the HUVECs. The testing results indicated that low concentration of MgO nanoparticles exhibited non-cytotoxicity.

  18. Cytotoxicity of glass ionomer cements containing silver nanoparticles

    PubMed Central

    Magalhães, Ana-Paula-Rodrigues; Pires, Wanessa-Carvalho; Pereira, Flávia-Castro; Silveira-Lacerda, Elisângela-Paula; Carrião, Marcus-Santos; Bakuzis, Andris-Figueiroa; Souza-Costa, Carlos-Alberto; Lopes, Lawrence-Gonzaga; Estrela, Carlos

    2015-01-01

    Background Some studies have investigated the possibility of incorporating silver nanoparticles (NAg) into dental materials to improve their antibacterial properties. However, the potential toxic effect of this material on pulp cells should be investigated in order to avoid additional damage to the pulp tissue. This study evaluated the cytotoxicity of conventional and resin-modified glass ionomer cements (GIC) with and without addition of NAg. Material and Methods NAg were added to the materials at two different concentrations by weight: 0.1% and 0.2%. Specimens with standardized dimensions were prepared, immersed in 400 µL of culture medium and incubated at 37°C and 5% CO2 for 48 h to prepare GIC liquid extracts, which were then incubated in contact with cells for 48 h. Culture medium and 0.78% NAg solution were used as negative and positive controls, respectively. Cell viability was determined by MTT and Trypan Blue assays. ANOVA and the Tukey test (α=0.05) were used for statistical analyses. Results Both tests revealed a significant decrease in cell viability in all groups of resin modified cements (p<0.001). There were no statistically significant differences between groups with and without NAg (p>0.05). The differences in cell viability between any group of conventional GIC and the negative control were not statistically significant (p>0.05). Conclusions NAg did not affect the cytotoxicity of the GIC under evaluation. Key words:Glass ionomer cements, totoxicity, cell culture techniques, nanotechnology, metal nanoparticles. PMID:26644839

  19. 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 μg/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.

  20. High-content screening as a universal tool for fingerprinting of cytotoxicity of nanoparticles.

    PubMed

    Jan, Edward; Byrne, Stephen J; Cuddihy, Meghan; Davies, Anthony M; Volkov, Yuri; Gun'ko, Yurii K; Kotov, Nicholas A

    2008-05-01

    Recent advances and progress in nanobiotechnology have demonstrated many nanoparticles (NPs) as potential and novel drug delivery vehicles, therapeutic agents, and contrast agents and luminescent biological labels for bioimaging. The emergence of new biomedical applications based on NPs signifies the need to understand, compare, and manage their cytotoxicity. In this study, we demonstrated the use of high-content screening assay (HCA) as a universal tool to probe the cytotoxicity of NPs and specifically cadmium telluride quantum dots (CdTe QDs) and gold NPs (Au NPs) in NG108-15 murine neuroblastoma cells and HepG2 human hepatocellular carcinoma cells. Neural cells represent special interest for NP-induced cytotoxicity because the optical and electrical functionalities of materials necessary for neural imaging and interfacing are matched well with the properties of many NPs. In addition, the cellular morphology of neurons is particularly suitable for automated high content screening. HepG2 cells represent a good model for high content screening studies since they are commonly used as a surrogate for human hepatocytes in pharmaceutical studies. We found the CdTe QDs to induce primarily apoptotic response in a time- and dosage-dependent manner and produce different toxicological profiles and responses in undifferentiated and differentiated neural cells. Au NPs were found to inhibit the proliferation and intracellular calcium release of HepG2 cells.

  1. Cytotoxicity of TiO{sub 2} nanoparticles towards freshwater sediment microorganisms at low exposure concentrations

    SciTech Connect

    Kumari, Jyoti; Kumar, Deepak; Mathur, Ankita; Naseer, Arif; Kumar, Ravi Ranjan; Thanjavur Chandrasekaran, Prathna; Chaudhuri, Gouri; Pulimi, Mrudula; Raichur, Ashok M.; Babu, S.; Chandrasekaran, Natarajan; Nagarajan, R.; Mukherjee, Amitava

    2014-11-15

    There is a persistent need to assess the effects of TiO{sub 2} nanoparticles on the aquatic ecosystem owing to their increasing usage in consumer products and risk of environmental release. The current study is focused on TiO{sub 2} nanoparticle-induced acute toxicity at sub-ppm level (≤1 ppm) on the three different freshwater sediment bacterial isolates and their consortium under two different irradiation (visible light and dark) conditions. The consortium of the bacterial isolates was found to be less affected by the exposure to the nanoparticles compared to the individual cells. The oxidative stress contributed considerably towards the cytotoxicity under both light and dark conditions. A statistically significant increase in membrane permeability was noted under the dark conditions as compared to the light conditions. The optical and fluorescence microscopic images showed aggregation and chain formation of the bacterial cells, when exposed to the nanoparticles. The electron microscopic (SEM, TEM) observations suggested considerable damage of cells and bio-uptake of nanoparticles. The exopolysaccrides (EPS) production and biofilm formation were noted to increase in the presence of the nanoparticles, and expression of the key genes involved in biofilm formation was studied by RT-PCR. - Highlights: • Toxicity of NPs towards freshwater sediment bacteria at sub-ppm concentrations. • Decreased toxicity of the nanoparticles in the consortium of microorganisms. • Enhanced bacterial resistance through EPS and biofilm formation in the presence of NPs. • Considerable surface damage of cells and internalization of NPs. • Gene expression analyses related to biofilm formation in the presence of NPs.

  2. 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.

  3. Dose-dependent cytotoxicity of clinically relevant cobalt nanoparticles and ions on macrophages in vitro.

    PubMed

    Kwon, Young-Min; Xia, Zhidao; Glyn-Jones, Sion; Beard, David; Gill, Harinderjit S; Murray, David W

    2009-04-01

    Despite the satisfactory short-term implant survivorship of metal-on-metal hip resurfacing arthroplasty, periprosthetic soft-tissue masses such as pseudotumours are being increasingly reported. Cytotoxic effects of cobalt or chromium have been suggested to play a role in its aetiology. The aim of this study was to investigate the effects of clinically relevant metal nanoparticles and ions on the viability of macrophages in vitro. A RAW 264.7 murine macrophage cell line was cultured in the presence of either: (1) cobalt, chromium and titanium nanoparticles sized 30-35 nm; or (2) cobalt sulphate and chromium chloride. Two methods were used to quantify cell viability: Alamar Blue assay and Live/Dead assay. The cytotoxicity was observed only with cobalt. Cobalt nanoparticles and ions demonstrated dose-dependent cytotoxic effects on macrophages in vitro: the cytotoxic concentrations of nanoparticles and ions were 1 x 10(12) particles ml(-1) and 1000 microM, respectively. The high concentration of cobalt nanoparticles required for cytotoxicity of macrophages in vitro suggests that increased production of cobalt nanoparticles in vivo, due to excessive MoM implant wear, may lead to local adverse biological effects. Therefore, cytotoxicity of high concentrations of metal nanoparticles phagocytosed by macrophages located in the periprosthetic tissues may be an important factor in pathogenesis of pseudotumours.

  4. Mild Hypothermia Attenuates the Anesthetic Isoflurane-Induced Cytotoxicity

    PubMed Central

    Li, Cheng; Dong, Yuanlin; Chen, Dan; Xie, Zhongcong; Zhang, Yiying

    2017-01-01

    The commonly used inhalation anesthetic isoflurane has been reported to induce DNA damage and cytotoxicity. However, the methods to attenuate these effects remain largely to be determined. Mild hypothermia has neuroprotective effects. We therefore set out to assess whether mild hypothermia could protect the isoflurane-induced DNA damage and cytotoxicity. Moreover, we investigated the underlying mechanisms by assessing the effects of mild hypothermia on the isoflurane-induced changes in ATP levels. H4 human neuroglioma cells were treated with 2% isoflurane for 3 or 6 h with and without mild hypothermia (35°C). We assessed the cell viability by using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and lactate dehydrogenase (LDH) assay. We determined DNA damage by measuring levels of phosphorylation of the histone protein H2A variant X at Ser139 (γH2A.X), the marker of DNA damage. We also measured ATP levels in the cells. Here we showed that the treatment with 2% isoflurane for 6 h induced cytotoxicity and DNA damage in the cells. Moreover, the treatment with 2% isoflurane for 3 h decreased ATP levels without inducing cytotoxicity. Mild hypothermia attenuated the isoflurane-induced cytotoxicity, DNA damage, and ATP reduction in the cells. Taken together, these data suggest that the isoflurane-induced reduction in ATP levels occurred before the isoflurane-induced cytotoxicity. Isoflurane may induce DNA damage and cause cytotoxicity through reducing ATP levels. Mild hypothermia would ameliorate isoflurane-induced DNA damage and cytotoxicity by attenuating the isoflurane-induced reduction in ATP levels. These pilot studies have established a system and will promote the future investigations of anesthesia neurotoxicity. PMID:28228717

  5. Mild Hypothermia Attenuates the Anesthetic Isoflurane-Induced Cytotoxicity.

    PubMed

    Li, Cheng; Dong, Yuanlin; Chen, Dan; Xie, Zhongcong; Zhang, Yiying

    2017-01-01

    The commonly used inhalation anesthetic isoflurane has been reported to induce DNA damage and cytotoxicity. However, the methods to attenuate these effects remain largely to be determined. Mild hypothermia has neuroprotective effects. We therefore set out to assess whether mild hypothermia could protect the isoflurane-induced DNA damage and cytotoxicity. Moreover, we investigated the underlying mechanisms by assessing the effects of mild hypothermia on the isoflurane-induced changes in ATP levels. H4 human neuroglioma cells were treated with 2% isoflurane for 3 or 6 h with and without mild hypothermia (35°C). We assessed the cell viability by using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and lactate dehydrogenase (LDH) assay. We determined DNA damage by measuring levels of phosphorylation of the histone protein H2A variant X at Ser139 (γH2A.X), the marker of DNA damage. We also measured ATP levels in the cells. Here we showed that the treatment with 2% isoflurane for 6 h induced cytotoxicity and DNA damage in the cells. Moreover, the treatment with 2% isoflurane for 3 h decreased ATP levels without inducing cytotoxicity. Mild hypothermia attenuated the isoflurane-induced cytotoxicity, DNA damage, and ATP reduction in the cells. Taken together, these data suggest that the isoflurane-induced reduction in ATP levels occurred before the isoflurane-induced cytotoxicity. Isoflurane may induce DNA damage and cause cytotoxicity through reducing ATP levels. Mild hypothermia would ameliorate isoflurane-induced DNA damage and cytotoxicity by attenuating the isoflurane-induced reduction in ATP levels. These pilot studies have established a system and will promote the future investigations of anesthesia neurotoxicity.

  6. Propofol Enhances Hemoglobin-Induced Cytotoxicity in Neurons

    PubMed Central

    Yuan, Jing; Cui, Guiyun; Li, Wenlu; Zhang, Xiaoli; Wang, Xiaoying; Zheng, Hui; Zhang, Jian; Xiang, Shuanglin; Xie, Zhongcong

    2016-01-01

    BACKGROUND It has been increasingly suggested that propofol protects against hypoxic-/ischemic-induced neuronal injury. As evidenced by hemorrhage-induced stroke, hemorrhage into the brain may also cause brain damage. Whether propofol protects against hemorrhage-induced brain damage remains unknown. Therefore, in this study, we investigated the effects of propofol on hemoglobin-induced cytotoxicity in cultured mouse cortical neurons. METHODS Neurons were prepared from the cortex of embryonic 15-day-old mice. Hemoglobin was used to induce cytotoxicity in the neurons. The neurons were then treated with propofol for 4 hours. Cytotoxicity was determined by lactate dehydrogenase release assay. Caspase-3 activation was examined by Western blot analysis. Finally, the free radical scavenger U83836E was used to examine the potential involvement of oxidative stress in propofol’s effects on hemoglobin-induced cytotoxicity. RESULTS We found that treatment with hemoglobin induced cytotoxicity in the neurons. Propofol enhanced hemoglobin-induced cytotoxicity. Specifically, there was a significant difference in the amount of lactate dehydrogenase release between hemoglobin plus saline (19.84% ± 5.38%) and hemoglobin plus propofol (35.79% ± 4.41%) in mouse cortical neurons (P = 0.00058, Wilcoxon Mann-Whitney U test, n = 8 in the control group or the treatment group). U83836E did not attenuate the enhancing effects of propofol on hemoglobin-induced cytotoxicity in the neurons, and propofol did not significantly affect caspase-3 activation induced by hemoglobin. These data suggested that caspase-3 activation and oxidative stress might not be the underlying mechanisms by which propofol enhanced hemoglobin-induced cytotoxicity. Moreover, these data suggested that the neuroprotective effects of propofol would be dependent on the condition of the brain injury, which will need to be confirmed in future studies. CONCLUSIONS These results from our current proof-of-concept study should

  7. Comparison of nanoparticle-mediated transfection methods for DNA expression plasmids: efficiency and cytotoxicity

    PubMed Central

    2011-01-01

    Background Reproducibly high transfection rates with low methodology-induced cytotoxic side effects are essential to attain the required effect on targeted cells when exogenous DNA is transfected. Different approaches and modifications such as the use of nanoparticles (NPs) are being evaluated to increase transfection efficiencies. Several studies have focused on the attained transfection efficiency after NP-mediated approaches. However, data comparing toxicity of these novel approaches with conventional methods is still rare. Transfection efficiency and methodology-induced cytotoxicity were analysed after transfection with different NP-mediated and conventional approaches. Two eukaryotic DNA-expression-plasmids were used to transfect the mammalian cell line MTH53A applying six different transfection protocols: conventional transfection reagent (FuGENE HD, FHD), FHD in combination with two different sizes of stabilizer-free laser-generated AuNPs (PLAL-AuNPs_S1,_S2), FHD and commercially available AuNPs (Plano-AuNP), and two magnetic transfection protocols. 24 h post transfection efficiency of each protocol was analysed using fluorescence microscopy and GFP-based flow cytometry. Toxicity was assessed measuring cell proliferation and percentage of propidium iodide (PI%) positive cells. Expression of the respective recombinant proteins was evaluated by immunofluorescence. Results The addition of AuNPs to the transfection protocols significantly increased transfection efficiency in the pIRES-hrGFPII-eIL-12 transfections (FHD: 16%; AuNPs mean: 28%), whereas the magnet-assisted protocols did not increase efficiency. Ligand-free PLAL-AuNPs had no significant cytotoxic effect, while the ligand-stabilized Plano-AuNPs induced a significant increase in the PI% and lower cell proliferation. For pIRES-hrGFPII-rHMGB1 transfections significantly higher transfection efficiency was observed with PLAL-AuNPs (FHD: 31%; PLAL-AuNPs_S1: 46%; PLAL-AuNPs_S2: 50%), while the magnet

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

    NASA Astrophysics Data System (ADS)

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

    2006-02-01

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

  9. Evaluation of cytotoxic, oxidative stress, proinflammatory and genotoxic effect of silver nanoparticles in human lung epithelial cells.

    PubMed

    Suliman Y, Al Omar; Ali, Daoud; Alarifi, Saud; Harrath, Abdul Halim; Mansour, Lamjed; Alwasel, Saleh Hamad

    2015-02-01

    Silver nanoparticles are increasingly used in various products, due to their antibacterial properties. Despite its wide spread use, only little information on possible adverse health effects exists. Therefore, the aim of this study was to assess the toxic potential of silver nanoparticles (<100 nm) in human lung epithelial (A549) cells and the underlying mechanism of its cellular toxicity. Silver nanoparticles induced dose and time-dependent cytotoxicity in A549 cells demonstrated by MTT and LDH assays. Silver nanoparticles were also found to induce oxidative stress in dose and time-dependent manner indicated by depletion of GSH and induction of ROS, LPO, SOD, and catalase. Further, the activities of caspases and the level of proinflammatory cytokines, namely interleukin-1β (IL-1β) and interleukin-6 (IL-6) were significantly higher in treated cells. DNA damage, as measured by single cell gel electrophoresis, was also dose and time-dependent signicants in A549 cells. This study investigating the effects of silver nanoparticles in human lung epithelial cells has provided valuable insights into the mechanism of potential toxicity induced by silver nanoparticles and warrants more careful assessment of silver nanoparticles before their industrial applications.

  10. In vitro cellular uptake and cytotoxic effect of functionalized nickel nanoparticles on leukemia cancer cells.

    PubMed

    Guo, Dadong; Wu, Chunhui; Li, Xiaomao; Jiang, Hui; Wang, Xuemei; Chen, Baoan

    2008-05-01

    Nickel nanoparticles (Ni NPs) have been applied in a wide range of areas because of their unique structure and properties such as catalysts, high-density magnetic recording media and others. However, little effort has been paid to their biological application and the concrete effect of Ni NPs on biological systems is still unknown. In this study, the possibility of the utilization of the magnetic Ni NPs in cancer cell studies was explored and the effects of the Ni NPs capped with positively charged tetraheptylammonium on leukemia K562 cells in vitro were investigated. Our observations of optical microscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM) studies indicate that the morphological changes of cancer cells induced by Ni NPs could be apparently observed. The results of 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay, DNA fragmentation and flow cytometry studies demonstrate that the Ni NPs could exert cytotoxicity to leukemia K562 cells at high concentration, and subsequently induce both apoptosis and necrosis of target cancer cells, whilst it had little impact on target cells when at low concentration. Meanwhile, functionalized Ni NPs with positively charged groups could enhance the permeability of cell membrane and facilitate the cellular uptake of outer target molecules into cancer cells. These findings reveal the potential mechanism of Ni NPs to target cancer cells which could induce the cytotoxicity to leukemia cancer cells and suggest the possibility for applications of the Ni NPs in related clinical and biomedical areas.

  11. On-Chip Evaluation of Shear Stress Effect on Cytotoxicity of Mesoporous Silica Nanoparticles

    PubMed Central

    Kim, Donghyuk; Lin, Yu-Shen; Haynes, Christy L.

    2011-01-01

    In this work, nanotoxicity in the bloodstream was modeled and the cytotoxicity of sub-50 nm mesoporous silica nanoparticles to human endothelial cells was investigated under microfluidic flow conditions. Compared to traditional in vitro cytotoxicity assays performed under static conditions, unmodified mesoporous silica nanoparticles show higher and shear stress-dependent toxicity to endothelial cells under flow conditions. Interestingly, even under flow conditions, highly organo-modified mesoporous silica nanoparticles show no significant toxicity to endothelial cells. This paper clearly demonstrates that shear stress is an important factor to be considered in in vitro nanotoxicology assessments and provides a simple device for pursuing this consideration. PMID:22032307

  12. Synthesis of ZnO nanoparticles and evaluation of antioxidant and cytotoxic activity.

    PubMed

    Das, Dhaneswar; Nath, Bikash Chandra; Phukon, Pinkee; Kalita, Amarjyoti; Dolui, Swapan Kumar

    2013-11-01

    ZnO nanoparticles were synthesized by thermal decomposition method and were characterized by UV-vis spectroscopy, XRD, SEM, EDX and TEM analysis. The resultant nanoparticles are nearly spherical and size is in the range of 40-50 nm. The antioxidant behavior of ZnO nanoparticles was assessed by scavenging free radicals of 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) with varying nanoparticle concentration and time interval individually. The DPPH scavenging activity was monitored by UV-vis spectrophotometer. ZnO nanoparticles were also showing cytotoxic activity which was studied by hemolytic potentiality test.

  13. An interdisciplinary computational/experimental approach to evaluate drug-loaded gold nanoparticle tumor cytotoxicity

    PubMed Central

    Curtis, Louis T; England, Christopher G; Wu, Min; Lowengrub, John; Frieboes, Hermann B

    2016-01-01

    Aim: Clinical translation of cancer nanotherapy has largely failed due to the infeasibility of optimizing the complex interaction of nano/drug/tumor/patient parameters. We develop an interdisciplinary approach modeling diffusive transport of drug-loaded gold nanoparticles in heterogeneously-vascularized tumors. Materials & methods: Evaluated lung cancer cytotoxicity to paclitaxel/cisplatin using novel two-layer (hexadecanethiol/phosphatidylcholine) and three-layer (with high-density-lipoprotein) nanoparticles. Computer simulations calibrated to in-vitro data simulated nanotherapy of heterogeneously-vascularized tumors. Results: Evaluation of free-drug cytotoxicity between monolayer/spheroid cultures demonstrates a substantial differential, with increased resistance conferred by diffusive transport. Nanoparticles had significantly higher efficacy than free-drug. Simulations of nanotherapy demonstrate 9.5% (cisplatin) and 41.3% (paclitaxel) tumor radius decrease. Conclusion: Interdisciplinary approach evaluating gold nanoparticle cytotoxicity and diffusive transport may provide insight into cancer nanotherapy. PMID:26829163

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

    PubMed Central

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

    2013-01-01

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

  15. 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

  16. Synthesis, characterization, and cytotoxicity of glutathione-PEG-iron oxide magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Haddad, Paula S.; Santos, Marconi C.; de Guzzi Cassago, Carolina Aparecida; Bernardes, Juliana S.; de Jesus, Marcelo Bispo; Seabra, Amedea B.

    2016-12-01

    Recently, increasing interest is spent on the synthesis of superparamagnetic iron oxide nanoparticles, followed by their characterization and evaluation of cytotoxicity towards tumorigenic cell lines. In this work, magnetite (Fe3O4) nanoparticles were synthesized by the polyol method and coated with polyethylene glycol (PEG) and glutathione (GSH), leading to the formation of PEG-Fe3O4 and GSH-PEG-Fe3O4 nanoparticles. The nanoparticles were characterized by state-of-the-art techniques: dynamic light scattering (DLS), atomic force microscopy (AFM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and superconducting quantum interference device (SQUID) magnetic measurements. PEG-Fe3O4 and GSH-PEG-Fe3O4 nanoparticles have crystallite sizes of 10 and 5 nm, respectively, indicating compression in crystalline lattice upon addition of GSH on the nanoparticle surface. Both nanoparticles presented superparamagnetic behavior at room temperature, and AFM images revealed the regular spherical shape of the nanomaterials and the absence of particle aggregation. The average hydrodynamic sizes of PEG-Fe3O4 and GSH-PEG-Fe3O4 nanoparticles were 69 ± 37 and 124 nm ± 75 nm, respectively. The cytotoxicity of both nanoparticles was screened towards human prostatic carcinoma cells (PC-3). The results demonstrated a decrease in PC-3 viability upon treatment with PEG-Fe3O4 or GSH-PEG-Fe3O4 nanoparticles in a concentration-dependent manner. However, the cytotoxicity was not time-dependent. Due to the superparamagnetic behavior of PEG-Fe3O4 or GSH-PEG-Fe3O4 nanoparticles, upon the application of an external magnetic field, those nanoparticles can be guided to the target site yielding local toxic effects to tumor cells with minimal side effects to normal tissues, highlighting the promising uses of iron oxide nanoparticles in biomedical applications.

  17. Cytotoxicity of β-D-glucose/sucrose-coated silver nanoparticles depends on cell type, nanoparticles concentration and time of incubation

    NASA Astrophysics Data System (ADS)

    Vergallo, Cristian; Panzarini, Elisa; Carata, Elisabetta; Ahmadi, Meysam; Mariano, Stefania; Tenuzzo, Bernardetta Anna; Dini, Luciana

    2016-06-01

    The use of silver NanoParticles (AgNPs) in several consumer commercialized products, like food contact materials, medical devices and cosmetics has increased significantly, owing to their antibacterial and antifungal properties. Even though the NPs are widely diffused, due to the great variety in size, coating or shape, controversial data on their possible detrimental health effects still exist. Herein, by performing an easy and fast green method synthesis, we used β-D-glucose/sucrose to stabilize AgNPs and avoid the release of cytotoxic soluble silver ions Ag+ in the culture medium. The cytotoxic effects of these β-D-Glucose/Sucrose-Coated AgNPs (AgNPs-GS) was assessed on two cell culture models, which are human liver HepG2 and human Peripheral Blood Lymphocytes (PBLs) cells. AgNPs-GS, as determined by Transmission Electron Microscopy (TEM) analyses, had an average diameter of 30±5 nm, a spherical shape and were well-dispersed in the freshly-prepared solution. In addition, they were found spectrophotometrically stable throughout the experiment. Cytotoxicity, determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay, was evaluated by using two AgNPs-GS amounts, indicated as highest (10×103 of NPs/cell) and lowest (2×103 NPs/cell) concentration for 6, 12 and 24 h. The highest concentration of AgNPs-GS was significantly cytotoxic for both HepG2 and PBLs cells at all times, when compared with the negative control; conversely, the lowest amount of AgNPs-GS was toxic only for HepG2 cells. A significant increase of Reactive Oxygen Species (ROS) levels, determined by Nitro Blue Tetrazolium (NBT) reduction assay, was observed only in PBLs after treatment with NPs, by reaching maximum levels after the incubation with the lowest amount of NPs for 24 h. Significant morphological changes, depending on NPs/cell amount, characteristic of cell toxicity, like shape, cytoplasm, and nucleus alterations, were observed in lymphocytes and Hep

  18. Synthesis of silver nanoparticles using flavonoids: hesperidin, naringin and diosmin, and their antibacterial effects and cytotoxicity

    NASA Astrophysics Data System (ADS)

    Sahu, Nidhi; Soni, Deepika; Chandrashekhar, B.; Satpute, D. B.; Saravanadevi, Sivanesan; Sarangi, B. K.; Pandey, R. A.

    2016-07-01

    Three different flavonoids -hesperidin, naringin and diosmin (constituents of citrus plants) were used for the synthesis of silver nanoparticles (AgNPs). Aqueous solutions of pure flavonoids (0.2 mg mL-1) mixed with 1 mM AgNO3 solution were exposed to bright sunlight to prepare the nanoparticles. Characterization of the synthesized nanoparticles by UV-Visible spectrophotometer, X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy revealed that the synthesized silver nanoparticles were 10-80 nm in size and polydispersed in nature. Bactericidal effect against common pathogens and cytotoxicity of the synthesized silver nanoparticles was investigated on human promyelocytic leukemic (HL-60) cells. It is concluded that AgNPs synthesized using Naringin as reducing agent showed higher stability and better antibacterial and cytotoxic activities.

  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

  20. Size- and coating-dependent cytotoxicity and genotoxicity of silver nanoparticles evaluated using in vitro standard assays.

    PubMed

    Guo, Xiaoqing; Li, Yan; Yan, Jian; Ingle, Taylor; Jones, Margie Yvonne; Mei, Nan; Boudreau, Mary D; Cunningham, Candice K; Abbas, Mazhar; Paredes, Angel M; Zhou, Tong; Moore, Martha M; Howard, Paul C; Chen, Tao

    2016-11-01

    The physicochemical characteristics of silver nanoparticles (AgNPs) may greatly alter their toxicological potential. To explore the effects of size and coating on the cytotoxicity and genotoxicity of AgNPs, six different types of AgNPs, having three different sizes and two different coatings, were investigated using the Ames test, mouse lymphoma assay (MLA) and in vitro micronucleus assay. The genotoxicities of silver acetate and silver nitrate were evaluated to compare the genotoxicity of nanosilver to that of ionic silver. The Ames test produced inconclusive results for all types of the silver materials due to the high toxicity of silver to the test bacteria and the lack of entry of the nanoparticles into the cells. Treatment of L5718Y cells with AgNPs and ionic silver resulted in concentration-dependent cytotoxicity, mutagenicity in the Tk gene and the induction of micronuclei from exposure to nearly every type of the silver materials. Treatment of TK6 cells with these silver materials also resulted in concentration-dependent cytotoxicity and significantly increased micronucleus frequency. With both the MLA and micronucleus assays, the smaller the AgNPs, the greater the cytotoxicity and genotoxicity. The coatings had less effect on the relative genotoxicity of AgNPs than the particle size. Loss of heterozygosity analysis of the induced Tk mutants indicated that the types of mutations induced by AgNPs were different from those of ionic silver. These results suggest that AgNPs induce cytotoxicity and genotoxicity in a size- and coating-dependent manner. Furthermore, while the MLA and in vitro micronucleus assay (in both types of cells) are useful to quantitatively measure the genotoxic potencies of AgNPs, the Ames test cannot.

  1. In vitro evaluation of the cytotoxicity and cellular uptake of CMCht/PAMAM dendrimer nanoparticles by glioblastoma cell models

    NASA Astrophysics Data System (ADS)

    Pojo, M.; Cerqueira, S. R.; Mota, T.; Xavier-Magalhães, A.; Ribeiro-Samy, S.; Mano, J. F.; Oliveira, J. M.; Reis, R. L.; Sousa, N.; Costa, B. M.; Salgado, A. J.

    2013-05-01

    Glioblastoma (GBM) is simultaneously the most common and most malignant subtype tumor of the central nervous system. These are particularly dramatic diseases ranking first among all human tumor types for tumor-related average years of life lost and for which curative therapies are not available. Recently, the use of nanoparticles as drug delivery systems (DDS) for tumor treatment has gained particular interest. In an attempt to evaluate the potential of carboxymethylchitosan/poly(amidoamine) (CMCht/PAMAM) dendrimer nanoparticles as a DDS, we aimed to evaluate its cytotoxicity and internalization efficiency in GBM cell models. CMCht/PAMAM-mediated cytotoxicity was evaluated in a GBM cell line (U87MG) and in human immortalized astrocytes (hTERT/E6/E7) by MTS and double-stranded DNA quantification. CMCht/PAMAM internalization was assessed by double fluorescence staining. Both cells lines present similar internalization kinetics when exposed to a high dose (400 μg/mL) of these nanoparticles. However, the internalization rate was higher in tumor GBM cells as compared to immortalized astrocytes when cells were exposed to lower doses (200 μg/mL) of CMCht/PAMAM for short periods (<24 h). After 48 h of exposure, both cell lines present 100 % of internalization efficiency for the tested concentrations. Importantly, short-term exposures (1, 6, 12, 24, and 48 h) did not show cytotoxicity, and long-term exposures (7 days) to CMCht/PAMAM induced only low levels of cytotoxicity in both cell lines ( 20 % of decrease in metabolic activity). The high efficiency and rate of internalization of CMCht/PAMAM we show here suggest that these nanoparticles may be an attractive DDS for brain tumor treatment in the future.

  2. The noncellular reduction of MTT tetrazolium salt by TiO₂ 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 50μg/ml), induced by the TiO2-MTT reaction. This type of artifacts may lead to underestimated toxicity or false proliferation results.

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

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

  4. In vitro cytotoxicity of Fe-Cr-Nb-B magnetic nanoparticles under high frequency electromagnetic field

    NASA Astrophysics Data System (ADS)

    Chiriac, Horia; Petreus, Tudor; Carasevici, Eugen; Labusca, Luminita; Herea, Dumitru-Daniel; Danceanu, Camelia; Lupu, Nicoleta

    2015-04-01

    The heating potential, cytotoxicity, and efficiency of Fe68.2Cr11.5Nb0.3B20 magnetic nanoparticles (MNPs), as such or coated with a chitosan layer, to decrease the cell viability in a cancer cell culture model by using high frequency alternating magnetic fields (AMF) have been studied. The specific absorption rate varied from 215 W/g for chitosan-free MNPs to about 190 W/g for chitosan-coated ones, and an equilibrium temperature of 46 °C was reached when chitosan-coated MNPs were subjected to AMF. The chitosan-free Fe68.2Cr11.5Nb0.3B20 MNPs proved a good biocompatibility and low cytotoxicity in all testing conditions, while the chitosan-coated ones induced strong tumoricidal effects when a cell-particle simultaneous co-incubation approach was used. In high frequency AMF, the particle-mediated heat treatment has proved to be a critical cause for decreasing in vitro the viability of a cancer cell line.

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

    PubMed

    Xu, Min; Zhao, Yuefang; Feng, Min

    2012-08-07

    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.

  6. 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.

  7. 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.

  8. Reduced Cationic Nanoparticle Cytotoxicity Based on Serum Masking of Surface Potential

    PubMed Central

    McConnell, Kellie I.; Shamsudeen, Sabeel; Meraz, Ismail M.; Mahadevan, Thiruvillamalai S.; Ziemys, Arturas; Rees, Paul; Summers, Huw D.; Serda, Rita E.

    2016-01-01

    Functionalization of nanoparticles with cationic moieties, such as polyethyleneimine (PEI), enhances binding to the cell membrane; however, it also disrupts the integrity of the cell’s plasma and vesicular membranes, leading to cell death. Primary fibroblasts were found to display high surface affinity for cationic iron oxide nanoparticles and greater sensitivity than their immortalized counterparts. Treatment of cells with cationic nanoparticles in the presence of incremental increases in serum led to a corresponding linear decrease in cell death. The surface potential of the nanoparticles also decreased linearly as serum increased and this was strongly and inversely correlated with cell death. While low doses of nanoparticles were rendered non-toxic in 25% serum, large doses overcame the toxic threshold. Serum did not reduce nanoparticle association with primary fibroblasts, indicating that the decrease in nanoparticle cytotoxicity was based on serum masking of the PEI surface, rather than decreased exposure. Primary endothelial cells were likewise more sensitive to the cytotoxic effects of cationic nanoparticles than their immortalized counterparts, and this held true for cellular responses to cationic microparticles despite the much lower toxicity of microparticles compared to nanoparticles. PMID:27301181

  9. Suppression of nanoparticle cytotoxicity approaching in vivo serum concentrations: limitations of in vitro testing for nanosafety

    NASA Astrophysics Data System (ADS)

    KimPresent Address: Institute Of Pharmaceutical Sciences, Department Of Chemistry; Applied Biosciences, Eth Zurich, Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland., Jong Ah; SalvatiPresent Address: Division Of Pharmacokinetics, Toxicology; Targeting, Department Of Pharmacy, Antonius Deusinglaan 1, 9713 Av Groningen, The Netherlands., Anna; ÅbergPresent Address: Groningen Institute Of Biomolecular Sciences; Biotechnology, University Of Groningen, Nijenborgh 4, 9747 Ag Groningen, The Netherlands., Christoffer; Dawson, Kenneth A.

    2014-11-01

    Nanomaterials challenge paradigms of in vitro testing because unlike molecular species, biomolecules in the dispersion medium modulate their interactions with cells. Exposing cells to nanoparticles known to cause cell death, we observed cytotoxicity suppression by increasing the amount of serum in the dispersion medium towards in vivo-relevant conditions.Nanomaterials challenge paradigms of in vitro testing because unlike molecular species, biomolecules in the dispersion medium modulate their interactions with cells. Exposing cells to nanoparticles known to cause cell death, we observed cytotoxicity suppression by increasing the amount of serum in the dispersion medium towards in vivo-relevant conditions. Electronic supplementary information (ESI) available: Experimental procedures; cell viability, proliferation and endocytosis levels of cultures grown in the relevant media; cellular uptake and physicochemical characterisation by DCS of silica nanoparticles; physicochemical characterisation by DLS of the amino-modified polystyrene nanoparticles used in the relevant biological media. See DOI: 10.1039/c4nr04970e

  10. Evaluation of the Cytotoxic Behavior of Fungal Extracellular Synthesized Ag Nanoparticles Using Confocal Laser Scanning Microscope

    PubMed Central

    Salaheldin, Taher A.; Husseiny, Sherif M.; Al-Enizi, Abdullah M.; Elzatahry, Ahmed; Cowley, Alan H.

    2016-01-01

    Silver nanoparticles have been synthesized by subjecting a reaction medium to a Fusarium oxysporum biomass at 28 °C for 96 h. The biosynthesized Ag nanoparticles were characterized on the basis of their anticipated peak at 405 nm using UV-Vis-NIR spectroscopy. Structural confirmation was evident from the characteristic X-ray diffraction (XRD) pattern, high-resolution transmission electron Microscopy (HRTEM) and the particle size analyzer. The Ag nanoparticles were of dimension 40 ± 5 nm and spherical in shape. The study mainly focused on using the confocal laser scanning microscope (CLSM) to examine the cytotoxic activities of fungal synthesized Ag nanoparticles on a human breast carcinoma cell line MCF7 cell, which featured remarkable vacuolation, thus indicating a potent cytotoxic activity. PMID:26950118

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

    SciTech Connect

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

    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

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

    PubMed

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

    2014-07-01

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

  13. Aluminum doping tunes band gap energy level as well as oxidative stress-mediated cytotoxicity of ZnO nanoparticles in MCF-7 cells

    PubMed Central

    Akhtar, Mohd Javed; Alhadlaq, Hisham A.; Alshamsan, Aws; Majeed Khan, M.A.; Ahamed, Maqusood

    2015-01-01

    We investigated whether Aluminum (Al) doping tunes band gap energy level as well as selective cytotoxicity of ZnO nanoparticles in human breast cancer cells (MCF-7). Pure and Al-doped ZnO nanoparticles were prepared by a simple sol-gel method. Characterization study confirmed the formation of single phase of AlxZn1-xO nanocrystals with the size range of 33–55 nm. Al-doping increased the band gap energy of ZnO nanoparticles (from 3.51 eV for pure to 3.87 eV for Al-doped ZnO). Al-doping also enhanced the cytotoxicity and oxidative stress response of ZnO nanoparticles in MCF-7 cells. The IC50 for undoped ZnO nanoparticles was 44 μg/ml while for the Al-doped ZnO counterparts was 31 μg/ml. Up-regulation of apoptotic genes (e.g. p53, bax/bcl2 ratio, caspase-3 & caspase-9) along with loss of mitochondrial membrane potential suggested that Al-doped ZnO nanoparticles induced apoptosis in MCF-7 cells through mitochondrial pathway. Importantly, Al-doping did not change the benign nature of ZnO nanoparticles towards normal cells suggesting that Al-doping improves the selective cytotoxicity of ZnO nanoparticles toward MCF-7 cells without affecting the normal cells. Our results indicated a novel approach through which the inherent selective cytotoxicity of ZnO nanoparticles against cancer cells can be further improved. PMID:26347142

  14. Aluminum doping tunes band gap energy level as well as oxidative stress-mediated cytotoxicity of ZnO nanoparticles in MCF-7 cells.

    PubMed

    Akhtar, Mohd Javed; Alhadlaq, Hisham A; Alshamsan, Aws; Majeed Khan, M A; Ahamed, Maqusood

    2015-09-08

    We investigated whether Aluminum (Al) doping tunes band gap energy level as well as selective cytotoxicity of ZnO nanoparticles in human breast cancer cells (MCF-7). Pure and Al-doped ZnO nanoparticles were prepared by a simple sol-gel method. Characterization study confirmed the formation of single phase of Al(x)Zn(1-x)O nanocrystals with the size range of 33-55 nm. Al-doping increased the band gap energy of ZnO nanoparticles (from 3.51 eV for pure to 3.87 eV for Al-doped ZnO). Al-doping also enhanced the cytotoxicity and oxidative stress response of ZnO nanoparticles in MCF-7 cells. The IC50 for undoped ZnO nanoparticles was 44 μg/ml while for the Al-doped ZnO counterparts was 31 μg/ml. Up-regulation of apoptotic genes (e.g. p53, bax/bcl2 ratio, caspase-3 &caspase-9) along with loss of mitochondrial membrane potential suggested that Al-doped ZnO nanoparticles induced apoptosis in MCF-7 cells through mitochondrial pathway. Importantly, Al-doping did not change the benign nature of ZnO nanoparticles towards normal cells suggesting that Al-doping improves the selective cytotoxicity of ZnO nanoparticles toward MCF-7 cells without affecting the normal cells. Our results indicated a novel approach through which the inherent selective cytotoxicity of ZnO nanoparticles against cancer cells can be further improved.

  15. Aluminum doping tunes band gap energy level as well as oxidative stress-mediated cytotoxicity of ZnO nanoparticles in MCF-7 cells

    NASA Astrophysics Data System (ADS)

    Akhtar, Mohd Javed; Alhadlaq, Hisham A.; Alshamsan, Aws; Majeed Khan, M. A.; Ahamed, Maqusood

    2015-09-01

    We investigated whether Aluminum (Al) doping tunes band gap energy level as well as selective cytotoxicity of ZnO nanoparticles in human breast cancer cells (MCF-7). Pure and Al-doped ZnO nanoparticles were prepared by a simple sol-gel method. Characterization study confirmed the formation of single phase of AlxZn1-xO nanocrystals with the size range of 33-55 nm. Al-doping increased the band gap energy of ZnO nanoparticles (from 3.51 eV for pure to 3.87 eV for Al-doped ZnO). Al-doping also enhanced the cytotoxicity and oxidative stress response of ZnO nanoparticles in MCF-7 cells. The IC50 for undoped ZnO nanoparticles was 44 μg/ml while for the Al-doped ZnO counterparts was 31 μg/ml. Up-regulation of apoptotic genes (e.g. p53, bax/bcl2 ratio, caspase-3 & caspase-9) along with loss of mitochondrial membrane potential suggested that Al-doped ZnO nanoparticles induced apoptosis in MCF-7 cells through mitochondrial pathway. Importantly, Al-doping did not change the benign nature of ZnO nanoparticles towards normal cells suggesting that Al-doping improves the selective cytotoxicity of ZnO nanoparticles toward MCF-7 cells without affecting the normal cells. Our results indicated a novel approach through which the inherent selective cytotoxicity of ZnO nanoparticles against cancer cells can be further improved.

  16. Probing cytotoxicity of nanoparticles and organic compounds using scanning proton microscopy, scanning electron microscopy and fluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Tong, Yongpeng; Li, Changming; Liang, Feng; Chen, Jianmin; Zhang, Hong; Liu, Guoqing; Sun, Huibin; Luong, John H. T.

    2008-12-01

    Scanning proton microscopy, scanning electron microscopy (SEM) and fluorescence microscopy have been used to probe the cytotoxicity effect of benzo[a]pyrene (BaP), ethidium bromide (EB) and nanoparticles (ZnO, Al 2O 3 and TiO 2) on a T lymphoblastic leukemia Jurkat cell line. The increased calcium ion (from CaCl 2) in the culture medium stimulated the accumulation of BaP and EB inside the cell, leading to cell death. ZnO, Al 2O 3 and TiO 2 nanoparticles, however, showed a protective effect against these two organic compounds. Such inorganic nanoparticles complexed with BaP or EB which became less toxic to the cell. Fe 2O 3 nanoparticles as an insoluble particle model scavenged by macrophage were investigated in rats. They were scavenged out of the lung tissue about 48 h after infection. This result suggest that some insoluble inorganic nanoparticles of PM (particulate matters) showed protective effects on organic toxins induced acute toxic effects as they can be scavenged by macrophage cells. Whereas, some inorganic ions such as calcium ion in PM may help environmental organic toxins to penetrate cell membrane and induce higher toxic effect.

  17. Biosynthesis of hematite nanoparticles and its cytotoxic effect on HepG2 cancer cells.

    PubMed

    Rajendran, Kumar; Karunagaran, Vithiya; Mahanty, Biswanath; Sen, Shampa

    2015-03-01

    Iron oxide nanoparticles were gaining significant importance in a variety of applications due to its paramagnetic properties and biocompatibility. Various chemical methods were employed for hematite nanoparticle synthesis which require special equipment or a complex production process. In this study, protein capped crystalline hexagonal hematite (α-Fe2O3) nanoparticles were synthesized by green approach using culture supernatant of a newly isolated bacterium, Bacillus cereus SVK1 at ambient conditions. The synthesized nanoparticles were characterized by electron microscopy, X-ray diffraction, UV-visible spectroscopy and Fourier transform infrared spectroscopic analysis. Nanoparticles were evaluated for its possible anticancer activity against HepG2 liver cancer cells by MTT assay. Hematite nanoparticles with an average diameter of 30.2 nm, exhibited a significant cytotoxicity toward HepG2 cells in a concentration-dependent manner (CTC50=704 ng/ml).

  18. Cytotoxic Induction and Photoacoustic Imaging of Breast Cancer Cells Using Astaxanthin-Reduced Gold Nanoparticles

    PubMed Central

    Bharathiraja, Subramaniyan; Manivasagan, Panchanathan; Quang Bui, Nhat; Oh, Yun-Ok; Lim, In Gweon; Park, Suhyun; Oh, Junghwan

    2016-01-01

    Astaxanthin, a kind of photosynthetic pigment, was employed for gold nanoparticle formation. Nanoparticles were characterized using Ulteraviolet-Visible (UV-Vis) spectroscopy, transmission electron microscopy, and X-ray diffraction, and the possible presence of astaxanthin functional groups were analyzed by Fourier transform infrared spectroscopy (FTIR). The cytotoxic effect of synthesized nanoparticles was evaluated against MDA-MB-231 (human breast cancer cells) using a tetrazolium-based assay, and synthesized nanoparticles exhibited dose-dependent toxicity. The morphology upon cell death was differentiated through fluorescent microscopy using different stains that predicted apoptosis. The synthesized nanoparticles were applied in ultrasound-coupled photoacoustic imaging to obtain good images of treated cells. Astaxanthin-reduced gold nanoparticle has the potential to act as a promising agent in the field of photo-based diagnosis and therapy. PMID:28335206

  19. Multi wall carbon nanotubes induce oxidative stress and cytotoxicity in human embryonic kidney (HEK293) cells.

    PubMed

    Reddy, Anreddy Rama Narsimha; Reddy, Yellu Narsimha; Krishna, Devarakonda Rama; Himabindu, Vurimindi

    2010-06-04

    The present study was aimed at evaluating the potential toxicity and the general mechanism involved in multi wall carbon nanotubes (MWCNT)-induced cytotoxicity using human embryonic kidney cell line (HEK293) cells. Two multi wall carbon nanotubes (coded as MWCNT1, size: 90-150nm and MWCNT2, size: 60-80nm) used in this study are MWCNT1 (produced by the electric arc method and size of the nanotubes was 90-150nm) and MWCNT2 (produced by the chemical vapor deposition method with size of 60-80nm). To elucidate the possible mechanisms of MWCNT induced cytotoxicity, cell viability, mitochondrial function (MTT assay), cell membrane damage (LDH assay), reduced glutathione (GSH), interleukin-8 (IL-8) and lipid peroxidation levels were quantitatively assessed under carbon nanotubes exposed (48h) conditions. Exposure of different sizes of two carbon nanotubes at dosage levels between 3 and 300mug/ml decreased cell viability in a concentration dependent manner. The IC(50) values (concentration of nanoparticles to induce 50% cell mortality) of two (MWCNT1, MWCNT2) nanoparticles were found as 42.10 and 36.95mug/ml. Exposure of MWCNT (10-100mug/ml) to HEK cells resulted in concentration dependent cell membrane damage (as indicated by the increased levels of LDH), increased production of IL-8, increased TBARS and decreased intracellular glutathione levels. The cytotoxicity and oxidative stress was significantly more in MWCNT2 exposed cells than MWCNT1. In summary, exposure of carbon nanotubes resulted in a concentration dependent cytotoxicity in cultured HEK293 cells that was associated with increased oxidative stress.

  20. 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 67μg/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.

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

    SciTech Connect

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

    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.

  2. The silver ions contribution into the cytotoxic activity of silver and silver halides nanoparticles

    NASA Astrophysics Data System (ADS)

    Klimov, A. I.; Zherebin, P. M.; Gusev, A. A.; Kudrinskiy, A. A.; Krutyakov, Y. A.

    2015-11-01

    The biocidal action of silver nanoparticles capped with sodium citrate and silver halides nanoparticles capped with non-ionic surfactant polyoxyethylene(20)sorbitan monooleate (Tween 80®) against yeast cells Saccharomyces cerevisiae was compared to the effect produced by silver nitrate and studied through the measurement of cell loss and kinetics of K+ efflux from the cells. The cytotoxicity of the obtained colloids was strongly correlated with silver ion content in the dispersions. The results clearly indicated that silver and silver halides nanoparticles destroyed yeast cells through the intermediate producing of silver ions either by dissolving of salts or by oxidation of silver.

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

    PubMed Central

    2014-01-01

    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. PMID:25242904

  4. 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.

  5. Caffeine augments Alprazolam induced cytotoxicity in human cell lines.

    PubMed

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

    2009-09-01

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

  6. Cytotoxicity of chitosan/streptokinase nanoparticles as a function of size: An artificial neural networks study.

    PubMed

    Baharifar, Hadi; Amani, Amir

    2016-01-01

    Predicting the size and toxicity of chitosan/streptokinase nanoparticles at various values of processing parameters was the aim of this study. For the first time, a comprehensive model could be developed to determine the cytotoxicity of the nanoparticles as a function of their size. Then, artificial neural networks were used for identifying main factors influencing self-assembly prepared nanoparticles size and cytotoxicity. Three variables included polymer concentration; pH and stirring time were used for a modeling study. A second modeling was performed to evaluate the influence of particles' size on toxicity. Experimentally data modeled using ANNs was validated against unseen data. The response surfaces generated from the software demonstrated that chitosan concentration is the dominant factor with a direct effect on size. Results also showed that the most important factor in determining the particles' toxicity is size--smaller particles showed more toxic effects, regardless of the effect of other input parameters. From the Clinical Editor: The understanding of toxicity of nanoparticles is of prime importance. In this article, the authors generated a model to visualize the relationship between nanoparticle size and its cellular toxicity, using chitosan/streptokinase nanoparticles. The data generated here would help the design of future nanoparticles of appropriate sizes for the application in the clinical setting.

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

    PubMed

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

    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 μg/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.

  8. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2011-07-01

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

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

    PubMed Central

    2011-01-01

    The evaluation of the toxicity of magnetic nanoparticles (MNPs) has attracted much attention in recent years. The current study aimed to investigate the cytotoxic effects of Fe3O4, oleic acid-coated Fe3O4 (OA-Fe3O4), and carbon-coated Fe (C-Fe) nanoparticles on human hepatoma BEL-7402 cells and the mechanisms. WST-1 assay demonstrated that the cytotoxicity of three types of MNPs was in a dose-dependent manner. G1 (Fe3O4 and OA-Fe3O4) phase and G2 (C-Fe) phase cell arrests and apoptosis induced by MNPs were detected by flow cytometry analysis. The increase in apoptosis was accompanied with the Bax over-expression, mitochondrial membrane potential decrease, and the release of cytochrome C from mitochondria into cytosol. Moreover, apoptosis was further confirmed by morphological and biochemical hallmarks, such as swollen mitochondria with lysing cristae and caspase-3 activation. Our results revealed that certain concentrations of the three types of MNPs affect BEL-7402 cells viability via cell arrest and inducing apoptosis, and the MNPs-induced apoptosis is mediated through the mitochondrial-dependent pathway. The influence potency of MNPs observed in all experiments would be: C-Fe > Fe3O4 > OA-Fe3O4. PMID:21801413

  11. Different hydroxyapatite magnetic nanoparticles for medical imaging: Its effects on hemostatic, hemolytic activity and cellular cytotoxicity.

    PubMed

    Laranjeira, Marta S; Moço, Ana; Ferreira, Jorge; Coimbra, Susana; Costa, Elísio; Santos-Silva, Alice; Ferreira, Paulo J; Monteiro, Fernando J

    2016-10-01

    Magnetic nanoparticles (MNPs) should be highly biocompatible, stable and safely eliminated from the body, and can therefore be successfully used in modern medicine. Synthetic hydroxyapatite (HAP) has well established biocompatible and non-inflammatory properties, as well as a highly stable and flexible structure that allows for an easy incorporation of magnetic ions. This study characterized and compared the in vitro cytotoxicity and hemocompatibility of hydroxyapatite MNPs doped with different ions (Gd(3+/)Fe(2+)/Fe(3+)/Co(2+)). HAP doped with 10% of Gd and Fe(III) presented the highest magnetic moments. Our results showed that Gd doped HAP nanoparticles are non-cytotoxic, hemocompatible, non-hemolytic and non-thrombogenic, in contrast with Fe(III) doped HAP that can be considered thrombogenic. For these reasons we propose that, Gd doped HAP nanoparticles have the most potential for application as a MRI contrast agents. However, use of Fe (III) doped HAP as MRI contrast agents should be further investigated.

  12. Fluorescent chitosan functionalized magnetic polymeric nanoparticles: Cytotoxicity and in vitro evaluation of cellular uptake.

    PubMed

    Kaewsaneha, Chariya; Jangpatarapongsa, Kulachart; Tangchaikeeree, Tienrat; Polpanich, Duangporn; Tangboriboonrat, Pramuan

    2014-11-01

    Nanoparticles possessing magnetic and fluorescent properties were fabricated by the covalent attachment of fluorescein isothiocyanate onto magnetic polymeric nanoparticles functionalized by chitosan. The synthesized magnetic polymeric nanoparticles-chitosan/fluorescein isothiocyanate were successfully used for labeling the living organ and blood-related cancer cells, i.e., HeLa, Hep G2, and K562 cells. The cytotoxicity test of nanoparticles at various incubation times indicated the high cell viability (>90%) without morphological change. The confocal microscopy revealed that they could pass through cell membrane within 2 h for K562 cells and 3 h for HeLa and Hep G2 cells and then confine inside cytoplasm of all types of tested cells for at least 24 h. Therefore, the synthesized magnetic polymeric nanoparticles-chitosan/fluorescein isothiocyanate would potentially be used as cell tracking in theranostic applications.

  13. Lack of in Vivo Antibody Dependent Cellular Cytotoxicity with Antibody Containing Gold Nanoparticles

    PubMed Central

    2016-01-01

    Antibody-dependent cellular cytotoxicity (ADCC) is a cytolytic mechanism that can elicit in vivo antitumor effects and can play a significant role in the efficacy of antibody treatments for cancer. Here, we prepared cetuximab, panitumumab, and rituximab containing gold nanoparticles and investigated their ability to produce an ADCC effect in vivo. Cetuximab treatment of EGFR-expressing H1975 tumor xenografts showed significant tumor regression due to the ADCC activity of the antibody in vivo, while the control antibody, panitumumab, did not. However, all three antibody containing nanoparticles are not able to suppress tumor growth in the same in vivo mouse model. The antibody containing nanoparticles localized in the tumors and did not suppress the immune function of the animals, so the lack of tumor growth suppression of the cetuximab containing nanoparticle suggests that immobilizing antibodies onto a nanoparticle significantly decreases the ability of the antibody to promote an ADCC response. PMID:25879583

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

    PubMed Central

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

    2014-01-01

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

  15. Cytotoxic effects of ZnO nanoparticles on mouse testicular cells

    PubMed Central

    Han, Zhe; Yan, Qi; Ge, Wei; Liu, Zhi-Guo; Gurunathan, Sangiliyandi; De Felici, Massimo; Shen, Wei; Zhang, Xi-Feng

    2016-01-01

    Background Nanoscience and nanotechnology are developing rapidly, and the applications of nanoparticles (NPs) have been found in several fields. At present, NPs are widely used in traditional consumer and industrial products, however, the properties and safety of NPs are still unclear and there are concerns about their potential environmental and health effects. The aim of the present study was to investigate the potential toxicity of ZnO NPs on testicular cells using both in vitro and in vivo systems in a mouse experimental model. Methods ZnO NPs with a crystalline size of 70 nm were characterized with various analytical techniques, including ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and atomic force microscopy. The cytotoxicity of the ZnO NPs was examined in vitro on Leydig cell and Sertoli cell lines, and in vivo on the testes of CD1 mice injected with single doses of ZnO NPs. Results ZnO NPs were internalized by Leydig cells and Sertoli cells, and this resulted in cytotoxicity in a time- and dose-dependent manner through the induction of apoptosis. Apoptosis likely occurred as a consequence of DNA damage (detected as γ-H2AX and RAD51 foci) caused by increase in reactive oxygen species associated with loss of mitochondrial membrane potential. In addition, injection of ZnO NPs in male mice caused structural alterations in the seminiferous epithelium and sperm abnormalities. Conclusion These results demonstrate that ZnO NPs have the potential to induce apoptosis in testicular cells likely through DNA damage caused by reactive oxygen species, with possible adverse consequences for spermatogenesis and therefore, male fertility. This suggests that evaluating the potential impacts of engineered NPs is essential prior to their mass production, to address both the environmental and human health concerns and also to develop sustainable and safer nanomaterials. PMID:27785022

  16. 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.

  17. Size, Loading Efficiency, and Cytotoxicity of Albumin-Loaded Chitosan Nanoparticles: An Artificial Neural Networks Study.

    PubMed

    Baharifar, Hadi; Amani, Amir

    2017-01-01

    When designing nanoparticles for drug delivery, many variables such as size, loading efficiency, and cytotoxicity should be considered. Usually, smaller particles are preferred in drug delivery because of longer blood circulation time and their ability to escape from immune system, whereas smaller nanoparticles often show increased toxicity. Determination of parameters which affect size of particles and factors such as loading efficiency and cytotoxicity could be very helpful in designing drug delivery systems. In this work, albumin (as a protein drug model)-loaded chitosan nanoparticles were prepared by polyelectrolyte complexation method. Simultaneously, effects of 4 independent variables including chitosan and albumin concentrations, pH, and reaction time were determined on 3 dependent variables (i.e., size, loading efficiency, and cytotoxicity) by artificial neural networks. Results showed that concentrations of initial materials are the most important factors which may affect the dependent variables. A drop in the concentrations decreases the size directly, but they simultaneously decrease loading efficiency and increase cytotoxicity. Therefore, an optimization of the independent variables is required to obtain the most useful preparation.

  18. Tamoxifen-loaded poly(L-lactide) nanoparticles: Development, characterization and in vitro evaluation of cytotoxicity.

    PubMed

    Altmeyer, Clescila; Karam, Thaysa Ksiaskiewcz; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2016-03-01

    In this study, poly(L-lactide) (PLA) nanoparticles containing Tamoxifen (Tmx) were developed using an emulsion/solvent evaporation method, observing the influence of surfactants and their concentrations on mean particle size and drug entrapment. Nanoparticles were characterized in terms of size, morphology, polydispersity, interaction drug-polymer and in vitro drug release profile. Cytotoxicity over erythrocytes and tumor cells was assessed. The optimized formulation employed as surfactant 1% polyvinyl alcohol. Mean particle size was 155±4 nm (n=3) and Tmx encapsulation efficiency was 85±8% (n=3). The in vitro release profile revealed a biphasic release pattern diffusion-controlled with approximately 24% of drug released in 24 h followed by a sustained release up to 120 h (30% of Tmx released). PLA nanoparticles containing Tmx presented a very low index of hemolysis (less than 10%), in contrast to free Tmx that was significantly hemolytic. Tmx-loaded PLA nanoparticles showed IC50 value 2-fold higher than free Tmx, but considering the prolonged Tmx release from nanoparticles, cytotoxicity on tumor cells was maintained after nanoencapsulation. Thus, PLA nanoparticles are promising carriers for controlled delivery of Tmx with potential application in cancer treatment.

  19. Analysis of the Cytotoxicity of Carbon-Based Nanoparticles, Diamond and Graphite, in Human Glioblastoma and Hepatoma Cell Lines

    PubMed Central

    Wierzbicki, Mateusz; Jaworski, Sławomir; Kutwin, Marta; Sawosz, Ewa; Chwalibog, André; Pijanowska, Dorota Genowefa; Pluta, Krzysztof Dariusz

    2015-01-01

    Nanoparticles have attracted a great deal of attention as carriers for drug delivery to cancer cells. However, reports on their potential cytotoxicity raise questions of their safety and this matter needs attentive consideration. In this paper, for the first time, the cytotoxic effects of two carbon based nanoparticles, diamond and graphite, on glioblastoma and hepatoma cells were compared. First, we confirmed previous results that diamond nanoparticles are practically nontoxic. Second, graphite nanoparticles exhibited a negative impact on glioblastoma, but not on hepatoma cells. The studied carbon nanoparticles could be a potentially useful tool for therapeutics delivery to the brain tissue with minimal side effects on the hepatocytes. Furthermore, we showed the influence of the nanoparticles on the stable, fluorescently labeled tumor cell lines and concluded that the labeled cells are suitable for drug cytotoxicity tests. PMID:25816103

  20. Analysis of the cytotoxicity of carbon-based nanoparticles, diamond and graphite, in human glioblastoma and hepatoma cell lines.

    PubMed

    Zakrzewska, Karolina Ewa; Samluk, Anna; Wierzbicki, Mateusz; Jaworski, Sławomir; Kutwin, Marta; Sawosz, Ewa; Chwalibog, André; Pijanowska, Dorota Genowefa; Pluta, Krzysztof Dariusz

    2015-01-01

    Nanoparticles have attracted a great deal of attention as carriers for drug delivery to cancer cells. However, reports on their potential cytotoxicity raise questions of their safety and this matter needs attentive consideration. In this paper, for the first time, the cytotoxic effects of two carbon based nanoparticles, diamond and graphite, on glioblastoma and hepatoma cells were compared. First, we confirmed previous results that diamond nanoparticles are practically nontoxic. Second, graphite nanoparticles exhibited a negative impact on glioblastoma, but not on hepatoma cells. The studied carbon nanoparticles could be a potentially useful tool for therapeutics delivery to the brain tissue with minimal side effects on the hepatocytes. Furthermore, we showed the influence of the nanoparticles on the stable, fluorescently labeled tumor cell lines and concluded that the labeled cells are suitable for drug cytotoxicity tests.

  1. Cytotoxicity and physicochemical characterization of iron–manganese-doped sulfated zirconia nanoparticles

    PubMed Central

    Al-Fahdawi, Mohamed Qasim; Rasedee, Abdullah; Al-Qubaisi, Mothanna Sadiq; Alhassan, Fatah H; Rosli, Rozita; El Zowalaty, Mohamed Ezzat; Naadja, Seïf-Eddine; Webster, Thomas J; Taufiq-Yap, Yun Hin

    2015-01-01

    Iron–manganese-doped sulfated zirconia nanoparticles with both Lewis and Brønsted acidic sites were prepared by a hydrothermal impregnation method followed by calcination at 650°C for 5 hours, and their cytotoxicity properties against cancer cell lines were determined. The characterization was carried out using X-ray diffraction, thermogravimetric analysis, Fourier transform infrared spectroscopy, Brauner–Emmett–Teller (BET) surface area measurements, X-ray fluorescence, X-ray photoelectron spectroscopy, zeta size potential, and transmission electron microscopy (TEM). The cytotoxicity of iron–manganese-doped sulfated zirconia nanoparticles was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays against three human cancer cell lines (breast cancer MDA-MB231 cells, colon carcinoma HT29 cells, and hepatocellular carcinoma HepG2 cells) and two normal human cell lines (normal hepatocyte Chang cells and normal human umbilical vein endothelial cells [HUVECs]). The results suggest for the first time that iron–manganese-doped sulfated zirconia nanoparticles are cytotoxic to MDA-MB231 and HepG2 cancer cells but have less toxicity to HT29 and normal cells at concentrations from 7.8 μg/mL to 500 μg/mL. The morphology of the treated cells was also studied, and the results supported those from the cytotoxicity study in that the nanoparticle-treated HepG2 and MDA-MB231 cells had more dramatic changes in cell morphology than the HT29 cells. In this manner, this study provides the first evidence that iron–manganese-doped sulfated zirconia nanoparticles should be further studied for a wide range of cancer applications without detrimental effects on healthy cell functions. PMID:26425082

  2. Comparison of cytotoxic and inflammatory responses of photoluminescent silicon nanoparticles with silicon micron-sized particles in RAW 264.7 macrophages.

    PubMed

    Choi, Jonghoon; Zhang, Qin; Reipa, Vytas; Wang, Nam Sun; Stratmeyer, Melvin E; Hitchins, Victoria M; Goering, Peter L

    2009-01-01

    Photoluminescent silicon nanoparticles have a bright and stable fluorescence and are promising candidates for bio-imaging, cell staining and drug delivery. With increasing development of nanotechnology applications for biomedicine, an understanding of the potential toxicity of nanoparticles is needed to assess safety concerns for clinical applications. The objective of this study was to compare biological responses of silicon nanoparticles (SNs, 3 nm diameter) with silicon microparticles (SMs, approximately 100-3000 nm diameter) in cultured murine macrophages (RAW 264.7) using standard protocols for assessing cytotoxicity/cell viability and inflammatory responses developed for micron-sized particles. SNs and SMs were exposed to macrophages with and without addition of endotoxin lipopolysaccharide (LPS), a positive inducer of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and nitric oxide (NO). Cytotoxicity was assayed using the dye exclusion and MTT assays. Cell supernatants were assayed for production TNF-alpha, IL-6 and NO. SNs at concentrations < or = 20 microg ml(-1) exhibited no cytotoxicity or inflammatory responses; however, SNs and SMs >20 and 200 microg ml(-1), respectively, increased cytotoxicity compared with controls. SMs induced concentration-related increases in TNF-alpha and IL-6 production; in contrast, the production of these cytokines was shown to decrease with increasing concentrations of SNs. NO production was not induced by SNs or SMs alone. Fluorescence microscopy demonstrated that SNs were associated with the macrophages, either internalized or attached to cell membranes. In conclusion, evaluating differences in biological responses for nanoparticles compared with microparticles of the same material may help improve tests to assess biological responses of nanoparticles that may be used in biomedical applications.

  3. Cytotoxicity of various types of gold-mesoporous silica nanoparticles in human breast cancer cells.

    PubMed

    Liu, Guomu; Li, Qiongshu; Ni, Weihua; Zhang, Nannan; Zheng, Xiao; Wang, Yingshuai; Shao, Dan; Tai, Guixiang

    2015-01-01

    Recently, gold nanoparticles (AuNPs) have shown promising biological applications due to their unique electronic and optical properties. However, the potential toxicity of AuNPs remains a major hurdle that impedes their use in clinical settings. Mesoporous silica is very suitable for the use as a coating material for AuNPs and might not only reduce the cytotoxicity of cetyltrimethylammonium bromide-coated AuNPs but might also facilitate the loading and delivery of drugs. Herein, three types of rod-like gold-mesoporous silica nanoparticles (termed bare AuNPs, core-shell Au@mSiO2NPs, and Janus Au@mSiO2NPs) were specially designed, and the effects of these AuNPs on cellular uptake, toxic behavior, and mechanism were then systematically studied. Our results indicate that bare AuNPs exerted higher toxicity than the Au@mSiO2NPs and that Janus Au@mSiO2NPs exhibited the lowest toxicity in human breast cancer MCF-7 cells, consistent with the endocytosis capacity of the nanoparticles, which followed the order, bare AuNPs > core-shell Au@mSiO2NPs > Janus Au@mSiO2NPs. More importantly, the AuNPs-induced apoptosis of MCF-7 cells exhibited features that were characteristic of intracellular reactive oxygen species (ROS) generation, activation of c-Jun-N-terminal kinase (JNK) phosphorylation, an enhanced Bax-to-Bcl-2 ratio, and loss of the mitochondrial membrane potential. Simultaneously, cytochrome c was released from mitochondria, and the caspase-3/9 cascade was activated. Moreover, both ROS scavenger (N-acetylcysteine) and JNK inhibitor (SP600125) partly blocked the induction of apoptosis in all AuNPs-treated cells. Taken together, these findings suggest that all AuNPs induce apoptosis through the ROS-/JNK-mediated mitochondrial pathway. Thus, Janus Au@mSiO2NPs exhibit the potential for applications in biomedicine, thus aiding the clinical translation of AuNPs.

  4. Cytotoxicity and colloidal behavior of polystyrene latex nanoparticles toward filamentous fungi in isotonic solutions.

    PubMed

    Nomura, Toshiyuki; Tani, Shuji; Yamamoto, Makoto; Nakagawa, Takumi; Toyoda, Shunsuke; Fujisawa, Eri; Yasui, Akiko; Konishi, Yasuhiro

    2016-04-01

    The effects of surface physicochemical properties of functionalized polystyrene latex (PSL) nanoparticles (NPs) and model filamentous fungi Aspergillus oryzae and Aspergillus nidulans cultivated in different environment (aqueous and atmospheric environment) on the colloidal behavior and cytotoxicity were investigated in different isotonic solutions (154 mM NaCl and 292 mM sucrose). When the liquid cultivated fungal cells were exposed to positively charged PSL NPs in 154 mM NaCl solution, the NPs were taken into A. oryzae, but not A. nidulans. Atomic force microscopy revealed that the uptake of NPs was more readily through the cell wall of A. oryzae because of its relatively softer cell wall compared with A. nidulans. In contrast, the positively charged PSL NPs entirely covered the liquid cultivated fungal cell surfaces and induced cell death in 292 mM sucrose solution because of the stronger electrostatic attractive force between the cells and NPs compared with in 154 mM NaCl. When the agar cultivated fungal cells were exposed to the positively charged PSL NPs, both fungal cells did not take the NPs inside the cells. Contact angle measurement revealed that the hydrophobin on the agar cultivated cell surfaces inhibited the uptake of NPs because of its relatively more hydrophobic cell surface compared with the liquid cultivated cells.

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

    PubMed Central

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

    2013-01-01

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

  6. 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.

  7. Comparison of cytotoxicity and genotoxicity effects of silver nanoparticles on human cervix and breast cancer cell lines.

    PubMed

    Juarez-Moreno, K; Gonzalez, E B; Girón-Vazquez, N; Chávez-Santoscoy, R A; Mota-Morales, J D; Perez-Mozqueda, L L; Garcia-Garcia, M R; Pestryakov, A; Bogdanchikova, N

    2016-11-04

    The wide application of silver nanoparticles (AgNPs) has pointed out the need to evaluate their potential risk and toxic effects on human health. Herein, the cytotoxic effects of Argovit™ AgNPs were evaluated on eight cancer cell lines. Further cytotoxic studies were performed in gynecological cancer cell lines from cervical (HeLa) and breast (MDA-MB-231 and MCF7) cancer. In both cases, the half maximal inhibitory concentration (IC50) of AgNPs produced the formation of reactive oxygen species (ROS) after 24 h of incubation, but it was not statistically significant compared with untreated cells. However, HeLa, MDA-MB-231, and MCF7 cells treated with the maximal IC of AgNPs induced the formation of ROS either at 12 or 24 h of incubation. Genotoxicity achieved by comet assay in HeLa, MDA-MB-231, and MCF7 cells revealed that exposure to IC50 of AgNPs does not induced noticeable DNA damage in the cells. However, the IC of AgNPs provoked severe DNA damage after 12 and 24 h of exposure. We conclude that, Argovit (polyvinylpyrrolidone-coated AgNPs) induce a cytotoxic effect in a time and dose-dependent manner in all the eight cancer cell lines tested. Nevertheless, the genotoxic effect is mainly restricted by the concentration effect. The results contribute to explore new therapeutic applications of AgNPs for malignances in murine models and to study in deep the cytotoxic and genotoxic effects of AgNPs in healthy cells at the surrounding tissue of the neoplasia.

  8. 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 Brønsted 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 μg/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 Brønsted acidic sites should be further studied for a wide range of anticancer and antibacterial applications. PMID:25632233

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

    NASA Astrophysics Data System (ADS)

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

    2012-01-01

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

  10. Synthesis and cytotoxicity study of magnesium ferrite-gold core-shell nanoparticles.

    PubMed

    Nonkumwong, Jeeranan; Pakawanit, Phakkhananan; Wipatanawin, Angkana; Jantaratana, Pongsakorn; Ananta, Supon; Srisombat, Laongnuan

    2016-04-01

    In this work, the core-magnesium ferrite (MgFe2O4) nanoparticles were prepared by hydrothermal technique. Completed gold (Au) shell coating on the surfaces of MgFe2O4 nanoparticles was obtained by varying core/shell ratios via a reduction method. Phase identification, morphological evolution, optical properties, magnetic properties and cytotoxicity to mammalian cells of these MgFe2O4 core coated with Au nanoparticles were examined by using a combination of X-ray diffraction, scanning electron microscopy, transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy, UV-visible spectroscopy (UV-vis), vibrating sample magnetometry and resazurin microplate assay techniques. In general, TEM images revealed different sizes of the core-shell nanoparticles generated from various core/shell ratios and confirmed the completed Au shell coating on MgFe2O4 core nanoparticles via suitable core/shell ratio with particle size less than 100 nm. The core-shell nanoparticle size and the quality of coating influence the optical properties of the products. The UV-vis spectra of complete coated MgFe2O4-Au core-shell nanoparticles exhibit the absorption bands in the near-Infrared (NIR) region indicating high potential for therapeutic applications. Based on the magnetic property measurement, it was found that the obtained MgFe2O4-Au core-shell nanoparticles still exhibit superparamagnetism with lower saturation magnetization value, compared with MgFe2O4 core. Both of MgFe2O4 and MgFe2O4-Au core-shell also showed in vitro non-cytotoxicity to mouse areola fibroblast (L-929) cell line.

  11. Size-dependent cytotoxicity of yttrium oxide nanoparticles on primary osteoblasts in vitro

    NASA Astrophysics Data System (ADS)

    Zhou, Guoqiang; Li, Yunfei; Ma, Yanyan; Liu, Zhu; Cao, Lili; Wang, Da; Liu, Sudan; Xu, Wenshi; Wang, Wenying

    2016-05-01

    Yttrium oxide nanoparticles are an excellent host material for the rare earth metals and have high luminescence efficiency providing a potential application in photodynamic therapy and biological imaging. In this study, the effects of yttrium oxide nanoparticles with four different sizes were investigated using primary osteoblasts in vitro. The results demonstrated that the cytotoxicity generated by yttrium oxide nanoparticles depended on the particle size, and smaller particles possessed higher toxicological effects. For the purpose to elucidate the relationship between reactive oxygen species generation and cell damage, cytomembrane integrity, intracellular reactive oxygen species level, mitochondrial membrane potential, cell apoptosis rate, and activity of caspase-3 in cells were then measured. Increased reactive oxygen species level was also observed in a size-dependent way. Thus, our data demonstrated that exposure to yttrium oxide nanoparticles resulted in a size-dependent cytotoxicity in cultured primary osteoblasts, and reactive oxygen species generation should be one possible damage pathway for the toxicological effects produced by yttrium oxide particles. The results may provide useful information for more rational applications of yttrium oxide nanoparticles in the future.

  12. Evaluation of cytotoxicity, immune compatibility and antibacterial activity of biogenic silver nanoparticles.

    PubMed

    Składanowski, M; Golinska, P; Rudnicka, K; Dahm, H; Rai, M

    2016-12-01

    The study was focused on assessment of antibacterial activity, cytotoxicity and immune compatibility of biogenic silver nanoparticles (AgNPs) synthesized from Streptomyces sp. NH28 strain. Nanoparticles were biosynthesized and characterized by UV-Vis spectroscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, nanoparticle tracking analysis system and zeta potential. Antibacterial activity was tested against Gram-positive and Gram-negative bacteria; minimal inhibitory concentration was recorded. Cytotoxicity was estimated using L929 mouse fibroblasts via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Biocompatibility of AgNPs was performed using THP1-XBlue™ cells. Biogenic AgNPs presented high antibacterial activity against all tested bacteria. Minimum inhibitory concentration of AgNPs against bacterial cells was found to be in range of 1.25-10 μg/mL. Silver nanoparticles did not show any harmful interaction to mouse fibroblast cell line, and no activation of nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) cells was observed at concentration below 10 µg/mL. The half-maximal inhibitory concentration (IC50) value was established at 64.5 μg/mL. Biological synthesis of silver can be used as an effective system for formation of metal nanoparticles. Biosynthesized AgNPs can be used as an antibacterial agent, which can be safe for eukaryotic cells.

  13. A systematic study of antibacterial silver nanoparticles: efficiency, enhanced permeability, and cytotoxic effects

    NASA Astrophysics Data System (ADS)

    Azócar, Manuel I.; Tamayo, Laura; Vejar, Nelson; Gómez, Grace; Zhou, Xiangrong; Thompsom, George; Cerda, Enrique; Kogan, Marcelo J.; Salas, Edison; Paez, Maritza A.

    2014-09-01

    We report here a systematic study of the antibacterial behavior of silver nanoparticles coated with fatty acids (oleic: AgNP-O, linoleic: AgNP-L, and palmitic acids: AgNP-P) in water. We have found remarkable differences in their capability to penetrate bacteria cell over a broader range of particle size of 4-96 nm compared to previously reported work, and a variable toxicity depending on the particles size. Our results indicate that silver nanoparticles stabilized with oleic acid showed clear advantages in antibacterial activity, penetration inside the bacteria cells, cytotoxicity, time effectiveness, efficiency, and stability against light.

  14. Peptide-Induced Antiviral Protection by Cytotoxic T Cells

    NASA Astrophysics Data System (ADS)

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

    1991-02-01

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

  15. In vitro cytotoxicity assays of solid lipid nanoparticles in epithelial and dermal cells

    NASA Astrophysics Data System (ADS)

    Ridolfi, D. M.; Marcato, P. D.; Machado, D.; Silva, R. A.; Justo, G. Z.; Durán, N.

    2011-07-01

    In recent years, the interest in nanostructured systems to drug delivery has increased because they offer several advantages over conventional dosage forms. Solid Lipid Nanoparticles (SLN) have been highlighted among these systems because they have advantages such as high physical stability, protection against drug degradation and ease of scale-up and manufacturing, without using organic solvent. The aim of this work was to evaluate the potential of SLN, by in vitro cytotoxicity assays, for dermal drug delivery. SLN of three different lipids were prepared by hot high pressure homogenization and the cytotoxicity was assessed by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test in mouse 3T3 fibroblasts and human HaCaT keratinocytes. SLN showed no cytotoxic potential suggesting a great potential for dermal application.

  16. Cellular uptake and cytotoxicity of positively charged chitosan gold nanoparticles in human lung adenocarcinoma cells

    NASA Astrophysics Data System (ADS)

    Choi, Seon Young; Jang, Soo Hwa; Park, Jin; Jeong, Saeromi; Park, Jin Ho; Ock, Kwang Su; Lee, Kangtaek; Yang, Sung Ik; Joo, Sang-Woo; Ryu, Pan Dong; Lee, So Yeong

    2012-12-01

    Cellular uptake, cytotoxicity, and mechanisms of cytotoxicity of the positively charged Au nanoparticles (NPs) were examined in A549 cells, which are one of the most characterized pulmonary cellular systems. Positively charged Au NPs were prepared by chemical reduction using chitosan. The dimension and surface charge of Au NPs were examined by transmission electron microscopy (TEM), dynamic light scattering, and zeta potential measurements. The uptake of Au NPs into A549 cells was also monitored using TEM and dark-field microscopy (DFM) and z-stack confocal microRaman spectroscopy. DFM live cell imaging was also performed to monitor the entry of chitosan Au NPs in real time. The cytotoxic assay, using both methylthiazol tetrazolium and lactate dehydrogenase assays revealed that positively charged Au NPs decreased cell viability. Flow cytometry, DNA fragmentation, real-time PCR, and western blot analysis suggest that positively charged chitosan Au NPs provoke cell damage through both apoptotic and necrotic pathways.

  17. Polymer nanoparticles for cross-presentation of exogenous antigens and enhanced cytotoxic T-lymphocyte immune response

    PubMed Central

    Song, Chanyoung; Noh, Young-Woock; Lim, Yong Taik

    2016-01-01

    Effective induction of an antigen-specific cytotoxic T lymphocyte (CTL) immune response is one of the key goals of cancer immunotherapy. We report the design and fabrication of polyethylenimine (PEI)-coated polymer nanoparticles (NPs) as efficient antigen-delivery carriers that can induce antigen cross-presentation and a strong CTL response. After synthesis of poly(d,l-lactide-co-glycolide) (PLGA) NPs containing ovalbumin (OVA) by the double-emulsion solvent-evaporation method, cationic-charged PLGA NPs were generated by coating them with PEI. In a methyl tetrazolium salt assay, no discernible cytotoxic effect of PEI-coated PLGA (OVA) NPs was observed. The capacity and mechanism of PEI-coated PLGA (OVA) NPs for antigen delivery and cross-presentation on dendritic cells (DCs) were determined by fluorescence microscopy and flow cytometry. PEI-coated PLGA (OVA) NPs were internalized efficiently via phagocytosis or macropinocytosis in DCs and induced efficient cross-presentation of the antigen on MHC class I molecules via both endosome escape and a lysosomal processing mechanism. The DCs treated with PEI-coated PLGA (OVA) NPs induced a release of IL-2 cytokine from OVA-specific CD8-OVA1.3 T cells more efficiently than DCs treated with PLGA (OVA) NPs. Therefore, the PEI-coated PLGA (OVA) NPs can induce antigen cross-presentation and are expected to be used for induction of a strong CTL immune response and for efficient anticancer immunotherapy. PMID:27540289

  18. Characterization of the effector cells in Con A-induced cytotoxicity against HEp 2 tumour targets.

    PubMed

    Pócsik, E; González-Cabello, R; Benedek, K; Perl, A; Láng, I; Gergely, P

    1983-01-01

    Con A-induced cytotoxic activity of human lymphocyte subpopulations obtained by cell fractionation procedures was studied in a test system using human epipharynx carcinoma cells (HEp 2) as targets. Only T lymphocytes were cytotoxic, non-T cells exerted no cytotoxic activity, but enhanced the adherence of the tumour cells. Tnon-G lymphocytes (Fc-receptor negative T cells) were more active than TG cells (Fc-receptor-positive T cells) in mediating the Con A-induced cytotoxic reaction.

  19. Cytotoxicity and genotoxicity of silver nanoparticles in human cells.

    PubMed

    AshaRani, P V; Low Kah Mun, Grace; Hande, Manoor Prakash; Valiyaveettil, Suresh

    2009-02-24

    Silver nanoparticles (Ag-np) are being used increasingly in wound dressings, catheters, and various household products due to their antimicrobial activity. The toxicity of starch-coated silver nanoparticles was studied using normal human lung fibroblast cells (IMR-90) and human glioblastoma cells (U251). The toxicity was evaluated using changes in cell morphology, cell viability, metabolic activity, and oxidative stress. Ag-np reduced ATP content of the cell caused damage to mitochondria and increased production of reactive oxygen species (ROS) in a dose-dependent manner. DNA damage, as measured by single cell gel electrophoresis (SCGE) and cytokinesis blocked micronucleus assay (CBMN), was also dose-dependent and more prominent in the cancer cells. The nanoparticle treatment caused cell cycle arrest in G(2)/M phase possibly due to repair of damaged DNA. Annexin-V propidium iodide (PI) staining showed no massive apoptosis or necrosis. The transmission electron microscopic (TEM) analysis indicated the presence of Ag-np inside the mitochondria and nucleus, implicating their direct involvement in the mitochondrial toxicity and DNA damage. A possible mechanism of toxicity is proposed which involves disruption of the mitochondrial respiratory chain by Ag-np leading to production of ROS and interruption of ATP synthesis, which in turn cause DNA damage. It is anticipated that DNA damage is augmented by deposition, followed by interactions of Ag-np to the DNA leading to cell cycle arrest in the G(2)/M phase. The higher sensitivity of U251 cells and their arrest in G(2)/M phase could be explored further for evaluating the potential use of Ag-np in cancer therapy.

  20. Cytotoxicity of Organic Surface Coating Agents Used for Nanoparticles Synthesis and Stability

    PubMed Central

    Zhang, Ying; Newton, Brandon; Lewis, Eybriunna; Fu, Peter P.; Kafoury, Ramzi; Ray, Paresh C.; Yu, Hongtao

    2015-01-01

    Impact on health by nanomaterials has become a public concern with the great advances of nanomaterials for various applications. Surface coating agents are an integral part of nanoparticles, but not enough attention has been paid during toxicity tests of nanoparticles. As a result, there are inconsistent toxicity results for certain nanomaterials. In this study, we explore the cytotoxicity of eleven commonly used surface coating agents in two cell lines, human epidermal keratinocyte (HaCaT) and lung fibroblast (CRL-1490) cells, at surface coating agent concentrations of 3, 10, 30, and 100 μM. Two exposure time points, 2 h and 24 h, were employed for the study. Six of the eleven surface coating agents are cytotoxic, especially those surfactants with long aliphatic chains, both cationic (cetyltrimethylammonium bromide, oleylamine, tetraoctylammonium bromide, and hexadecylamine) and anionic (sodium dodecylsulfate). In addition, exposure time and the use of different cell lines also affect the cytotoxicity results. Therefore, factors such as cell lines used and exposure times must be considered when conducting toxicity tests or comparing cytotoxicity results. PMID:25746383

  1. Comparative study of cytotoxicity of ferromagnetic nanoparticles and magnetitecontaining polyelectrolyte microcapsules

    NASA Astrophysics Data System (ADS)

    Minaeva, O. V.; Brodovskaya, E. P.; Pyataev, M. A.; Gerasimov, M. V.; Zharkov, M. N.; Yurlov, I. A.; Kulikov, O. A.; Kotlyarov, A. A.; Balykova, L. A.; Kokorev, A. V.; Zaborovskiy, A. V.; Pyataev, N. A.; Sukhorukov, G. B.

    2017-01-01

    The cytotoxicity of magnetite nanoparticles (MNP) stabilized with citrate acidand polyelectrolyte multilayer microcapsules containing these particles in the shell is analyzed. Microcapsules were prepared by co-precipitation of iron (II) and (III) chlorides. Polyelectrolyte microcapsules synthesized by the layer-by-layer method from biodegradable polymers polyarginine and dextran sulfate. Cytotoxicity of the synthesized objects was studied on the L929 cells culture and human leucocytes. It was also investigated the phagocytic activity of leukocytes for the MNP and magnetite containing polyelectrolyte microcapsules (MCPM). A set of tests (MTT assay, neutral red uptake assay, lactate dehydrogenase release assay) was used to study the cytotoxicity in vitro. All the tests have shown that the magnetic nanoparticles have a greater cytotoxicity in comparison with microcapsules containing an equivalent amount of magnetite. In contrast to the mouse fibroblast culture, human leukocytes were more resistant to the toxic effects of magnetite. At the concentrations used in our studies no significant reduction in the viability of leukocytes has been registered. Both MNP and MCPM undergo phagocytosis, however, the phagocytic activity of leukocytes for these particles was lower than for the standard objects (latex microparticles).

  2. 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

    2016-01-01

    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.

  3. Comparative cytotoxicity of dolomite nanoparticles in human larynx HEp2 and liver HepG2 cells.

    PubMed

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

    2015-06-01

    Dolomite is a natural mineral of great industrial and commercial importance. With the advent of nanotechnology, natural minerals including dolomite in the form of nanoparticles (NPs) are being utilized in various applications to improve the quality of products. However, safety or toxicity information of dolomite NPs is largely lacking. This study evaluated the cytotoxicity of dolomite NPs in two widely used in vitro cell culture models: human airway epithelial (HEp2) and human liver (HepG2) cells. Concentration-dependent decreased cell viability and damaged cell membrane integrity revealed the cytotoxicity of dolomite NPs. We further observed that dolomite NPs induce oxidative stress in a concentration-dependent manner, as indicated by depletion of glutathione and induction of reactive oxygen species (ROS) and lipid peroxidation. Quantitative real-time PCR data demonstrated that the mRNA level of tumor suppressor gene p53 and apoptotic genes (bax, CASP3 and CASP9) were up-regulated whereas the anti-apoptotic gene bcl-2 was down-regulated in HEp2 and HepG2 cells exposed to dolomite NPs. Moreover, the activity of apoptotic enzymes (caspase-3 and caspase-9) was also higher in both kinds of cells treated with dolomite NPs. It is also worth mentioning that HEp2 cells seem to be marginally more susceptible to dolomite NPs exposure than HepG2 cells. Cytotoxicity induced by dolomite NPs was efficiently prevented by N-acetyl cysteine treatment, which suggests that oxidative stress is primarily responsible for the cytotoxicity of dolomite NPs in both HEp2 and HepG2 cells. Toxicity mechanisms of dolomite NPs warrant further investigations at the in vivo level.

  4. Effects of different surface modifying agents on the cytotoxic and antimicrobial properties of ZnO nanoparticles.

    PubMed

    Esparza-González, S C; Sánchez-Valdés, S; Ramírez-Barrón, S N; Loera-Arias, M J; Bernal, J; Meléndez-Ortiz, H Iván; Betancourt-Galindo, R

    2016-12-01

    Zinc oxide (ZnO) nanoparticles (NPs) have received considerable attention in the medical field because of their antibacterial properties, primarily for killing and reducing the activity of numerous microorganisms. The purpose of this study was to determine whether surface-modified ZnO NPs exhibit different properties compared with unmodified ZnO. The antimicrobial and cytotoxic properties of modified ZnO NPs as well as their effects on inflammatory cytokine production were evaluated. ZnO NPs were prepared using a wet chemical method. Then, the surfaces of these NPs were modified using 3-aminopropyltriethoxysilane (APTES) and dimethyl sulfoxide (DMSO) as modifying agents via a chemical hydrolysis method. According to infrared spectroscopy analysis (FTIR), the structure of the ZnO remained unchanged after modification. Antibacterial assays demonstrated that APTES modification is more effective at inducing an antimicrobial effect against Gram-negative bacteria than against Gram-positive bacteria. Cytotoxicity studies showed that cell viability was dose-dependent; moreover, pristine and APTES-modified ZnO exhibited low cytotoxicity, whereas DMSO-modified ZnO exhibited toxicity even at a low NP concentration. An investigation of inflammatory cytokine production demonstrated that the extent of stimulation was related to the ZnO NP concentration but not to the surface modification, except for IFN-γ and IL-10, which were not detected even at high NP concentrations.

  5. Biosynthesis of Silver Nanoparticles Using Taxus yunnanensis Callus and Their Antibacterial Activity and Cytotoxicity in Human Cancer Cells

    PubMed Central

    Xia, Qian Hua; Ma, Yan Jun; Wang, Jian Wen

    2016-01-01

    Plant constituents could act as chelating/reducing or capping agents for synthesis of silver nanoparticles (AgNPs). The green synthesis of AgNPs has been considered as an environmental friendly and cost-effective alternative to other fabrication methods. The present work described the biosynthesis of AgNPs using callus extracts from Taxus yunnanensis and evaluated their antibacterial activities in vitro and potential cytotoxicity in cancer cells. Callus extracts were able to reduce silver nitrate at 1 mM in 10 min. Transmission electron microscope (TEM) indicated the synthesized AgNPs were spherical with the size range from 6.4 to 27.2 nm. X-ray diffraction (XRD) confirmed the AgNPs were in the form of nanocrystals. Fourier transform infrared spectroscopy (FTIR) suggested phytochemicals in callus extracts were possible reducing and capping agents. The AgNPs exhibited effective inhibitory activity against all tested human pathogen bacteria and the inhibition against Gram-positive bacteria was stronger than that of Gram-negative bacteria. Furthermore, they exhibited stronger cytotoxic activity against human hepatoma SMMC-7721 cells and induced noticeable apoptosis in SMMC-7721 cells, but showed lower cytotoxic against normal human liver cells (HL-7702). Our results suggested that biosynthesized AgNPs could be an alternative measure in the field of antibacterial and anticancer therapeutics. PMID:28335288

  6. Cytotoxicity of Silver Nanoparticle and Chitin-Nanofiber Sheet Composites Caused by Oxidative Stress

    PubMed Central

    Kinoda, Jun; Ishihara, Masayuki; Hattori, Hidemi; Nakamura, Shingo; Fukuda, Koichi; Yokoe, Hidetaka

    2016-01-01

    Size-controlled spherical silver nanoparticles (<10 nm) and chitin-nanofiber sheet composites (Ag NPs/CNFS) have previously been reported to have strong antimicrobial activity in vitro. Although Ag NPs/CNFS have strong antimicrobial activity, their cytotoxicity has not been investigated. This study was performed to evaluate the effects of Ag NPs/CNFS on cytotoxicity for fibroblasts in vitro and healing delay of wound repair in vivo, focused on oxidative stress. Cytotoxic activities of Ag NPs/CNFS were investigated using a fibroblast cell proliferation assay, nitric oxide/nitrogen dioxide (NO/NO2) measurement of the cell lysates in vitro, inhibitory effects of Ag NPs/CNFS on healing-impaired wound repair using diabetic mice in vivo, 8-hydroxy-2′-deoxyguanosine (8-OHdG) immunohistochemical staining of the skin sections, and generation of carbonyl protein in the wound was performed to evaluate cytotoxicity with oxidative stress. Ag NPs/CNFS exhibited cytotoxicity for fibroblasts and a significant increase of total NO/NO2 levels in the cell lysates in vitro and increased levels of 8-OHdG and carbonyl proteins in vivo. Although wound repair in the continuously Ag NPs/CNFS-treated group was delayed, it could be mitigated by washing the covered wound with saline. Thus, Ag NPs/CNFS may become accepted as an anti-infectious wound dressing. PMID:28335317

  7. 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

  8. Cellular targets and mechanisms in the cytotoxic action of non-biodegradable engineered nanoparticles.

    PubMed

    Fröhlich, Eleonore

    2013-11-01

    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.

  9. Lipid peroxidation and cytotoxicity induced by respirable volcanic ash.

    PubMed

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

    2014-06-15

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

  10. Photoluminescence, cytotoxicity and in vitro imaging of hexagonal terbium phosphate nanoparticles doped with europium.

    PubMed

    Di, Weihua; Li, Jie; Shirahata, Naoto; Sakka, Yoshio; Willinger, Marc-Georg; Pinna, Nicola

    2011-03-01

    Luminescent TbPO4 nanoparticles were synthesized via a citric-acid-mediated hydrothermal route. Eu3+ doping of TbPO4 enables an efficient Tb3+-to-Eu3+ energy transfer, leading to a four-fold increase of the absolute emission quantum yield (QY), compared to that of undoped TbPO4. To check the potential of biological use, we conducted in vitro biological experiments on human cervical carcinoma HeLa cells incubated with TbPO4:Eu nanoparticles. TbPO4:Eu nanoparticles can be successfully internalized into the cells, and they show bright intracellular luminescence and very low cytotoxicity. Photoluminescence intensity dependence upon time demonstrates that Eu3+-doped TbPO4 nanoparticles are highly resistant to photobleaching. Our present work represents a demonstration of the use of rare-earth-based nanocrystals as a biological labeling agent because they combine several advantages including high emission quantum yield, long luminescence lifetime, low cytotoxicity and high photostability.

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

    PubMed Central

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

    2015-01-01

    It is necessary to understand the cellular uptake and cytotoxicity of food-grade delivery systems, such as β-lactoglobulin (β-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 β-lg nanoparticles, such as particle size and zeta-potential value, and their cellular uptakes and cytotoxicity in Caco-2 cells. Physicochemical properties of β-lg nanoparticles were evaluated using particle size analyzer. Flow cytometry and confocal laser scanning microscopy were used to investigate cellular uptake and cytotoxicity of β-lg nanoparticles. The β-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 β-lg nanoparticles. Non-cytotoxicity was observed in Caco-2 cells treated with β-lg nanoparticles. There was an increase in cellular uptake of β-lg nanoparticles with a decrease in particle size and an increase in zeta-potential value. Cellular uptake β-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 β-lg nanoparticles play an important role in the cellular uptake. The β-lg nanoparticles can be used as a delivery system in foods due to its high cellular uptake and non-cytotoxicity. PMID:25656189

  12. 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

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

    PubMed Central

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

    2010-01-01

    Magnetic nanoparticles are promising molecular imaging agents due to their relative high relaxivity and the potential to modify surface functionality to tailor biodistribution. In this work we describe the synthesis of magnetic nanoparticles using organic solvents with organometallic precursors. This method results in nanoparticles that are highly crystalline, and have uniform size and shape. The ability to create a monodispersion of particles of the same size and shape results in unique magnetic properties that can be useful for biomedical applications with MR imaging. Before these nanoparticles can be used in biological applications, however, means are needed to make the nanoparticles soluble in aqueous solutions and the toxicity of these nanoparticles needs to be studied. We have developed two methods to surface modify and transfer these nanoparticles to the aqueous phase using the biocompatible co-polymer, Pluronic F127. Cytotoxicity was found to be dependent on the coating procedure used. Nanoparticle effects on a cell-culture model was quantified using concurrent assaying; a LDH assay to determine cytotoxicity and an MTS assay to determine viability for a 24 hour incubation period. Concurrent assaying was done to insure that nanoparticles did not interfere with the colorimetric assay results. This report demonstrates that a monodispersion of nanoparticles of uniform size and shape can be manufactured. Initial cytotoxicity testing of new molecular imaging agents need to be carefully constructed to avoid interference and erroneous results. PMID:20623517

  14. Synthesis and characterization of genistein conjugated with gold nanoparticles and the study of their cytotoxic properties.

    PubMed

    Stolarczyk, Elżbieta U; Stolarczyk, Krzysztof; Łaszcz, Marta; Kubiszewski, Marek; Maruszak, Wioleta; Olejarz, Wioletta; Bryk, Dorota

    2017-01-01

    Gold nanoparticles conjugated with drug substances are used in diagnostics and therapies. Apart from the combinations involving gold nanoparticles conjugated with drug substances through linkers, a direct bonding is also known. In our paper the example of such a direct bonding between gold nanoparticles and genistein (AuNPs-GE) is presented. This conjugate was obtained in a one-pot synthesis and the formation of AuNPs-GE was monitored in terms of color change and UV-Vis spectroscopy. It has been shown that genistein reduces Au(3+) ions to spherical Au(0) nanocrystallites and acts as a stabilizing agent. The efficiency of the purification of the conjugate from free genistein was controlled by the capillary electrophoresis. Gold nanoparticles are homogeneously shaped and have a narrow range of size from 14 to 33nm and the size of the nanoparticles modified with genistein is around 64.64±0.41nm, as measured by the TEM and DSL techniques, respectively. The zeta potential of the gold nanoparticles modified with genistein is -19.32±0.82mV and suggests a high stability of the nanoparticles and lower toxicity for the normal cells. The identity of genistein on the gold nanoparticles was proved by the electrochemistry, NMR and Raman spectroscopy. The mechanism of the conjugate forming has been proposed. The coverage of gold nanoparticles with genistein 5.09% (m/m) has been calculated from the TGA analysis. Moreover, it has been proved that the obtained conjugate is characterized by a high cytotoxic activity towards cancer cells, as observed in the cell line test.

  15. Nitric oxide-releasing nanoparticles: synthesis, characterization, and cytotoxicity to tumorigenic cells

    NASA Astrophysics Data System (ADS)

    Pelegrino, Milena T.; Silva, Letícia C.; Watashi, Carolina M.; Haddad, Paula S.; Rodrigues, Tiago; Seabra, Amedea B.

    2017-02-01

    Nitric oxide (NO) is involved in several biological processes, including toxicity against tumor cells. The aim of this study was to synthesize, characterize, and evaluate the cytotoxicity of NO-releasing chitosan nanoparticles. A thiol-containing molecule, mercaptosuccinic acid (MSA), was encapsulated (encapsulation efficiency of 99%) in chitosan/sodium tripolyphosphate nanoparticles (CS NPs). The obtained nanoparticles showed an average hydrodynamic size of 108.40 ± 0.96 nm and polydispersity index of 0.26 ± 0.01. MSA-CS NPs were nitrosated leading to S-nitroso-MSA-CS NPs, which act as NO donor. The cytotoxicity of CS NPs, MSA-CS NPs, and S-nitroso-MSA-CS NPs were evaluated in several tumor cells, including human hepatocellular carcinoma (HepG2), mouse melanoma (B16F10), and human chronic myeloid leukemia (K562) cell lines and Lucena-1, a vincristine-resistant K562 cell line. Both CS NPs and MSA-CS NPs did not cause toxic effects in these cells, whereas S-nitroso-MSA-CS NPs caused potent cytotoxic effects in all the tested tumor cell lines. The half-maximal inhibitory concentration values of S-nitroso-MSA-CS NPs were 19.7, 10.5, 22.8, and 27.8 μg·mL-1 for HepG2, B16F10, K562, and Lucena-1 cells, respectively. In contrast, S-nitroso-MSA-CS NPs exhibited lower cytotoxic to non-tumorigenic melanocytes (Melan-A) when compared with melanoma B16F10. Therefore, the results highlight the potential use of NO-releasing CS NPs in antitumor chemotherapy.

  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. Evaluation of cytotoxicity, morphological alterations and oxidative stress in Chinook salmon cells exposed to copper oxide nanoparticles.

    PubMed

    Srikanth, Koigoora; Pereira, Eduarda; Duarte, Armando C; Rao, Janapala Venkateswara

    2016-05-01

    The current study is aimed to study cytotoxicity and oxidative stress mediated changes induced by copper oxide nanoparticles (CuO NPs) in Chinook salmon cells (CHSE-214). To this end, a number of biochemical responses are evaluated in CHSE-214 cells which are as follows [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] MTT, neutral red uptake (NRU), lactate dehydrogenase (LDH), protein carbonyl (PC), lipid peroxidation (LPO), oxidised glutathione (GSSG), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione sulfo-transferase (GST), superoxide dismutase (SOD), catalase (CAT), 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and reactive oxygen species (ROS), respectively. The 50% inhibition concentration (IC50) of CuO NPs to CHSE-214 cells after 24 h exposure was found to be 19.026 μg ml(-1). Viability of cells was reduced by CuO NPs, and the decrease was dose dependent as revealed by the MTT and NRU assay. CHSE-214 cells exposed to CuO NPs induced morphological changes. Initially, cells started to detach from the surface (12 h), followed by polyhedric, fusiform appearance (19 h) and finally the cells started to shrink. Later, the cells started losing their cellular contents leading to their death only after 24 h. LDH, PC, LPO, GSH, GPx, GST, SOD, CAT, 8-OHdG and ROS responses were seen significantly increased with the increase in the concentration of CuO NPs when compared to their respective controls. However, significant decrease in GSSG was perceptible in CHSE-214 cells exposed to CuO NPs in a dose-dependent manner. Our data demonstrated that CuO NPs induced cytotoxicity in CHSE-214 cells through the mediation of oxidative stress. The current study provides a baseline for the CuO NPs-mediated cytotoxic assessment in CHSE-214 cells for the future studies.

  18. Cytotoxicity and inflammation in human alveolar epithelial cells following exposure to occupational levels of gold and silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Bachand, George D.; Allen, Amy; Bachand, Marlene; Achyuthan, Komandoor E.; Seagrave, Jean Clare; Brozik, Susan M.

    2012-10-01

    While inhalation represents one of the most likely routes of exposure, the toxicity and response of nanoparticles at concentrations expected from such an exposure are not well understood. Here we characterized the in vitro response of human A549 adenocarcinomic alveolar epithelial cells following exposure to gold (AuNP) and silver (AgNP) nanoparticles at levels approximating an occupational exposure. Changes in neither oxidative stress nor cytotoxicity were significantly affected by exposure to AgNPs and AuNPs, regardless of NP type (Ag vs. Au), concentration, surface ligand (citrate or tannic acid), or size. An inflammatory response was, however, observed in response to 20 nm AgNPs and 20 nm AuNPs, where significant differences in the release of interleukin (IL)-8 but not IL-6 were observed. Additional data demonstrated that increased IL-8 secretion was strongly dependent on both nanoparticle size and concentration. Overall these data suggest that, while not acutely toxic, occupational exposure to AuNPs and AgNPs may trigger a significant inflammatory response in alveolar epithelium. Moreover, the differential responses in IL-8 and IL-6 secretion suggest that NPs may induce a response pathway that is distinct from those commonly elicited by allergens and pathogens.

  19. Monodisperse polyvinylpyrrolidone-coated CoFe2O4 nanoparticles: Synthesis, characterization and cytotoxicity study

    NASA Astrophysics Data System (ADS)

    Wang, Guangshuo; Ma, Yingying; Mu, Jingbo; Zhang, Zhixiao; Zhang, Xiaoliang; Zhang, Lina; Che, Hongwei; Bai, Yongmei; Hou, Junxian; Xie, Hailong

    2016-03-01

    In this study, monodisperse cobalt ferrite (CoFe2O4) nanoparticles were prepared successfully with various additions of polyvinylpyrrolidone (PVP) by sonochemical method, in which PVP served as a stabilizer and dispersant. The effects and roles of PVP on the morphology, microstructure and magnetic properties of the obtained CoFe2O4 were investigated in detail by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and superconducting quantum interference device (SQUID). It was found that PVP-coated CoFe2O4 showed relatively well dispersion with narrow size distribution. The field-dependent magnetization curves indicated superparamagnetic behavior of PVP-coated CoFe2O4 with moderate saturation magnetization and hydrophilic character at room temperature. More importantly, the in vitro cytotoxicity testing exhibited negligible cytotoxicity of as-prepared PVP-CoFe2O4 even at the concentration as high as 150 μg/mL after 24 h treatment. Considering the superparamagnetic properties, hydrophilic character and negligible cytotoxicity, the monodisperse CoFe2O4 nanoparticles hold great potential in a variety of biomedical applications.

  20. Cytotoxicity of gold nanoparticles with different structures and surface-anchored chiral polymers.

    PubMed

    Deng, Jun; Yao, Mengyun; Gao, Changyou

    2017-02-15

    Nanoparticles (NPs) can have profound effects on cell biology. However, the potential adverse effects of gold nanoparticles (AuNPs) with different surface chirality and structures have not been elucidated. In this study, monolayers of poly(acryloyl-l(d)-valine (l(d)-PAV) chiral molecules were anchored on the surfaces of gold nanocubes (AuNCs) and nanooctahedras (AuNOs), respectively. The l-PAV-AuNCs and d-PAV-AuNCs, or the l-PAV-AuNOs and d-PAV-AuNOs, had identical physicochemical properties in terms of size, morphology and ligand density except of the reverse molecular chirality on the particle surfaces, respectively. The l-PAV capped AuNCs and AuNOs exhibited larger cytotoxicity to A549 cells than the D-PAV coated ones, and the PAV-AuNOs had larger cytotoxicity than PAV-AuNCs when being capped with the same type of enantiomers, respectively. The cytotoxicity was positively correlated with the cellular uptake amount, and thereby the production of intracellular reactive oxygen species (ROS).

  1. Silicon dioxide nanoparticles increase macrophage atherogenicity: Stimulation of cellular cytotoxicity, oxidative stress, and triglycerides accumulation.

    PubMed

    Petrick, Lauren; Rosenblat, Mira; Paland, Nicole; Aviram, Michael

    2016-06-01

    Nanoparticle research has focused on their toxicity in general, while increasing evidence points to additional specific adverse effects on atherosclerosis development. Arterial macrophage cholesterol and triglyceride (TG) accumulation and foam cell formation are the hallmark of early atherogenesis, leading to cardiovascular events. To investigate the in vitro atherogenic effects of silicon dioxide (SiO2 ), J774.1 cultured macrophages (murine cell line) were incubated with SiO2 nanoparticle (SP, d = 12 nm, 0-20 µg/mL), followed by cellular cytotoxicity, oxidative stress, TG and cholesterol metabolism analyses. A significant dose-dependent increase in oxidative stress (up to 164%), in cytotoxicity (up to 390% measured by lactate dehydrogenase (LDH) release), and in TG content (up to 63%) was observed in SiO2 exposed macrophages compared with control cells. A smaller increase in macrophage cholesterol mass (up to 22%) was noted. TG accumulation in macrophages was not due to a decrease in TG cell secretion or to an increased TG biosynthesis rate, but was the result of attenuated TG hydrolysis secondary to decreased lipase activity and both adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein expression (by 42 and 25%, respectively). Overall, SPs showed pro-atherogenic effects on macrophages as observed by cytotoxicity, increased oxidative stress and TG accumulation. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 713-723, 2016.

  2. Cytotoxicity and genotoxicity induced by coal and coal fly ash particles samples in V79 cells.

    PubMed

    León-Mejía, Grethel; Silva, Luis F O; Civeira, Matheus S; Oliveira, Marcos L S; Machado, Miriana; Villela, Izabel Vianna; Hartmann, Andreas; Premoli, Suziane; Corrêa, Dione Silva; Da Silva, Juliana; Henriques, João Antônio Pêgas

    2016-12-01

    Exposure to coal and coal ashes can cause harmful effects in in vitro and in vivo systems, mainly by the induction of oxidative damage. The aim of this work was to assess cytotoxic and genotoxic effects using the V79 cell line treated with coal and coal fly ash particles derived from a coal power plant located in Santa Catarina, Brazil. Two coal samples (COAL11 and COAL16) and two coal fly ash samples (CFA11 and CFA16) were included in this study. COAL16 was co-firing with a mixture of fuel oil and diesel oil. The comet assay data showed that exposure of V79 cells to coal and coal fly ash particles induced primary DNA lesions. Application of lesion-specific endonucleases (FPG and ENDO III) demonstrated increased DNA effects indicating the presence of high amounts of oxidative DNA lesions. The cytokinesis-block micronucleus cytome assay analysis showed that exposure of V79 cells to high concentrations of coal and coal fly ash particles induced cytotoxic effects (apoptosis and necrosis) and chromosomal instability (nucleoplasmic bridges, nuclear buds, and micronucleus (MN) formation). These results may be associated with compounds contained in the surface of the particles as hazardous elements, ultrafine/nanoparticles, and polycyclic aromatic hydrocarbons (PAHs) which were detected in the samples. Graphical abstract ᅟ.

  3. Poly(lactic acid) nanoparticles loaded with ursolic acid: Characterization and in vitro evaluation of radical scavenging activity and cytotoxicity.

    PubMed

    Antônio, Emilli; Antunes, Osmar Dos Reis; de Araújo, Isis Souza; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2017-02-01

    The purpose of this study was to develop poly(lactic acid) (PLA) nanoparticles containing ursolic acid (UA) by an emulsification-solvent evaporation technique and evaluate the radical scavenging activity over hypochlorous acid (HOCl) and cytotoxicity over erythrocytes and tumor cells. Nanoparticles were successfully obtained and presented mean size of 246nm with spherical or slightly oval morphology, negative zeta potential and 96% of UA encapsulation efficiency. Analyses of FTIR, XRD and DSC-DTG suggest interaction/complexation of UA with PLA matrix and drug amorphization promoted by nanoencapsulation process. Stability study showed that room temperature was the best condition for nanoparticles storage. The in vitro release study showed UA was released from the polymeric matrix over two constants (α, β), suggesting a second order kinetics. After 120h of assay, 60% of UA were released by diffusion. In the HOCl scavenging activity, after 72h of assay UA-loaded nanoparticles presented the same efficacy of free drug. In cytotoxicity test over red blood cells, UA-loaded nanoparticles showed less toxicity on cells than free drug. The cytotoxicity assay over melanoma cells line (B16-F10) showed after 72h that nanoparticles were able to reduce the cell viability in 70%. PLA nanoparticles showed be potential carriers for UA maintaining the antioxidant and antitumor activity of the UA and decreasing its cytotoxicity over normal cells.

  4. Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells.

    PubMed

    Ahamed, Maqusood; Akhtar, Mohd Javed; Siddiqui, Maqsood A; Ahmad, Javed; Musarrat, Javed; Al-Khedhairy, Abdulaziz A; AlSalhi, Mohamad S; Alrokayan, Salman A

    2011-05-10

    Due to the interesting magnetic and electrical properties with good chemical and thermal stabilities, nickel ferrite nanoparticles are being utilized in many applications including magnetic resonance imaging, drug delivery and hyperthermia. Recent studies have shown that nickel ferrite nanoparticles produce cytotoxicity in mammalian cells. However, there is very limited information concerning the toxicity of nickel ferrite nanoparticles at the cellular and molecular level. The aim of this study was to investigate the cytotoxicity, oxidative stress and apoptosis induction by well-characterized nickel ferrite nanoparticles (size 26 nm) in human lung epithelial (A549) cells. Nickel ferrite nanoparticles induced dose-dependent cytotoxicity in A549 cells demonstrated by MTT, NRU and LDH assays. Nickel ferrite nanoparticles were also found to induce oxidative stress evidenced by generation of reactive oxygen species (ROS) and depletion of antioxidant glutathione (GSH). Further, co-treatment with the antioxidant L-ascorbic acid mitigated the ROS generation and GSH depletion due to nickel ferrite nanoparticles suggesting the potential mechanism of oxidative stress. Quantitative real-time PCR analysis demonstrated that following the exposure of A549 cells to nickel ferrite nanoparticles, the level of mRNA expressions of cell cycle checkpoint protein p53 and apoptotic proteins (bax, caspase-3 and caspase-9) were significantly up-regulated, whereas the expression of anti-apoptotic proteins (survivin and bcl-2) were down-regulated. Moreover, activities of caspase-3 and caspase-9 enzymes were also significantly higher in nickel ferrite nanoparticles exposed cells. To the best of our knowledge this is the first report showing that nickel ferrite nanoparticles induced apoptosis in A549 cells through ROS generation and oxidative stress via p53, survivin, bax/bcl-2 and caspase pathways.

  5. Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke

    PubMed Central

    Azzopardi, David; Patel, Kharishma; Jaunky, Tomasz; Santopietro, Simone; Camacho, Oscar M.; McAughey, John; Gaça, Marianna

    2016-01-01

    Abstract Electronic cigarettes (E-cigarettes) are a potential means of addressing the harm to public health caused by tobacco smoking by offering smokers a less harmful means of receiving nicotine. As e-cigarettes are a relatively new phenomenon, there are limited scientific data on the longer-term health effects of their use. This study describes a robust in vitro method for assessing the cytotoxic response of e-cigarette aerosols that can be effectively compared with conventional cigarette smoke. This was measured using the regulatory accepted Neutral Red Uptake assay modified for air–liquid interface (ALI) exposures. An exposure system, comprising a smoking machine, traditionally used for in vitro tobacco smoke exposure assessments, was adapted for use with e-cigarettes to expose human lung epithelial cells at the ALI. Dosimetric analysis methods using real-time quartz crystal microbalances for mass, and post-exposure chemical analysis for nicotine, were employed to detect/distinguish aerosol dilutions from a reference Kentucky 3R4F cigarette and two commercially available e-cigarettes (Vype eStick and ePen). ePen aerosol induced 97%, 94% and 70% less cytotoxicity than 3R4F cigarette smoke based on matched EC50 values at different dilutions (1:5 vs. 1:153 vol:vol), mass (52.1 vs. 3.1 μg/cm2) and nicotine (0.89 vs. 0.27 μg/cm2), respectively. Test doses where cigarette smoke and e-cigarette aerosol cytotoxicity were observed are comparable with calculated daily doses in consumers. Such experiments could form the basis of a larger package of work including chemical analyses, in vitro toxicology tests and clinical studies, to help assess the safety of current and next generation nicotine and tobacco products. PMID:27690199

  6. Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke.

    PubMed

    Azzopardi, David; Patel, Kharishma; Jaunky, Tomasz; Santopietro, Simone; Camacho, Oscar M; McAughey, John; Gaça, Marianna

    2016-07-01

    Electronic cigarettes (E-cigarettes) are a potential means of addressing the harm to public health caused by tobacco smoking by offering smokers a less harmful means of receiving nicotine. As e-cigarettes are a relatively new phenomenon, there are limited scientific data on the longer-term health effects of their use. This study describes a robust in vitro method for assessing the cytotoxic response of e-cigarette aerosols that can be effectively compared with conventional cigarette smoke. This was measured using the regulatory accepted Neutral Red Uptake assay modified for air-liquid interface (ALI) exposures. An exposure system, comprising a smoking machine, traditionally used for in vitro tobacco smoke exposure assessments, was adapted for use with e-cigarettes to expose human lung epithelial cells at the ALI. Dosimetric analysis methods using real-time quartz crystal microbalances for mass, and post-exposure chemical analysis for nicotine, were employed to detect/distinguish aerosol dilutions from a reference Kentucky 3R4F cigarette and two commercially available e-cigarettes (Vype eStick and ePen). ePen aerosol induced 97%, 94% and 70% less cytotoxicity than 3R4F cigarette smoke based on matched EC50 values at different dilutions (1:5 vs. 1:153 vol:vol), mass (52.1 vs. 3.1 μg/cm(2)) and nicotine (0.89 vs. 0.27 μg/cm(2)), respectively. Test doses where cigarette smoke and e-cigarette aerosol cytotoxicity were observed are comparable with calculated daily doses in consumers. Such experiments could form the basis of a larger package of work including chemical analyses, in vitro toxicology tests and clinical studies, to help assess the safety of current and next generation nicotine and tobacco products.

  7. Resveratrol-loaded Nanoparticles Induce Antioxidant Activity against Oxidative Stress

    PubMed Central

    Kim, Jae-Hwan; Park, Eun-Young; Ha, Ho-Kyung; Jo, Chan-Mi; Lee, Won-Jae; Lee, Sung Sill; Kim, Jin Wook

    2016-01-01

    Resveratrol acts as a free radical scavenger and a potent antioxidant in the inhibition of numerous reactive oxygen species (ROS). The function of resveratrol and resveratrol-loaded nanoparticles in protecting human lung cancer cells (A549) against hydrogen peroxide was investigated in this study. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay was performed to evaluate the antioxidant properties. Resveratrol had substantially high antioxidant capacity (trolox equivalent antioxidant capacity value) compared to trolox and vitamin E since the concentration of resveratrol was more than 50 μM. Nanoparticles prepared from β-lactoglobulin (β-lg) were successfully developed. The β-lg nanoparticle showed 60 to 146 nm diameter in size with negatively charged surface. Non-cytotoxicity was observed in Caco-2 cells treated with β-lg nanoparticles. Fluorescein isothiocynate-conjugated β-lg nanoparticles were identified into the cell membrane of Caco-2 cells, indicating that nanoparticles can be used as a delivery system. Hydrogen peroxide caused accumulation of ROS in a dose- and time-dependent manner. Resveratrol-loaded nanoparticles restored H2O2-induced ROS levels by induction of cellular uptake of resveratrol in A549 cells. Furthermore, resveratrol activated nuclear factor erythroid 2-related factor 2-Kelch ECH associating protein 1 (Nrf2-Keap1) signaling in A549 cells, thereby accumulation of Nrf2 abundance, as demonstrated by western blotting approach. Overall, these results may have implications for improvement of oxidative stress in treatment with nanoparticles as a biodegradable and non-toxic delivery carrier of bioactive compounds. PMID:26732454

  8. 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.

  9. Cytotoxic effect of silver nanoparticles synthesized from Padina tetrastromatica on breast cancer cell line

    NASA Astrophysics Data System (ADS)

    Gnana Selvi, B. Clara; Madhavan, J.; Santhanam, Amutha

    2016-09-01

    In recent years researchers were attracted towards marine sources due to the presence of active components in it. Seaweeds were widely used in pharmaceutical research for their known biological activities. The biological synthesis method of silver nanoparticles (AgNPs) using Padina tetrastromatica seaweed extract and their cytotoxicity against breast cancer MCF-7 cells was reported in this study. The synthesized AgNPs using seaweed extract were subjected to x-ray diffraction, UV-visible spectroscopy, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, transmission electron microscope, energy dispersive x-ray, zeta potential to elucidate the structural, morphology, size as well as surface potential parameters. An absorption peak at 430 nm in UV-visible spectrum reveals the excitation and surface plasmon resonance of AgNPs. FE-SEM micrographs exhibits the biosynthesized AgNPs, which are pre-dominantly round shaped and the size ranges between 40-50 nm. The zeta potential value of -27.6 mV confirms the stable nature of biosynthesized silver nanoparticles. Furthermore, the biological synthesized Ag NPs exhibited a dose-dependent cytotoxicity against human breast cancer cell (MCF-7) and the inhibitory concentration (IC50) was found for AgNPs against MCF-7 at 24 h incubation. Biological method of synthesizing silver nanoparticles shows a environmental friendly property which helps in effective electrifying usage in many fields.

  10. Cytotoxicity of functionalized polystyrene latex nanoparticles toward lactic acid bacteria, and comparison with model microbes

    NASA Astrophysics Data System (ADS)

    Nomura, Toshiyuki; Kuriyama, Yuta; Tokumoto, Hayato; Konishi, Yasuhiro

    2015-02-01

    The cytotoxicity and colloidal behavior of surface-functionalized polystyrene latex (PSL) nanoparticles (NPs) (nominal diameter: 100 nm) toward a model gram positive bacterium Lactococcus lactis JCM 5805 were examined. Nearly all the L. lactis cells exposed to the negatively charged PSL NPs survived because the surface of the bacterial cell was charged negatively, and the NPs therefore hardly adhere to the cell surface. In contrast, the positively charged PSL NPs adhered to the L. lactis cell surface but were not entrapped within the cell, and cell death subsequently occurred. The bacterial growth curves after the toxic NP exposure suggested that NP toxicity did not affect the specific growth phase, but did affect lag time. These results indicated that the cells were damaged by the cell disruption that resulted from the adhesion of the NPs to the cell surface. Finally, the cytotoxicity of the toxic, positively charged PSL NPs toward L. lactis was compared with that displayed toward a model gram negative bacterium Escherichia coli and a model eukaryote Saccharomyces cerevisiae. The cytotoxic behaviors of NPs on L. lactis and E. coli were similar, and depended not on the bacterial surface structure, but rather the environmental ionic strength. In contrast, the cytotoxicity of the prokaryote bacteria was higher than that toward the model eukaryote S. cerevisiae. The difference between the NP sensitivities of the prokaryote and eukaryote resulted from the prokaryote's lack of an endocytotic pathway.

  11. L-Leucine for gold nanoparticles synthesis and their cytotoxic effects evaluation.

    PubMed

    Berghian-Grosan, Camelia; Olenic, Liliana; Katona, Gabriel; Perde-Schrepler, Maria; Vulcu, Adriana

    2014-11-01

    This work reports the preparation of water-soluble leucine capped gold nanoparticles by two single-step synthesis methods. The first procedure involves a citrate reduction approach where the citrate is used as reducing agent and leucine as capping/stabilizing agent. Different sizes of gold nanoparticles, citrate reduced and stabilized by leucine, Leu-AuNPs-C, with the mean diameters in the range of 21-56 nm, were obtained by varying the macroscopic parameters such as: concentration of the gold precursor solution, Au (III):citrate molar ratio and leucine pH. In the second procedure, leucine acts both as reducing and stabilizing agent, allowing us to obtain spherical gold nanoparticles, Leu-AuNPs, with a majority of 80 % (with the mean diameter of 63 nm). This proves that leucine is an appropriate reductant for the formation of water-soluble and stable gold nanoparticles colloids. The characterization of the leucine coated gold nanoparticles was carried out by TEM, UV-Vis and FT-IR analysis. The cytotoxic effect of Leu-AuNPs-C and Leu-AuNPs was also evaluated.

  12. Formation and Cytotoxicity of Nanoparticles and Nanocubes Prepared from Gold and Silver Salts

    NASA Astrophysics Data System (ADS)

    Banker, Daniel; Dorrell, Skyler; Ivey, Prescott; Scurti, Joseph; Dobbins, Tabbetha

    Photothermal therapy is the use of electromagnetic radiation as the treatment for medical conditions such as cancer. Noble metal nanoparticles and nanocubes are brought to an excited state with laser light and as a result they release vibrational energy in the form of heat, which can be used to kill targeted cancer cells. Wet chemistry gives the basics for the preparation of nanoparticles and nanocubes. Using HAuCl4, AgNO3, tri-sodium citrate and other chemicals, we were able to successfully create gold and silver nanoparticles and nanocubes. The goal is to make sure that 3T3 cells can survive in a nanoparticle or nanocube doped medium so that we can then observe their reaction to photothermal effects. Cell culture techniques were done to 3T3 cells to keep them alive before the testing of cytotoxicity. Photothermal effect refers to the way that our nanoparticles or nanocubes can be photoexcited to release enough heat to kill the cells. We used a UV-Vis spectrophotometer to ensure that the correct wavelength laser. Assuming that the cells will survive living in the doped medium, a medium that has had nanomaterials introduced into it, we will use a high powered laser to observe what the excitation does to the cells since the photothermal effect should result in dead cells.

  13. Antimicrobial, Antioxidant and Cytotoxic Activity of Silver Nanoparticles Synthesized by Leaf Extract of Erythrina suberosa (Roxb.)

    PubMed Central

    Mohanta, Yugal K.; Panda, Sujogya K.; Jayabalan, Rasu; Sharma, Nanaocha; Bastia, Akshaya K.; Mohanta, Tapan K.

    2017-01-01

    In this experiment, biosynthesized silver nanoparticles (AgNPs) were synthesized using aqueous leaf extract of Erythrina suberosa (Roxb.). The biosynthesis of silver nanoparticle was continuously followed by UV-vis spectrophotometric analysis. The response of the phytoconstituents resides in E. suberusa during synthesis of stable AgNPs were analyzed by ATR- fourier-transform infrared spectroscopy. Further, the size, charge, and polydispersity nature of AgNPs were studied using dynamic light scattering spectroscopy. The morphology of the nanoparticles was determined by scanning electron microscopy. Current result shows core involvement of plant extracts containing glycosides, flavonoids, and phenolic compounds played a crucial role in the biosynthesis of AgNPs. The antimicrobial activities of silver nanoparticles were evaluated against different pathogenic bacterium and fungi. The antioxidant property was studied by radical scavenging (DPPH) assay and cytotoxic activity was evaluated against A-431 osteosarcoma cell line by MTT assay. The characteristics of the synthesized silver nanoparticles suggest their application as a potential antimicrobial and anticancer agent. PMID:28367437

  14. 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

    2015-06-14

    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.

  15. QSAR model for cytotoxicity of SiO2 nanoparticles on human lung fibroblasts

    NASA Astrophysics Data System (ADS)

    Toropova, Alla P.; Toropov, Andrey A.; Benfenati, Emilio; Korenstein, Rafi

    2014-02-01

    The possibility of building up predictive model for cytotoxicity of SiO2-nanoparticles (SiO2-NPs) by means of so-called optimal descriptors which are mathematical functions of size and concentration of SiO2-NPs is demonstrated with data on sixteen systems' "size-concentration." The calculation has been carried out by means of the CORAL software (http://www.insilico.eu/coral/). The statistical quality of the best model for the cytotoxic inhibition ratio (%) of human lung fibroblasts cultured in the media containing different concentrations of SiO2-NPs which is measured by MTT assay is the following: n = 10, r 2 = 0.9837, s = 2.53 %, F = 483 (training set) and n = 6, r 2 = 0.9269, s = 7.94 % (test set). The perspectives of this approach are discussed.

  16. Nanoparticle-induced pulmonary toxicity.

    PubMed

    Li, Jasmine Jia'en; Muralikrishnan, Sindu; Ng, Cheng-Teng; Yung, Lin-Yue Lanry; Bay, Boon-Huat

    2010-09-01

    In recent decades, advances in nanotechnology engineering have given rise to the rapid development of many novel applications in the biomedical field. However, studies into the health and safety of these nanomaterials are still lacking. The main concerns are the adverse effects to health caused by acute or chronic exposure to nanoparticles (NPs), especially in the workplace environment. The lung is one of the main routes of entry for NPs into the body and, hence, a likely site for accumulation of NPs. Once NPs enter the interstitial air spaces and are quickly taken up by alveolar cells, they are likely to induce toxic effects. In this review, we highlight the different aspects of lung toxicity resulting from NP exposure, such as generation of oxidative stress, DNA damage and inflammation leading to fibrosis and pneumoconiosis, and the underlying mechanisms causing pulmonary toxicity.

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

    SciTech Connect

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

    2012-01-01

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

  18. Silica-coated manganite and Mn-based ferrite nanoparticles: a comparative study focused on cytotoxicity

    NASA Astrophysics Data System (ADS)

    Kaman, Ondřej; Dědourková, Tereza; Koktan, Jakub; Kuličková, Jarmila; Maryško, Miroslav; Veverka, Pavel; Havelek, Radim; Královec, Karel; Turnovcová, Karolína; Jendelová, Pavla; Schröfel, Adam; Svoboda, Ladislav

    2016-04-01

    Magnetic oxide nanoparticles provide a fascinating tool for biological research and medicine, serving as contrast agents, magnetic carriers, and core materials of theranostic systems. Although the applications rely mostly on iron oxides, more complex oxides such as perovskite manganites may provide a much better magnetic performance. To assess the risk of their potential use, in vitro toxicity of manganite nanoparticles was thoroughly analysed and compared with another prospective system of Mn-Zn ferrite nanoparticles. Magnetic nanoparticles of La0.63Sr0.37MnO3 manganite were prepared by two distinct methods, namely the molten salt synthesis and the traditional sol-gel route, whereas nanoparticles of Mn0.61Zn0.42Fe1.97O4 ferrite, selected as a comparative material, were synthesized by a new procedure under hydrothermal conditions. Magnetic cores were coated with silica and, moreover, several samples of manganite nanoparticles with different thicknesses of silica shell were prepared. The size-fractionated and purified products were analysed using transmission electron microscopy, dynamic light scattering, measurement of the zeta-potential dependence on pH, IR spectroscopy, and SQUID magnetometry. The silica-coated products with accurately determined concentration by atomic absorption spectroscopy were subjected to a robust evaluation of their cytotoxicity by four different methods, including detailed analysis of the concentration dependence of toxicity, analysis of apoptosis, and experiments on three different cell lines. The results, comparing two manganese-containing systems, clearly indicated superior properties of the Mn-Zn ferrite, whose silica-coated nanoparticles show very limited toxic effects and thus constitute a promising material for bioapplications.

  19. Antimicrobial and cytotoxicity evaluation of colloidal chitosan - silver nanoparticles - fluoride nanocomposites.

    PubMed

    Freire, Priscila L L; Albuquerque, Allan J R; Farias, Isabela A P; da Silva, Teresinha Gonçalves; Aguiar, Jaciana Santos; Galembeck, André; Flores, Miguel A P; Sampaio, Fabio C; Stamford, Thayza Christina Montenegro; Rosenblatt, Aronita

    2016-12-01

    The present study aimed to evaluate the antimicrobial activity and cytotoxicity of colloidal chitosan - silver nanoparticle - fluoride nanocomposites (CChAgNpFNc), with different silver nanoparticle shapes and sizes. The syntheses of CChAgNpFNc were performed with silver nitrate added to a chitosan solution, addition of a sodium borohydride solution and solid sodium fluoride. Solution of ascorbic acid was added to synthesize larger silver nanoparticles. CChAgNpFNc obtained: S1- 100% spherical, 8.7±3.1nm; S2- 97% spherical, 15.0±7.9nm and 2.5% triangular, 22.2±9.5nm; S3- 77.3% spherical, 31.8±10.4nm, 15.9% triangular, 27.1±10.1nm and 6.8% elliptical, 33.2±7.8nm; and S4- 75.2% spherical, 43.2±14.3nm; 23.3% triangular 38.2±14.8nm, and 1.5% elliptical 38.4±11.6nm. The CChAgNpFNc showed antimicrobial activity against Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa and Candida albicans, by microdilution technique. The influence on the growth of microorganisms was evaluated using a fluorescence assay, and showed an increasing lag phase and a decreasing log phase. Cytotoxicity was investigated using Artemia salina and MTT assays. The S3 and S4 samples exhibited low cytotoxicity. The S1 and S2 samples inhibited murine macrophages and revealed lethal dose concentrations above 1000mg/mL that were classified as moderately toxic. Thus, CChAgNpFNc are potential options for the control of multiple-drug-resistant microorganisms and do not represent substantial risks to human health.

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

    PubMed

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

    2013-05-15

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

  1. Oxidative stress pathways involved in cytotoxicity and genotoxicity of titanium dioxide (TiO2) nanoparticles on cells constitutive of alveolo-capillary barrier in vitro.

    PubMed

    Hanot-Roy, Maïté; Tubeuf, Emilie; Guilbert, Ariane; Bado-Nilles, Anne; Vigneron, Pascale; Trouiller, Bénédicte; Braun, Anne; Lacroix, Ghislaine

    2016-06-01

    The health risks of nanoparticles remain a serious concern given their prevalence from industrial and domestic use. The primary route of titanium dioxide nanoparticle exposure is inhalation. The extent to which nanoparticles contribute to cellular toxicity is known to associate induction of oxidative stress. To investigate this problem further, the effect of titanium dioxide nanoparticles was examined on cell lines representative of alveolo-capillary barrier. The present study showed that all nanoparticle-exposed cell lines displayed ROS generation. Macrophage-like THP-1 and HPMEC-ST1.6R microvascular cells were sensitive to endogenous redox changes and underwent apoptosis, but not alveolar epithelial A549 cells. Genotoxic potential of titanium dioxide nanoparticles was investigated using the activation of γH2AX, activation of DNA repair proteins and cell cycle arrest. In the sensitive cell lines, DNA damage was persistent and activation of DNA repair pathways was observed. Moreover, western blot analysis showed that specific pathways associated with cellular stress response were activated concomitantly with DNA repair or apoptosis. Nanoparticles-induced oxidative stress is finally signal transducer for further physiological effects including genotoxicity and cytotoxicity. Within activated pathways, HSP27 and SAPK/JNK proteins appeared as potential biomarkers of intracellular stress and of sensitivity to endogenous redox changes, respectively, enabling to predict cell behavior.

  2. Adsorption at cell surface and cellular uptake of silica nanoparticles with different surface chemical functionalizations: impact on cytotoxicity

    NASA Astrophysics Data System (ADS)

    Kurtz-Chalot, A.; Klein, J. P.; Pourchez, J.; Boudard, D.; Bin, V.; Alcantara, G. B.; Martini, M.; Cottier, M.; Forest, V.

    2014-11-01

    Silica nanoparticles are particularly interesting for medical applications because of the high inertness and chemical stability of silica material. However, at the nanoscale their innocuousness must be carefully verified before clinical use. The aim of this study was to investigate the in vitro biological toxicity of silica nanoparticles depending on their surface chemical functionalization. To that purpose, three kinds of 50 nm fluorescent silica-based nanoparticles were synthesized: (1) sterically stabilized silica nanoparticles coated with neutral polyethylene glycol molecules, (2) positively charged silica nanoparticles coated with amine groups, and (3) negatively charged silica nanoparticles coated with carboxylic acid groups. RAW 264.7 murine macrophages were incubated for 20 h with each kind of nanoparticles. Their cellular uptake and adsorption at the cell membrane were assessed by a fluorimetric assay, and cellular responses were evaluated in terms of cytotoxicity, pro-inflammatory factor production, and oxidative stress. Results showed that the highly positively charged nanoparticle were the most adsorbed at cell surface and triggered more cytotoxicity than other nanoparticle types. To conclude, this study clearly demonstrated that silica nanoparticles surface functionalization represents a key parameter in their cellular uptake and biological toxicity.

  3. Anti-platelet agents augment cisplatin nanoparticle cytotoxicity by enhancing tumor vasculature permeability and drug delivery

    NASA Astrophysics Data System (ADS)

    Pandey, Ambarish; Sarangi, Sasmit; Chien, Kelly; Sengupta, Poulomi; Papa, Anne-Laure; Basu, Sudipta; Sengupta, Shiladitya

    2014-11-01

    Tumor vasculature is critically dependent on platelet mediated hemostasis and disruption of the same can augment delivery of nano-formulation based chemotherapeutic agents which depend on enhanced permeability and retention for tumor penetration. Here, we evaluated the role of Clopidogrel, a well-known inhibitor of platelet aggregation, in potentiating the tumor cytotoxicity of cisplatin nano-formulation in a murine breast cancer model. In vivo studies in murine syngeneic 4T1 breast cancer model showed a significant greater penetration of macromolecular fluorescent nanoparticles after clopidogrel pretreatment. Compared to self-assembling cisplatin nanoparticles (SACNs), combination therapy with clopidogrel and SACN was associated with a 4 fold greater delivery of cisplatin to tumor tissue and a greater reduction in tumor growth as well as higher survival rate. Clopidogrel enhances therapeutic efficiency of novel cisplatin based nano-formulations agents by increasing tumor drug delivery and can be used as a potential targeting agent for novel nano-formulation based chemotherapeutics.

  4. Hyperoxia Induces Inflammation and Cytotoxicity in Human Adult Cardiac Myocytes.

    PubMed

    Hafner, Christina; Wu, Jing; Tiboldi, Akos; Hess, Moritz; Mitulovic, Goran; Kaun, Christoph; Krychtiuk, Konstantin Alexander; Wojta, Johann; Ullrich, Roman; Tretter, Eva Verena; Markstaller, Klaus; Klein, Klaus Ulrich

    2017-04-01

    Supplemental oxygen (O2) is used as adjunct therapy in anesthesia, emergency, and intensive care medicine. We hypothesized that excessive O2 levels (hyperoxia) can directly injure human adult cardiac myocytes (HACMs). HACMs obtained from the explanted hearts of transplantation patients were exposed to constant hyperoxia (95% O2), intermittent hyperoxia (alternating 10 min exposures to 5% and 95% O2), constant normoxia (21% O2), or constant mild hypoxia (5% O2) using a bioreactor. Changes in cell morphology, viability as assessed by lactate dehydrogenase (LDH) release and trypan blue (TB) staining, and secretion of vascular endothelial growth factor (VEGF), macrophage migration inhibitory factor (MIF), and various pro-inflammatory cytokines (interleukin, IL; chemokine C-X-C motif ligand, CXC; granulocyte-colony stimulating factor, G-CSF; intercellular adhesion molecule, ICAM; chemokine C-C motif ligand, CCL) were compared among treatment groups at baseline (0 h) and after 8, 24, and 72 h of treatment. Changes in HACM protein expression were determined by quantitative proteomic analysis after 48 h of exposure. Compared with constant normoxia and mild hypoxia, constant hyperoxia resulted in a higher TB-positive cell count, greater release of LDH, and elevated secretion of VEGF, MIF, IL-1β, IL-6, IL-8, CXCL-1, CXCL-10, G-CSF, ICAM-1, CCL-3, and CCL-5. Cellular inflammation and cytotoxicity gradually increased and was highest after 72 h of constant and intermittent hyperoxia. Quantitative proteomic analysis revealed that hypoxic and hyperoxic O2 exposure differently altered the expression levels of proteins involved in cell-cycle regulation, energy metabolism, and cell signaling. In conclusion, constant and intermittent hyperoxia induced inflammation and cytotoxicity in HACMs. Cell injury occurred earliest and was greatest after constant hyperoxia, but even relatively brief repeating hyperoxic episodes induced a substantial inflammatory response.

  5. Evaluation of antioxidative, protective effect against H2O2 induced cytotoxicity, and cytotoxic activities of three different Quercus species.

    PubMed

    Söhretoğlu, Didem; Sabuncuoğlu, Suna; Harput, U Şebnem

    2012-02-01

    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 cytotoxicity as well as their cytotoxic activity against Hep-2 human larynx epidermoid carcinoma cell line of the MeOH and water extracts of the barks of Quercus cerris var. cerris, Quercusmacranthera subsp. syspirensis and Quercus aucheri were investigated for the first time. Total phenolic content of the extracts was also evaluated by Folin-Ciocalteu method. Results demonstrated that the extracts showed strong radical scavenging activity comparable to those of standard compounds. Extracts also showed good protective effect against H2O2 induced cytotoxicity on human erythrocytes comparing to ascorbic acid. On the other hand, while each extract showed dose dependent cytotoxic activity, MeOH extract of Q.macranthera subsp. syspirensis showed the strongest cytotoxicity against the tested cell line. Taken together, the results showed that Quercus species may be a promising alternative to synthetic substances as natural compound with high antioxidant and antiproliferative activities.

  6. A role of ZnO nanoparticle electrostatic properties in cancer cell cytotoxicity

    PubMed Central

    Wingett, Denise; Louka, Panagiota; Anders, Catherine B; Zhang, Jianhui; Punnoose, Alex

    2016-01-01

    ZnO nanoparticles (NPs) have previously been shown to exhibit selective cytotoxicity against certain types of cancerous cells suggesting their potential use in biomedical applications. In this study, we investigate the effect of surface modification of ZnO NPs on their cytotoxicity to both cancerous and primary T cells. Our results show that polyacrylic acid capping produces negatively charged ZnO NPs that are significantly more toxic compared to uncapped positively charged NPs of identical size and composition. In contrast, the greatest selectivity against cancerous cells relative to normal cells is observed with cationic NPs. In addition, differences in NP cytotoxicity inversely correlate with NP hydrodynamic size, propensity for aggregation, and dissolution profiles. The generation of reactive oxygen species (ROS) was also observed in the toxicity mechanism with anionic NPs generating higher levels of mitochondrial superoxide without appreciably affecting glutathione levels. Additional experiments evaluated the combined effects of charged ZnO NPs and nontoxic cationic or anionic CeO2 NPs. Results show that the CeO2 NPs offer protective effects against cytotoxicity from anionic ZnO NPs via antioxidant properties. Altogether, study data indicate that surface modification of NPs and resulting changes in their surface charge affect the level of intracellular ROS production, which can be ameliorated by the CeO2 ROS scavenger, suggesting that ROS generation is a dominant mechanism of ZnO NP cytotoxicity. These findings demonstrate the importance of surface electrostatic properties for controlling NP toxicity and illustrate an approach for engineering NPs with desired properties for potential use in biological applications. PMID:27486313

  7. In vitro cytotoxicity of superparamagnetic iron oxide nanoparticles on neuronal and glial cells. Evaluation of nanoparticle interference with viability tests.

    PubMed

    Costa, Carla; Brandão, Fátima; Bessa, Maria João; Costa, Solange; Valdiglesias, Vanessa; Kiliç, Gözde; Fernández-Bertólez, Natalia; Quaresma, Pedro; Pereira, Eulália; Pásaro, Eduardo; Laffon, Blanca; Teixeira, João Paulo

    2016-03-01

    Superparamagnetic iron oxide nanoparticles (ION) have attracted great interest for use in several biomedical fields. In general, they are considered biocompatible, but little is known of their effects on the human nervous system. The main objective of this work was to evaluate the cytotoxicity of two ION (magnetite), coated with silica and oleic acid, previously determining the possible interference of the ION with the methodological procedures to assure the reliability of the results obtained. Human neuroblastoma SHSY5Y and glioblastoma A172 cells were exposed to different concentrations of ION (5-300 µg ml(-1)), prepared in complete and serum-free cell culture medium for three exposure times (3, 6 and 24 h). Cytotoxicity was evaluated by means of the MTT, neutral red uptake and alamar blue assays. Characterization of the main physical-chemical properties of the ION tested was also performed. Results demonstrated that both ION could significantly alter absorbance readings. To reduce these interferences, protocols were modified by introducing additional washing steps and cell-free systems. Significant decreases in cell viability were observed for both cell lines in specific conditions by all assays. In general, oleic acid-coated ION were less cytotoxic than silica-coated ION; besides, a serum-protective effect was observed for both ION studied and cell lines. These results contribute to increase the knowledge of the potential harmful effects of ION on the human nervous system. Understanding these effects is essential to establish satisfactory regulatory policies on the safe use of magnetite nanoparticles in biomedical applications.

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

    PubMed

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

    2013-01-01

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

  9. Mycoplasma pneumoniae induces cytotoxic activity in guinea pig bronchoalveolar cells

    SciTech Connect

    Kist, M.; Koester, H.; Bredt, W.

    1985-06-01

    Precultured guinea pig alveolar macrophages (AM) and freshly harvested alveolar cells (FHAC) activated by interaction with Mycoplasma pneumoniae were cytotoxic for xenogeneic /sup 75/selenomethionine-labeled tumor target cells. Phagocytosis of whole opsonized or nonopsonized M. pneumoniae cells was more effective in eliciting cytotoxicity than uptake of sonicated microorganisms. The addition of living mycoplasma cells to the assay system enhanced the cytotoxic effect considerably. Target cells were significantly more susceptible to the cytotoxic action of phagocytes if they were coated with mycoplasma antigen or cocultured together with M. pneumoniae. The activation of the phagocytes could be inhibited by 2-deoxy-D-glucose but not by antimicrobial substances suppressing mycoplasma protein synthesis. It was accompanied by /sup 51/Cr release without detectable signs of cell damage. The supernatants of activated cells were cytotoxic for approximately 24 h. Inhibition, release, and cytotoxic activity indicate the necessity of an intact metabolism of the effector cells and suggest a secretion of cytotoxic substances.

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

    PubMed

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

    2012-12-11

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

  11. 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

  12. Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster

    PubMed Central

    Ng, Cheng Teng; Yong, Liang Qing; Hande, Manoor Prakash; Ong, Choon Nam; Yu, Liya E; Bay, Boon Huat; Baeg, Gyeong Hun

    2017-01-01

    Background Although zinc oxide nanoparticles (ZnO NPs) have been widely used, there has been an increasing number of reports on the toxicity of ZnO NPs. However, study on the underlying mechanisms under in vivo conditions is insufficient. Methods In this study, we investigated the toxicological profiles of ZnO NPs in MRC5 human lung fibroblasts in vitro and in an in vivo model using the fruit fly Drosophila melanogaster. A comprehensive study was conducted to evaluate the uptake, cytotoxicity, reactive oxygen species (ROS) formation, gene expression profiling and genotoxicity induced by ZnO NPs. Results For in vitro toxicity, the results showed that there was a significant release of extracellular lactate dehydrogenase and decreased cell viability in ZnO NP-treated MRC5 lung cells, indicating cellular damage and cytotoxicity. Generation of ROS was observed to be related to significant expression of DNA Damage Inducible Transcript (DDIT3) and endoplasmic reticulum (ER) to nucleus signaling 1 (ERN1) genes, which are ER stress-related genes. Oxidative stress induced DNA damage was further verified by a significant release of DNA oxidation product, 8-hydroxydeoxyguanosine (8-OHdG), as well as by the Comet assay. For the in vivo study using the fruit fly D. melanogaster as a model, significant toxicity was observed in F1 progenies upon ingestion of ZnO NPs. ZnO NPs induced significant decrease in the egg-to-adult viability of the flies. We further showed that the decreased viability is closely associated with ROS induction by ZnO NPs. Removal of one copy of the D. melanogaster Nrf2 alleles further decreased the ZnO NPs-induced lethality due to increased production of ROS, indicating that nuclear factor E2-related factor 2 (Nrf2) plays important role in ZnO NPs-mediated ROS production. Conclusion The present study suggests that ZnO NPs induced significant oxidative stress-related cytotoxicity and genotoxicity in human lung fibroblasts in vitro and in D. melanogaster in

  13. Studies on the cytotoxicity of diamond nanoparticles against human cancer cells and lymphocytes.

    PubMed

    Adach, Kinga; Fijalkowski, Mateusz; Gajek, Gabriela; Skolimowski, Janusz; Kontek, Renata; Blaszczyk, Alina

    2016-07-25

    Detonation nanodiamonds (DND) are a widely studied group of carbon nanomaterials. They have the ability to adsorb a variety of biomolecules and drugs onto their surfaces, and additionally their surfaces may be subjected to chemical functionalization by covalent bonds. We present a procedure for the purification and surface oxidation of diamond nanoparticles, which were then tested by spectroscopic analysis such as ATR-FTIR, Raman spectroscopy, and thermogravimetric analysis. We also examined the zeta potential of the tested material. Analysis of the cytotoxic effect of nanodiamonds against normal lymphocytes derived from human peripheral blood, the non-small cell lung cancer cell line (A549) and the human colorectal adenocarcinoma cell line (HT29) was performed using MTT colorimetric assay. Evaluation of cell viability was performed after 1-h and 24-h treatment with the tested nanoparticles applied at concentrations ranging from 1 μg/ml to 100 μg/ml. We found that the survival of the examined cells was strongly associated with the presence of serum proteins in the growth medium. The incubation of cells with nanodiamonds in the presence of serum did not exert a significant effect on cell survival, while the cell treatment in a serum-free medium resulted in a decrease in cell survival compared to the negative control. The role of purification and functionalization of nanodiamonds on their cytotoxicity was also demonstrated.

  14. Green synthesis of NiO nanoparticles using Moringa oleifera extract and their biomedical applications: Cytotoxicity effect of nanoparticles against HT-29 cancer cells.

    PubMed

    Ezhilarasi, A Angel; Vijaya, J Judith; Kaviyarasu, K; Maaza, M; Ayeshamariam, A; Kennedy, L John

    2016-11-01

    Green protocols for the synthesis of nickel oxide nanoparticles using Moringa oleifera plant extract has been reported in the present study as they are cost effective and ecofriendly, moreover this paper records that the nickel oxide (NiO) nanoparticles prepared from green method shows better cytotoxicity and antibacterial activity. The NiO nanoparticles were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), High resolution transmission electron microscopy (HRTEM), Energy dispersive X-ray analysis (EDX), and Photoluminescence spectroscopy (PL). The formation of a pure nickel oxide phase was confirmed by XRD and FTIR. The synthesized NiO nanoparticles was single crystalline having face centered cubic phase and has two intense photoluminescence emissions at 305.46nm and 410nm. The formation of nano- and micro-structures was confirmed by HRTEM. The in-vitro cytotoxicity and cell viability of human cancer cell HT-29 (Colon Carcinoma cell lines) and antibacterial studies against various bacterial strains were studied with various concentrations of nickel oxide nanoparticles prepared from Moringa oleifera plant extract. MTT assay measurements on cell viability and morphological studies proved that the synthesized NiO nanoparticles posses cytotoxic activity against human cancer cells and the various zones of inhibition (mm), obtained revealed the effective antibacterial activity of NiO nanoparticles against various Gram positive and Gram negative bacterial pathogens.

  15. Effects of fullerenol nanoparticles on acetamiprid induced cytoxicity and genotoxicity in cultured human lung fibroblasts.

    PubMed

    Çavaş, Tolga; Çinkılıç, Nilüfer; Vatan, Özgür; Yılmaz, Dilek

    2014-09-01

    The aim of this study was to investigate the effects of water soluble fullerene (fullerenol) nanoparticles on the in vitro genotoxicity induced by the insecticide acetamiprid. Healthy human lung cells (IMR-90) were treated with fullerenol C60(OH)n (n: 18-22) alone and in combination with acetamiprid for 24h. The micronucleus test, comet assay and γ-H2AX foci formation assays were used as genotoxicity endpoints. Cytotoxicity was evaluated using the clonogenic assay. The maximum tested concentration of fullerenol (1.600 μg/ml) induced 77% survival where as the lowest concentration (25 μg/ml) was not cytotoxic where as acetamiprid was cytotoxic. Fullerenol did not induce genotoxicity at tested concentrations (50-1600 μg/L). On the other hand, acetamiprid (>50 μM) significantly induced formation of micronuclei, and double and single stranded DNA breaks in IMR-90 cells. For simultaneous exposure studies, two non-cytotoxic concentrations (50 and 200 μg/ml) of fullerenol and three cytotoxic concentrations of acetamiprid (100, 200 and 400 μM) were selected. As a result, we observed that co-exposure with fullerenol significantly reduced the cytotoxicity and genotoxicity of acetamiprid in IMR-90 cells. Our results indicated the protective effect of water soluble fullerene particles on herbicide induced genotoxicity.

  16. Cytotoxicity induced by engineered silver nanocrystallites is dependent on surface coatings and cell types.

    PubMed

    Suresh, Anil K; Pelletier, Dale A; Wang, Wei; Morrell-Falvey, Jennifer L; Gu, Baohua; Doktycz, Mitchel J

    2012-02-07

    Due to their unique antimicrobial properties silver nanocrystallites have garnered substantial attention and are used extensively for biomedical applications as an additive to wound dressings, surgical instruments and bone substitute materials. They are also released into unintended locations such as the environment or biosphere. Therefore it is imperative to understand the potential interactions, fate and transport of nanoparticles with environmental biotic systems. Numerous factors including the composition, size, shape, surface charge, and capping molecule of nanoparticles are known to influence cell cytotoxicity. Our results demonstrate that the physical/chemical properties of the silver nanoparticles including surface charge, differential binding and aggregation potential, which are influenced by the surface coatings, are a major determining factor in eliciting cytotoxicity and in dictating potential cellular interactions. In the present investigation, silver nanocrystallites with nearly uniform size and shape distribution but with different surface coatings, imparting overall high negativity to high positivity, were synthesized. These nanoparticles included poly(diallyldimethylammonium) chloride-Ag, biogenic-Ag, colloidal-Ag (uncoated), and oleate-Ag with zeta potentials +45 ± 5, -12 ± 2, -42 ± 5, and -45 ± 5 mV, respectively; the particles were purified and thoroughly characterized so as to avoid false cytotoxicity interpretations. A systematic investigation on the cytotoxic effects, cellular response, and membrane damage caused by these four different silver nanoparticles was carried out using multiple toxicity measurements on mouse macrophage (RAW-264.7) and lung epithelial (C-10) cell lines. Our results clearly indicate that the cytotoxicity was dependent on various factors such as surface charge and coating materials used in the synthesis, particle aggregation, and the cell-type for the different silver nanoparticles that were investigated. Poly

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

    PubMed

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

    2013-06-07

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

  18. Low cytotoxic trace element selenium nanoparticles and their differential antimicrobial properties against S. aureus and E. coli

    NASA Astrophysics Data System (ADS)

    Tran, Phong A.; O'Brien-Simpson, Neil; Reynolds, Eric C.; Pantarat, Namfon; Biswas, Dhee P.; O'Connor, Andrea J.

    2016-01-01

    Antimicrobial agents that have no or low cytotoxicity and high specificity are desirable to have no or minimal side effects. We report here the low cytotoxicity of polyvinyl alcohol-stabilized selenium (Se) nanoparticles and their differential effects on growth of S. aureus, a gram-positive bacterium and E. coli, a gram-negative bacterium. The nanoparticles were synthesised through redox reactions in an aqueous environment at room temperature and were characterised using UV visible spectrophotometry, transmission electron microscopy, dynamic light scattering and x-ray photoelectron spectroscopy. The nanoparticles showed low toxicity toward fibroblasts which remained more than 70% viable at Se concentrations as high as 128 ppm. The nanoparticles also exhibited very low haemolysis with only 18% of maximal lysis observed at a Se concentration of 128 ppm. Importantly, the nanoparticles showed strong growth inhibition toward S. aureus at a concentration as low as 1 ppm. Interestingly, growth of E. coli was unaffected at all concentrations tested. This study therefore strongly suggests that these nanoparticles should be investigated further to understand this differential effect as well as for potential advanced antimicrobial applications such as S. aureus infection—resisting, non-cytotoxic coatings for medical devices.

  19. 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

    2015-04-01

    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.

  20. Antibacterial activity and cytotoxicity of multi-walled carbon nanotubes decorated with silver nanoparticles

    PubMed Central

    Seo, Youngmin; Hwang, Jangsun; Kim, Jieun; Jeong, Yoon; Hwang, Mintai P; Choi, Jonghoon

    2014-01-01

    Recently, various nanoscale materials, including silver (Ag) nanoparticles, have been actively studied for their capacity to effectively prevent bacterial growth. A critical challenge is to enhance the antibacterial properties of nanomaterials while maintaining their biocompatibility. The conjugation of multiple nanomaterials with different dimensions, such as spherical nanoparticles and high-aspect-ratio nanotubes, may increase the target-specific antibacterial capacity of the consequent nanostructure while retaining an optimal biocompatibility. In this study, multi-walled carbon nanotubes (MWCNTs) were treated with a mixture of acids and decorated with Ag nanoparticles via a chemical reduction of Ag cations by ethanol solution. The synthesized Ag-MWCNT complexes were characterized by transmission electron microscopy, X-ray diffractometry, and energy-dispersive X-ray spectroscopy. The antibacterial function of Ag-MWCNTs was evaluated against Methylobacterium spp. and Sphingomonas spp. In addition, the biocompatibility of Ag-MWCNTs was evaluated using both mouse liver hepatocytes (AML 12) and human peripheral blood mononuclear cells. Finally, we determined the minimum amount of Ag-MWCNTs required for a biocompatible yet effective antibacterial treatment modality. We report that 30 μg/mL of Ag-MWCNTs confers antibacterial functionality while maintaining minimal cytotoxicity toward both human and animal cells. The results reported herein would be beneficial for researchers interested in the efficient preparation of hybrid nanostructures and in determining the minimum amount of Ag-MWCNTs necessary to effectively hinder the growth of bacteria. PMID:25336943

  1. Antibacterial activity and cytotoxicity of multi-walled carbon nanotubes decorated with silver nanoparticles.

    PubMed

    Seo, Youngmin; Hwang, Jangsun; Kim, Jieun; Jeong, Yoon; Hwang, Mintai P; Choi, Jonghoon

    2014-01-01

    Recently, various nanoscale materials, including silver (Ag) nanoparticles, have been actively studied for their capacity to effectively prevent bacterial growth. A critical challenge is to enhance the antibacterial properties of nanomaterials while maintaining their biocompatibility. The conjugation of multiple nanomaterials with different dimensions, such as spherical nanoparticles and high-aspect-ratio nanotubes, may increase the target-specific antibacterial capacity of the consequent nanostructure while retaining an optimal biocompatibility. In this study, multi-walled carbon nanotubes (MWCNTs) were treated with a mixture of acids and decorated with Ag nanoparticles via a chemical reduction of Ag cations by ethanol solution. The synthesized Ag-MWCNT complexes were characterized by transmission electron microscopy, X-ray diffractometry, and energy-dispersive X-ray spectroscopy. The antibacterial function of Ag-MWCNTs was evaluated against Methylobacterium spp. and Sphingomonas spp. In addition, the biocompatibility of Ag-MWCNTs was evaluated using both mouse liver hepatocytes (AML 12) and human peripheral blood mononuclear cells. Finally, we determined the minimum amount of Ag-MWCNTs required for a biocompatible yet effective antibacterial treatment modality. We report that 30 μg/mL of Ag-MWCNTs confers antibacterial functionality while maintaining minimal cytotoxicity toward both human and animal cells. The results reported herein would be beneficial for researchers interested in the efficient preparation of hybrid nanostructures and in determining the minimum amount of Ag-MWCNTs necessary to effectively hinder the growth of bacteria.

  2. Cytotoxic interactions of bare and coated NaGdF4:Yb(3+):Er(3+) nanoparticles with macrophage and fibroblast cells.

    PubMed

    Wysokińska, E; Cichos, J; Zioło, E; Bednarkiewicz, A; Strządała, L; Karbowiak, M; Hreniak, D; Kałas, W

    2016-04-01

    The lanthanide nano-compounds are well suited to serve as fluorescent and magnetic contrast agents and luminescent labels. Although they are considered as promising materials for bio-imaging and bio-sensors in vivo or in vitro, the amount of data is still insufficient for deep understanding the toxicity of these nanomaterials. This knowledge is of great importance in the light of growing use of the biofunctionalized nanoparticles, which raises some questions about safety of these materials. Despite lanthanide-doped NaGdF4 nanocrystals are considered as non-toxic, here we present the data showing the fatal effect of newly synthetized NaGdF4:Yb(3+):Er(3+) on chosen types of cells. Our studies were performed on two cell lines NIH3T3 fibroblasts, and RAW264.7 macrophages. Cytotoxic properties of NaGdF4:Yb(3+):Er(3+) nanoparticles and their biological effects were studied by assessing cell culture viability (MTS), proliferation and apoptosis. Bare NaGdF4:Yb(3+):Er(3+) nanocrystals were cytotoxic and induced apoptosis of both NIH3T3 and RAW264.7 cells. Their cytotoxicity was reduced by PEGylation, at the expense of minimizing direct interactions between the compound and the cell. On the other hand, coating with silica reduced cell death induced by Yb(3+):Er(3+) codoped NaGdF4 nanocrystals (but proliferation was still inhibited). The NH2-modified silica coated nanoparticles were clearly less cytotoxic than pristine nanoparticles, which suggests that both, silica and PEG coatings are reasonable approaches to decrease cytotoxicity of the nanocrystal labels. The silica and PEG shell, should also enable and simplify further bio-functionalization of these luminescent labels. The authors acknowledge the financial support from: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences (IITD PAN) grant no. 3/15, Polish Ministry of Science and Higher Education, Grant N N507 499538 and from the Wroclaw Research Centre EIT+ within the project "The Application of

  3. Dose-dependent cytotoxicity evaluation of graphite nanoparticles for diamond-like carbon film application on artificial joints.

    PubMed

    Liao, T T; Deng, Q Y; Wu, B J; Li, S S; Li, X; Wu, J; Leng, Y X; Guo, Y B; Huang, N

    2017-01-24

    While a diamond-like carbon (DLC)-coated joint prosthesis represents the implant of choice for total hip replacement in patients, it also leads to concern due to the cytotoxicity of wear debris in the form of graphite nanoparticles (GNs), ultimately limiting its clinical use. In this study, the cytotoxicity of various GN doses was evaluated. Mouse macrophages and osteoblasts were incubated with GNs (<30 nm diameter), followed by evaluation of cytotoxicity by means of assessing inflammatory cytokines, results of alkaline phosphatase assays, and related signaling protein expression. Cytotoxicity evaluation showed that cell viability decreased in a dose-dependent manner (10-100 μg ml(-1)), and steeply declined at GNs concentrations greater than 30 μg ml(-1). Noticeable cytotoxicity was observed as the GN dose exceeded this threshold due to upregulated receptor of activator of nuclear factor kB-ligand expression and downregulated osteoprotegerin expression. Meanwhile, activated macrophage morphology was observed as a result of the intense inflammatory response caused by the high doses of GNs (>30 μg ml(-1)), as observed by the increased release of TNF-α and IL-6. The results suggest that GNs had a significant dose-dependent cytotoxicity in vitro, with a lethal dose of 30 μg ml(-1) leading to dramatic increases in cytotoxicity. Our GN cytotoxicity evaluation indicates a safe level for wear debris-related arthropathy and could propel the clinical application of DLC-coated total hip prostheses.

  4. Effect of capping agents on the cytotoxicity of silver nanoparticles in human normal and cancer skin cell lines

    NASA Astrophysics Data System (ADS)

    Netchareonsirisuk, Ponsawan; Puthong, Songchan; Dubas, Stephan; Palaga, Tanapat; Komolpis, Kittinan

    2016-11-01

    Silver nanoparticles (AgNPs) are among the most widely used nanomaterials in medical and consumer products. However, safety in the uses of AgNPs is still controversial. The toxicity of AgNPs toward various cell types has been reported to depend on the surface properties of the nanoparticles. In this study, the effect of AgNPs with the average size of 5-15 nm on the viability of the CCD-986SK human normal skin fibroblast cell line and A375 human malignant melanoma cell line was evaluated. Comparative toxicity studies, based on MTT assay, were performed by using either sodium alginate or poly (4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSMA) as capping agent in the nanoparticle preparation. The cytotoxicity tests revealed that AgNO3 alone was highly toxic to both cell types while both alginate and PSSMA alone were not toxic. AgNPs capped with alginate were selectively toxic to the cancer cell line but not to the normal cell line while AgNPs capped with PSSMA were toxic to both cancer and normal cell lines. Judging from the 50 % inhibition concentration (IC50), it was found that the cancer cell line was more sensitive to AgNPs than the normal cell line. Study on the mode of cell death by annexin V and propidium iodide staining revealed that AgNPs induced more apoptotic cell death (84-90 %) than necrosis (8-12 %) in the skin cancer cell line. These results suggest that the toxicity of AgNPs depended on the type of capping agent and the type of cell line.

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

    SciTech Connect

    Niu, Lu; Li, Yang; Li, Xiaojie; Gao, Xue; Su, Xingguang

    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.

  6. Characterization of acetaminophen-induced cytotoxicity in target tissues

    PubMed Central

    Guo, Chao; Xie, Guojie; Su, Min; Wu, Xinmou; Lu, Xiuli; Wu, Ka; Wei, Chaohe

    2016-01-01

    Acetaminophen (APAP), commonly used in clinical prescription, has time- and dose-dependent side effects. Thus, further animal study warrants to be investigated to assess possible adverse effect of APAP application. Here, we conducted pre-clinical research to elucidate the molecular mechanism regarding APAP-mediated toxicological action. Our data showed that serous/urinary and hepatic/renal APAP concentrations were significantly increased when compared with normal control, which the liver tissue showed the highest level. As an acute liver damage model induced by APAP, absolute liver weight, serum enzyme (ALT), urine protein content were notably elevated. Representatively, APAP-damaged liver resulted in increased pro-apoptotic Bax and compensatory Ki-67 positive cells, while the number of anti-apoptotic Bcl2 positive cells was reduced. In addition, the immunoactivity markers for NF-κB, TRL4, TNF-α in the kidney were increased, respectively. Furthermore, intracellular TRL4 and TNF-α mRNAs in the liver and kidney showed significant up-regulation. In summary, our current findings demonstrate that APAP-mediated the specific cytotoxicity is linked to the molecular mechanisms of facilitating apoptosis and inflammatory stress in the liver and kidney. PMID:27830028

  7. MECHANISMS OF ASCORBATE-INDUCED CYTOTOXICITY IN PANCREATIC CANCER

    PubMed Central

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

    2009-01-01

    Purpose Pharmacological concentrations of ascorbate may be effective in cancer therapeutics. We hypothesized that ascorbate concentrations achievable with intravenous dosing would be cytotoxic in pancreatic cancer where the five-year survival is < 3%. Experimental Design Pancreatic cancer cell lines were treated with ascorbate (0, 5, and 10 mM) for one hour, then viability and clonogenic survival were determined. Pancreatic tumor cells were delivered subcutaneously into the flank region of nude mice and allowed to grow at which time they were randomized to receive either ascorbate (4 g/kg) or osmotically equivalent saline (1 M) i.p. for two weeks. Results There was a time and dose-dependent increase in measured H2O2 production with increased concentrations of ascorbate. Ascorbate decreased viability in all pancreatic cancer cell lines, but had no effect on an immortalized pancreatic ductal epithelial cell line. Ascorbate decreased clonogenic survival of the pancreatic cancer cell lines, which was reversed by treatment of cells with scavengers of H2O2. Treatment with ascorbate induced a caspase-independent cell death that was associated with autophagy. In vivo, treatment with ascorbate inhibited tumor growth and prolonged survival. Conclusions These results demonstrate that pharmacological doses of ascorbate, easily achievable in humans, may have potential for therapy in pancreatic cancer. PMID:20068072

  8. Magnetic induced heating of nanoparticle solutions

    SciTech Connect

    Murph, S. Hunyadi; Brown, M.; Coopersmith, K.; Fulmer, S.; Sessions, H.; Ali, M.

    2016-12-02

    Magnetic induced heating of nanoparticles (NP) provides a useful advantage for many energy transfer applications. This study aims to gain an understanding of the key parameters responsible for maximizing the energy transfer leading to nanoparticle heating through the use of simulations and experimental results. It was found that magnetic field strength, NP concentration, NP composition, and coil size can be controlled to generate accurate temperature profiles in NP aqueous solutions.

  9. 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 γH2AX 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 γH2AX 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

  10. Shape and surface effects on the cytotoxicity of nanoparticles: Gold nanospheres versus gold nanostars.

    PubMed

    Favi, Pelagie Marlene; Gao, Ming; Johana Sepúlveda Arango, Liuda; Ospina, Sandra Patricia; Morales, Mariana; Pavon, Juan Jose; Webster, Thomas Jay

    2015-11-01

    Gold nanoparticles are materials with unique optical properties that have made them very attractive for numerous biomedical applications. With the increasing discovery of techniques to synthesize novel nanoparticles such as star-shaped gold nanoparticles for biomedical applications, the safety and performance of these new nanomaterials must be systematically assessed before use. In this study, gold nanostars (AuNSTs) with multibranched surface structures were synthesized, and their influence on the cytotoxicity of human skin fibroblasts and rat fat pad endothelial cells (RFPECs) were assessed and compared with that of gold nanospheres (AuNSPs) with unbranched surfaces. Results showed that the AuNSPs with diameters of approximately 61.46 nm showed greater toxicity with fibroblast cells and RFPECs compared with the synthesized AuNSTs with diameters of approximately 33.69 nm. The AuNSPs were lethal at concentrations of 40 μg/mL for both cell lines, whereas the AuNSTs were less toxic at higher concentrations (400 μg/mL). The calculated IC50 (50% inhibitory concentration) values of the AuNSPs exposed to fibroblast cells were greater at 1 and 4 days of culture (26.4 and 27.7 μg/mL, respectively) compared with the RFPECs (13.6 and 13.8 μg/mL, respectively), indicating that the AuNSPs have a greater toxicity to endothelial cells. It was proposed that possible factors that could be promoting the reduced toxicity effects of the AuNSTs to fibroblast cells and RFPECs, compared with the AuNSPs may be size, surface chemistry, and shape of the gold nanoparticles. The reduced cell toxicity observed with the AuNSTs suggests that AuNSTs may be a promising material for use in biomedical applications.

  11. Synthesis, characterization and cytotoxic evaluation of chitosan nanoparticles: in vitro liver cancer model

    NASA Astrophysics Data System (ADS)

    Loutfy, Samah A.; Alam El-Din, Hanaa M.; Elberry, Mostafa H.; Allam, Nanis G.; Hasanin, M. T. M.; Abdellah, Ahmed M.

    2016-09-01

    To evaluate the cytotoxic effect of chitosan nanoparticles (CS-NPs) on an in vitro human liver cancer cell model (HepG2) and their possible application as a drug delivery system, we synthesized water-soluble CS-NPs, investigated their properties and extensively evaluated their cytotoxic activity on the cellular and molecular levels. A human liver cancer cell line was used as a model of human liver cancer. The CS-NPs were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy, and zeta analysis. The cytotoxic effects of the CS-NPs on HepG2 cells were monitored by sulforhodamine B colorimetric assays for cytotoxicity screening and flow cytometric analysis. Molecular investigations including DNA fragmentation and the expression of some apoptotic genes on the transcriptional RNA level were conducted. Treatment of HepG2 with different concentrations of 150 nm diameter CS-NPs did not show alteration of cell morphology after 24 h of cell exposure. Also, when cells were treated with 100 μg ml-1 of CS-NPs, 12% of them were killed and IC50 reached 239 μg ml-1 after 48 h of cell exposure. Flow cytometry evaluation of the CS-NPs revealed mild accumulation in the G2/M phase followed by cellular DNA fragmentation after 48 h of cell exposure. Extensive evaluation of the cytotoxic effect of the CS-NPs showed messenger RNA (mRNA) apoptotic gene expression (p53, Bak, Caspase3) after 24 h of cell exposure with no expression of the mRNA of the caspase 3 gene after 48 h of cell exposure, suggesting the involvement of an intrinsic apoptotic caspase-independent pathway by increasing the exposure time of 100 μg ml-1 of the CS-NPs. The engineered CS-NPs were controlled to a 150 nm size and charges of 40 mV and a concentration of 100 μg ml-1 revealed a genotoxic effect on HepG2 after 48 h of cell exposure through intrinsic apoptotic caspase-independent mechanisms. Further quantitative analysis on the molecular and protein levels is still required

  12. Piper betle-mediated synthesis, characterization, antibacterial and rat splenocyte cytotoxic effects of copper oxide nanoparticles.

    PubMed

    Praburaman, Loganathan; Jang, Jum-Suk; Muthusamy, Govarthanan; Arumugam, Sengottaiyan; Manoharan, Koildhasan; Cho, Kwang-Min; Min, Cho; Kamala-Kannan, Seralathan; Byung-Taek, Oh

    2016-09-01

    The study reports a simple, inexpensive, and eco-friendly synthesis of copper oxide nanoparticles (CuONPs) using Piper betle leaf extract. Formation of CuONPs was confirmed by UV-visible spectroscopy at 280 nm. Transmission electron microscopy (TEM) images showed that the CuONPs were spherical, with an average size of 50-100 nm. The scanning electron microscopy (SEM)-energy dispersive spectroscopy (EDS) peak was observed approximately at 1 and 8 keV. The X-ray diffraction (XRD) studies indicated that the particles were crystalline in nature. CuONPs effectively inhibited the growth of phytopathogens Ralstonia solanacearum and Xanthomonas axonopodis. The cytotoxic effect of the synthesized CuONPs was analyzed using rat splenocytes. The cell viability was decreased to 94% at 300 μg/mL.

  13. The impact of nanoparticle protein corona on cytotoxicity, immunotoxicity and target drug delivery

    PubMed Central

    Corbo, Claudia; Molinaro, Roberto; Parodi, Alessandro; Toledano Furman, Naama E; Salvatore, Francesco; Tasciotti, Ennio

    2016-01-01

    In a perfect sequence of events, nanoparticles (NPs) are injected into the bloodstream where they circulate until they reach the target tissue. The ligand on the NP surface recognizes its specific receptor expressed on the target tissue and the drug is released in a controlled manner. However, once injected in a physiological environment, NPs interact with biological components and are surrounded by a protein corona (PC). This can trigger an immune response and affect NP toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the NP–PC interactions and discuss how the PC can be used to modulate both cytotoxicity and the immune response as well as to improve the efficacy of targeted delivery of nanocarriers. PMID:26653875

  14. The impact of nanoparticle protein corona on cytotoxicity, immunotoxicity and target drug delivery.

    PubMed

    Corbo, Claudia; Molinaro, Roberto; Parodi, Alessandro; Toledano Furman, Naama E; Salvatore, Francesco; Tasciotti, Ennio

    2016-01-01

    In a perfect sequence of events, nanoparticles (NPs) are injected into the bloodstream where they circulate until they reach the target tissue. The ligand on the NP surface recognizes its specific receptor expressed on the target tissue and the drug is released in a controlled manner. However, once injected in a physiological environment, NPs interact with biological components and are surrounded by a protein corona (PC). This can trigger an immune response and affect NP toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the NP-PC interactions and discuss how the PC can be used to modulate both cytotoxicity and the immune response as well as to improve the efficacy of targeted delivery of nanocarriers.

  15. 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

  16. Folate Conjugated Cellulose Nanocrystals Potentiate Irreversible Electroporation-induced Cytotoxicity for the Selective Treatment of Cancer Cells.

    PubMed

    Colacino, Katelyn R; Arena, Christopher B; Dong, Shuping; Roman, Maren; Davalos, Rafael V; Lee, Yong W

    2015-12-01

    Cellulose nanocrystals are rod-shaped, crystalline nanoparticles that have shown prom-ise in a number of industrial applications for their unique chemical and physical properties. However, investigations of their abilities in the biomedical field are limited. The goal of this study is to show the potential use of folic acid-conjugated cellulose nanocrystals in the potentiation of irreversible electroporation-induced cell death in folate receptor (FR)-positive cancers. We optimized key pulse parameters including pulse duration, intensity, and incubation time with nanoparticles prior to electroporation. FR-positive cancer cells, KB and MDA-MB-468, were preincubated with cellulose nanocrystals (CNCs) conjugated with the targeting molecule folic acid (FA), 10 and 20 min respectively, prior to application of the optimized pulse electric field (PEF), 600 and 500 V/cm respectively. We have shown cellulose nanocrystals' ability to potentiate a new technique for tumor ablation, irreversible electroporation. Pre-incubation with FA-conjugated CNCs (CNC-FA) has shown a significant increase in cytotoxicity induced by irreversible electroporation in FR-positive cancer cells, KB and MDA-MB-468. Non-targeted CNCs (CNC-COOH) did not potentiate IRE when preincubated at the same parameters as previously stated in these cell types. In addition, CNC-FA did not potentiate irreversible electroporation-induced cytotoxicity in a FR-negative cancer cell type, A549. Without changing irreversible electroporation parameters it is possible to increase the cytotoxic effect on FR-positive cancer cells by exploiting the specific binding of FA to the FR, while not causing further damage to FR-negative tissue.

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

    NASA Astrophysics Data System (ADS)

    Ge, Gaoyuan; Wu, Hengfang; Xiong, Fei; Zhang, Yu; Guo, Zhirui; Bian, Zhiping; Xu, Jindan; Gu, Chunrong; Gu, Ning; Chen, Xiangjian; Yang, Di

    2013-05-01

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

  18. Cytotoxicity of cuprous oxide nanoparticles to fish blood cells: hemolysis and internalization

    NASA Astrophysics Data System (ADS)

    Chen, Li Qiang; Kang, Bin; Ling, Jian

    2013-03-01

    Cuprous oxide nanoparticles (Cu2O NPs) possess unique physical and chemical properties which are employed in a broad variety of applications. However, little is known about the adverse effects of Cu2O NPs on organisms. In the current study, in vitro cytotoxicity of Cu2O NPs (ca. 60 nm in diameter) to the blood cells of freshwater fish Carassius auratus was evaluated. A concentration-dependent hemolytic activity of Cu2O NPs to red blood cells (RBCs) and the phagocytosis of Cu2O NPs by leukocytes were revealed. The results showed that dosages of Cu2O NPs greater than 40 μg/mL were toxic to blood cells, and could cause serious membrane damage to RBCs. The EC50 value of Cu2O NPs as obtained from RBCs and whole blood exposure was 26 and 63 μg/mL, respectively. The generation of reactive oxygen species and the direct interaction between Cu2O NPs and the cell membrane were suggested as the possible mechanism for cytotoxicity, and the intrinsic hemolytic active of Cu2O NPs was the main contributor to the toxicity rather than solubilized copper ions. The adsorption of plasma proteins on the surfaces of Cu2O NPs led to their aggregation in whole blood, and aggregate formation can significantly alleviate the hemolytic effect and subsequently mediate the phagocytosis of Cu2O NPs by leukocytes.

  19. 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 μg/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

  20. Shape-dependent antibacterial effects of non-cytotoxic gold nanoparticles

    PubMed Central

    Penders, Jelle; Stolzoff, Michelle; Hickey, Daniel J; Andersson, Martin; Webster, Thomas J

    2017-01-01

    Gold nanoparticles (AuNPs) of various shapes (including spheres, stars and flowers), with similar dimensions, were synthesized and evaluated for their antibacterial effects toward Staphylococcus aureus, a bacterium responsible for numerous life-threatening infections worldwide. Optical growth curve measurements and Gompertz modeling showed significant AuNP shape- and concentration-dependent decreases in bacterial growth with increases in bacterial growth lag time. To evaluate prospective use in in vivo systems, the cytotoxicity of the same AuNPs was evaluated toward human dermal fibroblasts in vitro by 3-(4,5 dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) viability assays and confocal microscopy. No indication of any mammalian cell toxicity or morphological effects was found. Additionally, it was observed that the AuNPs were readily internalized in fibroblasts after 4 days of incubation. Most importantly, the results of the present study showed that gold nanoflowers in particular possessed the most promising non-cytotoxic mammalian cell behavior with the greatest shape-dependent antibacterial activity-promising properties for their future investigation in a wide range of anti-infection applications.

  1. Enhancement of radiation cytotoxicity in breast-cancer cells by localized attachment of gold nanoparticles.

    PubMed

    Kong, Tao; Zeng, Jie; Wang, Xiaoping; Yang, Xiaoyan; Yang, Jing; McQuarrie, Steve; McEwan, Alexander; Roa, Wilson; Chen, Jie; Xing, James Z

    2008-09-01

    Gold nanoparticles (GNPs) and modified GNPs having two kinds of functional molecules, cysteamine (AET) and thioglucose (Glu), are synthesized. Cell uptake and radiation cytotoxicity enhancement in a breast-cancer cell line (MCF-7) versus a nonmalignant breast-cell line (MCF-10A) are studied. Transmission electron microscopy (TEM) results show that cancer cells take up functional Glu-GNPs significantly more than naked GNPs. The TEM results also indicate that AET-capped GNPs are mostly bound to the MCF-7 cell membrane, while Glu-GNPs enter the cells and are distributed in the cytoplasm. After MCF-7 cell uptake of Glu-GNPs, or binding of AET-GNPs, the in vitro cytotoxicity effects are observed at 24, 48, and 72 hours. The results show that these functional GNPs have little or no toxicity to these cells. To validate the enhanced killing effect on cancer cells, various forms of radiation are applied such as 200 kVp X-rays and gamma-rays, to the cells, both with and without functional GNPs. By comparison with irradiation alone, the results show that GNPs significantly enhance cancer killing.

  2. Study of serum interaction with a cationic nanoparticle: Implications for in vitro endocytosis, cytotoxicity and genotoxicity.

    PubMed

    Merhi, Maysaloun; Dombu, Christophe Youta; Brient, Alizée; Chang, Jiang; Platel, Anne; Le Curieux, Frank; Marzin, Daniel; Nesslany, Fabrice; Betbeder, Didier

    2012-02-14

    We used well-characterized and positively charged nanoparticles (NP(+)) to investigate the importance of cell culture conditions, specifically the presence of serum and proteins, on NP(+) physicochemical characteristics, and the consequences for their endocytosis and genotoxicity in bronchial epithelial cells (16HBE14o-). NP(+) surface charge was significantly reduced, proportionally to NP(+)/serum and NP(+)/BSA ratios, while NP(+) size was not modified. Microscopy studies showed high endocytosis of NP(+) in 16HBE14o-, and serum/proteins impaired this internalization in a dose-dependent manner. Toxicity studies showed no cytotoxicity, even for very high doses of NP(+). No genotoxicity was observed with classic comet assay while primary oxidative DNA damage was observed when using the lesion-specific repair enzyme, formamidopyrimidine DNA-glycosylase (FPG). The micronucleus test showed NP(+) genotoxicity only for very high doses that cannot be attained in vivo. The low toxicity of these NP(+) might be explained by their high exocytosis from 16HBE14o- cells. Our results confirm the importance of serum and proteins on nanoparticles endocytosis and genotoxicity.

  3. Cytotoxic and anti-angiogenic paclitaxel solubilized and permeation-enhanced by natural product nanoparticles

    PubMed Central

    Liu, Zhijun; Zhang, Fang; Koh, Gar Yee; Dong, Xin; Hollingsworth, Javoris; Zhang, Jian; Russo, Paul S.; Yang, Peiying; Stout, Rhett W.

    2014-01-01

    Paclitaxel (PTX) is one of the most potent intravenous chemotherapeutic agents to date, yet an oral formulation has been problematic due to its low solubility and permeability. Using the recently discovered solubilizing properties of rubusoside (RUB), we investigated this unique PTX-RUB formulation. Paclitaxel was solubilized by RUB in water to levels of 1.6 to 6.3 mg/mL at 10 to 40% weight/volume. These, nanomicellar, PTX-RUB complexes were dried to a powder which was subsequently reconstituted in physiologic solutions. After 2.5 hrs in gastric fluid 85 to 99% of PTX-RUB remained soluble, while 79 to 96% remained soluble in intestinal fluid. The solubilization of PTX was mechanized by the formation of water-soluble spherical nanomicelles between PTX and RUB with an average diameter of 6.6 nm. Compared with Taxol®, PTX-RUB nanoparticles were nearly four times more permeable in Caco-2 cell monocultures. In a side-by-side comparison with DMSO-solubilized PTX, PTX-RUB maintained the same level of cytotoxicity against three human cancer cell lines with IC50 values ranging from 4 nM to 20 nM. Additionally, tubular formation and migration of HUVECs were inhibited at levels as low as 5 nM. These chemical and biological properties demonstrated by the PTX-RUB nanoparticles may improve oral bioavailability and enable further pharmacokinetic, toxicologic, and efficacy investigations. PMID:25243454

  4. Cytotoxic and antiangiogenic paclitaxel solubilized and permeation-enhanced by natural product nanoparticles.

    PubMed

    Liu, Zhijun; Zhang, Fang; Koh, Gar Yee; Dong, Xin; Hollingsworth, Javoris; Zhang, Jian; Russo, Paul S; Yang, Peiying; Stout, Rhett W

    2015-02-01

    Paclitaxel (PTX) is one of the most potent intravenous chemotherapeutic agents to date, yet an oral formulation has been problematic because of its low solubility and permeability. Using the recently discovered solubilizing properties of rubusoside (RUB), we investigated the unique PTX-RUB formulation. PTX was solubilized by RUB in water to levels of 1.6-6.3 mg/ml at 10-40% weight/volume. These nanomicellar PTX-RUB complexes were dried to a powder, which was subsequently reconstituted in physiologic solutions. After 2.5 h, 85-99% of PTX-RUB remained soluble in gastric fluid, whereas 79-96% remained soluble in intestinal fluid. The solubilization of PTX was mechanized by the formation of water-soluble spherical nanomicelles between PTX and RUB, with an average diameter of 6.6 nm. Compared with Taxol, PTX-RUB nanoparticles were nearly four times more permeable in Caco-2 cell monocultures. In a side-by-side comparison with dimethyl sulfoxide-solubilized PTX, PTX-RUB maintained the same level of cytotoxicity against three human cancer cell lines with IC50 values ranging from 4 to 20 nmol/l. In addition, tubule formation and migration of human umbilical vein endothelial cells were inhibited at levels as low as 5 nmol/l. These chemical and biological properties demonstrated by the PTX-RUB nanoparticles may improve oral bioavailability and enable further pharmacokinetic, toxicologic, and efficacy investigations.

  5. Active targeted nanoparticles: Preparation, physicochemical characterization and in vitro cytotoxicity effect

    PubMed Central

    Heidarian, Sh.; Derakhshandeh, K.; Adibi, H.; Hosseinzadeh, L.

    2015-01-01

    In this study, the folate decorated biodegradable poly (lactide-co-glycolide) (PLGA) nanoparticles were developed for tumor targeting of anticancer agents. Due to the overexpression of the folate receptor on tumor surface, the folate has been efficiently employed as a targeting moiety for various anticancer agents to avoid their non-specific attacks on normal tissues and also to increase their cellular uptake within target cells. Folate conjugate PLGA was synthesized successfully and its chemical structure was evaluated by FTIR, DSC and 1HNMR spectroscopy. PLGA-folate nanoparticles (PLGA-Fol NPs) were prepared by nanoprecipitation method, adopting PLGA as a drug carrier, folic acid as a targeting ligand and 9-nitrocampthotecin as a model anticancer drug. The average size and encapsulation efficiency of the prepared PLGA-Fol NPs were found to be around 115 ± 12 nm and 57%, respectively. In vitro release profile indicated that nearly 85% of the drug was released in 50 h. The in vitro intracellular uptakes of PLGA-Fol NPs showed greater cytotoxicity on cancer cell lines compared to non-folate mediated carriers. PMID:26600851

  6. The applicability of conventional cytotoxicity assays to predict safety/toxicity of mesoporous silica nanoparticles, silver and gold nanoparticles and multi-walled carbon nanotubes.

    PubMed

    Mannerström, Marika; Zou, Jing; Toimela, Tarja; Pyykkö, Ilmari; Heinonen, Tuula

    2016-12-01

    Developing new, validated methods for screening of the effects of nanomaterials is a huge and expensive task. It is therefore necessary to try to employ already existing and validated methods, developed for chemicals. In the present study cytotoxicity of gold (Au) and silver (Ag) nanoparticles (NP), two different mesoporous silica nanoparticles (MSNP), and multi-walled carbon nanotubes (MWCNT) were investigated in BALB/c 3T3 fibroblasts, NR8383 macrophages, and U937 monocytes using standard assays, namely WST-1 and NRU. In addition, preliminary attempts were made to investigate ENM-mediated effects on cell motility as a potential end point for NP toxicity. AgNPs were most toxic to BALB/c 3T3 fibroblasts while other ENMs were insignificantly toxic. NR8383 macrophages were most sensitive cells, as in addition to AgNPs, also MWCNTs were toxic to NR8383 cells. AgNP was toxic also to U937 cells, other ENMs had minor effect. Different media resulted in different-sized aggregates of the same ENMs. AgNP inhibited BALB/c motility most, whereas NR8383 motility was inhibited most by MWCNTs. In conclusion, conventional cytotoxicity assays are better suited to rank the order of toxicity of different nanoparticles instead of producing accurate IC50 data. Moreover, using immune cells, especially macrophages together with fibroblasts, would bring more relevant predictions of ENM cytotoxicity as immune cells may discover cytotoxicity that is not captured by BALB/c 3T3 cells alone.

  7. Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes

    PubMed Central

    Tang, Qin; Cui, Jianyu; Tian, Zhonghua; Sun, Jiangchuan; Wang, Zhigang; Chang, Shufang; Zhu, Shenyin

    2017-01-01

    Background Photodynamic therapy and sonodynamic therapy are developing, minimally invasive, and site-specific modalities for cancer therapy. A combined strategy PSDT (photodynamic therapy followed by sonodynamic therapy) has been proposed in this study. Here, we aimed to develop novel biodegradable poly(DL-lactide-co-glycolic acid) phase-transition nanoparticles simultaneously loaded with oxygen and indocyanine green (OI-NPs) and to investigate the cytotoxic effects and the potential mechanisms of OI-NP–mediated PSDT on MH7A synoviocytes. Methods The OI-NPs were prepared using a modified double emulsion method and the physicochemical properties were determined. The cellular uptake of OI-NPs was detected by confocal microscopy and flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, flow cytometry, and Hoechst 33342/propidium iodide double staining were used to determine the cytotoxic effect of OI-NP–mediated PSDT on MH7A cells. Fluorescence microscope and fluorescence microplate reader were used to detect reactive oxygen species (ROS) generation. Results The OI-NPs were a stable and efficient carrier to deliver oxygen and indocyanine green, and enhanced cellular uptake was observed in MH7A cells with the nanoparticles. OI-NP–mediated PSDT caused more serious cell damage and more evident cell apoptosis, compared with other groups. Furthermore, increased generation of intracellular ROS was detected in MH7A cells treated with PSDT. Interestingly, the OI-NP–mediated PSDT-induced cell viability loss was effectively rescued by pretreatment with the ROS scavenger N-acetylcysteine. Conclusion Multifunctional OI-NPs were successfully developed and characterized for the combined delivery of oxygen and indocyanine green, and OI-NP–mediated PSDT would be a potential cytotoxic treatment for MH7A cells. This study may provide a novel strategy for the treatment of RA and develop a model of theranostic application through phase

  8. Dose dependent cytotoxicity of pranoprofen in cultured human corneal endothelial cells by inducing apoptosis.

    PubMed

    Li, Yi-Han; Wen, Qian; Fan, Ting-Jun; Ge, Yuan; Yu, Miao-Miao; Sun, Ling-Xiao; Zhao, Yu

    2015-01-01

    Pranoprofen (PPF), a non-steroidal anti-inflammatory drugs (NSAIDs), is often used in keratitis treatment in clinic. Several studies have assessed in vitro the cytotoxicity of topical NSAIDs to corneal epithelial cells due to its importance for predicting human corneal toxicity. Damage by cytotoxic drugs can result in excessive loss of human corneal endothelial (HCE) cells which lead to decompensation of the endothelium and eventual loss of visual acuity. However, the endothelial cytotoxicity of PPF has not yet been reported using an in vitro model of HCE cells. This study assessed the cytotoxicity of PPF to HCE cells and its underlying mechanism. Cellular viability was determined using inverted phase contrast light microscopy, and plasma membrane permeability, genomic DNA fragmentation, and ultrastructure were detected by acridine orange/ethidium bromide staining, DNA agarose gel electrophoresis, and transmission electron microscopy (TEM), respectively. The results on cellular viability showed that PPF at concentrations ranging from 0.0625 to 1.0 g/l had poignant cytotoxicity to HCE cells, and the extent of its cytotoxicity was dose- and time-dependent. Further characterization indicated that PPF induced plasma membrane permeability elevation, DNA fragmentation, and apoptotic body formation, proving its apoptosis inducing effect on HCE cells. In conclusion, PPF above 0.0625 g/l has poignant cytotoxicity on HCE cells in vitro by inducing cell apoptosis, and should be carefully employed in eye clinic.

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

    PubMed

    Jeevitha, D; Amarnath, Kanchana

    2013-01-01

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

  10. Polymeric nanoparticles for oral delivery of 5-fluorouracil: Formulation optimization, cytotoxicity assay and pre-clinical pharmacokinetics study.

    PubMed

    Mattos, Ana Cristina de; Altmeyer, Clescila; Tominaga, Tania Toyomi; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2016-03-10

    Poly(lactic acid) (PLA) or poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) blend nanoparticles were developed loading 5-fluorouracil (5-FU), an antitumor agent broadly used in therapy. A 2(3) factorial experimental design was conducted to indicate an optimal formulation and demonstrate the influence of the interactions of components on the mean particle size and drug encapsulation efficiency. Optimized PLA nanoparticles presented 294nm and 51% of 5-FU encapsulation efficiency and PLA-PEG blend nanoparticles presented 283nm and 55% of 5-FU encapsulation efficiency. In vitro release assay demonstrated after 320h about 50% of 5-FU was released from PLA and PLA-PEG blend nanoparticles. Release kinetics of 5-FU from nanoparticles followed second order and the release mechanism calculated by Korsmeyer-Peppas model was diffusion and erosion. In the assessment of cytotoxicity over Hep-2 tumor cells, PLA or PLA-PEG blend nanoparticles presented similar IC50 value than free 5-FU. Pharmacokinetic parameters after oral administration of 5-FU were improved by nanoencapsulation. Bioavailability, Cmax, Tmax, t1/2 and distribution volume were significantly improved, while clearance were decreased. PEG presence in nanoparticles didn't influence physicochemical and biological parameters evaluated. PLA and PLA-PEG nanoparticles can be potential carriers for oral delivery of 5-FU.

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

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

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

  12. Cytotoxic effects of gold nanoparticles exposure employing in vitro animal cell culture system as part of nanobiosafety

    NASA Astrophysics Data System (ADS)

    Ambwani, Sonu; Kakade Datta, P.; Kandpal, Deepika; Arora, Sandeep; Ambwani, Tanuj Kumar

    2016-04-01

    Metal Nanoparticles are exploited in different fields that include biomedical sector where they are utilized in drug and gene delivery, biosensors, cancer treatment and diagnostic tools. Despite of their benefits, there has been serious concerns about possible side effects of several nanoparticles. Gold nanoparticles (AuNPs) are exploited for bio-imaging, biosensing, drug delivery, transfection and diagnosis. These nanoparticles may get released into the environment in high amounts at all stages of production, recycling and disposal. Since the manufacture and use of nanoparticles are increasing, humans/ animals are more likely to be exposed occupationally or via consumer products and the environment. The emergence of the new field of nanotoxicity has spurred great interest in a wide variety of materials and their possible effects on living systems. Animal cell culture system is considered as a sensitive indicator against exposure of such materials. Keeping in view the above scenario, present study was carried out to evaluate effect of AuNPs exposure in primary and cell line culture system employing chicken embryo fibroblast (CEF) culture and HeLa cell line culture through MTT assay. Minimum cytotoxic dose was found to be 60 µg/ml and 50 µg/ml in CEF and HeLa cells, respectively. Thus, it could be inferred that even a very low concentration of AuNPs could lead to cytotoxic effects in cell culture based studies.

  13. Radotinib induces high cytotoxicity in c-KIT positive acute myeloid leukemia cells.

    PubMed

    Heo, Sook-Kyoung; Noh, Eui-Kyu; Kim, Jeong Yi; Jo, Jae-Cheol; Choi, Yunsuk; Koh, SuJin; Baek, Jin Ho; Min, Young Joo; Kim, Hawk

    2017-03-18

    Previously, we reported that radotinib, a BCR-ABL1 tyrosine kinase inhibitor, induced cytotoxicity in acute myeloid leukemia (AML) cells. However, the effects of radotinib in the subpopulation of c-KIT-positive AML cells were unclear. We observed that low-concentration radotinib had more potent cytotoxicity in c-KIT-positive cells than c-KIT-negative cells from AML patients. To address this issue, cell lines with high c-KIT expression, HEL92.1.7, and moderate c-KIT expression, H209, were selected. HEL92.1.7 cells were grouped into intermediate and high c-KIT expression populations. The cytotoxicity of radotinib against the HEL92.1.7 cell population with intermediate c-KIT expression was not different from that of the population with high c-KIT expression. When H209 cells were grouped into c-KIT expression-negative and c-KIT expression-positive populations, radotinib induced cytotoxicity in the c-KIT-positive population, but not the c-KIT-negative population. Thus, radotinib induces cytotoxicity in c-KIT-positive cells, regardless of the c-KIT expression intensity. Therefore, radotinib induces significant cytotoxicity in c-KIT-positive AML cells, suggesting that radotinib is a potential target agent for the treatment of c-KIT-positive malignancies including AML.

  14. 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.

  15. Cytotoxicity of atropine to human corneal endothelial cells by inducing mitochondrion-dependent apoptosis.

    PubMed

    Wen, Qian; Fan, Ting-Jun; Tian, Cheng-Lei

    2016-07-01

    Atropine, a widely used topical anticholinergic drug, might have adverse effects on human corneas in vivo. However, its cytotoxic effect on human corneal endothelium (HCE) and its possible mechanisms are unclear. Here, we investigated the cytotoxicity of atropine and its underlying cellular and molecular mechanisms using an in vitro model of HCE cells and verified the cytotoxicity using cat corneal endothelium (CCE) in vivo. Our results showed that atropine at concentrations above 0.3125 g/L could induce abnormal morphology and viability decline in a dose- and time-dependent manner in vitro. The cytotoxicity of atropine was proven by the induced density decrease and abnormality of morphology and ultrastructure of CCE cells in vivo. Meanwhile, atropine could also induce dose- and time-dependent elevation of plasma membrane permeability, G1 phase arrest, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation of HCE cells. Moreover, 2.5 g/L atropine could also induce caspase-2/-3/-9 activation, mitochondrial transmembrane potential disruption, downregulation of anti-apoptotic Bcl-2 and Bcl-xL, upregulation of pro-apoptotic Bax and Bad, and upregulation of cytoplasmic cytochrome c and apoptosis-inducing factor. In conclusion, atropine above 1/128 of its clinical therapeutic dosage has a dose- and time-dependent cytotoxicity to HCE cells in vitro which is confirmed by CCE cells in vivo, and its cytotoxicity is achieved by inducing HCE cell apoptosis via a death receptor-mediated mitochondrion-dependent signaling pathway. Our findings provide new insights into the cytotoxicity and apoptosis-inducing effect of atropine which should be used with great caution in eye clinic.

  16. Cytotoxicity of atropine to human corneal endothelial cells by inducing mitochondrion-dependent apoptosis

    PubMed Central

    Wen, Qian; Tian, Cheng-Lei

    2016-01-01

    Atropine, a widely used topical anticholinergic drug, might have adverse effects on human corneas in vivo. However, its cytotoxic effect on human corneal endothelium (HCE) and its possible mechanisms are unclear. Here, we investigated the cytotoxicity of atropine and its underlying cellular and molecular mechanisms using an in vitro model of HCE cells and verified the cytotoxicity using cat corneal endothelium (CCE) in vivo. Our results showed that atropine at concentrations above 0.3125 g/L could induce abnormal morphology and viability decline in a dose- and time-dependent manner in vitro. The cytotoxicity of atropine was proven by the induced density decrease and abnormality of morphology and ultrastructure of CCE cells in vivo. Meanwhile, atropine could also induce dose- and time-dependent elevation of plasma membrane permeability, G1 phase arrest, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation of HCE cells. Moreover, 2.5 g/L atropine could also induce caspase-2/-3/-9 activation, mitochondrial transmembrane potential disruption, downregulation of anti-apoptotic Bcl-2 and Bcl-xL, upregulation of pro-apoptotic Bax and Bad, and upregulation of cytoplasmic cytochrome c and apoptosis-inducing factor. In conclusion, atropine above 1/128 of its clinical therapeutic dosage has a dose- and time-dependent cytotoxicity to HCE cells in vitro which is confirmed by CCE cells in vivo, and its cytotoxicity is achieved by inducing HCE cell apoptosis via a death receptor-mediated mitochondrion-dependent signaling pathway. Our findings provide new insights into the cytotoxicity and apoptosis-inducing effect of atropine which should be used with great caution in eye clinic. PMID:27022135

  17. Comparative Cytotoxic Evaluation of Free and Sodium Alginate Nanoparticle-Encapsulated ICD-85 on Primary Lamb Kidney Cells

    PubMed Central

    Zare Mirakabadi, Abbas; Moradhaseli, Saeed

    2013-01-01

    Background Current anti-cancer drug therapy results in systemic side effects due to non-specific uptake by normal healthy noncancerous tissues. To alleviate this difficulty, many attempts have been devoted to the development of new delivery systems such as polymeric Nanoparticles (NPs). In this study, we prepared ICD-85 NPs based on sodium alginate and analyzed the cytotoxic activity of ICD-85 NPs relative to free ICD-85 on primary lamb kidney cells. Methods ICD-85 loaded sodium alginate nanoparticles were prepared by ionic gelation method and were characterized by the particle size, size distribution and Fourier Transform Infrared (FT-IR) spectroscopy. The in vitro cytotoxicity was evaluated by MTT assay and membrane integrity was evaluated by measuring Lactate Dehydrogenase (LDH) activity. The morphological alterations of untreated and treated cells were assessed by light inverted microscope. Results MTT assay showed that ICD-85 NPs could significantly decrease the in vitro cytotoxicity on primary lamb kidney cells compared to the free ICD-85. The IC10 value at 72 hours was increased from 9±2.7 μg/ml for free ICD-85 to 52±4.3 μg/ml for ICD-85 NPs. LDH assay demonstrated that free ICD-85 had dose-dependent cytotoxicity on primary lamb kidney cells while ICD-85 NPs exhibited significantly decreased cytotoxicity at equivalent concentrations. Moreover, morphological analysis showed no significant difference between control and treated cells with ICD-85 NPs. Conclusion Based on the results obtained in the present study it can be concluded that encapsulation of ICD-85 with sodium alginate nanoparticles can reduce its necrotic effect on primary lamb kidney cells. PMID:25250126

  18. Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

    PubMed Central

    Choi, Yun-Jung; Park, Jung-Hyun; Han, Jae Woong; Kim, Eunsu; Jae-Wook, Oh; Lee, Seung Yoon; Kim, Jin-Hoi; Gurunathan, Sangiliyandi

    2016-01-01

    The cancer stem cell (CSC) hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs) have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs). In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells) and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH) and CD133 by fluorescence-activated cell sorting (FACS). The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and mitochondrial membrane potential (mt-MP). The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells) and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells). These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells. PMID:27973444

  19. Etoposide induced cytotoxicity mediated by ROS and ERK in human kidney proximal tubule cells

    PubMed Central

    Shin, Hyeon-Jun; Kwon, Hyuk-Kwon; Lee, Jae-Hyeok; Anwar, Muhammad Ayaz; Choi, Sangdun

    2016-01-01

    Etoposide (ETO) is a commonly used chemotherapeutic drug that inhibits topoisomerase II activity, thereby leading to genotoxicity and cytotoxicity. However, ETO has limited application due to its side effects on normal organs, especially the kidney. Here, we report the mechanism of ETO-induced cytotoxicity progression in human kidney proximal tubule (HK-2) cells. Our results show that ETO perpetuates DNA damage, activates mitogen-activated protein kinase (MAPK), and triggers morphological changes, such as cell and nuclear swelling. When NAC, a well-known reactive oxygen species (ROS) scavenger, is co-treated with ETO, it inhibits an ETO-induced increase in mitochondrial mass, mitochondrial DNA (ND1 and ND4) copy number, intracellular ATP level, and mitochondrial biogenesis activators (TFAM, PGC-1α and PGC-1β). Moreover, co-treatment with ETO and NAC inhibits ETO-induced necrosis and cell swelling, but not apoptosis. Studies using MAPK inhibitors reveal that inhibition of extracellular signal regulated kinase (ERK) protects ETO-induced cytotoxicity by inhibiting DNA damage and caspase 3/7 activity. Eventually, ERK inhibitor treated cells are protected from ETO-induced nuclear envelope (NE) rupture and DNA leakage through inhibition of caspase activity. Taken together, these data suggest that ETO mediates cytotoxicity in HK-2 cells through ROS and ERK pathways, which highlight the preventive avenues in ETO-induced cytotoxicity in kidney. PMID:27666530

  20. Green synthesis and characterization of silver nanoparticles using alcoholic flower extract of Nyctanthes arbortristis and in vitro investigation of their antibacterial and cytotoxic activities.

    PubMed

    Gogoi, Nayanmoni; Babu, Punuri Jayasekhar; Mahanta, Chandan; Bora, Utpal

    2015-01-01

    Here we report the synthesis of silver nanoparticles using ethanolic flower extract of Nyctanthes arbortristis, UVvisible spectra and TEM indicated the successful formation of silver nanoparticles. Crystalline nature of the silver nanoparticles was confirmed by X-ray diffraction. Fourier Transform Infra-Red Spectroscopy analysis established the capping of the synthesized silver nanoparticles with phytochemicals naturally occurring in the ethanolic flower extract of N. arbortristis. The synthesized silver nanoparticles showed antibacterial activity against the pathogenic strain of Escherichia coli MTCC 443. Furthermore, cytotoxicity of the silver nanoparticles was tested on mouse fibroblastic cell line (L929) and found to be non-toxic, which thus proved their biocompatibility. Antibacterial activity and cytotoxicity assay carried out in this study open up an important perspective of the synthesized silver nanoparticles.

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

    NASA Astrophysics Data System (ADS)

    Ispas, Cristina R.

    . 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.

  2. Cytotoxic effect of ZnS nanoparticles on primary mouse retinal pigment epithelial cells.

    PubMed

    Bose, Karthikeyan; Lakshminarasimhan, Harini; Sundar, Krishnan; Kathiresan, Thandavarayan

    2016-11-01

    The multiple properties of zinc sulphide nanoparticles (ZnS-NPs) are attracting great attention in the field of chemical and biological research. ZnS-NPs also find their application in biosensor and photocatalysis. Zinc is an important metal ion in retina and its deficiency leads to age-related macular degeneration. As of now, not much research is available on bio-interaction of ZnS as nanoform with retinal pigment epithelial (RPE) cells. RPE cells in the retina help in maintaining normal photoreceptor function and vision. To begin with, ZnS-NPs were synthesized and characterized using UV-visible spectra, X-ray diffraction, Fourier transform infrared spectrum, transmission electron microscopy and dynamic light scattering. Followed by the confirmation of nanoparticles, our study extended to investigate the impact of ZnS-NPs in primary mouse RPE (MRPE) cells at different concentrations. ZnS-NPs showed dose-dependent cytotoxicity in MRPE cells and no changes were observed in cells' tight intactness at minimal concentration. In addition, exposure to ZnS-NPs increased cellular permeability in dose- and time-dependent manner in MRPE cells. The findings from DCFH-DA analysis revealed that ZnS-NPs-treated cells had elevated level of reactive oxygen species and partial activation of cell apoptosis was identified after exposure to ZnS-NPs at higher concentration. Furthermore, pre-treatment of the primary MRPE cells with ZnS-NPs led to phosphorylation of Akt (Ser 473), which indicates the crucial role of ZnS-NPs in regulating cell survival at minimal concentration. Altogether, this study enumerates requisite dose of using ZnS-NPs to maintain healthy RPE cells and contributes to future studies in development of therapeutic drug and drug carrier for ocular-related disorders.

  3. Effects of Iron-Oxide Nanoparticle Surface Chemistry on Uptake Kinetics and Cytotoxicity in CHO-K1 Cells

    PubMed Central

    Hanot, Camille C.; Choi, Young Suk; Anani, Tareq B.; Soundarrajan, Dharsan; David, Allan E.

    2015-01-01

    Superparamagnetic iron-oxide nanoparticles (SPIONs) show great promise for multiple applications in biomedicine. While a number of studies have examined their safety profile, the toxicity of these particles on reproductive organs remains uncertain. The goal of this study was to evaluate the cytotoxicity of starch-coated, aminated, and PEGylated SPIONs on a cell line derived from Chinese Hamster ovaries (CHO-K1 cells). We evaluated the effect of particle diameter (50 and 100 nm) and polyethylene glycol (PEG) chain length (2k, 5k and 20k Da) on the cytotoxicity of SPIONs by investigating cell viability using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. The kinetics and extent of SPION uptake by CHO-K1 cells was also studied, as well as the resulting generation of intracellular reactive oxygen species (ROS). Cell toxicity profiles of SPIONs correlated strongly with their cellular uptake kinetics, which was strongly dependent on surface properties of the particles. PEGylation caused a decrease in both uptake and cytotoxicity compared to aminated SPIONs. Interestingly, 2k Da PEG-modifed SPIONs displayed the lowest cellular uptake and cytotoxicity among all studied particles. These results emphasize the importance of surface coatings when engineering nanoparticles for biomedical applications. PMID:26729108

  4. Periodic table-based descriptors to encode cytotoxicity profile of metal oxide nanoparticles: a mechanistic QSTR approach.

    PubMed

    Kar, Supratik; Gajewicz, Agnieszka; Puzyn, Tomasz; Roy, Kunal; Leszczynski, Jerzy

    2014-09-01

    Nanotechnology has evolved as a frontrunner in the development of modern science. Current studies have established toxicity of some nanoparticles to human and environment. Lack of sufficient data and low adequacy of experimental protocols hinder comprehensive risk assessment of nanoparticles (NPs). In the present work, metal electronegativity (χ), the charge of the metal cation corresponding to a given oxide (χox), atomic number and valence electron number of the metal have been used as simple molecular descriptors to build up quantitative structure-toxicity relationship (QSTR) models for prediction of cytotoxicity of metal oxide NPs to bacteria Escherichia coli. These descriptors can be easily obtained from molecular formula and information acquired from periodic table in no time. It has been shown that a simple molecular descriptor χox can efficiently encode cytotoxicity of metal oxides leading to models with high statistical quality as well as interpretability. Based on this model and previously published experimental results, we have hypothesized the most probable mechanism of the cytotoxicity of metal oxide nanoparticles to E. coli. Moreover, the required information for descriptor calculation is independent of size range of NPs, nullifying a significant problem that various physical properties of NPs change for different size ranges.

  5. 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.

  6. Cytotoxic cells induced after Chlamydia psittaci infection in mice

    SciTech Connect

    Lammert, J.K.

    1982-03-01

    The ability of spleen cells from Chlamydia psittaci-infected mice to lyse C. psittaci-infected and uninfected target cell monolayers was studied. The cytotoxicity assay used was a terminal label method in which the number of adherent target cells surviving the interaction with effector cells was determined by measuring the uptake of (3H)uridine by such cells. It was observed that in the first few days postinfection (3 to 5), spleens contained cells that lysed infected and uninfected targets with equal efficiency. Subsequently, infected targets were killed primarily. The activity of effector spleen cells for infected targets continued, although at a reduced level, beyond 21 days postinfection. Intact effector cells were required since a disruption by sonication resulted in a loss of cytotoxicity. The enhanced killing observed with infected targets was also observed when target cells were sensitized with heat- or UV-inactivated C. psittaci. This study suggests that the induction of cytotoxic cells after C. psittaci infection may contribute to the ability of the host to control multiplication of the microorganism.

  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. Investigation of the cytotoxicity of aluminum oxide nanoparticles and nanowires and their localization in L929 fibroblasts and RAW264 macrophages.

    PubMed

    Hashimoto, Masanori; Sasaki, Jun-Ichi; Imazato, Satoshi

    2016-02-01

    The biological responses of aluminum oxide (Al2 O3 ) nanoparticles (NPs) and nanowires (NWs) in cultured fibroblasts (L929) and macrophages (RAW264) were evaluated from their cytotoxicities and micromorphologic properties. Cultured cells were exposed to Al2 O3 NPs (13 nm diameter) and Al2 O3 NWs (2-6 × 200-400 nm). Cytotoxicity and genotoxicity were examined by immunostaining with fluorescence microscopy, and nanomaterial localization was studied by using scanning electron microscopy and transmission electron microscopy. The NPs were cytotoxic and genotoxic, whereas the NWs were not. The scanning electron microscopy images showed that the NPs aggregate more on the cell surface than do the NWs. The transmission electron microscopy images showed that the NPs were internalized into the vesicle and nuclei, for both cell types. In contrast, numerous solid NWs were observed as large aggregates in vesicles, but not in nuclei. Nuclear damage was confirmed by measuring cell viability and by immunostaining for NPs. The chemical changes induced by the NPs in the vesicles or cells may cause cell damage because of their large surface area per volume. The extent of NW entrapment was not sufficient to lower the viability of either cell type.

  9. Leptin- or troglitazone-induced lipopenia protects islets from interleukin 1beta cytotoxicity.

    PubMed Central

    Shimabukuro, M; Koyama, K; Lee, Y; Unger, R H

    1997-01-01

    Interleukin 1beta (IL-1beta)-induced beta cell cytotoxicity has been implicated in the autoimmune cytotoxicity of insulin-dependent diabetes mellitus. These cytotoxic effects may be mediated by nitric oxide (NO). Since long-chain fatty acids (FFA), like IL-1beta, upregulate inducible nitric oxide synthase and enhance NO generation in islets, it seemed possible that islets might be protected from IL-1beta-induced damage by lowering their lipid content. We found that IL-1beta-induced NO production varied directly and islet cell viability inversely with islet triglyceride (TG) content. Fat-laden islets of obese rats were most vulnerable to IL-1beta, while moderately fat-depleted islets of food-restricted normal rats were less vulnerable than those of free-feeding normal rats. Severely lipopenic islets of rats made chronically hyperleptinemic by adenoviral leptin gene transfer resisted IL-1beta cytotoxicity even at 300 pg/ml, the maximal concentration. Troglitazone lowered islet TG in cultured islets from both normal rats and obese, leptin-resistant rats and reduced NO production and enhanced cell survival. We conclude that measures that lower islet TG content protect against IL-1beta-induced NO production and cytotoxicity. Leptin or troglitazone could provide in vivo protection against insulin-dependent diabetes mellitus. PMID:9312173

  10. Cytotoxicity control of silicon nanoparticles by biopolymer coating and ultrasound irradiation for cancer theranostic applications

    NASA Astrophysics Data System (ADS)

    Sviridov, A. P.; Osminkina, L. A.; Kharin, A. Yu; Gongalsky, M. B.; Kargina, J. V.; Kudryavtsev, A. A.; Bezsudnova, Yu I.; Perova, T. S.; Geloen, A.; Lysenko, V.; Timoshenko, V. Yu

    2017-03-01

    Silicon nanoparticles (SiNPs) prepared by mechanical grinding of luminescent porous silicon were coated with a biopolymer (dextran) and investigated as a potential theranostic agent for bioimaging and sonodynamic therapy. Transmission electron microscopy, photoluminescence and Raman scattering measurements of dextran-coated SiNPs gave evidence of their enhanced stability in water. In vitro experiments confirmed the lower cytotoxicity of the dextran-coated NPs in comparison with uncoated ones, especially for high concentrations of about 2 mg ml‑1. Efficient uptake of the NPs by cancer cells was found using bioimaging in the optical transmittance and photoluminescence modes. Treatment of the cells with uptaken SiNPs by therapeutic ultrasound for 5–20 min resulted in a strong decrease in the number of living cells, while the total number of cells remained nearly unchanged. The obtained data indicate a ‘mild’ effect of the combined action of ultrasonic irradiation and SiNPs on cancer cells. The observed results reveal new opportunities for controlling the photoluminescent and sonosensitizing properties of silicon-based NPs for applications in the diagnostics and mild therapy of cancer.

  11. Radiopacity and cytotoxicity of Portland cement associated with niobium oxide micro and nanoparticles

    PubMed Central

    MESTIERI, Leticia Boldrin; TANOMARU-FILHO, Mário; GOMES-CORNÉLIO, Ana Livia; SALLES, Loise Pedrosa; BERNARDI, Maria Inês Basso; GUERREIRO-TANOMARU, Juliane Maria

    2014-01-01

    Objective Mineral Trioxide Aggregate (MTA) is composed of Portland Cement (PC) and bismuth oxide (BO). Replacing BO for niobium oxide (NbO) microparticles (Nbµ) or nanoparticles (Nbη) may improve radiopacity and bioactivity. The aim of this study was to evaluate the radiopacity and cytotoxicity of the materials: 1) PC; 2) White MTA; 3) PC+30% Nbµ; 4) PC+30% Nbη. Material and Methods For the radiopacity test, specimens of the different materials were radiographed along an aluminum step-wedge. For cell culture assays, Saos-2 osteoblastic-cells (ATCC HTB-85) were used. Cell viability was evaluated through MTT assay, and bioactivity was assessed by alkaline phosphatase activity assay. Results The results demonstrated higher radiopacity for MTA, followed by Nbµ and Nbη, which had similar values. Cell culture analysis showed that PC and PC+NbO associations promoted greater cell viability than MTA. Conclusions It was concluded that the combination of PC+NbO is a potential alternative for composition of MTA. PMID:25591023

  12. Comparison of the cytotoxic effect of polystyrene latex nanoparticles on planktonic cells and bacterial biofilms

    NASA Astrophysics Data System (ADS)

    Nomura, Toshiyuki; Fujisawa, Eri; Itoh, Shikibu; Konishi, Yasuhiro

    2016-06-01

    The cytotoxic effect of positively charged polystyrene latex nanoparticles (PSL NPs) was compared between planktonic bacterial cells and bacterial biofilms using confocal laser scanning microscopy, atomic force microscopy, and a colony counting method. Pseudomonas fluorescens, which is commonly used in biofilm studies, was employed as the model bacteria. We found that the negatively charged bacterial surface of the planktonic cells was almost completely covered with positively charged PSL NPs, leading to cell death, as indicated by the NP concentration being greater than that required to achieve single layer coverage. In addition, the relationship between surface coverage and cell viability of P. fluorescens cells correlated well with the findings in other bacterial cells ( Escherichia coli and Lactococcus lactis). However, most of the bacterial cells that formed the biofilm were viable despite the positively charged PSL NPs being highly toxic to planktonic bacterial cells. This indicated that bacterial cells embedded in the biofilm were protected by self-produced extracellular polymeric substances (EPS) that provide resistance to antibacterial agents. In conclusion, mature biofilms covered with EPS exhibit resistance to NP toxicity as well as antibacterial agents.

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

    PubMed

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

    2010-01-01

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

  14. Cytotoxicity Evaluation and Magnetic Characteristics of Mechano-thermally Synthesized CuNi Nanoparticles for Hyperthermia

    NASA Astrophysics Data System (ADS)

    Amrollahi, P.; Ataie, A.; Nozari, A.; Seyedjafari, E.; Shafiee, A.

    2015-03-01

    CuNi alloys are very well known, both in academia and industry, based on their wide range of applications. In the present investigation, the previously synthesized Cu0.5Ni0.5 nanoparticles (NPs) by mechano-thermal method were studied more extensively. Phase composition and morphology of the samples were studied by employing x-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM) techniques. The Curie temperature ( T c) was determined by differential scanning calorimetry (DSC). In vitro cytotoxicity was studied through methyl-thiazolyl-tetrazolium (MTT) assay. XRD and FESEM results indicated the formation of single-phase Cu0.5Ni0.5. TEM micrographs showed that the mean particle size of powders is 20 nm. DSC results revealed that T c of mechano-thermally synthesized Cu0.5Ni0.5 is 44 °C. The MTT assay results confirmed the viability and proliferation of human bone marrow stem cells in contact with Cu0.5Ni0.5 NPs. In summary, the fabricated particles were demonstrated to have potential in low concentrations for cancer treatment applications.

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

    PubMed

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

    2015-02-05

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

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

  17. Cytotoxicity of Nanoparticles Contained in Food on Intestinal Cells and the Gut Microbiota

    PubMed Central

    Fröhlich, Esther E.; Fröhlich, Eleonore

    2016-01-01

    Toxicity of nanoparticles (NPs) upon oral exposure has been studied in animals using physiological changes, behavior, histology, and blood analysis for evaluation. The effects recorded include the combination of the action on cells of the exposed animal and the reaction of the microorganisms that populate the external and internal surfaces of the body. The importance of these microorganisms, collectively termed as microbiota, for the health of the host has been widely recognized. They may also influence toxicity of NPs but these effects are difficult to differentiate from toxicity on cells of the gastrointestinal tract. To estimate the likelihood of preferential damage of the microbiota by NPs the relative sensitivity of enterocytes and bacteria was compared. For this comparison NPs with antimicrobial action present in consumer products were chosen. The comparison of cytotoxicity with Escherichia coli as representative for intestinal bacteria and on gastrointestinal cells revealed that silver NPs damaged bacteria at lower concentrations than enterocytes, while the opposite was true for zinc oxide NPs. These results indicate that silver NPs may cause adverse effects by selectively affecting the gut microbiota. Fecal transplantation from NP-exposed animals to unexposed ones offers the possibility to verify this hypothesis. PMID:27058534

  18. 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-Castañón, 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 100 ppm of AgNPs of 9.5±1.1 nm. However, AgNPs at high concentrations (>10 ppm) 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.

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

    PubMed

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

    2014-08-14

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

  20. Study of Cytotoxic and Therapeutic Effects of Stable and Purified Silver Nanoparticles on Tumor Cells

    PubMed Central

    Nallathamby, Prakash D.; Xu, Xiao-Hong Nancy

    2010-01-01

    We have synthesized and purified silver nanoparticles (Ag NPs) (11.3 ± 2.3 nm) that are stable (non-aggregated) in cell culture medium and inside single living cells. We have developed new imaging methods to characterize sizes and number of single NPs in the medium and in single living cells in real-time and determine their stability (non-aggregation) in the medium and in single living cells at single NP resolution. These new approaches allow us to study toxic and therapeutic effects of single Ag NPs on tumor cells (L929, mouse fibroblast cells) with determined sizes and concentrations (doses) of NPs over time at single NP and single cell resolution. We found that Ag NPs inhibited the growth and division of tumor cells and their nuclei, at a dose and time dependent manner, showing significant inhibitory effects and abnormal cells with giant undivided nuclei or multiple nuclei beyond 12 h incubation. The results show that Ag NPs inhibited the segregation of chromosomes, but not their replications. Intracellular Ag NPs were well distributed in the cell population, and located in the nuclei and cytoplasm with higher number in the cytoplasm. This study demonstrates the possibility of using Ag NPs to inhibit the growth and division of the tumor cells and their cytotoxicity for potential therapeutic treatments, and offers a new method to count the number of single NPs in the medium for characterization their concentration and stability at single NP resolution over time. PMID:20648292

  1. Cytotoxicity control of silicon nanoparticles by biopolymer coating and ultrasound irradiation for cancer theranostic applications.

    PubMed

    Sviridov, A P; Osminkina, L A; Kharin, A Yu; Gongansky, M B; Kargina, J V; Kudryavtsev, A A; Bezsudnova, Yu I; Perova, T S; Geloen, A; Lysenko, V; Timoshenko, V Yu

    2017-03-10

    Silicon nanoparticles (SiNPs) prepared by mechanical grinding of luminescent porous silicon were coated with a biopolymer (dextran) and investigated as a potential theranostic agent for bioimaging and sonodynamic therapy. Transmission electron microscopy, photoluminescence and Raman scattering measurements of dextran-coated SiNPs gave evidence of their enhanced stability in water. In vitro experiments confirmed the lower cytotoxicity of the dextran-coated NPs in comparison with uncoated ones, especially for high concentrations of about 2 mg ml(-1). Efficient uptake of the NPs by cancer cells was found using bioimaging in the optical transmittance and photoluminescence modes. Treatment of the cells with uptaken SiNPs by therapeutic ultrasound for 5-20 min resulted in a strong decrease in the number of living cells, while the total number of cells remained nearly unchanged. The obtained data indicate a 'mild' effect of the combined action of ultrasonic irradiation and SiNPs on cancer cells. The observed results reveal new opportunities for controlling the photoluminescent and sonosensitizing properties of silicon-based NPs for applications in the diagnostics and mild therapy of cancer.

  2. 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.

  3. Cisplatin-induced self-assembly of graphene oxide sheets into spherical nanoparticles for damaging sub-cellular DNA.

    PubMed

    Nandi, Aditi; Mallick, Abhik; More, Piyush; Sengupta, Poulomi; Ballav, Nirmalya; Basu, Sudipta

    2017-01-24

    This report describes the hitherto unobserved cisplatin induced self-assembly of 2D-graphene oxide sheets into 3D-spherical nano-scale particles. These nanoparticles can encompass dual DNA damaging drugs simultaneously. A combination of confocal microscopy, gel electrophoresis and flow cytometry studies clearly demonstrated that these novel nanoparticles can internalize into cancer cells by endocytosis, localize into lysosomes, and damage DNA, leading to apoptosis. Cell viability assays indicated that these nanoparticles were more cytotoxic towards cancer cells compared to healthy cells.

  4. Metabolic-induced cytotoxicity of diosbulbin B in CYP3A4-expressing cells.

    PubMed

    Jiang, Ji-Zong; Yang, Bao-Hua; Ji, Li-Li; Yang, Li; Mao, Yu-Chang; Hu, Zhuo-Han; Wang, Zheng-Tao; Wang, Chang-Hong

    2017-02-01

    As a candidate antitumor agent, diosbulbin B (DB) can induce serious liver toxicity and other adverse reactions. DB is mainly metabolized by CYP3A4 in vitro and in vivo, but the cytotoxicity and anti-tumor mechanisms of DB have yet to be clarified. This study aimed to determine whether the cytotoxicity and anti-tumor effects of DB are related to the metabolism-induced activation of CYP3A4 in various cell models, including CYP-free NIH3T3 cells, primary rat hepatocytes, HepG2 and L02 cells of high CYP3A4 expression and wild-type. Results showed that DB did not markedly decrease the viability of NIH3T3 cells. DB metabolites, obtained from the metabolism by mouse liver microsomes, did not elicit cytotoxicity on NIH3T3 cells either. By contrast, DB could induce significant cytotoxicity on primary rat hepatocytes. The DB induced cytotoxicity on HepG2 or L02 cells with high CYP3A4 expression were stronger than those on wild-type cells. As a metabolic biomarker, the metabolite conjugate (M31) of DB with GSH was detected in the incubation system. A higher amount of M31 was generated in the transfected HepG2 and L02 cells than in the wild-type cells at different time points. Ketoconazole, however, could restrain DB induced cytotoxicity on primary rat hepatocytes and in CYP3A4 transfected HepG2 and L02 cells. Therefore, the cytotoxicity of DB was closely related to CYP3A4-metabolized reactive DB metabolites.

  5. Copper(I) oxide nanoparticle and tryptophan as its biological conjugate: a modulation of cytotoxic effects

    NASA Astrophysics Data System (ADS)

    Maity, Mritunjoy; Pramanik, Sumit Kumar; Pal, Uttam; Banerji, Biswadip; Maiti, Nakul Chandra

    2014-01-01

    Recent investigations indicated that copper oxide nanoparticles can selectively induce apoptosis and effectively suppress the proliferation of tumor cells. Thus, it showed a great potential to be used as a drug for cancer treatment. Here we report an easy synthesis of spheroidal cuprous oxide nanoparticles (CuNPs) and their organic conjugate with l-tryptophan (Trp) using surfactant, sodium dodecyl sulfate as a capping reagent. The particles looked golden yellow and showed a strong affinity to bind blood carrier proteins such as bovine serum albumin and human serum albumin. However, both optical behavior and texture of the particles altered upon conjugation with Trp. The average size of the CuNPs was estimated to be 70 nm as appeared under transmission electron microscope or atomic force microscope. The biological conjugate with Trp was 85 nm and looked light sky blue in aqueous suspension. The surface of the conjugated nanoparticles was smoother than the bare CuNPs. The CuNPs were found to be toxic to different cultured cancerous cells; however, conjugation with Trp attenuated the toxicity, and indicated its possible utility in developing a drug candidate for cancer in a controlled fashion. Reduced toxicity also indicated a possible use of the conjugated particle as a drug delivery system.

  6. Light-triggered liposomal cargo delivery platform incorporating photosensitizers and gold nanoparticles for enhanced singlet oxygen generation and increased cytotoxicity

    PubMed Central

    Kautzka, Zofia; Clement, Sandhya; Goldys, Ewa M; Deng, Wei

    2017-01-01

    We developed light-triggered liposomes incorporating 3–5 nm hydrophobic gold nanoparticles and Rose Bengal (RB), a well-known photosensitizer used for photodynamic therapy. Singlet oxygen generated by these liposomes with 532 nm light illumination was characterized for varying the molar ratio of lipids and gold nanoparticles while keeping the amount of RB constant. Gold nanoparticles were found to enhance the singlet oxygen generation rate, with a maximum enhancement factor of 1.75 obtained for the molar ratio of hydrogenated soy l-α-phosphatidylcholine:1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(hexanoylamine):gold of 57:5:17 compared with liposomes loaded with RB alone. The experimental results could be explained by the local electric field enhancement caused by gold nanoparticles. We further assessed cellular cytotoxicity of gold-loaded liposomes by encapsulating an antitumor drug, doxorubicin (Dox); such Dox-loaded liposomes were applied to human colorectal cancer cells (HCT116) and exposed to light. Gold-loaded liposomes containing RB and Dox where Dox release was triggered by light were found to exhibit higher cytotoxicity compared with the liposomes loaded with RB and Dox alone. Our results indicate that gold-loaded liposomes incorporating photosensitizers may serve as improved agents in photodynamic therapy and chemotherapy. PMID:28203076

  7. Galactoxyloglucan-doxorubicin nanoparticles exerts superior cytotoxic effects on cancer cells-A mechanistic and in silico approach.

    PubMed

    Joseph, Manu M; G, Aswathy; T K, Manojkumar; T T, Sreelekha

    2016-11-01

    Galactoxyloglucan (PST001), isolated from seed kernel of Tamarindus indica is a non-toxic immunostimlatory agent with selective cytotoxicity on cancer cells. Toxicity associated with the chemotherapeutic drug doxorubicin (Dox) is the major barrier in its clinical application. Stable, spherically shaped PST-Dox nanoparticles with an average size of 10nm were prepared via ionic gelation of Dox with PST001 which displayed a pH dependent cumulative Dox release kinetics. PST-Dox nanoparticles demonstrated cancer-specific enhanced cytotoxic effects than PST001 and Dox in cancer cells by enhanced cellular uptake of Dox through the induction of apoptosis, sparing normal cells and RBCs. Elucidation of molecular mechanism by whole genome microarray revealed down-regulation of tyrosine kinase oncogenic pathways as PST-Dox mode of action. An in silico model of PST-Dox was developed and computed the activity against topoisomerase IIß, human Abl kinase and protein tyrosine kinases. Computational studies further affirmed the findings of genomic and proteomic investigations with an increased interaction energy between PST-Dox complexes with target system than with Dox and PST001 alone. The important findings and profoundly restrained methodologies highlighted in the current study will accelerate the therapeutic potential of this nanoparticle formulation for substantial clinical studies and testing in several cancers. To conclude, PST-Dox nanoparticles represent a superior drug delivery nanosystem for the effective treatment of cancer even though detailed investigations are warranted.

  8. Vincristine and ɛ-viniferine-loaded PLGA-b-PEG nanoparticles: pharmaceutical characteristics, cellular uptake and cytotoxicity.

    PubMed

    Öğünç, Yüksel; Demirel, Müzeyyen; Yakar, Arzu; İncesu, Zerrin

    2017-02-02

    The objective of this study was to prepare the ɛ-viniferine and vincristine-loaded PLGA-b-PEG nanoparticle and to investigate advantages of these formulations on the cytotoxicity of HepG2 cells. Prepared nanoparticle has shown a homogeneous distribution with 113 ± 0.43 nm particle size and 0.323 ± 0.01 polydispersity index. Zeta potential was determined as -35.03 ± 1.0 mV. The drug-loading percentages were 6.01 ± 0.23 and 2.01 ± 0.07 for ɛ-viniferine and vincristine, respectively. The cellular uptake efficiency of coumarin-6-loaded nanoparticles was increased up to 87.8% after 4 h. Nanoparticles loaded with high concentrations of both drugs showed a cytotoxic effect on HepG2 cells, having the percentage of cell viability of between 43.23% and 47.37%. Unfortunately, the percentage of apoptotic cells after treated with drugs-loaded nanaoparticles (10.93%) was similar to free forms of drugs (12.1%) that might be due to low ɛ-viniferine release in biological pH at 24 h.

  9. Cytotoxicity, tumor targeting and PET imaging of sub-5 nm KGdF4 multifunctional rare earth nanoparticles

    NASA Astrophysics Data System (ADS)

    Cao, Xinmin; Cao, Fengwen; Xiong, Liqin; Yang, Yang; Cao, Tianye; Cai, Xi; Hai, Wangxi; Li, Biao; Guo, Yixiao; Zhang, Yimin; Li, Fuyou

    2015-08-01

    Ultrasmall sub-5 nm KGdF4 rare earth nanoparticles were synthesized as multifunctional probes for fluorescent, magnetic, and radionuclide imaging. The cytotoxicity of these nanoparticles in human glioblastoma U87MG and human non-small cell lung carcinoma H1299 cells was evaluated, and their application for in vitro and in vivo tumor targeted imaging has also been demonstrated.Ultrasmall sub-5 nm KGdF4 rare earth nanoparticles were synthesized as multifunctional probes for fluorescent, magnetic, and radionuclide imaging. The cytotoxicity of these nanoparticles in human glioblastoma U87MG and human non-small cell lung carcinoma H1299 cells was evaluated, and their application for in vitro and in vivo tumor targeted imaging has also been demonstrated. Electronic supplementary information (ESI) available: Details of the experimental section as well as EDXA, XRD, zeta potential, FTIR, TGA, stability, TEM, Z scanning, ICP-MS, and MicroPET/CT images. See DOI: 10.1039/c5nr03374h

  10. Follicular lymphoma: in vitro effects of combining lymphokine-activated killer (LAK) cell-induced cytotoxicity and rituximab- and obinutuzumab-dependent cellular cytotoxicity (ADCC) activity.

    PubMed

    García-Muñoz, Ricardo; López-Díaz-de-Cerio, Ascensión; Feliu, Jesus; Panizo, Angel; Giraldo, Pilar; Rodríguez-Calvillo, Mercedes; Grande, Carlos; Pena, Esther; Olave, Mayte; Panizo, Carlos; Inogés, Susana

    2016-04-01

    Follicular lymphoma (FL) is a disease of paradoxes-incurable but with a long natural history. We hypothesized that a combination of lymphokine-activated killer (LAK) cells and monoclonal antibodies might provide a robust synergistic treatment and tested this hypothesis in a phase II clinical trial (NCT01329354). In this trial, in addition to R-CHOP, we alternated the administration of only rituximab with rituximab and autologous LAK cells that were expanded ex vivo. Our objective was to determine the in vitro capability of LAK cells generated from FL patients to produce cytotoxicity against tumor cell lines and to determine rituximab- and obinutuzumab-induced cytotoxicity via antibody-dependent cellular cytotoxicity (ADCC) activity. We analyzed the LAK cell-induced cytotoxicity and rituximab (R)- and obinutuzumab (GA101)-induced ADCC activity. We show that LAK cells generated from FL patients induce cytotoxicity against tumor cell lines. R and GA101 enhance cytolysis through ADCC activity of LAK cells. Impaired LAK cell cytotoxicity and ADCC activity were detected in 50 % of patients. Percentage of NK cells in LAK infusions were correlated with the R- and GA101-induced ADCC. Our results indicate that the combination of R or GA101 and LAK cells should be an option as frontline maintenance therapy in patients with FL.

  11. Natural chlorophyll but not chlorophyllin prevents heme-induced cytotoxic and hyperproliferative effects in rat colon.

    PubMed

    de Vogel, Johan; Jonker-Termont, Denise S M L; Katan, Martijn B; van der Meer, Roelof

    2005-08-01

    Diets high in red meat and low in green vegetables are associated with an increased risk of colon cancer. In rats, dietary heme, mimicking red meat, increases colonic cytotoxicity and proliferation of the colonocytes, whereas addition of chlorophyll from green vegetables inhibits these heme-induced effects. Chlorophyllin is a water-soluble hydrolysis product of chlorophyll that inhibits the toxicity of many planar aromatic compounds. The present study investigated whether chlorophyllins could inhibit the heme-induced luminal cytotoxicity and colonic hyperproliferation as natural chlorophyll does. Rats were fed a purified control diet, the control diet supplemented with heme, or a heme diet with 1.2 mmol/kg diet of chlorophyllin, copper chlorophyllin, or natural chlorophyll for 14 d (n = 8/group). The cytotoxicity of fecal water was determined with an erythrocyte bioassay and colonic epithelial cell proliferation was quantified in vivo by [methyl-(3)H]thymidine incorporation into newly synthesized DNA. Exfoliation of colonocytes was measured as the amount of rat DNA in feces using quantitative PCR analysis. Heme caused a >50-fold increase in the cytotoxicity of the fecal water, a nearly 100% increase in proliferation, and almost total inhibition of exfoliation of the colonocytes. Furthermore, the addition of heme increased TBARS in fecal water. Chlorophyll, but not the chlorophyllins, completely prevented these heme-induced effects. In conclusion, inhibition of the heme-induced colonic cytotoxicity and epithelial cell turnover is specific for natural chlorophyll and cannot be mimicked by water-soluble chlorophyllins.

  12. Cytotoxic activity of interferon alpha induced dendritic cells as a biomarker of glioblastoma

    NASA Astrophysics Data System (ADS)

    Mishinov, S. V.; Stupak, V. V.; Tyrinova, T. V.; Leplina, O. Yu.; Ostanin, A. A.; Chernykh, E. R.

    2016-08-01

    Dendritic cells (DCs) are the most potent antigen presenting cells that can play direct role in anti-tumor immune response as killer cells. DC tumoricidal activity can be stimulated greatly by type I IFN (IFNα and IFNβ). In the present study, we examined cytostatic and cytotoxic activity of monocyte-derived IFNα-induced DCs generated from patients with brain glioma and evaluated the potential use of these parameters in diagnostics of high-grade gliomas. Herein, we demonstrated that patient DCs do not possess the ability to inhibit the growth of tumor HEp-2 cell line but low-grade and high-grade glioma patients do not differ significantly in DC cytostatic activity. However, glioma patient DCs are characterized by reduced cytotoxic activity against HEp-2 cells. The impairment of DC cytotoxic function is observed mainly in glioblastoma patients. The cytotoxic activity of DCs against HEp-2 cells below 9% is an informative marker for glioblastomas.

  13. Determining the size and concentration dependence of gold nanoparticles in vitro cytotoxicity (IC50) test using WST-1 assay

    NASA Astrophysics Data System (ADS)

    Rosli, Nur Shafawati binti; Rahman, Azhar Abdul; Aziz, Azlan Abdul; Shamsuddin, Shaharum

    2015-04-01

    Gold nanoparticles (AuNPs) received a great deal of attention for biomedical applications, especially in diagnostic imaging and therapeutics. Even though AuNPs have potential benefits in biomedical applications, the impact of AuNPs on human and environmental health still remains unclear. The use of AuNPs which is a high-atomic-number materials, provide advantages in terms of radiation dose enhancement. However, before this can become a clinical reality, cytotoxicity of the AuNPs has to be carefully evaluated. Cytotoxicity test is a rapid, standardized test that is very sensitive to determine whether the nanoparticles produced are harmful or benign on cellular components. In this work the size and concentration dependence of AuNPs cytotoxicity in breast cancer cell lines (MCF-7) are tested by using WST-1 assay. The sizes of AuNPs tested were 13 nm, 50 nm, and 70 nm. The cells were seeded in the 96-well plate and were treated with different concentrations of AuNPs by serial dilution for each size of AuNPs. The high concentration of AuNPs exhibit lower cell viability compared to low concentration of AuNPs. We quantified the toxicity of AuNPs in MCF-7 cell lines by determining the IC50 values in WST-1 assays. The IC50 values (inhibitory concentrations that effected 50% growth inhibition) of 50 nm AuNPs is lower than 13 nm and 70 nm AuNPs. Mean that, 50nm AuNPs are more toxic to the MCF-7 cells compared to smaller and larger sizes AuNPs. The presented results clearly indicate that the cytotoxicity of AuNPs depend not only on the concentration, but also the size of the nanoparticles.

  14. Relationship between phenol-induced cytotoxicity and experimental inhibition rate constant or a theoretical parameter.

    PubMed

    Fujisawa, S; Kadoma, Y

    2012-06-01

    We synthesized various dimer forms of 2-methoxyphenols and 2-tert-butylphenols, as dimers such as curcumin exhibit potent antioxidant and anti-inflammatory activity. We investigated the QSARs between the cytotoxicity and independent variables; kinetic parameters (inhibition rate constant (kinh/kp), stoichiometric factor (n)) or DFT-based theoretical parameters (i.e. phenolic O-H bond dissociation enthalpy (BDE), ionization potential according to Koopman's theorem (IP), LUMO, absolute hardness (η), electronegativity (χ) and electrophilicity (ω)) for 2-methoxyphenols and 2- tert- or 2,6-di-tert-butylphenols. The cytotoxicity of these phenols against human tumor cells (HSG, HL60) and/or human gingival fibroblasts (HGF) showed a marked negative linear relationship to kinh/kp, suggesting that the cytotoxicity of phenols may be related to radical reactions. By contrast, a linear relationship between the cytotoxicity and η-term was demonstrated; 2-methoxyphenols showed a negative slope, whereas 2-tert- or 2,6-di-tert-butylphenols showed a positive slope. Also, the cytotoxicity of tert-butylphenols was linearly dependent on the LUMO-term, showing a positive slope. The cytotoxicity of methoxy-substituted monophenols toward both HSG and HGF cells was related to both log P and η- terms. Also, that of X-phenols toward murine L-1210 cells was related to both log P and η or IP-terms, determined from a dataset reported by Zhang et al., 1998. It was concluded that the phenol-induced cytotoxicity was attributable to radical reactions resulting from the terms (kinh/kp, IP, η, and LUMO) in QSAR. The LUMO-dependent cytotoxicity of 2-tert- or 2,6-di-tert-butylphenols may be related to their quinone oxidation products. Experimental and theoretical parameters provide a useful approach for analysis of the cytotoxicity for phenolic compounds.

  15. 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.

  16. The effect of antioxidants on glycated albumin-induced cytotoxicity in bovine retinal pericytes.

    PubMed

    Kim, Jaetaek; Kim, Kwang-seok; Shinn, Jong-wook; Oh, Yeon-sahng; Kim, Heung-tae; Jo, Inho; Shinn, Soon-hyun

    2002-04-12

    Loss of retinal pericytes is the initial deficit in the early stage of diabetic retinopathy. Glycated albumin (GA) forms under hyperglycemic conditions and exists in the retinal blood vessels of diabetic patients with retinopathy. In this study, using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction test, we investigated whether GA induces cytotoxicity in cultured bovine retinal pericytes, and whether the antioxidants, l-ascorbic acid, Trolox, and probucol, provide any protection from GA-mediated cytotoxicity. GA induced pericyte death in a dose-dependent manner. With increasing time, GA-induced cytotoxicity also increased despite no strict time dependence. Furthermore, this cell death was found to be mediated both by apoptosis, which was confirmed by apoptosis-specific fluorescent staining of nuclei and cell membranes, and mitochondrial damage, as elucidated by electron microscopy. All three antioxidants used in this study partially protected against GA-induced pericyte death, suggesting that oxidative stress plays a role in GA-induced pericyte death. The results indicate that GA induces cell death in cultured bovine retinal pericytes, and that certain antioxidants may reduce this cytotoxicity.

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

    NASA Astrophysics Data System (ADS)

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

    2003-05-01

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

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

    PubMed Central

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

    2014-01-01

    The establishment of verifiably safe nanotechnology requires the development of assessment tools to identify hazardous nanomaterial properties that could be modified to improve nanomaterial safety. While there is a lot of debate of what constitutes appropriate safety screening methods, one approach is to use the assessment of cellular injury pathways to collect knowledge about hazardous material properties that could lead to harm to humans and the environment. We demonstrate the use of a multi-parameter cytotoxicity assay that evaluates toxic oxidative stress to compare the effects of titanium dioxide (TiO2), cerium oxide (CeO2) and zinc oxide (ZnO) nanoparticles in bronchial epithelial and macrophage cell lines. The nanoparticles were chosen based on their volume of production and likelihood of spread to the environment. Among the materials, dissolution of ZnO nanoparticles and Zn2+ release were capable of ROS generation and activation of an integrated cytotoxic pathway that includes intracellular calcium flux, mitochondrial depolarization, and plasma membrane leakage. These responses were chosen based on the compatibility of the fluorescent dyes that contemporaneously assess their response characteristics by a semi-automated epifluorescence procedure. Purposeful reduction of ZnO cytotoxicity was achieved by iron doping, which changed the material matrix to slow Zn2+ release. In summary, we demonstrate the utility of a rapid throughput, integrated biological oxidative stress response pathway to perform hazard ranking of a small batch of metal oxide nanoparticles, in addition to showing how this assay can be used to improve nanosafety by decreasing ZnO dissolution through Fe doping. PMID:20043640

  19. 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 μg/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

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  1. Fucan-coated silver nanoparticles synthesized by a green method induce human renal adenocarcinoma cell death.

    PubMed

    Rocha Amorim, Monica Oliveira; Lopes Gomes, Dayanne; Dantas, Larisse Araujo; Silva Viana, Rony Lucas; Chiquetti, Samanta Cristina; Almeida-Lima, Jailma; Silva Costa, Leandro; Oliveira Rocha, Hugo Alexandre

    2016-12-01

    Polysaccharides containing sulfated L-fucose are often called fucans. The seaweed Spatoglossum schröederi synthesizes three fucans, among which fucan A is the most abundant. This polymer is not cytotoxic against various normal cell lines and is non-toxic to rats when administered at high doses. In addition, it exhibits low toxicity against tumor cells. With the aim of increasing the toxicity of fucan A, silver nanoparticles containing this polysaccharide were synthesized using a green chemistry method. The mean size of these nanoparticles was 210nm. They exhibited a spherical shape and negative surface charge and were stable for 14 months. When incubated with cells, these nanoparticles did not show any toxic effects against various normal cell lines; however, they decreased the viability of various tumor cells, especially renal adenocarcinoma cells 786-0. Flow cytometry analyses showed that the nanoparticles induced cell death responses of 786-0 cells through necrosis. Assays performed with several renal cell lines (HEK, VERO, MDCK) showed that these nanoparticles only induce death of 786-0 cells. The data obtained herein leads to the conclusion that fucan A nanoparticles are promising agents against renal adenocarcinoma.

  2. Secondary metabolites, cytotoxic response by neutral red retention and protective effect against H2O2 induced cytotoxicity of Sedum caespitosum.

    PubMed

    Söhretoğlu, Didem; Sabuncuoğlu, Suna

    2012-01-01

    The EtOAc, n-BuOH and H20 subextracts of the crude MeOH extract of the aerial parts of Sedum caespitosum (cav.) Dc. were screened for cytotoxicity using the neutral red assay in Chinese hamster ovary cells as well as their protective effect against H2O2 induced cytotoxicity in human red blood cells. While the extracts did not show cytotoxicity, they displayed a protective effect compared to a blank and ascorbic acid. Gallic acid (1), kaempferol 3-O-alpha-rhamnopyranoside (2), quercetin 3-O-beta-glucopyranoside (3), quercetin 3-O-alpha-rhamnopyranoside (4) and myricetin 3-O-alpha-rhamnopyranoside (5) were isolated from the EtOAc extract and identified by 1D- and 2D-NMR. The protective effects of the isolated compounds against H2O2 induced cytotoxicity in human red blood cells were evaluated and 5 was the most active.

  3. Novel self-micellizing anticancer lipid nanoparticles induce cell death of colorectal cancer cells.

    PubMed

    Sundaramoorthy, Pasupathi; Baskaran, Rengarajan; Mishra, Siddhartha Kumar; Jeong, Keun-Yeong; Oh, Seung Hyun; Kyu Yoo, Bong; Kim, Hwan Mook

    2015-11-01

    In the present study, we developed a novel drug-like self-micellizing anticancer lipid (SMAL), and investigated its anticancer activity and effects on cell death pathways in human colorectal cancer (CRC) cell lines. Three self-assembled nanoparticles were prepared, namely, SMAL102 (lauramide derivative), SMAL104 (palmitamide derivative), and SMAL108 (stearamide derivative) by a thin-film hydration technique, and were characterized for physicochemical and biological parameters. SMAL102 were nanosized (160.23 ± 8.11 nm) with uniform spherical shape, while SMAL104 and SMAL108 did not form spherical shape but formed large size nanoparticles and irregular in shape. Importantly, SMAL102 showed a cytotoxic effect towards CRC cell lines (HCT116 and HT-29), and less toxicity to a normal colon fibroblast cell line (CCD-18Co). Conversely, SMAL104 and SMAL108 did not have an anti-proliferative effect on CRC cell lines. SMAL102 nanoparticles were actively taken up by CRC cell lines, localized in the cell membrane, and exhibited remarkable cytotoxicity in a concentration-dependent manner. The normal colon cell line showed significantly less cellular uptake and non-cytotoxicity as compared with the CRC cell lines. SMAL102 nanoparticles induced caspase-3, caspase-9, and PARP cleavage in HT-29 cells, indicating the induction of apoptosis; whereas LC3B was activated in HCT116 cells, indicating autophagy-induced cell death. Collectively, these results demonstrate that SMAL102 induced cell death via activation of apoptosis and autophagy in CRC cell lines. The present study could be a pioneer for further preclinical and clinical development of such compounds.

  4. Role of Fe doping in tuning the band gap of TiO2 for the photo-oxidation-induced cytotoxicity paradigm.

    PubMed

    George, Saji; Pokhrel, Suman; Ji, Zhaoxia; Henderson, Bryana L; Xia, Tian; Li, LinJiang; Zink, Jeffrey I; Nel, André E; Mädler, Lutz

    2011-07-27

    UV-light-induced electron-hole (e(-)/h(+)) pair generation with free radical production in TiO(2)-based nanoparticles is a major conceptual paradigm for biological injury. However, to date, this hypothesis has been difficult to experimentally verify due to the high energy of UV light that is intrinsically highly toxic to biological systems. Here, a versatile flame spray pyrolysis (FSP) synthetic process has been exploited to synthesize a library of iron-doped (0-10 wt%) TiO(2) nanoparticles. These particles have been tested for photoactivation-mediated cytotoxicity using near-visible light exposure. The reduction in TiO(2) band gap energy with incremental levels of Fe loading maintained the nanoparticle crystalline structure in spite of homogeneous Fe distribution (demonstrated by XRD, HRTEM, SAED, EFTEM, and EELS). Photochemical studies showed that band gap energy was reciprocally tuned proportional to the Fe content. The photo-oxidation capability of Fe-doped TiO(2) was found to increase during near-visible light exposure. Use of a macrophage cell line to evaluate cytotoxic and ROS production showed increased oxidant injury and cell death in parallel with a decrease in band gap energy. These findings demonstrate the importance of band gap energy in the phototoxic response of the cell to TiO(2) nanoparticles and reflect the potential of this material to generate adverse effects in humans and the environment during high-intensity light exposure.

  5. Role of Fe doping in tuning the band gap of TiO2 for photo-oxidation induced cytotoxicity paradigm

    PubMed Central

    George, Saji; Pokhrel, Suman; Ji, Zhaoxia; Henderson, Bryana L.; Xia, Tian; Li, LinJiang; Zink, Jeffrey I.; Nel, André E.; Mädler, Lutz

    2014-01-01

    UV-Light induced electron-hole (e−/h+) pair generation and free radical production in TiO2 based nanoparticles is a major conceptual paradigm for biological injury. However, to date, this hypothesis has been difficult to experimentally verify due to the high energy of UV light that is intrinsically highly toxic to biological systems. Here, a versatile flame spray pyrolysis (FSP) synthetic process has been exploited to synthesize a library of iron doped (0–10 at wt%) TiO2 nanoparticles. These particles have been tested for photoactivation-mediated cytotoxicity using near-visible light exposure. The reduction in TiO2 band gap energy with incremental levels of Fe loading maintained the nanoparticle crystalline structure in spite of homogeneous Fe distribution (demonstrated by XRD, HRTEM, SAED, EFTEM, and EELS). Photochemical studies showed that band gap energy was reciprocally tuned proportional to the Fe content. The photo-oxidation capability of Fe-doped TiO2 was found to increase during near-visible light exposure. Use of a macrophage cell line to evaluate cytotoxic and ROS production showed increased oxidant injury and cell death in parallel with a decrease in band gap energy. These findings demonstrate the importance of band gap energy in the phototoxic response of the cell to TiO2 nanoparticles and reflect the potential of this material to generate adverse effects in humans and the environment during high intensity light exposure. PMID:21678906

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

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

  7. Immune checkpoint inhibitors enhance cytotoxicity of cytokine-induced killer cells against human myeloid leukaemic blasts.

    PubMed

    Poh, Su Li; Linn, Yeh Ching

    2016-05-01

    We studied whether blockade of inhibitory receptors on cytokine-induced killer (CIK) cells by immune checkpoint inhibitors could increase its anti-tumour potency against haematological malignancies. CIK cultures were generated from seven normal donors and nine patients with acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or multiple myeloma (MM). The inhibitory receptors B and T lymphocyte attenuator, CD200 receptor, lymphocyte activation gene-3 (LAG-3) and T cell immunoglobulin and mucin-domain-containing-3 (TIM-3) were present at variable percentages in most CIK cultures, while cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed death-1 (PD-1) and killer cell immunoglobulin-like receptors (KIR2DL1/2/3) were expressed at low level in most cultures. Without blockade, myeloid leukaemia cells were susceptible to autologous and allogeneic CIK-mediated cytotoxicity. Blockade of KIR, LAG-3, PD-1 and TIM-3 but not CTLA-4 resulted in remarkable increase in killing against these targets, even in those with poor baseline cytotoxicity. ALL and MM targets were resistant to CIK-mediated cytotoxicity, and blockade of receptors did not increase cytotoxicity to a meaningful extent. Combination of inhibitors against two receptors did not further increase cytotoxicity. Interestingly, potentiation of CIK killing by blocking antibodies was not predicted by expression of receptors on CIK and their respective ligands on the targets. Compared to un-activated T and NK cells, blockade potentiated the cytotoxicity of CIK cells to a greater degree and at a lower E:T ratio, but without significant increase in cytotoxicity against normal white cell. Our findings provide the basis for clinical trial combining autologous CIK cells with checkpoint inhibitors for patients with AML.

  8. Synthesis, characterization and cytotoxicity of glutathione- and PEG-glutathione-superparamagnetic iron oxide nanoparticles for nitric oxide delivery

    NASA Astrophysics Data System (ADS)

    Santos, M. C.; Seabra, A. B.; Pelegrino, M. T.; Haddad, P. S.

    2016-03-01

    Superparamagnetic iron oxide nanoparticles (SPIONs), with appropriate surface coatings, are commonly used for biomedical applications, such as drug delivery. For the successful application of SPIONs, it is necessary that the nanoparticles have well-defined morphological, structural and magnetic characteristics, in addition to high stability and biocompatibility in biological environments. The present work is focused on the synthesis and characterization of SPIONs, which were prepared using the co-precipitation method and have great potential for drug delivery. The surfaces of the SPIONs were functionalized with the tripeptide glutathione (GSH) and poly(ethylene glycol) (PEG) to form GSH-SPIONs and PEG-GSH-SPIONs. The structural, morphological, magnetic properties and the cytotoxicity of the obtained nanoparticles were characterized using different techniques. The results showed that the nanoparticles have a mean diameter of 10 nm in the solid state and are superparamagnetic at room temperature. No cytotoxicity was observed for either nanoparticle (up to 500 μg L-1) on mouse normal fibroblasts (3T3 cell line) or acute T cell leukemia (Jurkat cell line) after 24 h of incubation. Free thiol groups (SH) on the surfaces of GSH-SPIONs and PEG-GSH-SPIONs were nitrosated, leading to the formation of S-nitrosated SPIONs, which act as a nitric oxide (NO) donor. The amounts of NO released from GSNO-SPIONs and PEG-GSNO-SPIONs were (124.0 ± 1.0) μmol and (33.2 ± 5.1) μmol of NO per gram, respectively. This study highlights the successful capping of the SPION surfaces with antioxidant GSH and biocompatible PEG, which improved the dispersion and biocompatibility of the NPs in aqueous/biological environments, thereby enhancing the potential uses of SPIONs as drug delivery systems, such as a NO donor vehicle, in biomedical applications.

  9. Synthesis-Dependent Surface Defects and Morphology of Hematite Nanoparticles and Their Effect on Cytotoxicity in Vitro.

    PubMed

    Cardillo, Dean; Tehei, Moeava; Hossain, Md Shahriar; Islam, Md Monirul; Bogusz, Kathrin; Shi, Dongqi; Mitchell, David; Lerch, Michael; Rosenfeld, Anatoly; Corde, Stéphanie; Konstantinov, Konstantin

    2016-03-09

    In this study, we investigate the toxicity of hematite (α-Fe2O3) nanoparticles on the Madin-Darby Canine Kidney (MDCK) cell line. The oxide particles have been synthesized through two different methods and annealing conditions. These two methods, spray precipitation and precipitation, resulted in particles with rod-like and spherical morphology and feature different particle sizes, surface features, and magnetic properties. Through flow cytometry it was found that particle morphology heavily influences the degree to which the nanomaterials are internalized into the cells. It was also found that the ability of the nanoparticles to generate free radicals species is hindered by the formation of tetrahedrally coordinated maghemite-like (γ-Fe2O3) spinel defects on the surfaces of the particles. The combination of these two factors resulted in variable cytotoxic effects of the hematite nanoparticles synthesized with different conditions. This article highlights the importance on the fabrication method, materials properties, and surface characteristics on the cytotoxicity of hematite nanomaterials.

  10. Comprehensive optimization of a single-chain variable domain antibody fragment as a targeting ligand for a cytotoxic nanoparticle.

    PubMed

    Zhang, Kathy; Geddie, Melissa L; Kohli, Neeraj; Kornaga, Tad; Kirpotin, Dmitri B; Jiao, Yang; Rennard, Rachel; Drummond, Daryl C; Nielsen, Ulrik B; Xu, Lihui; Lugovskoy, Alexey A

    2015-01-01

    Antibody-targeted nanoparticles have the potential to significantly increase the therapeutic index of cytotoxic anti-cancer therapies by directing them to tumor cells. Using antibodies or their fragments requires careful engineering because multiple parameters, including affinity, internalization rate and stability, all need to be optimized. Here, we present a case study of the iterative engineering of a single chain variable fragment (scFv) for use as a targeting arm of a liposomal cytotoxic nanoparticle. We describe the effect of the orientation of variable domains, the length and composition of the interdomain protein linker that connects VH and VL, and stabilizing mutations in both the framework and complementarity-determining regions (CDRs) on the molecular properties of the scFv. We show that variable domain orientation can alter cross-reactivity to murine antigen while maintaining affinity to the human antigen. We demonstrate that tyrosine residues in the CDRs make diverse contributions to the binding affinity and biophysical properties, and that replacement of non-essential tyrosines can improve the stability and bioactivity of the scFv. Our studies demonstrate that a comprehensive engineering strategy may be required to identify a scFv with optimal characteristics for nanoparticle targeting.

  11. Silver nanoparticles: Significance of physicochemical properties and assay interference on the interpretation of in vitro cytotoxicity studies.

    PubMed

    Riaz Ahmed, Kausar B; Nagy, Amber M; Brown, Ronald P; Zhang, Qin; Malghan, Subhas G; Goering, Peter L

    2017-02-01

    Silver nanoparticles (AgNPs) have generated a great deal of interest in the research, consumer product, and medical product communities due to their antimicrobial and anti-biofouling properties. However, in addition to their antimicrobial action, concerns have been expressed about the potential adverse human health effects of AgNPs. In vitro cytotoxicity studies often are used to characterize the biological response to AgNPs and the results of these studies may be used to identify hazards associated with exposure to AgNPs. Various factors, such as nanomaterial size (diameter), surface area, surface charge, redox potential, surface functionalization, and composition play a role in the development of toxicity in in vitro test systems. In addition, the interference of AgNPs with in vitro cytotoxicity assays may result in false negative or false positive results in some in vitro biological tests. The goal of this review is to: 1) summarize the impact of physical-chemical parameters, including size, shape, surface chemistry and aggregate formation on the in vitro cytotoxic effects of AgNPs; and 2) explore the nature of AgNPs interference in in vitro cytotoxicity assays.

  12. 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 ºC 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 μl with IC 50 value of 50 μl. This method will be useful in the biosynthesis of nanoparticles.

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

    PubMed Central

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

    2012-01-01

    Oral exposure to high concentrations of hexavalent chromium [Cr(VI)] induces intestinal redox changes, villus cytotoxicity, crypt hyperplasia, and intestinal tumors in mice. To assess the effects of Cr(VI) in a cell model relevant to the intestine, undifferentiated (proliferating) and differentiated (confluent) Caco-2 cells were treated with Cr(VI), hydrogen peroxide or rotenone for 2–24 hours. DNA damage was then assessed by nuclear staining intensity of 8-hydroxydeoxyguanosine (8-OHdG) and phosphorylated histone variant H2AX (γ-H2AX) measured by high content analysis methods. In undifferentiated Caco-2, all three chemicals increased 8-OHdG and γ-H2AX staining at cytotoxic concentrations, whereas only 8-OHdG was elevated at non-cytotoxic concentrations at 24 hr. Differentiated Caco-2 were more resistant to cytotoxicity and DNA damage than undifferentiated cells, and there were no changes in apoptotic markers p53 or annexin-V. However, Cr(VI) induced a dose-dependent translocation of the unfolded protein response transcription factor ATF6 into the nucleus. Micronucleus (MN) formation was assessed in CHO-K1 and A549 cell lines. Cr(VI) increased MN frequency in CHO-K1 only at highly cytotoxic concentrations. Relative to the positive control Mitomycin-C, Cr(VI) only slightly increased MN frequency in A549 at mildly cytotoxic concentrations. The results demonstrate that Cr(VI) genotoxicity correlates with cytotoxic concentrations, and that H2AX phosphorylation occurs at higher concentrations than oxidative DNA damage in proliferating Caco-2 cells. The findings suggest that in vitro genotoxicity of Cr(VI) is primarily oxidative in nature at low concentrations. Implications for in vivo intestinal toxicity of Cr(VI) will be discussed. PMID:22905163

  14. 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 μM, 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 μM in incubation periods of 24, 48, 72, and 96 h with MTT assay. Exposure of cells to 500 and 1,000 μM cobalt chloride caused significant decrease in cell survival. A biphasic survival profile of cells was observed at 1-25 μM 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 μM of CoCl(2) for 24 h and ≥ 100 μM 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.

  15. 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.

  16. 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 96 h, 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.

  17. Lantana camara Linn root extract-mediated gold nanoparticles and their in vitro antioxidant and cytotoxic potentials.

    PubMed

    Ramkumar, Rajendiran; Balasubramani, Govindasamy; Raja, Ramalingam Karthik; Raja, Manickam; Govindan, Raji; Girija, Easwaradas Kreedapathy; Perumal, Pachiappan

    2017-01-09

    The Lantana camara Linn root extract derived gold nanoparticles (Au NPs) were characterized by Ultraviolet-Visible spectroscopy, X-ray diffraction, fourier transform-infrared, high resolution transmission electron microscopy, selected area electron diffraction pattern and energy dispersive X-ray analyses. In DPPH assay, the inhibitory concentration (IC50) of Au NPs and gallic acid was 24.17 and 5.39 μg/ml, whereas, for cytotoxicity assay, the IC50 of Au NPs was 17.72 and 32.98 μg/ml on MBA-MB-231 and Vero cells, respectively. Thus, the Au NPs possess significant in vitro antioxidant and cytotoxic properties which could be considered as potential alternate for the development of anticancer drug in future.

  18. 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.

  19. Fast intracellular dissolution and persistent cellular uptake of silver nanoparticles in CHO-K1 cells: implication for cytotoxicity.

    PubMed

    Jiang, Xiumei; Miclăuş, Teodora; Wang, Liming; Foldbjerg, Rasmus; Sutherland, Duncan S; Autrup, Herman; Chen, Chunying; Beer, Christiane

    2015-03-01

    Toxicity of silver nanoparticles (Ag NPs) has been reported both in vitro and in vivo. However, the intracellular stability and chemical state of Ag NPs are still not very well studied. In this work, we systematically investigated the cellular uptake pathways, intracellular dissolution and chemical species, and cytotoxicity of Ag NPs (15.9 ± 7.6 nm) in Chinese hamster ovary cell subclone K1 cells, a cell line recommended by the OECD for genotoxicity studies. Quantification of intracellular nanoparticle uptake and ion release was performed through inductively coupled plasma mass spectrometry. X-ray absorption near-edge structure (XANES) was employed to assess the chemical state of intracellular silver. The toxic potential of Ag NPs and Ag(+) was evaluated by cell viability, reactive oxygen species (ROS) production and live-dead cell staining. The results suggest that cellular uptake of Ag NPs involves lipid-raft-mediated endocytosis and energy-independent diffusion. The degradation study shows that Ag NPs taken up into cells dissolved quickly and XANES results directly indicated that the internalized Ag was oxidized to Ag-O- species and then stabilized in silver-sulfur (Ag-S-) bonds within the cells. Subsequent cytotoxicity studies show that Ag NPs decrease cell viability and increase ROS production. Pre-incubation with N-acetyl-L-cysteine, an efficient antioxidant and Ag(+) chelator, diminished the cytotoxicity caused by Ag NPs or Ag(+) exposure. Our study suggests that the cytotoxicity mechanism of Ag NPs is related to the intracellular release of silver ions, followed by their binding to SH-groups, presumably coming from amino acids or proteins, and affecting protein functions and the antioxidant defense system of cells.

  20. Biogenic synthesis of metal nanoparticles from actinomycetes: biomedical applications and cytotoxicity.

    PubMed

    Golinska, Patrycja; Wypij, Magdalena; Ingle, Avinash P; Gupta, Indarchand; Dahm, Hanna; Rai, Mahendra

    2014-10-01

    Biogenic synthesis of metal nanoparticles has been well proved by using bacteria, fungi, algae, actinomycetes, plants, etc. Among the different microorganisms used for the synthesis of metal nanoparticles, actinomycetes are less known. Although, there are reports, which have shown that actinomycetes are efficient candidates for the production of metal nanoparticles both intracellularly and extracellularly. The nanoparticles synthesized by the members of actinomycetes present good polydispersity and stability and possess significant biocidal activities against various pathogens. The present review focuses on biological synthesis of metal nanoparticles and their application in medicine. In addition, the toxicity of these biogenic metal nanoparticles to human beings and environment has also been discussed.

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

    PubMed Central

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

    2013-01-01

    Background Magnetic nanoparticles in a variable magnetic field are able to produce heat. This heat (42-45°C) has more selective effect on fast dividing cancer cells than normal tissues. Methods In this work magnetite nanoparticles have been prepared via co-precipitation and phase identification was performed by powder x-ray diffraction (XRD). Magnetic parameters of the prepared nanoparticles were measured by a Vibrating Sample Magnetometer (VSM). A sensitive thermometer has been used to measure the increase of temperature in the presence of an alternating magnetic field. To evaluate the cytotoxicity of nanoparticles, the suspended magnetite nanoparticles in liquid paraffin, doxorubicin and a mixture of both were added to the MDA-MB-468 cells in separate 15 ml tubes and left either in the RT or in the magnetic field for 30 min. Cell survival was measured by trypan blue exclusion assay and flow cytometer. Particle size distribution of the nanoparticles was homogeneous with a mean particles size of 10 nm. A 15°C temperature increase was achieved in presence of an AC magnetic field after 15 min irradiation. Results Biological results showed that magnetite nanoparticles alone were not cytotoxic at RT, while in the alternative magnetic filed more than 50% of cells were dead. Doxorubicin alone was not cytotoxic during 30 min, but in combination with magnetite more than 80% of the cells were killed. Conclusion It could be concluded that doxorubicin and magnetite nanoparticles in an AC magnetic field had combinatory effects against cells. PMID:23799178

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

    PubMed Central

    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

  3. Oxidative stress induced by pure and iron-doped amorphous silica nanoparticles in subtoxic conditions.

    PubMed

    Napierska, Dorota; Rabolli, Virginie; Thomassen, Leen C J; Dinsdale, David; Princen, Catherine; Gonzalez, Laetitia; Poels, Katrien L C; Kirsch-Volders, Micheline; Lison, Dominique; Martens, Johan A; Hoet, Peter H

    2012-04-16

    Amorphous silica nanoparticles (SiO₂-NPs) have found broad applications in industry and are currently intensively studied for potential uses in medical and biomedical fields. Several studies have reported cytotoxic and inflammatory responses induced by SiO₂-NPs in different cell types. The present study was designed to examine the association of oxidative stress markers with SiO₂-NP induced cytotoxicity in human endothelial cells. We used pure monodisperse amorphous silica nanoparticles of two sizes (16 and 60 nm; S16 and S60) and a positive control, iron-doped nanosilica (16 nm; SFe), to study the generation of hydroxyl radicals (HO·) in cellular-free conditions and oxidative stress in cellular systems. We investigated whether SiO₂-NPs could influence intracellular reduced glutathione (GSH) and oxidized glutathione (GSSG) levels, increase lipid peroxidation (malondialdehyde (MDA) and 4-hydroxyalkenal (HAE) concentrations), and up-regulate heme oxygenase-1 (HO-1) mRNA expression in the studied cells. None of the particles, except SFe, produced ROS in cell-free systems. We found significant modifications for all parameters in cells treated with SFe nanoparticles. At cytotoxic doses of S16 (40-50 μg/mL), we detected weak alterations of intracellular glutathione (4 h) and a marked induction of HO-1 mRNA (6 h). Cytotoxic doses of S60 elicited similar responses. Preincubation of cells being exposed to SiO₂-NPs with an antioxidant (5 mM N-acetylcysteine, NAC) significantly reduced the cytotoxic activity of S16 and SFe (when exposed up to 25 and 50 μg/mL, respectively) but did not protect cells treated with S60. Preincubation with NAC significantly reduced HO-1 mRNA expression in cells treated with SFe but did not have any effect on HO-1 mRNA level in cell exposed to S16 and S60. Our study demonstrates that the chemical composition of the silica nanoparticles is a dominant factor in inducing oxidative stress.

  4. Novel application of the CORAL software to model cytotoxicity of metal oxide nanoparticles to bacteria Escherichia coli.

    PubMed

    Toropov, Andrey A; Toropova, Alla P; Benfenati, Emilio; Gini, Giuseppina; Puzyn, Tomasz; Leszczynska, Danuta; Leszczynski, Jerzy

    2012-11-01

    Convenient to apply and available on the Internet software CORAL (http://www.insilico.eu/CORAL) has been used to build up quantitative structure-activity relationships (QSAR) for prediction of cytotoxicity of metal oxide nanoparticles to bacteria Escherichia coli (minus logarithm of concentration for 50% effect pEC50). In this study six random splits of the data into the training and test set were examined. It has been shown that the CORAL provides a reliable tool that could be used to build up a QSAR of the pEC50.

  5. Prevention of phosphine-induced cytotoxicity by nutrients in HepG2 cells

    PubMed Central

    Rashedinia, Marzieh; Jamshidzadeh, Akram; Mehrabadi, Abbas Rezaiean; Niknahad, Hossein

    2016-01-01

    Background & objectives: Phosphides used as an insecticide and rodenticide, produce phosphine (PH3) which causes accidental and intentional poisoning cases and deaths. There is no specific treatment or antidote available for PH3 poisoning. It is suggested that PH3-induced toxicity is associated with adenosine triphosphate (ATP) depletion; therefore, in this study the effect of some nutrients was evaluated on PH3 cytotoxicity in a cell culture model. Methods: PH3 was generated from reaction of zinc phosphide (10 mM) with water in the closed culture medium of HepG2 cells, and cytotoxicity was measured after one and three hours of incubation. ATP, glutathione (GSH) and lipid peroxidation were also assessed at one or three hours post-incubation. ATP suppliers including dihydroxyacetone, glyceraldehyde and fructose were added to the culture medium 10 min before PH3 generation to prevent or reduce phosphine-induced cytotoxicity. Results: Phosphine caused about 30 and 66 per cent cell death at one and three hours of incubation, respectively. ATP content of the cells was depleted to 14.7 per cent of control at one hour of incubation. ATP suppliers were able to prevent cytotoxicity and ATP depletion induced by PH3. Dihydroxyacetone, α-ketoglutarate, fructose and mannitol restored the ATP content of the cells from 14.7 per cent to about 40, 34, 32 and 30 per cent, respectively. Lipid peroxidation and GSH depletion were not significantly induced by zinc phosphide in this study. Interpretation & conclusions: The results supported the hypothesis that phosphine-induced cytotoxicity was due to decrease of ATP levels. ATP suppliers could prevent its toxicity by generating ATP through glycolysis. α-keto compounds such as dihydroxyacetone and α-ketoglutarate may bind to phosphine and restore mitochondrial respiration. PMID:28256464

  6. Laser-Induced Transfer of Metal Nanoparticles

    NASA Astrophysics Data System (ADS)

    Kuznetsov, Arseniy I.; Koch, Jürgen; Chichkov, Boris N.

    2010-10-01

    A novel approach for the fabrication of metallic micro- and nanostructures based on femtosecond laser-induced transfer of metallic nanodroplets is developed. The size of the transferred droplets depends on the volume of laser-molten metal and can be varied by changing the laser beam focus on the sample surface and the metal film thickness. Controllable fabrication of high quality spherical gold micro- and nanoparticles with sizes between 170 nm and 1500 nm is realized. Fabrication of miscellaneous structures consisting of gold particles as elementary building blocks is demonstrated.

  7. Pulmonary surfactant augments cytotoxicity of silica nanoparticles: Studies on an in vitro air-blood barrier model.

    PubMed

    Kasper, Jennifer Y; Feiden, Lisa; Hermanns, Maria I; Bantz, Christoph; Maskos, Michael; Unger, Ronald E; Kirkpatrick, C James

    2015-01-01

    The air-blood barrier is a very thin membrane of about 2.2 µm thickness and therefore represents an ideal portal of entry for nanoparticles to be used therapeutically in a regenerative medicine strategy. Until now, numerous studies using cellular airway models have been conducted in vitro in order to investigate the potential hazard of NPs. However, in most in vitro studies a crucial alveolar component has been neglected. Before aspirated NPs encounter the cellular air-blood barrier, they impinge on the alveolar surfactant layer (10-20 nm in thickness) that lines the entire alveolar surface. Thus, a prior interaction of NPs with pulmonary surfactant components will occur. In the present study we explored the impact of pulmonary surfactant on the cytotoxic potential of amorphous silica nanoparticles (aSNPs) using in vitro mono- and complex coculture models of the air-blood barrier. Furthermore, different surface functionalisations (plain-unmodified, amino, carboxylate) of the aSNPs were compared in order to study the impact of chemical surface properties on aSNP cytotoxicity in combination with lung surfactant. The alveolar epithelial cell line A549 was used in mono- and in coculture with the microvascular cell line ISO-HAS-1 in the form of different cytotoxicity assays (viability, membrane integrity, inflammatory responses such as IL-8 release). At a distinct concentration (100 µg/mL) aSNP-plain displayed the highest cytotoxicity and IL-8 release in monocultures of A549. aSNP-NH2 caused a slight toxic effect, whereas aSNP-COOH did not exhibit any cytotoxicity. In combination with lung surfactant, aSNP-plain revealed an increased cytotoxicity in monocultures of A549, aSNP-NH2 caused a slightly augmented toxic effect, whereas aSNP-COOH did not show any toxic alterations. A549 in coculture did not show any decreased toxicity (membrane integrity) for aSNP-plain in combination with lung surfactant. However, a significant augmented IL-8 release was observed, but no

  8. Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells.

    PubMed

    Luo, Yi; Rana, Payal; Will, Yvonne

    2012-06-01

    Immunosuppressant cyclosporine A (CsA) treatment can cause severe side effects. Patients taking immunosuppressant after organ transplantation often display hyperlipidemia and obesity. Elevated levels of free fatty acids have been linked to the etiology of metabolic syndromes, nonalcoholic fatty liver and steatohepatitis. The contribution of free fatty acids to CsA-induced toxicity is not known. In this study we explored the effect of palmitic acid on CsA-induced toxicity in HepG2 cells. CsA by itself at therapeutic exposure levels did not induce detectible cytotoxicity in HepG2 cells. Co-treatment of palmitic acid and CsA resulted in a dose dependent increase in cytotoxicity, suggesting that fatty acid could sensitize cells to CsA-induced cytotoxicity at the therapeutic doses of CsA. A synergized induction of caspase-3/7 activity was also observed, indicating that apoptosis may contribute to the cytotoxicity. We demonstrated that CsA reduced cellular oxygen consumption which was further exacerbated by palmitic acid, implicating that impaired mitochondrial respiration might be an underlying mechanism for the enhanced toxicity. Inhibition of c-Jun N-terminal kinase (JNK) attenuated palmitic acid and CsA induced toxicity, suggesting that JNK activation plays an important role in mediating the enhanced palmitic acid/CsA-induced toxicity. Our data suggest that elevated FFA levels, especially saturated FFA such as palmitic acid, may be predisposing factors for CsA toxicity, and patients with underlying diseases that would elevate free fatty acids may be susceptible to CsA-induced toxicity. Furthermore, hyperlipidemia/obesity resulting from immunosuppressive therapy may aggravate CsA-induced toxicity and worsen the outcome in transplant patients.

  9. Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide

    NASA Astrophysics Data System (ADS)

    Freudenthal, Bret D.; Beard, William A.; Perera, Lalith; Shock, David D.; Kim, Taejin; Schlick, Tamar; Wilson, Samuel H.

    2015-01-01

    Oxidative stress promotes genomic instability and human diseases. A common oxidized nucleoside is 8-oxo-7,8-dihydro-2'-deoxyguanosine, which is found both in DNA (8-oxo-G) and as a free nucleotide (8-oxo-dGTP). Nucleotide pools are especially vulnerable to oxidative damage. Therefore cells encode an enzyme (MutT/MTH1) that removes free oxidized nucleotides. This cleansing function is required for cancer cell survival and to modulate Escherichia coli antibiotic sensitivity in a DNA polymerase (pol)-dependent manner. How polymerases discriminate between damaged and non-damaged nucleotides is not well understood. This analysis is essential given the role of oxidized nucleotides in mutagenesis, cancer therapeutics, and bacterial antibiotics. Even with cellular sanitizing activities, nucleotide pools contain enough 8-oxo-dGTP to promote mutagenesis. This arises from the dual coding potential where 8-oxo-dGTP(anti) base pairs with cytosine and 8-oxo-dGTP(syn) uses its Hoogsteen edge to base pair with adenine. Here we use time-lapse crystallography to follow 8-oxo-dGTP insertion opposite adenine or cytosine with human pol β, to reveal that insertion is accommodated in either the syn- or anti-conformation, respectively. For 8-oxo-dGTP(anti) insertion, a novel divalent metal relieves repulsive interactions between the adducted guanine base and the triphosphate of the oxidized nucleotide. With either templating base, hydrogen-bonding interactions between the bases are lost as the enzyme reopens after catalysis, leading to a cytotoxic nicked DNA repair intermediate. Combining structural snapshots with kinetic and computational analysis reveals how 8-oxo-dGTP uses charge modulation during insertion that can lead to a blocked DNA repair intermediate.

  10. Antimicrobial activity and cytotoxicity of cotton fabric coated with conducting polymers, polyaniline or polypyrrole, and with deposited silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Maráková, Nela; Humpolíček, Petr; Kašpárková, Věra; Capáková, Zdenka; Martinková, Lenka; Bober, Patrycja; Trchová, Miroslava; Stejskal, Jaroslav

    2017-02-01

    Cotton fabric was coated with conducting polymers, polyaniline or polypyrrole, in situ during the oxidation of respective monomers. Raman and FTIR spectra proved the complete coating of substrates. Polypyrrole content was 19.3 wt.% and that of polyaniline 6.0 wt.%. Silver nanoparticles were deposited from silver nitrate solutions of various concentrations by exploiting the reduction ability of conducting polymers. The content of silver was up to 11 wt.% on polypyrrole and 4 wt.% on polyaniline. The sheet resistivity of fabrics was determined. The conductivity was reduced after deposition of silver. The chemical cleaning reduced the conductivity by less than one order of magnitude for polypyrrole coating, while for polyaniline the decrease was more pronounced. The good antibacterial activity against S. aureus and E. coli and low cytotoxicity of polypyrrole-coated cotton, both with and without deposited silver nanoparticles

  11. Interferon-β 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-β (IFNβ) gene lipofection on tumor cell lines derived from three human cutaneous and four canine mucosal melanomas. The cytotoxicity of human IFNβ gene lipofection resulted higher or equivalent to that of the corresponding addition of the recombinant protein (rhIFNβ) to human cells. IFNβ gene lipofection was not cytotoxic for only one canine melanoma cell line. When cultured as monolayers, three human and three canine IFNβ-lipofected melanoma cell lines displayed a remarkable bystander effect. As spheroids, the same six cell lines were sensitive to IFNβ gene transfer, two displaying a significant multicell resistance phenotype. The effects of conditioned IFNβ-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 IFNβ, 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 IFNβ expression could be related to the resistance displayed by one human melanoma cell line. As IFNβ 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.

  12. 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, α = 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).

  13. Synergistic effects of nicotine on arecoline-induced cytotoxicity in human buccal mucosal fibroblasts.

    PubMed

    Chang, Y C; Hu, C C; Tseng, T H; Tai, K W; Lii, C K; Chou, M Y

    2001-09-01

    Areca quid chewing has been linked to oral submucous fibrosis and oral cancer. Arecoline, a major areca nut alkaloid, is considered to be the most important etiologic factor in the areca nut. In order to elucidate the pathobiological effects of arecoline, cytotoxicity assays, cellular glutathione S-transferase (GST) activity and lipid peroxidation assay were employed to investigate cultured human buccal mucosal fibroblasts. To date, there is a large proportion of areca quid chewers who are also smokers. Furthermore, nicotine, the major product of cigarette smoking, was added to test how it modulated the cytotoxicity of arecoline. At a concentration higher than 50 microg/ml, arecoline was shown to be cytotoxic to human buccal fibroblasts in a dose-dependent manner by the alamar blue dye colorimetric assay (P<0.05). In addition, arecoline significantly decreased GST activity in a dose-dependent manner (P<0.05). At concentrations of 100 microg/ml and 400 microg/ml, arecoline reduced GST activity about 21% and 46%, respectively, during a 24 h incubation period. However, arecoline at any test dose did not increase lipid peroxidation in the present human buccal fibroblast test system. The addition of extracellular nicotine acted synergistically on the arecoline-induced cytotoxicity. Arecoline at a concentration of 50 microg/ml caused about 30% of cell death over the 24 h incubation period. However, 2.5 mM nicotine enhanced the cytotoxic response and caused about 50% of cell death on 50 microg/ml arecoline-induced cytotoxicity. Taken together, arecoline may render human buccal mucosal fibroblasts more vulnerable to other reactive agents in cigarettes via GST reduction. The compounds of tobacco products may act synergistically in the pathogenesis of oral mucosal lesions in areca quid chewers. The data presented here may partly explain why patients who combined the habits of areca quid chewing and cigarette smoking are at greater risk of contracting oral cancer.

  14. Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells

    SciTech Connect

    Luo, Yi Rana, Payal; Will, Yvonne

    2012-06-01

    Immunosuppressant cyclosporine A (CsA) treatment can cause severe side effects. Patients taking immunosuppressant after organ transplantation often display hyperlipidemia and obesity. Elevated levels of free fatty acids have been linked to the etiology of metabolic syndromes, nonalcoholic fatty liver and steatohepatitis. The contribution of free fatty acids to CsA-induced toxicity is not known. In this study we explored the effect of palmitic acid on CsA-induced toxicity in HepG2 cells. CsA by itself at therapeutic exposure levels did not induce detectible cytotoxicity in HepG2 cells. Co-treatment of palmitic acid and CsA resulted in a dose dependent increase in cytotoxicity, suggesting that fatty acid could sensitize cells to CsA-induced cytotoxicity at the therapeutic doses of CsA. A synergized induction of caspase-3/7 activity was also observed, indicating that apoptosis may contribute to the cytotoxicity. We demonstrated that CsA reduced cellular oxygen consumption which was further exacerbated by palmitic acid, implicating that impaired mitochondrial respiration might be an underlying mechanism for the enhanced toxicity. Inhibition of c-Jun N-terminal kinase (JNK) attenuated palmitic acid and CsA induced toxicity, suggesting that JNK activation plays an important role in mediating the enhanced palmitic acid/CsA-induced toxicity. Our data suggest that elevated FFA levels, especially saturated FFA such as palmitic acid, may be predisposing factors for CsA toxicity, and patients with underlying diseases that would elevate free fatty acids may be susceptible to CsA-induced toxicity. Furthermore, hyperlipidemia/obesity resulting from immunosuppressive therapy may aggravate CsA-induced toxicity and worsen the outcome in transplant patients. -- Highlights: ► Palmitic acid and cyclosporine (CsA) synergistically increased cytotoxicity. ► The impairment of mitochondrial functions may contribute to the enhanced toxicity. ► Inhibition of JNK activity attenuated

  15. In vivo synthesis of europium selenide nanoparticles and related cytotoxicity evaluation of human cells.

    PubMed

    Kim, Eun Bee; Seo, Ji Min; Kim, Gi Wook; Lee, Sang Yup; Park, Tae Jung

    2016-12-01

    Nanotechnology strives to combine new materials for development of noble nanoparticles. As the nanoparticles exhibit unique optical, electronic, and magnetic properties depending on their composition, developing safe, cost-effective and environmentally friendly technologies for the synthesis have become an important issue. In this study, in vivo synthesis of europium selenide (EuSe) nanoparticles was performed using recombinant Escherichia coli cells expressing heavy-metal binding proteins, phytochelatin synthase and metallothionein. The formation of EuSe nanoparticles was confirmed by using UV-vis spectroscopy, spectrofluorometry, X-ray diffraction, energy dispersive X-ray and transmission electron microscopy. The synthesized EuSe nanoparticles exhibited high fluorescence intensities as well as strong magnetic properties. Furthermore, anti-cancer effect of EuSe nanoparticles against cancer cell lines was investigated. This strategy for the biogenic synthesis of nanoparticles has a great potential as bioimaging tools and drug carrying agents in biomedical fields due to its simplicity and nontoxicity.

  16. The role of ROS generation from magnetic nanoparticles in an alternating magnetic field on cytotoxicity

    PubMed Central

    Wydra, Robert J.; Rychahou, Piotr G.; Evers, B. Mark; Anderson, Kimberly W.; Dziubla, Thomas D.; Hilt, J. Zach

    2015-01-01

    Monosaccharide coated iron oxide nanoparticles were developed to selectively target colon cancer cell lines for magnetically mediated energy delivery therapy. The nanoparticles were prepared using a coupling reaction to attach the glucose functional group to the iron oxide core, and functionality was confirmed with physicochemical characterization techniques. The targeted nanoparticles were internalized into CT26 cells at a greater extent than non-targeted nanoparticles, and the nanoparticles were shown to be localized within lysosomes. Cells with internalized nanoparticles were exposed to an AMF to determine the potential to delivery therapy. Cellular ROS generation and apoptotic cell death was enhanced with field exposure. The nanoparticle coatings inhibit the Fenton-like surface generation of ROS suggesting a thermal or mechanical effect is more likely the source of the intracellular effect. PMID:26143604

  17. Biogenic silver nanoparticles from Abutilon indicum: their antioxidant, antibacterial and cytotoxic effects in vitro.

    PubMed

    Mata, Rani; Nakkala, Jayachandra Reddy; Sadras, Sudha Rani

    2015-04-01

    Green synthesis of silver nanoparticles using biological entities is gaining interest because of their potential applications in nano-medicine. Herein, we report the biological synthesis of Abutilon indicum silver nanoparticles (AIAgNPs) using aqueous Abutilon indicum leaf extract (AILE) and evaluation of their biological applications. TEM analysis revealed that the spherical biogenic AIAgNPs were found to be between 5 and 25 nm in size. The bioactive phyto-constituents such are condensed tannins of AILE were found to play a key role in the reduction and capping of AIAgNPs. The biological properties of AIAgNPs were premeditated as free radical scavenging activity, antibacterial effect and anti-proliferative activity. AIAgNPs were found to exhibit good free radical scavenging activities and the intense zone of inhibition displayed by them in six different pathogenic species indicate the potential antibacterial effect. Further, AIAgNPs showed a dose dependant anti-proliferative effect against COLO 205 (human colon cancer) and MDCK (normal) cells with an IC50 of 3 and 4 μg/mL and 100 and 75 μg/mL, respectively after 24 and 48 h. The morphological changes, chromatin condensation and membrane potential loss induced by AIAgNPs were evidenced by AO/EB and AnnexinV-Cy3 staining. The mitochondrial membrane potential (MMP) loss and G1/S transition cell cycle arrest in COLO 205 cells was evidenced in rhodamine123 staining and FACS analysis. The high levels of ROS as shown in DCF-DA staining could have played a major role in DNA fragmentation and eventually lead to apoptosis. The mode of action through the induction apoptosis by AIAgNPs in COLO 205 cells is exciting with promising application of nano-materials in biomedical research.

  18. Salidroside inhibits endogenous hydrogen peroxide induced cytotoxicity of endothelial cells.

    PubMed

    Zhao, Xingyu; Jin, Lianhai; Shen, Nan; Xu, Bin; Zhang, Wei; Zhu, Hongli; Luo, Zhengli

    2013-01-01

    Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L., shows potent antioxidant property. Herein, we investigated the protective effects of salidroside against hydrogen peroxide (H2O2)-induced oxidative damage in human endothelial cells (EVC-304). EVC-304 cells were incubated in the presence or absence of low steady states of H2O2 (3-4 µM) generated by glucose oxidase (GOX) with or without salidroside. 3(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) assays were performed, together with Hoechst 33258 staining and flow cytometric analysis using Annexin-V and propidium iodide (PI) label. The results indicated that salidroside pretreatment attenuated endogenous H2O2 induced apoptotic cell death in EVC-304 cells in a dose-dependent pattern. Furthermore, Western blot data revealed that salidroside inhibited activation of caspase-3, 9 and cleavage of poly(ADP-ribose) polymerase (PARP) induced by endogenous H2O2. It also decreased the expression of Bax and rescued the balance of pro- and anti-apoptotic proteins. All these results demonstrated that salidroside may present a potential therapy for oxidative stress in cardiovascular and cerebrovascular diseases.

  19. Engineered nanoparticles induce cell apoptosis: potential for cancer therapy

    PubMed Central

    Ma, Dan-Dan; Yang, Wan-Xi

    2016-01-01

    Engineered nanoparticles (ENPs) have been widely applied in industry, commodities, biology and medicine recently. The potential for many related threats to human health has been highlighted. ENPs with their sizes no larger than 100 nm are able to enter the human body and accumulate in organs such as brain, liver, lung, testes, etc, and cause toxic effects. Many references have studied ENP effects on the cells of different organs with related cell apoptosis noted. Understanding such pathways towards ENP induced apoptosis may aid in the design of effective cancer targeting ENP drugs. Such ENPs can either have a direct effect towards cancer cell apoptosis or can be used as drug delivery agents. Characteristics of ENPs, such as sizes, shape, forms, charges and surface modifications are all seen to play a role in determining their toxicity in target cells. Specific modifications of such characteristics can be applied to reduce ENP bioactivity and thus alleviate unwanted cytotoxicity, without affecting the intended function. This provides an opportunity to design ENPs with minimum toxicity to non-targeted cells. PMID:27056889

  20. Folate-modified Chitosan Nanoparticles Containing the IP-10 Gene Enhance Melanoma-specific Cytotoxic CD8+CD28+ T Lymphocyte Responses

    PubMed Central

    He, Jian; Duan, Siliang; Yu, Xia; Qian, Zhiyong; Zhou, Sufang; Zhang, Zhiyong; Huang, Xianing; Huang, Yong; Su, Jing; Lai, Chunhui; Meng, Jinyu; Zhou, Nuo; Lu, Xiaoling; Zhao, Yongxiang

    2016-01-01

    Background: Adoptive immunotherapy with cytotoxic T lymphocytes (CTLs) has great potential for the treatment of some malignant cancers. Therefore, augmenting the responses of tumor-specific CTLs is significant for the adoptive immunotherapy of melanoma. This study aimed to investigate the anti-tumor response of a combination therapy employing folate-modified chitosan nanoparticles containing IP-10 (interferon-γ-inducible protein-10) plus melanoma TRP2-specific CD8+CD28+ T cells. Methods: We prepared folate-modified chitosan nanoparticles containing the mouse IP-10 gene (FA-CS-mIP-10), and induced melanoma TRP2-specific CD8+CD28+ T cells by co-culturing them with artificial antigen-presenting cells. B16-bearing mice were treated with FA-CS-mIP-10, melanoma TRP2-specific CD8+CD28+ T cells, a combination of both, and the saline control. Tumor volumes and the survival time of mice were recorded. The proportion of myeloid-derived suppressor cells (MDSCs) infiltrating the tumor microenvironment and regulatory T cells (Tregs) in the spleen was analyzed by flow cytometry. We also detected the proliferation and angiogenesis of tumors by immunohistochemistry and apoptosis by TUNEL. Results: The combination therapy inhibited the progression of melanoma in vivo. Compared with other treatments, it more efficiently inhibited tumor growth and increased the survival time of mice. After treatment with combination therapy, the proportion of MDSCs and Tregs decreased, while the percentage of CXCR3+CD8+ T cells increased. Furthermore, combination therapy inhibited proliferation and promoted apoptosis of tumor cells and significantly inhibited tumor angiogenesis in vivo. Conclusion: We describe a novel strategy for improving the anti-tumor response of CD8+CD28+ CTLs by combining them with FA-CS-mIP-10 nanoparticles. PMID:27022421

  1. Biogenic-production of SnO2 nanoparticles and its cytotoxic effect against hepatocellular carcinoma cell line (HepG2).

    PubMed

    Roopan, Selvaraj Mohana; Kumar, Subramanian Hari Subbish; Madhumitha, Gunabalan; Suthindhiran, Krishnamurthy

    2015-02-01

    In this paper, we have established for the first time, the terrific efficiency of aqueous extract of agricultural waste dried peel of sugar apple (Annona squamosa) in the rapid synthesis of stable SnO2 nanoparticles. In topical years, the deployment of secondary metabolites from plant extract has emerged as a novel technology for the synthesis of various nanoparticles. In this paper, we have studied the potential of SnO2 nanoparticles assembly using agricultural waste source for the first time. The synthesized nanoparticles were characterized and confirmed as SnO2 nanoparticles by using UV-visible spectroscopy, XRD, and TEM analysis. The motivation of this study was to examine cytotoxicity study of SnO2 nanoparticles against hepatocellular carcinoma cell line (HepG2). SnO2 nanoparticles inhibited the cell proliferation in a dose- and time-dependent manner with an IC50 value of 148 μg/mL. The treated cells showed an altered morphology with increasing concentrations of SnO2 nanoparticles. Our result shows that the SnO2 nanoparticles exhibit moderate cytotoxicity towards the hepatocellular carcinoma (HepG2) at tested concentrations.

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

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

  3. 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.

  4. Serum Proteins Enhance Dispersion Stability and Influence the Cytotoxicity and Dosimetry of ZnO Nanoparticles in Suspension and Adherent Cancer Cell Models

    NASA Astrophysics Data System (ADS)

    Anders, Catherine B.; Chess, Jordan J.; Wingett, Denise G.; Punnoose, Alex

    2015-11-01

    Agglomeration and sedimentation of nanoparticles (NPs) within biological solutions is a major limitation in their use in many downstream applications. It has been proposed that serum proteins associate with the NP surface to form a protein corona that limits agglomeration and sedimentation. Here, we investigate the effect of fetal bovine serum (FBS) proteins on the dispersion stability, dosimetry, and NP-induced cytotoxicity of cationic zinc oxide nanoparticles (nZnO) synthesized via forced hydrolysis with a core size of 10 nm. Two different in vitro cell culture models, suspension and adherent, were evaluated by comparing a phosphate buffered saline (PBS) nZnO dispersion (nZnO/PBS) and an FBS-stabilized PBS nZnO dispersion (nZnO - FBS/PBS). Surface interactions of FBS on nZnO were analyzed via spectroscopic and optical techniques. Fourier transformed infrared spectroscopy (FTIR) confirmed the adsorption of negatively charged protein components on the cationic nZnO surface through the disappearance of surfaced-adsorbed carboxyl functional groups and the subsequent detection of vibrational modes associated with the protein backbone of FBS-associated proteins. Further confirmation of these interactions was noted in the isoelectric point shift of the nZnO from the characteristic pH of 9.5 to a pH of 6.1. In nZnO - FBS/PBS dispersions, the FBS reduced agglomeration and sedimentation behaviors to impart long-term improvements (>24 h) to the nZnO dispersion stability. Furthermore, mathematical dosimetry models indicate that nZnO - FBS/PBS dispersions had consistent NP deposition patterns over time unlike unstable nZnO/PBS dispersions. In suspension cell models, the stable nZnO - FBS/PBS dispersion resulted in a ~33 % increase in the NP-induced cytotoxicity for both Jurkat leukemic and Hut-78 lymphoma cancer cells. In contrast, the nZnO - FBS/PBS dispersion resulted in 49 and 71 % reductions in the cytotoxicity observed towards the adherent breast (T-47D) and prostate

  5. Serum Proteins Enhance Dispersion Stability and Influence the Cytotoxicity and Dosimetry of ZnO Nanoparticles in Suspension and Adherent Cancer Cell Models.

    PubMed

    Anders, Catherine B; Chess, Jordan J; Wingett, Denise G; Punnoose, Alex

    2015-12-01

    Agglomeration and sedimentation of nanoparticles (NPs) within biological solutions is a major limitation in their use in many downstream applications. It has been proposed that serum proteins associate with the NP surface to form a protein corona that limits agglomeration and sedimentation. Here, we investigate the effect of fetal bovine serum (FBS) proteins on the dispersion stability, dosimetry, and NP-induced cytotoxicity of cationic zinc oxide nanoparticles (nZnO) synthesized via forced hydrolysis with a core size of 10 nm. Two different in vitro cell culture models, suspension and adherent, were evaluated by comparing a phosphate buffered saline (PBS) nZnO dispersion (nZnO/PBS) and an FBS-stabilized PBS nZnO dispersion (nZnO - FBS/PBS). Surface interactions of FBS on nZnO were analyzed via spectroscopic and optical techniques. Fourier transformed infrared spectroscopy (FTIR) confirmed the adsorption of negatively charged protein components on the cationic nZnO surface through the disappearance of surfaced-adsorbed carboxyl functional groups and the subsequent detection of vibrational modes associated with the protein backbone of FBS-associated proteins. Further confirmation of these interactions was noted in the isoelectric point shift of the nZnO from the characteristic pH of 9.5 to a pH of 6.1. In nZnO - FBS/PBS dispersions, the FBS reduced agglomeration and sedimentation behaviors to impart long-term improvements (>24 h) to the nZnO dispersion stability. Furthermore, mathematical dosimetry models indicate that nZnO - FBS/PBS dispersions had consistent NP deposition patterns over time unlike unstable nZnO/PBS dispersions. In suspension cell models, the stable nZnO - FBS/PBS dispersion resulted in a ~33 % increase in the NP-induced cytotoxicity for both Jurkat leukemic and Hut-78 lymphoma cancer cells. In contrast, the nZnO - FBS/PBS dispersion resulted in 49 and 71 % reductions in the cytotoxicity observed towards the adherent breast (T-47D) and prostate

  6. Geno- and cytotoxicity induced on Cyprinus carpio by aluminum, iron, mercury and mixture thereof.

    PubMed

    Gómez-Oliván, Leobardo Manuel; Mendoza-Zenil, Youssef Paolo; SanJuan-Reyes, Nely; Galar-Martínez, Marcela; Ramírez-Durán, Ninfa; Rodríguez Martín-Doimeadios, Rosa Del Carmen; Rodríguez-Fariñas, Nuria; Islas-Flores, Hariz; Elizalde-Velázquez, Armando; García-Medina, Sandra; Pérez-Pastén Borja, Ricardo

    2017-01-01

    Metals such as Al, Fe and Hg are used in diverse anthropogenic activities. Their presence in water bodies is due mainly to domestic, agricultural and industrial wastewater discharges and constitutes a hazard for the organisms inhabiting these environments. The present study aimed to evaluate geno- and cytotoxicity induced by Al, Fe, Hg and the mixture of these metals on blood of the common carp Cyprinus carpio. Specimens were exposed to the permissible limits in water for human use and consumption according to the pertinent official Mexican norm [official Mexican norm NOM-127-SSA1-1994] Al (0.2mgL(-1)), Fe (0.3mgL(-1)), Hg (0.001mgL(-1)) and their mixture for 12, 24, 48, 72 and 96h. Biomarkers of genotoxicity (comet assay and micronucleus test) and cytotoxicity (caspase-3 activity and TUNEL assay) were evaluated. Significant increases relative to the control group (p<0.05) were observed in all biomarkers at all exposure times in all test systems; however, damage was greater when the metals were present as a mixture. Furthermore, correlations between metal concentrations and biomarkers of geno- and cytotoxicity were found only at certain exposure times. In conclusion, Al, Fe, Hg and the mixture of these metals induce geno- and cytotoxicity on blood of C. carpio.

  7. Functional role of CD95 ligand in concanavalin A-induced intestinal intraepithelial lymphocyte cytotoxicity.

    PubMed Central

    Ghoreschi, K; Muders, M; Enders, G A

    1998-01-01

    Freshly isolated murine intestinal intraepithelial lymphocytes (IEL) express CD95 ligand (CD95L), as shown by reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence-activated cell sorter (FACS) analysis. Between 15 and 25% of IEL could be stained with an antibody to CD95L. Therefore it was investigated whether the CD95L/CD95 pathway was effective in IEL cytotoxicity. Stimulation of IEL in vitro with concanavalin A (Con A) induced a strong cytotoxic response, which was much higher when using CD95-expressing target cells. This effect was most evident when comparing the specific lysis of CD95-transfected target cells of the leukaemia cell line L1210 with that of the untransfected parental cell line. In addition, an antibody to CD95 was able to dramatically reduce the specific lysis of CD95-expressing target cells. After stimulation with Con A, which is able to bind to CD95L, the effects were more obvious compared with the triggering of the T-cell receptor (TCR)-alphabeta or gamma delta. On the other hand, EGTA reduced the Con A-induced cytotoxicity. Together these findings support a role of the CD95L/CD95 pathway in IEL cytotoxicity, even though the reaction was Ca2+ sensitive. As a function, CD95L-expressing IEL should be able to contribute to the elimination of CD95-expressing target cells in the intestine. Images Figure 1 PMID:9893046

  8. 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

  9. Effect of PEG Molecular Weight on Stability, T2 contrast, Cytotoxicity, and Cellular Uptake of Superparamagnetic Iron Oxide Nanoparticles (SPIONs)

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2012-09-01

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

  11. Role of reactive oxygen species in cis-dichlorodiammineplatinum-induced cytotoxicity on bladder cancer cells.

    PubMed Central

    Miyajima, A.; Nakashima, J.; Yoshioka, K.; Tachibana, M.; Tazaki, H.; Murai, M.

    1997-01-01

    This study was undertaken to investigate the intracellular induction of reactive oxygen species (ROS) by cis-dichlorodiammineplatinum (CDDP) and the augmentation of their cytotoxicity in bladder cancer cells (KU7) by enhancement of ROS generation by the glutathione (GSH) depletors buthionine sulphoximine (BSO) and diethylmaleate (DEM). CDDP-induced cytotoxicity in KU7 cells and its modulation by GSH depletors were determined using spectrophotometric measurement with crystal violet staining. The effects of GSH depletors on intracellular GSH levels were confirmed using the GSH reductase-DTNB recycling method. Intracellular ROS generation induced by CDDP with or without GSH depletors was estimated from the amount of intracellular dichlorofluorescein (DCF), an oxidized product of dichlorofluorescein (DCFH), which was measured with an anchored cell analysis and sorting system. The cytotoxic effects of CDDP (IC50 15.0 +/- 2.5 microM) were significantly enhanced by BSO (IC50 9.3 +/- 2.6 microM, P < 0.01) and DEM (IC50 10.3 +/- 0.3 microM, P <0.01). BSO and DEM produced a significant depletion in intracellular GSH levels (9.6 +/- 0.4 nmol 10(-6) cells, 17.9 +/- 1.0 nmol 10(-6) cells) compared with the controls (30.5 +/- 0.6 nmol 10(-6) cells). Intracellular DCF production in KU7 cells treated with CDDP (1.35 +/- 0.33 microM) was significantly enhanced by the addition of BSO (4.43 +/- 0.33 microM) or DEM (3.12 +/- 0.22 microM) at 150 min. These results suggest that ROS may play a substantial role in CDDP-induced cytotoxicity and that GSH depletors augment its cytotoxicity through an enhancement of ROS generation in bladder cancer cells. PMID:9231920

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

    PubMed

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

    2000-08-01

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

  13. Autophagy induced by silica nanoparticles protects RAW264.7 macrophages from cell death.

    PubMed

    Marquardt, Clarissa; Fritsch-Decker, Susanne; Al-Rawi, Marco; Diabaté, Silvia; Weiss, Carsten

    2017-03-15

    Although the technological and economic benefits of engineered nanomaterials are obvious, concerns have been raised about adverse effects if such material is inhaled, ingested, applied to the skin or even released into the environment. Here we studied the cytotoxic effects of the most abundant nanomaterial, silica nanoparticles (SiO2-NPs), in murine RAW264.7 macrophages. SiO2-NPs dose-dependently induce membrane leakage and cell death without obvious involvement of reactive oxygen species. Interestingly, at low concentrations SiO2-NPs trigger autophagy, evidenced by morphological and biochemical hallmarks such as autophagolysosomes or increased levels of LC3-II, which serves to protect cells from cytotoxicity. Hence SiO2-NPs initiate an adaptive stress response which dependent on dose serve to balance survival and death and ultimately dictates the cellular fate.

  14. 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.

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

    PubMed

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

    2009-01-01

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

  16. Capsaicin induces cytotoxicity in pancreatic neuroendocrine tumor cells via mitochondrial action.

    PubMed

    Skrzypski, M; Sassek, M; Abdelmessih, S; Mergler, S; Grötzinger, C; Metzke, D; Wojciechowicz, T; Nowak, K W; Strowski, M Z

    2014-01-01

    Capsaicin (CAP), the pungent ingredient of chili peppers, inhibits growth of various solid cancers via TRPV1 as well as TRPV1-independent mechanisms. Recently, we showed that TRPV1 regulates intracellular calcium level and chromogranin A secretion in pancreatic neuroendocrine tumor (NET) cells. In the present study, we characterize the role of the TRPV1 agonist - CAP - in controlling proliferation and apoptosis of pancreatic BON and QGP-1 NET cells. We demonstrate that CAP reduces viability and proliferation, and stimulates apoptotic death of NET cells. CAP causes mitochondrial membrane potential loss, inhibits ATP synthesis and reduces mitochondrial Bcl-2 protein production. In addition, CAP increases cytochrome c and cleaved caspase 3 levels in cytoplasm. CAP reduces reactive oxygen species (ROS) generation. The antioxidant N-acetyl-l-cysteine (NAC) acts synergistically with CAP to reduce ROS generation, without affecting CAP-induced toxicity. TRPV1 protein reduction by 75% reduction fails to attenuate CAP-induced cytotoxicity. In summary, these results suggest that CAP induces cytotoxicity by disturbing mitochondrial potential, and inhibits ATP synthesis in NET cells. Stimulation of ROS generation by CAP appears to be a secondary effect, not related to CAP-induced cytotoxicity. These results justify further evaluation of CAP in modulating pancreatic NETs in vivo.

  17. Allium sativum L. extract prevents methyl mercury-induced cytotoxicity in peripheral blood leukocytes (LS).

    PubMed

    Abdalla, F H; Bellé, L P; De Bona, K S; Bitencourt, P E R; Pigatto, A S; Moretto, M B

    2010-01-01

    Adenosine deaminase (ADA) is involved in purine metabolism and plays a significant role in the immune system. The focus of this investigation was to examine the effects of low concentrations of organic mercury on ADA activity in human leukocytes and to investigate the relationship between these effects and cell death. We have examined the protective potential effects of Allium sativum extract (GaE) against Methylmercury (MeHg)-induced cytotoxic effects on human leucocytes under in vitro conditions. MeHg (0.05-10 microM) significantly decreased leukocyte viability (58.97% for MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) and 51.67% for Alamar Blue (AB) and this decrease was positively correlated to the MeHg-induced inhibition of ADA activity. N-acetylcysteine (NAC) and GaE prevented both the MeHg-induced cytotoxic effects on leukocytes according to MTT and AB assays and the effects on the ADA activity. The present results suggest that the protective effects of GaE against MeHg-induced leukocyte damage is related to the removal of oxidant species generated in the presence of MeHg due to the antioxidant efficacy of garlic constituents. It is important to point out that the intense presence of ADA in Leukocyte suspension (LS) highlights the relevant effects in the immune system and in vitro cytotoxicity of MeHg exposure.

  18. Role of Zn doping in oxidative stress mediated cytotoxicity of TiO2 nanoparticles in human breast cancer MCF-7 cells.

    PubMed

    Ahamed, Maqusood; Khan, M A Majeed; Akhtar, Mohd Javed; Alhadlaq, Hisham A; Alshamsan, Aws

    2016-07-22

    We investigated the effect of Zn-doping on structural and optical properties as well as cellular response of TiO2 nanoparticles (NPs) in human breast cancer MCF-7 cells. A library of Zn-doped (1-10 at wt%) TiO2 NPs was prepared. Characterization data indicated that dopant Zn was incorporated into the lattice of host TiO2. The average particle size of TiO2 NPs was decreases (38 to 28 nm) while the band gap energy was increases (3.35 eV-3.85 eV) with increasing the amount of Zn-doping. Cellular data demonstrated that Zn-doped TiO2 NPs induced cytotoxicity (cell viability reduction, membrane damage and cell cycle arrest) and oxidative stress (reactive oxygen species generation &glutathione depletion) in MCF-7 cells and toxic intensity was increases with increasing the concentration of Zn-doping. Molecular data revealed that Zn-doped TiO2 NPs induced the down-regulation of super oxide dismutase gene while the up-regulation of heme oxygenase-1 gene in MCF-7 cells. Cytotoxicity induced by Zn-doped TiO2 NPs was efficiently prevented by N-acetyl-cysteine suggesting that oxidative stress might be the primarily cause of toxicity. In conclusion, our data indicated that Zn-doping decreases the particle size and increases the band gap energy as well the oxidative stress-mediated toxicity of TiO2 NPs in MCF-7 cells.

  19. Role of Zn doping in oxidative stress mediated cytotoxicity of TiO2 nanoparticles in human breast cancer MCF-7 cells

    NASA Astrophysics Data System (ADS)

    Ahamed, Maqusood; Khan, M. A. Majeed; Akhtar, Mohd Javed; Alhadlaq, Hisham A.; Alshamsan, Aws

    2016-07-01

    We investigated the effect of Zn-doping on structural and optical properties as well as cellular response of TiO2 nanoparticles (NPs) in human breast cancer MCF-7 cells. A library of Zn-doped (1–10 at wt%) TiO2 NPs was prepared. Characterization data indicated that dopant Zn was incorporated into the lattice of host TiO2. The average particle size of TiO2 NPs was decreases (38 to 28 nm) while the band gap energy was increases (3.35 eV–3.85 eV) with increasing the amount of Zn-doping. Cellular data demonstrated that Zn-doped TiO2 NPs induced cytotoxicity (cell viability reduction, membrane damage and cell cycle arrest) and oxidative stress (reactive oxygen species generation & glutathione depletion) in MCF-7 cells and toxic intensity was increases with increasing the concentration of Zn-doping. Molecular data revealed that Zn-doped TiO2 NPs induced the down-regulation of super oxide dismutase gene while the up-regulation of heme oxygenase-1 gene in MCF-7 cells. Cytotoxicity induced by Zn-doped TiO2 NPs was efficiently prevented by N-acetyl-cysteine suggesting that oxidative stress might be the primarily cause of toxicity. In conclusion, our data indicated that Zn-doping decreases the particle size and increases the band gap energy as well the oxidative stress-mediated toxicity of TiO2 NPs in MCF-7 cells.

  20. Role of Zn doping in oxidative stress mediated cytotoxicity of TiO2 nanoparticles in human breast cancer MCF-7 cells

    PubMed Central

    Ahamed, Maqusood; Khan, M. A. Majeed; Akhtar, Mohd Javed; Alhadlaq, Hisham A.; Alshamsan, Aws

    2016-01-01

    We investigated the effect of Zn-doping on structural and optical properties as well as cellular response of TiO2 nanoparticles (NPs) in human breast cancer MCF-7 cells. A library of Zn-doped (1–10 at wt%) TiO2 NPs was prepared. Characterization data indicated that dopant Zn was incorporated into the lattice of host TiO2. The average particle size of TiO2 NPs was decreases (38 to 28 nm) while the band gap energy was increases (3.35 eV–3.85 eV) with increasing the amount of Zn-doping. Cellular data demonstrated that Zn-doped TiO2 NPs induced cytotoxicity (cell viability reduction, membrane damage and cell cycle arrest) and oxidative stress (reactive oxygen species generation & glutathione depletion) in MCF-7 cells and toxic intensity was increases with increasing the concentration of Zn-doping. Molecular data revealed that Zn-doped TiO2 NPs induced the down-regulation of super oxide dismutase gene while the up-regulation of heme oxygenase-1 gene in MCF-7 cells. Cytotoxicity induced by Zn-doped TiO2 NPs was efficiently prevented by N-acetyl-cysteine suggesting that oxidative stress might be the primarily cause of toxicity. In conclusion, our data indicated that Zn-doping decreases the particle size and increases the band gap energy as well the oxidative stress-mediated toxicity of TiO2 NPs in MCF-7 cells. PMID:27444578

  1. Enhanced neuroprotective effects of resveratrol delivered by nanoparticles on hydrogen peroxide-induced oxidative stress in rat cortical cell culture.

    PubMed

    Lu, Xiaowei; Xu, Huae; Sun, Bo; Zhu, Zhenshu; Zheng, Donghui; Li, Xiaolin

    2013-05-06

    Resveratrol (RES) has recently been reported as a potential antioxidant in treatment of ischemia/reperfusion injury through attenuating oxidative stress and apoptosis. However, application of RES is limited for its insolubility and short half-time. Latest evidence raises the possibility of developing nanoparticle-based delivery systems with improved solubility, stability and cytotoxicity of lipophilic drug. Here, we reported first a simple way to produce RES-loaded nanoparticles (RES-NPs) based on poly(N-vinylpyrrolidone)-b-poly(ε-caprolactone) polymer and further evaluated the protective effect of RES-NPs on hydrogen peroxide-induced oxidative stress and apoptosis in rat cortical cell culture. The controlled release pattern of RES-loaded nanoparticles was characterized by in vitro release experiments. Cytotoxicity tests proved cytocompatibility of these nanoparticles with neurons. Shown by coumarin-6 loaded nanoparticles, the uptake of nanoparticles by neurons was considered through endocytosis, which could lead to higher uptake efficiency at lower concentration. Thereby, the hypothesis is raised that RES-NPs could demonstrate enhanced neuroprotection compared to an equivalent dose of free RES at lower concentration, especially. It was further supported by enhanced reduction of LDH release, elimination of ROS and MDA, and attenuation of apoptosis signal (ratio of Bax/Bcl-2, activation of caspase-3). RES-NPs could be a potential treatment needing intensive research for ischemia/reperfusion related disorder including stroke.

  2. Transferrin-modified PLGA nanoparticles significantly increase the cytotoxicity of paclitaxel in bladder cancer cells by increasing intracellular retention

    NASA Astrophysics Data System (ADS)

    Jin, Shihua; Zhang, Yi; Yu, Chengfan; Wang, Gang; Zhang, Zhihong; Li, Ningchen; Na, Yanqun

    2014-10-01

    To improve the anticancer effects of paclitaxel (Tax) on bladder cancer, transferrin-modified and unmodified poly( d,l lactide- co-glycolide) nanoparticles (NPs) were generated to deliver Tax. The characteristics of the NPs and the drug-release profiles were evaluated. The cytotoxicity levels of blank NPs and Tax-loaded NPs in the bladder cancer cell lines MBT-2, J-82, and TCC Sup were determined. The uptakes and retentions of the NPs by the cell lines and the intracellular distribution of the NPs were also studied. The results showed similar NPs characteristics and drug-release profiles for NPs with and without transferrin modification. The sizes of NPs with and without transferrin modification were 206 and 278 nm, respectively; the Z-potentials were -23.5 and -24.3 mV, respectively; the drug loadings were 6.5 and 6.7 % w/w, respectively. No cytotoxicity was observed in the bladder cancer cells exposed to blank NPs. Both types of Tax-loaded NPs, however, had significantly higher cytotoxicity levels compared with the Tax solution in the bladder cancer cells. The transferrin-modified, Tax-loaded NPs were significantly more cytotoxic than the Tax-loaded NPs without modification in the MBT-2 and TCC Sup cells. There were no significant differences in NP uptakes between transferrin-modified and unmodified NPs in any of the three studied bladder cancer cell lines; however, the retentions of the modified NPs were significantly higher in the MBT-2 and TCC Sup cells. These findings suggest that NPs can significantly improve the anticancer effect of Tax in bladder cells. Furthermore, transferrin-modified NPs can improve the anticancer effect by increasing intracellular retention and not by increasing uptake. The transferrin-modified NPs are promising drug delivery vehicle for bladder cancer treatment.

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  4. Sulforaphane Protects the Liver against CdSe Quantum Dot-Induced Cytotoxicity

    PubMed Central

    Wang, Wei; He, Yan; Yu, Guodong; Li, Baolong; Sexton, Darren W.; Wileman, Thomas; Roberts, Alexandra A.; Hamilton, Chris J.; Liu, Ruoxi; Chao, Yimin; Shan, Yujuan; Bao, Yongping

    2015-01-01

    The potential cytotoxicity of cadmium selenide (CdSe) quantum dots (QDs) presents a barrier to their use in biomedical imaging or as diagnostic and therapeutic agents. Sulforaphane (SFN) is a chemoprotective compound derived from cruciferous vegetables which can up-regulate antioxidant enzymes and induce apoptosis and autophagy. This study reports the effects of SFN on CdSe QD-induced cytotoxicity in immortalised human hepatocytes and in the livers of mice. CdSe QDs induced dose-dependent cell death in hepatocytes with an IC50 = 20.4 μM. Pre-treatment with SFN (5 μM) increased cell viability in response to CdSe QDs (20 μM) from 49.5 to 89.3%. SFN induced a pro-oxidant effect characterized by depletion of intracellular reduced glutathione during short term exposure (3–6 h), followed by up-regulation of antioxidant enzymes and glutathione levels at 24 h. SFN also caused Nrf2 translocation into the nucleus, up-regulation of antioxidant enzymes and autophagy. siRNA knockdown of Nrf2 suggests that the Nrf2 pathway plays a role in the protection against CdSe QD-induced cell death. Wortmannin inhibition of SFN-induced autophagy significantly suppressed the protective effect of SFN on CdSe QD-induced cell death. Moreover, the role of autophagy in SFN protection against CdSe QD-induced cell death was confirmed using mouse embryonic fibroblasts lacking ATG5. CdSe QDs caused significant liver damage in mice, and this was decreased by SFN treatment. In conclusion, SFN attenuated the cytotoxicity of CdSe QDs in both human hepatocytes and in the mouse liver, and this protection was associated with the induction of Nrf2 pathway and autophagy. PMID:26402917

  5. Sulforaphane Protects the Liver against CdSe Quantum Dot-Induced Cytotoxicity.

    PubMed

    Wang, Wei; He, Yan; Yu, Guodong; Li, Baolong; Sexton, Darren W; Wileman, Thomas; Roberts, Alexandra A; Hamilton, Chris J; Liu, Ruoxi; Chao, Yimin; Shan, Yujuan; Bao, Yongping

    2015-01-01

    The potential cytotoxicity of cadmium selenide (CdSe) quantum dots (QDs) presents a barrier to their use in biomedical imaging or as diagnostic and therapeutic agents. Sulforaphane (SFN) is a chemoprotective compound derived from cruciferous vegetables which can up-regulate antioxidant enzymes and induce apoptosis and autophagy. This study reports the effects of SFN on CdSe QD-induced cytotoxicity in immortalised human hepatocytes and in the livers of mice. CdSe QDs induced dose-dependent cell death in hepatocytes with an IC50 = 20.4 μM. Pre-treatment with SFN (5 μM) increased cell viability in response to CdSe QDs (20 μM) from 49.5 to 89.3%. SFN induced a pro-oxidant effect characterized by depletion of intracellular reduced glutathione during short term exposure (3-6 h), followed by up-regulation of antioxidant enzymes and glutathione levels at 24 h. SFN also caused Nrf2 translocation into the nucleus, up-regulation of antioxidant enzymes and autophagy. siRNA knockdown of Nrf2 suggests that the Nrf2 pathway plays a role in the protection against CdSe QD-induced cell death. Wortmannin inhibition of SFN-induced autophagy significantly suppressed the protective effect of SFN on CdSe QD-induced cell death. Moreover, the role of autophagy in SFN protection against CdSe QD-induced cell death was confirmed using mouse embryonic fibroblasts lacking ATG5. CdSe QDs caused significant liver damage in mice, and this was decreased by SFN treatment. In conclusion, SFN attenuated the cytotoxicity of CdSe QDs in both human hepatocytes and in the mouse liver, and this protection was associated with the induction of Nrf2 pathway and autophagy.

  6. Synthesis of copper/nickel nanoparticles using newly synthesized Schiff-base metals complexes and their cytotoxicity/catalytic activities.

    PubMed

    Aazam, Elham S; El-Said, Waleed Ahmed

    2014-12-01

    Transition metal complexes compounds with Schiff bases ligand representing an important class of compounds that could be used to develop new metal-based anticancer agents and as precursors of metal NPs. Herein, 2,3-bis-[(3-ethoxy-2-hydroxybenzylidene)amino]but-2-enedinitrile Schiff base ligand and its corresponding copper/nickel complexes were synthesized. Also, we reported a facile and rapid method for synthesis nickel/copper nanoparticles based on thermal reduction of their complexes. Free ligand, its metal complexes and metals nanoparticles have been characterized based on elemental analysis, transmission electron microscopy, powder X-ray diffraction, magnetic measurements and by various spectroscopic (UV-vis, FT-IR, (1)H NMR, GC-MS) techniques. Additionally, the in vitro cytotoxic activity of free ligand and its complexes compounds were assessed against two cancer cell lines (HeLa and MCF-7 cells)and one healthy cell line (HEK293 cell). The copper complex was found to be active against these cancer cell lines at very low LD50 than the free ligand, while nickel complex did not show any anticancer activity against these cell lines. Also, the antibacterial activity of as-prepared copper nanoparticles were screened against Escherichia coli, which demonstrated minimum inhibitory concentration and minimum bactericidal concentration values lower than those values of the commercial Cu NPs as well as the previous reported values. Moreover, the synthesized nickel nanoparticles demonstrated remarkable catalytic performance toward hydrogenation of nitrobenzene that producing clean aniline with high selectivity (98%). This reactivity could be attributed to the high degree of dispersion of Ni nanoparticles.

  7. Anodically Grown Titania Nanotube Induced Cytotoxicity has Genotoxic Origins

    PubMed Central

    Mohamed, M. Sheikh; Torabi, Aida; Paulose, Maggie; Kumar, D. Sakthi; Varghese, Oomman K.

    2017-01-01

    Nanoarchitectures of titania (TiO2) have been widely investigated for a number of medical applications including implants and drug delivery. Although titania is extensively used in the food, drug and cosmetic industries, biocompatibility of nanoscale titania is still under careful scrutiny due to the conflicting reports on its interaction with cellular matter. For an accurate insight, we performed in vitro studies on the response of human dermal fibroblast cells toward pristine titania nanotubes fabricated by anodic oxidation. The nanotubes at low concentrations were seen to induce toxicity to the cells, whereas at higher concentrations the cell vitality remained on par with controls. Further investigations revealed an increase in the G0 phase cell population depicting that majority of cells were in the resting rather than active phase. Though the mitochondrial set-up did not exhibit any signs of stress, significantly enhanced reactive oxygen species production in the nuclear compartment was noted. The TiO2 nanotubes were believed to have gained access to the nuclear machinery and caused increased stress leading to genotoxicity. This interesting property of the nanotubes could be utilized to kill cancer cells, especially if the nanotubes are functionalized for a specific target, thus eliminating the need for any chemotherapeutic agents. PMID:28165491

  8. Anodically Grown Titania Nanotube Induced Cytotoxicity has Genotoxic Origins.

    PubMed

    Mohamed, M Sheikh; Torabi, Aida; Paulose, Maggie; Kumar, D Sakthi; Varghese, Oomman K

    2017-02-06

    Nanoarchitectures of titania (TiO2) have been widely investigated for a number of medical applications including implants and drug delivery. Although titania is extensively used in the food, drug and cosmetic industries, biocompatibility of nanoscale titania is still under careful scrutiny due to the conflicting reports on its interaction with cellular matter. For an accurate insight, we performed in vitro studies on the response of human dermal fibroblast cells toward pristine titania nanotubes fabricated by anodic oxidation. The nanotubes at low concentrations were seen to induce toxicity to the cells, whereas at higher concentrations the cell vitality remained on par with controls. Further investigations revealed an increase in the G0 phase cell population depicting that majority of cells were in the resting rather than active phase. Though the mitochondrial set-up did not exhibit any signs of stress, significantly enhanced reactive oxygen species production in the nuclear compartment was noted. The TiO2 nanotubes were believed to have gained access to the nuclear machinery and caused increased stress leading to genotoxicity. This interesting property of the nanotubes could be utilized to kill cancer cells, especially if the nanotubes are functionalized for a specific target, thus eliminating the need for any chemotherapeutic agents.

  9. Anodically Grown Titania Nanotube Induced Cytotoxicity has Genotoxic Origins

    NASA Astrophysics Data System (ADS)

    Mohamed, M. Sheikh; Torabi, Aida; Paulose, Maggie; Kumar, D. Sakthi; Varghese, Oomman K.

    2017-02-01

    Nanoarchitectures of titania (TiO2) have been widely investigated for a number of medical applications including implants and drug delivery. Although titania is extensively used in the food, drug and cosmetic industries, biocompatibility of nanoscale titania is still under careful scrutiny due to the conflicting reports on its interaction with cellular matter. For an accurate insight, we performed in vitro studies on the response of human dermal fibroblast cells toward pristine titania nanotubes fabricated by anodic oxidation. The nanotubes at low concentrations were seen to induce toxicity to the cells, whereas at higher concentrations the cell vitality remained on par with controls. Further investigations revealed an increase in the G0 phase cell population depicting that majority of cells were in the resting rather than active phase. Though the mitochondrial set-up did not exhibit any signs of stress, significantly enhanced reactive oxygen species production in the nuclear compartment was noted. The TiO2 nanotubes were believed to have gained access to the nuclear machinery and caused increased stress leading to genotoxicity. This interesting property of the nanotubes could be utilized to kill cancer cells, especially if the nanotubes are functionalized for a specific target, thus eliminating the need for any chemotherapeutic agents.

  10. How to assess cytotoxicity of (iron oxide-based) nanoparticles: a technical note using cationic magnetoliposomes.

    PubMed

    Soenen, Stefaan J H; De Cuyper, Marcel

    2011-01-01

    The range of different types of nanoparticles and their biomedical applications is rapidly growing, creating a need to thoroughly examine the effects these particles have on biological entities. One of the most commonly used nanoparticle types is iron oxide nanoparticles, which can be used as MRI contrast agents. The main research topic is the in vitro labeling of cells with iron oxide nanoparticles to render the cells detectable for MRI upon in vivo transplantation. For the correct evaluation of cell function and behavior in vivo, any effects of the nanoparticles on the cells must be completely ruled out. The present work provides a technical note where a detailed overview is given of several assays that could be useful to determine nanoparticle toxicity. The assays described focus on (i) nanoparticle internalization, (ii) immediate cell toxicity, (iii) cell proliferation, (iv) cell morphology, (v) cell functionality and (vi) cell physiology. Potential pitfalls, appropriate controls and advantages/disadvantages of the different assays are given. The main focus of this work is to provide a detailed guide to help other researchers in the field interested in setting up nanoparticle-toxicity studies.

  11. A cellular uptake and cytotoxicity properties study of gallic acid-loaded mesoporous silica nanoparticles on Caco-2 cells

    NASA Astrophysics Data System (ADS)

    Rashidi, Ladan; Vasheghani-Farahani, Ebrahim; Soleimani, Masoud; Atashi, Amir; Rostami, Khosrow; Gangi, Fariba; Fallahpour, Masoud; Tahouri, Mohammad Taher

    2014-03-01

    In this study, the effects of intracellular delivery of various concentrations of gallic acid (GA) as a semistable antioxidant, gallic acid-loaded mesoporous silica nanoparticles (MSNs-GA), and cellular uptake of nanoparticles into Caco-2 cells were investigated. MSNs were synthesized and loaded with GA, then characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, N2 adsorption isotherms, X-ray diffraction, and thermal gravimetric analysis. The cytotoxicity of MSNs and MSNs-GA at low and high concentrations were studied by means of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test and flow cytometry. MSNs did not show significant toxicity in various concentrations (0-500 μg/ml) on Caco-2 cells. For MSNs-GA, cell viability was reduced as a function of incubation time and different concentrations of nanoparticles. The in vitro GA release from MSNs-GA exhibited the same antitumor properties as free GA on Caco-2 cells. Flow cytometry results confirmed those obtained using MTT assay. TEM and fluorescent microscopy confirmed the internalization of MSNs by Caco-2 cells through nonspecific cellular uptake. MSNs can easily internalize into Caco-2 cells without deleterious effects on cell viability. The cell viability of Caco-2 cells was affected during MSNs-GA uptake. MSNs could be designed as suitable nanocarriers for antioxidants delivery.

  12. Carnosine's Effect on Amyloid Fibril Formation and Induced Cytotoxicity of Lysozyme

    PubMed Central

    Wu, Josephine W.; Liu, Kuan-Nan; How, Su-Chun; Chen, Wei-An; Lai, Chia-Min; Liu, Hwai-Shen; Hu, Chaur-Jong; Wang, Steven S. -S.

    2013-01-01

    Carnosine, a common dipeptide in mammals, has previously been shown to dissemble alpha-crystallin amyloid fibrils. To date, the dipeptide's anti-fibrillogensis effect has not been thoroughly characterized in other proteins. For a more complete understanding of carnosine's mechanism of action in amyloid fibril inhibition, we have investigated the effect of the dipeptide on lysozyme fibril formation and induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Our study demonstrates a positive correlation between the concentration and inhibitory effect of carnosine against lysozyme fibril formation. Molecular docking results show carnosine's mechanism of fibrillogenesis inhibition may be initiated by binding with the aggregation-prone region of the protein. The dipeptide attenuates the amyloid fibril-induced cytotoxicity of human neuronal cells by reducing both apoptotic and necrotic cell deaths. Our study provides solid support for carnosine's amyloid fibril inhibitory property and its effect against fibril-induced cytotoxicity in SH-SY5Y cells. The additional insights gained herein may pave way to the discovery of other small molecules that may exert similar effects against amyloid fibril formation and its associated neurodegenerative diseases. PMID:24349167

  13. Cytotoxic effects induced by combination of heliantriol B2 and dequalinium against human leukemic cell lines.

    PubMed

    Gurovic, M Soledad Vela; Lanza, A María Díaz; Adánez, María del Carmen Boyano; Omaña, M Cristina Estañ; Gómez, Irene Gañán; Murray, A Paula; López, Pilar Sancho

    2011-04-01

    Natural occurring compounds are considered an important source of antitumoral agents. In the present study, the cytotoxic potential of three pentacyclic triterpenes isolated from Chuquiraga erinacea (Asteraceae), against the human leukemic cell lines NB4 and K562 was assessed. Heliantriol B2 (HB2) showed the highest cytotoxic activity after 24 h treatment showing IC(50) values of 1.98 ± 0.12 µm and 3.52 ± 0.14 µm for NB4 and K562 cells, respectively. This activity was higher than that of the reference compound dequalinium (DQA). Apoptosis and necrosis induced by HB2 in both NB4 and K562 cell lines were analysed by Annexin V/PI labeling. Mitochondrial alterations including reactive oxygen species (ROS) production and mitochondrial transmembrane potential (ΔΨm) were also tested. The results demonstrated that HB2 induced cell death by apoptosis and necrosis and showed enhanced cytotoxic effects in combination with DQA. Besides, HB2 induced ROS overproduction in NB4 cells and a slight decrease of ΔΨm. Consequently, our findings prompt further studies on the HB2 mechanism of action and its selectivity to tumor cells in order to assess the potential of HB2 as an agent for cancer treatment.

  14. Menadione-induced cytotoxicity effects on human erythrocyte membranes studied by electron paramagnetic resonance.

    PubMed

    Trad, C H; Butterfield, D A

    1994-08-01

    Menadione (2-methyl-1,4-naphthoquinone) is cytotoxic to hepatocytes. In order to begin to investigate the changes in the physical state of membranes induced by this cytotoxic substance, electron paramagnetic resonance (EPR) spin-labeling techniques were used in conjunction with spin labels specific for cytoskeletal proteins, bilayer lipids, or cell-surface sialic acid or galactose to investigate erythrocyte membranes. We studied the molecular effects of oxidation of 200 microM menadione on the different membrane domains. The major findings are: (1) menadione increases protein-protein interactions (P < 0.001) of cytoskeletal proteins, (2) there is a slightly significant increase in the rotational motion of spin-labeled sialic acid (P < 0.05), while (3) the physical state of galactose residues was unaffected by menadione. Since glycophorin is coupled to the major cytoskeletal protein, spectrin, by protein 4.1, we suggest that menadione-induced oxidation could alter the conformation of protein 4.1. As a consequence, single or multiple sites of weakness could be induced leading to the alteration of the interactions of the cytoskeletal network and its anchoring domains in the membrane. These results are discussed with reference to possible mechanisms involved in the cytotoxic action of menadione.

  15. A genome-wide approach to identify genetic variants that contribute to etoposide-induced cytotoxicity.

    PubMed

    Huang, R Stephanie; Duan, Shiwei; Bleibel, Wasim K; Kistner, Emily O; Zhang, Wei; Clark, Tyson A; Chen, Tina X; Schweitzer, Anthony C; Blume, John E; Cox, Nancy J; Dolan, M Eileen

    2007-06-05

    Large interindividual variance has been observed in sensitivity to drugs. To comprehensively decipher the genetic contribution to these variations in drug susceptibility, we present a genome-wide model using human lymphoblastoid cell lines from the International HapMap consortium, of which extensive genotypic information is available, to identify genetic variants that contribute to chemotherapeutic agent-induced cytotoxicity. Our model integrated genotype, gene expression, and sensitivity of HapMap cell lines to drugs. Cell lines derived from 30 trios of European descent (Center d'Etude du Polymorphisme Humain population) and 30 trios of African descent (Yoruban population) were used. Cell growth inhibition at increasing concentrations of etoposide for 72 h was determined by using alamarBlue assay. Gene expression on 176 HapMap cell lines (87 Center d'Etude du Polymorphisme Humain population and 89 Yoruban population) was determined by using the Affymetrix GeneChip Human Exon 1.0ST Array. We evaluated associations between genotype and cytotoxicity, genotype and gene expression and correlated gene expression of the identified candidates with cytotoxicity. The analysis identified 63 genetic variants that contribute to etoposide-induced toxicity through their effect on gene expression. These include genes that may play a role in cancer (AGPAT2, IL1B, and WNT5B) and genes not yet known to be associated with sensitivity to etoposide. This unbiased method can be used to elucidate genetic variants contributing to a wide range of cellular phenotypes induced by chemotherapeutic agents.

  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.

  17. Rhododendrol, a depigmentation-inducing phenolic compound, exerts melanocyte cytotoxicity via a tyrosinase-dependent mechanism.

    PubMed

    Sasaki, Minoru; Kondo, Masatoshi; Sato, Kohji; Umeda, Mai; Kawabata, Keigo; Takahashi, Yoshito; Suzuki, Tamio; Matsunaga, Kayoko; Inoue, Shintaro

    2014-09-01

    Rhododendrol, an inhibitor of melanin synthesis developed for lightening/whitening cosmetics, was recently reported to induce a depigmentary disorder principally at the sites of repeated chemical contact. Rhododendrol competitively inhibited mushroom tyrosinase and served as a good substrate, while it also showed cytotoxicity against cultured human melanocytes at high concentrations sufficient for inhibiting tyrosinase. The cytotoxicity was abolished by phenylthiourea, a chelator of the copper ions at the active site, and by specific knockdown of tyrosinase with siRNA. Hence, the cytotoxicity appeared to be triggered by the enzymatic conversion of rhododendrol to active product(s). No reactive oxygen species were detected in the treated melanocytes, but up-regulation of the CCAAT-enhancer-binding protein homologous protein gene responsible for apoptosis and/or autophagy and caspase-3 activation were found to be tyrosinase dependent. These results suggest that a tyrosinase-dependent accumulation of ER stress and/or activation of the apoptotic pathway may contribute to the melanocyte cytotoxicity.

  18. UVA-induced phenoxyl radical formation: A new cytotoxic principle in photodynamic therapy.

    PubMed

    Volkmar, Christine M; Vukadinović-Walter, Britta; Opländer, Christian; Bozkurt, Ahmet; Korth, Hans-Gert; Kirsch, Michael; Mahotka, Csaba; Pallua, Norbert; Suschek, Christoph V

    2010-09-15

    Psoralens are regularly used in therapy in combination with ultraviolet A light irradiation (PUVA) to treat skin diseases such as psoriasis, vitiligo, and mycosis fungoides. PUVA therapy is also used within the scope of extracorporeal photopheresis to treat a variety of diseases that have a suspected involvement of pathogenic T cells, including rejection of organ transplants, graft-vs-host disease, cutaneous T cell lymphoma, and autoimmune disorders. Because psoralens are the only photosensitizers used in PUVA therapies and are considered to be responsible for a number of side effects, the identification of alternative drugs is of practical interest. Here we investigated the impact of activated Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a hydrophilic vitamin E analog lacking the phytyl tail, as an alternative photoactivatable agent with T cell cytotoxic properties. Despite the well-known antioxidative capacity of Trolox, we found that at low UVA doses and in the presence of supraphysiological concentration of nitrite, a natural constituent of human skin, this compound selectively enhances radical-mediated cytotoxicity toward T cells but not toward human skin fibroblasts, keratinocytes, or endothelial cells. The cytotoxic mechanism comprises a reaction of Trolox with photo-decomposition products of nitrite, which leads to increased Trolox phenoxyl radical formation, increased intracellular oxidative stress, and a consecutive induction of apoptosis and necrosis in fast proliferating T cells. Thus, the identified UVA/nitrite-induced phenoxyl radical formation provides an opportunity for a new cytotoxic photodynamic therapy.

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

    PubMed

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

    2011-09-01

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

  20. Paclitaxel molecularly imprinted polymer-PEG-folate nanoparticles for targeting anticancer delivery: Characterization and cellular cytotoxicity.

    PubMed

    Esfandyari-Manesh, Mehdi; Darvishi, Behrad; Ishkuh, Fatemeh Azizi; Shahmoradi, Elnaz; Mohammadi, Ali; Javanbakht, Mehran; Dinarvand, Rassoul; Atyabi, Fatemeh

    2016-05-01

    The aim of this work was to synthesize molecularly imprinted polymer-poly ethylene glycol-folic acid (MIP-PEG-FA) nanoparticles for use as a controlled release carrier for targeting delivery of paclitaxel (PTX) to cancer cells. MIP nanoparticles were synthesized by a mini-emulsion polymerization technique and then PEG-FA was conjugated to the surface of nanoparticles. Nanoparticles showed high drug loading and encapsulation efficiency, 15.6 ± 0.8 and 100%, respectively. The imprinting efficiency of MIPs was evaluated by binding experiments in human serum. Good selective binding and recognition were found in MIP nanoparticles. In vitro drug release studies showed that MIP-PEG-FA have a controlled release of PTX, because of the presence of imprinted sites in the polymeric structure, which makes it is suitable for sustained drug delivery. The drug release from polymeric nanoparticles was indeed higher at acidic pH. The molecular structure of MIP-PEG-FA was confirmed by Hydrogen-Nuclear Magnetic Resonance (H NMR), Fourier Transform InfraRed (FT-IR), and Attenuated Total Reflection (ATR) spectroscopy, and their thermal behaviors by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Scanning Electron Microscopy (SEM) and Photon Correlation Spectroscopy (PCS) results showed that nanoparticles have a smooth surface and spherical shape with an average size of 181 nm. MIP-PEG-FA nanoparticles showed a greater amount of intracellular uptake in folate receptor-positive cancer cells (MDA-MB-231 cells) in comparison with the non-folate nanoparticles and free PTX, with half maximal inhibitory concentrations (IC50) of 4.9 ± 0.9, 7.4 ± 0.5 and 32.8 ± 3.8 nM, respectively. These results suggest that MIP-PEG-FA nanoparticles could be a potentially useful drug carrier for targeting drug delivery to cancer cells.

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

    SciTech Connect

    Zheng, H.; Crowley, J.J.; Chan, J.C.; Hoffmann, H.; Hatherill, J.R.; Ishizaka, A.; Raffin, T.A. )

    1990-11-01

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

  2. Comparison of mycobacteria-induced cytotoxicity and inflammatory responses in human and mouse cell lines.

    PubMed

    Huttunen, K; Jussila, J; Hirvonen, M R; Iivanainen, E; Katila, M L

    2001-11-01

    Environmental mycobacteria, which are ubiquitous in nature, are also detected in moisture-damaged buildings. Their potential role inducing the adverse health effects associated with living in moisture damaged buildings requires clarification. To establish a model for these studies, we evaluated inflammatory responsiveness in different cell lines exposed to environmental mycobacterial species. Four mycobacterial isolates belonging to Mycobacterium avium complex and Mycobacterium terrae, recovered from the indoor air sampled when a moldy building was being demolished, were studied for their cytotoxicity and ability to stimulate the production of inflammatory mediators in mouse RAW264.7 and human 28SC macrophage cell lines, and human A549 lung epithelial cell line. Lipopolysaccharide (LPS) was used as a positive control. Production of cytokines (tumor necrosis factor alpha, TNF-alpha; interleukin 6, IL-6; and interleukin beta, IL-1beta) was analyzed immunochemically, nitric oxide (NO) by the Griess method, expression of inducible NO synthase with Western blot analysis, and cytotoxicity with the MTT test. Both human and mouse cells produced NO and IL-6 after mycobacterial exposure. Mouse macrophages also showed production of TNF-alpha induced by both mycobacteria and LPS, whereas the human cell lines failed to produce TNF-alpha after mycobacterial exposure and the human epithelial cell line also failed to respond to LPS. Similarly, only mouse macrophages produced IL-1beta. Mycobacterial exposure was not cytotoxic to human cells and was only slightly cytotoxic to mouse macrophages. The results indicate that environmental mycobacterial isolates from moldy buildings are capable of activating inflammatory mechanisms in both human and murine cells. The human and mouse cell lines, however, differ significantly in the grade and type of the responses.

  3. Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells

    SciTech Connect

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

    2014-08-01

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

  4. O-naphthoquinone isolated from Capraria biflora L. induces selective cytotoxicity in tumor cell lines.

    PubMed

    de S Wisintainer, G G N; Scola, G; Moura, S; Lemos, T L G; Pessoa, C; de Moraes, M O; Souza, L G S; Roesch-Ely, M; Henriques, J A P

    2015-12-21

    Biflorin is an o-naphthoquinone isolated from the roots of the plant Capraria biflora L. (Scrophulariaceae). In this study, the cytotoxic effects of biflorin were verified, and late apoptosis was detected in various cancer cell lines by in situ analysis. The cytotoxicity was further evaluated exclusively for 48 h of treatment in different tumor and non-tumor cell lines (Hep-2, HeLa, HT-29, A-375, and A-549, and HEK-293, respectively). The results indicated that biflorin induced selective cytotoxicity in tumor cells. HeLa cells were more susceptible to biflorin, followed by HT-29, A-549, A-375, and Hep-2 at all concentrations (range 5-50 μg/mL), and the highest half-maximal inhibitory concentration IC50 (56.01 ± 1.17 μg/mL) was observed in HEK-293 cells. Late apoptotic/necrotic events, observed by in situ immunostaining with Annexin V, varied with each cell line; an increase in late apoptotic events was observed corresponding to the increase in biflorin dosage. Hep-2 cells showed a greater percentage of late apoptotic events among the tumor cell lines when treated with higher concentrations of biflorin (69.63 ± 2.28%). The non-tumor HEK-293 line showed greater resistance to late apoptotic events, as well as a lower level of cytotoxicity (77.69 ± 6.68%) than the tested tumor lines. The data presented indicate that biflorin showed an important, possibly selective, cytotoxicity against tumor cell lines, thereby revealing a promising novel substance with potential anticancer activity for tumor therapy.

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

    PubMed

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

    1992-09-01

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

  6. Ceramide mediates FasL-induced caspase 8 activation in colon carcinoma cells to enhance FasL-induced cytotoxicity by tumor-specific cytotoxic T lymphocytes

    PubMed Central

    Coe, Genevieve L.; Redd, Priscilla S.; Paschall, Amy V.; Lu, Chunwan; Gu, Lilly; Cai, Houjian; Albers, Thomas; Lebedyeva, Iryna O.; Liu, Kebin

    2016-01-01

    FasL-mediated cytotoxicity is one of the mechanisms that CTLs use to kill tumor cells. However, human colon carcinoma often deregulates the Fas signaling pathway to evade host cancer immune surveillance. We aimed at testing the hypothesis that novel ceramide analogs effectively modulate Fas function to sensitize colon carcinoma cells to FasL-induced apoptosis. We used rational design and synthesized twenty ceramide analogs as Fas function modulators. Five ceramide analogs, IG4, IG7, IG14, IG17, and IG19, exhibit low toxicity and potent activity in sensitization of human colon carcinoma cells to FasL-induced apoptosis. Functional deficiency of Fas limits both FasL and ceramide analogs in the induction of apoptosis. Ceramide enhances FasL-induced activation of the MAPK, NF-κB, and caspase 8 despite induction of potent tumor cell death. Finally, a sublethal dose of several ceramide analogs significantly increased CTL-mediated and FasL-induced apoptosis of colon carcinoma cells. We have therefore developed five novel ceramide analogs that act at a sublethal dose to enhance the efficacy of tumor-specific CTLs, and these ceramide analogs hold great promise for further development as adjunct agents in CTL-based colon cancer immunotherapy. PMID:27487939

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

    SciTech Connect

    Kanipandian, Nagarajan; Ramesh, Ramar; Subramanian, Periyasamy

    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 μg/mL and 60 μg/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.

  8. Synthesis, characterization, and cytotoxicity of the plasmid EGFP-p53 loaded on pullulan-spermine magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Eslaminejad, Touba; Nematollahi-Mahani, Seyed Noureddin; Ansari, Mehdi

    2016-03-01

    Magnetic nanoparticles have been used as effective vehicles for the targeted delivery of therapeutic agents that can be controlled in their concentration and distribution to a desired part of the body by using externally driven magnets. This study focuses on the synthesis, characterization, and functionalization of pullulan-spermine (PS) magnetic nanoparticles for medical applications. Magnetite nanopowder was produced by thermal decomposition of goethite (FeOOH) in oleic acid and 1-octadecene; pullulan-spermine was deposited on the magnetite nanoparticles in the form of pullulan-spermine clusters. EGFP-p53 plasmid was loaded on functionalized iron oleate to transfer into cells. Synthesized nanoparticles were characterized by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), vibrating sample magnetometry (VSM), and transmission electron microscopy (TEM). The encapsulation efficiency and drug loading efficiency of the nanocomplexes were tested. FTIR studies showed the presence of oleic acid and 1-octadecene in the iron oleate nanopowder and verified the interaction between spermine and pullulan. The characteristic bands of PS in the spectrum of the pullulan-spermine-coated iron oleate (PSCFO) confirmed that PS covered the surface of the iron oleate particles. TEM studies showed the average size of the iron oleate nanopowder, the PSCFO, and the plasmid-carrying PSCFO (PSCFO/pEGFP-p53) to be 34±12 nm, 100±50 nm and 172±3 nm, respectively. Magnetic measurements revealed that magnetic saturation of the PSCFO was lower in comparison with the iron oleate nanopowder due to the presence of organic compounds in the former. In cytotoxicity tests performed using U87 cells as glioblastoma cells, a 92% survival rate was observed at 50 μg/μl of the plasmid-carrying PSCFO, with an IC50 value of 189 μg/μl.

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

    PubMed

    Zajc, I; Filipič, 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.

  10. 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.

  11. Preparation, characterization and in vitro cytotoxicity assay of curcumin loaded solid lipid nanoparticle in IMR32 neuroblastoma cell line.

    PubMed

    Rahman, Mohamed Habibur; Ramanathan, Muthiah; Sankar, Veintramuthu

    2014-09-01

    Curcumin (diferuloylmethane) possesses low bioavailability due to its poor solubility, permeability and rapid metabolism. Solid Lipid Nanoparticle of curcumin was prepared by high-speed homogenization technique. Stearic acid was used as a lipid, tween 80 as surfactant and various co surfactants were used for the preparation of SLN. The prepared SLN was characterized using zeta sizer, TEM analysis and the average particle size was found to be in the range of 80 nm - 200nm. The entrapment efficiency of the SLN was ~58 to 85%. The characteristic FTIR peaks suggest that the stearic acid is compatible with curcumin. MTT assay was performed on the optimized formulation and the results are indicative that curcumin SLN showed better cytotoxicity in low dose while compared to plain curcumin. The developed Cu-SLN can find its better place in the anticancer therapy.

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

    PubMed Central

    2011-01-01

    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 κB 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. PMID:21777482

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

    NASA Astrophysics Data System (ADS)

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

    2011-09-01

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

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

    PubMed

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

    2011-09-30

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

  15. Comparison of cytotoxicity and genotoxicity induced by the extracts of methanol and gasoline engine exhausts.

    PubMed

    Zhang, Zunzhen; Che, Wangjun; Liang, Ying; Wu, Mei; Li, Na; Shu, Ya; Liu, Fang; Wu, Desheng

    2007-09-01

    Gasoline engine exhaust has been considered a major source of air pollution in China, and methanol is considered as a potential substitute for gasoline fuel. In this study, the genotoxicity and cytotoxicity of organic extracts of condensate, particulate matters (PM) and semivolatile organic compounds (SVOC) of gasoline and absolute methanol engine exhaust were examined by using MTT assay, micronucleus assay, comet assay and Ames test. The results have showed that gasoline engine exhaust exhibited stronger cytotoxicity to human lung carcinoma cell lines (A549 cell) than methanol engine exhaust. Furthermore, gasoline engine exhaust increased micronucleus formation, induced DNA damage in A549 cells and increased TA98 revertants in the presence of metabolic activating enzymes in a concentration-dependent manner. In contrast, methanol engine exhaust failed to exhibit these adverse effects. The results suggest methanol may be used as a cleaner fuel for automobile.

  16. PPS nanoparticles as versatile delivery system to induce systemic and broad mucosal immunity after intranasal administration.

    PubMed

    Stano, Armando; van der Vlies, André J; Martino, Mikael M; Swartz, Melody A; Hubbell, Jeffrey A; Simeoni, Eleonora

    2011-01-17

    Degradable polymer nanoparticles (NPs, 50 nm) based on polypropylene sulfide (PPS) were conjugated to thiolated antigen and adjuvant proteins by reversible disulfide bonds and evaluated in mucosal vaccination. Ovalbumin was used as a model antigen, and antigen-conjugated NPs were administered intranasally in the mouse. We show penetration of nasal mucosae, transit via M cells, and uptake by antigen-presenting cells in the nasal-associated lymphoid tissue. Ovalbumin-conjugated NPs induced cytotoxic T lymphocytic responses in lung and spleen tissues, as well as humoral response in mucosal airways. Co-conjugation of the TLR5 ligand flagellin further enhanced humoral responses in the airways as well as in the distant vaginal and rectal mucosal compartments and induced cellular immune responses with a Th1 bias, in contrast with free flagellin. The PPS NP platform thus appears interesting as a platform for intranasally-administered mucosal vaccination for inducing broad mucosal immunity.

  17. The primary role of iron-mediated lipid peroxidation in the differential cytotoxicity caused by two varieties of talc nanoparticles on A549 cells and lipid peroxidation inhibitory effect exerted by ascorbic acid.

    PubMed

    Akhtar, Mohd Javed; Kumar, Sudhir; Murthy, Ramesh Chandra; Ashquin, Mohd; Khan, Mohd Imran; Patil, Govil; Ahmad, Iqbal

    2010-06-01

    Talc particles, the basic ingredient in different kinds of talc-based cosmetic and pharmaceutical products, pose a health risk to pulmonary and ovarian systems due to domestic and occupational exposures. Two types of talc nanoparticles depending on the source of geographical origin - indigenous- and commercial talc nanoparticles were assessed for their potential in vitro toxicity on A(549) cells; along with indigenous conventionally used microtalc particles. Cell viability, determined through live/dead staining and 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, decreased as a function of concentration, origin and size of particles. Both varieties of talc nanoparticles differentially induced lipid peroxidation (LPO), which was correlated with the pattern of lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) generation, and glutathione (GSH) depletion. Relatively higher cytotoxicity of indigenous nanotalc could be attributed to its higher content of iron as compared to commercial nanotalc. The known scavenger of ROS, l-ascorbic acid significantly inhibited LPO induction due to talc particles. Data suggest that nanotalc toxicity on A(549) cells was mediated through oxidative stress, wherein role of iron-mediated LPO was much pronounced in differential cytotoxicity.

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

    PubMed

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

    2007-07-01

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

  19. Quenching of chlorophyll fluorescence induced by silver nanoparticles.

    PubMed

    Queiroz, A M; Mezacasa, A V; Graciano, D E; Falco, W F; M'Peko, J-C; Guimarães, F E G; Lawson, T; Colbeck, I; Oliveira, S L; Caires, A R L

    2016-11-05

    The interaction between chlorophyll (Chl) and silver nanoparticles (AgNPs) was evaluated by analyzing the optical behavior of Chl molecules surrounded by different concentrations of AgNPs (10, 60, and 100nm of diameter). UV-Vis absorption, steady state and time-resolved fluorescence measurements were performed for Chl in the presence and absence of these nanoparticles. AgNPs strongly suppressed the Chl fluorescence intensity at 678nm. The Stern-Volmer constant (KSV) showed that fluorescence suppression is driven by the dynamic quenching process. In particular, KSV was nanoparticle size-dependent with an exponential decrease as a function of the nanoparticle diameter. Finally, changes in the Chl fluorescence lifetime in the presence of nanoparticles demonstrated that the fluorescence quenching may be induced by the excited electron transfer from the Chl molecules to the metal nanoparticles.

  20. Quenching of chlorophyll fluorescence induced by silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Queiroz, A. M.; Mezacasa, A. V.; Graciano, D. E.; Falco, W. F.; M'Peko, J.-C.; Guimarães, F. E. G.; Lawson, T.; Colbeck, I.; Oliveira, S. L.; Caires, A. R. L.

    2016-11-01

    The interaction between chlorophyll (Chl) and silver nanoparticles (AgNPs) was evaluated by analyzing the optical behavior of Chl molecules surrounded by different concentrations of AgNPs (10, 60, and 100 nm of diameter). UV-Vis absorption, steady state and time-resolved fluorescence measurements were performed for Chl in the presence and absence of these nanoparticles. AgNPs strongly suppressed the Chl fluorescence intensity at 678 nm. The Stern-Volmer constant (KSV) showed that fluorescence suppression is driven by the dynamic quenching process. In particular, KSV was nanoparticle size-dependent with an exponential decrease as a function of the nanoparticle diameter. Finally, changes in the Chl fluorescence lifetime in the presence of nanoparticles demonstrated that the fluorescence quenching may be induced by the excited electron transfer from the Chl molecules to the metal nanoparticles.

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

    PubMed

    Dasari, Thabitha P; Hwang, Huey-Min

    2010-11-01

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

  2. 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 μg/mL); hence, these particles were safe to use. PMID:24426782

  3. 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.

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

    PubMed

    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 μg/mL); hence, these particles were safe to use.

  5. Comparison of Cytotoxicity and Inhibition of Membrane ABC Transporters Induced by MWCNTs with Different Length and Functional Groups.

    PubMed

    Yu, Jing; Liu, Su; Wu, Bing; Shen, Zhuoyan; Cherr, Gary N; Zhang, Xu-Xiang; Li, Mei

    2016-04-05

    Experimental studies indicate that multiwalled carbon nanotubes (MWCNTs) have the potential to induce cytotoxicity. However, the reports are often inconsistent and even contradictory. Additionally, adverse effects of MWCNTs at low concentration are not well understood. In this study, we systemically compared adverse effects of six MWCNTs including pristine MWCNTs, hydroxyl-MWCNTs and carboxyl-MWCNTs of two different lengths (0.5-2 μm and 10-30 μm) on human hepatoma cell line HepG2. Results showed that MWCNTs induced cytotoxicity by increasing reactive oxygen species (ROS) generation and damaging cell function. Pristine short MWCNTs induced higher cytotoxicity than pristine long MWCNTs. Functionalization increased cytotoxicity of long MWCNTs, but reduced cytotoxicity of short MWCNTs. Further, our results indicated that the six MWCNTs, at nontoxic concentration, might not be environmentally safe as they inhibited ABC transporters' efflux capabilities. This inhibition was observed even at very low concentrations, which were 40-1000 times lower than their effective concentrations on cytotoxicity. The inhibition of ABC transporters significantly increased cytotoxicity of arsenic, a known substrate of ABC transporters, indicating a chemosensitizing effect of MWCNTs. Plasma membrane damage was likely the mechanism by which the six MWCNTs inhibited ABC transporter activity. This study provides insight into risk assessments of low levels of MWCNTs in the environment.

  6. Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma.

    PubMed

    Syed, Deeba N; Lall, Rahul K; Chamcheu, Jean Christopher; Haidar, Omar; Mukhtar, Hasan

    2014-12-01

    The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytotoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up-regulation of ER stress markers including IRE1α, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMP-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity.

  7. In vitro cytotoxicity evaluation of natural rubber latex film surface coated with PMMA nanoparticles.

    PubMed

    Anancharungsuk, Waranya; Polpanich, Duangporn; Jangpatarapongsa, Kulachart; Tangboriboonrat, Pramuan

    2010-07-01

    In order to increase surface roughness of the sulphur-prevulcanized natural rubber (SPNR) film and, hence, decrease the direct contact between the rubber and skin, the poly(methyl methacrylate) (PMMA) latex particles were deposited onto the SPNR film grafted with polyacrylamide (SPNR-g-PAAm). The surface coverage of PMMA particles on the SPNR-g-PAAm increased with increasing latex immersion time, particle size and concentration. Prior to the in vitro cytotoxicity evaluation on L-929 fibroblasts, the SPNR and SPNR-g-PAAm coated with PMMA particles were extracted by using the culture medium. Results showed that the cytotoxicity effect could be significantly reduced by coating PMMA particles onto the rubber film. At the extract concentrations of < or =12.5% for 24h at 37 degrees C, no toxicity potential was detected. The study will be helpful for development of gloves designed for the hypersensitive person.

  8. Cytotoxicity of gold nanoparticles in human neural precursor cells and rat cerebral cortex.

    PubMed

    Lee, Uhn; Yoo, Chan-Jong; Kim, Yong-Jung; Yoo, Young-Mi

    2016-03-01

    Nanoparticles are promising tools for the advancement of drug delivery, medical imaging, and as diagnostic sensor. Medical nanodevices should develop miniaturization, because it would be injected into a human body. Gold nanoparticles (GNPs) with different sizes and shapes have therapeutic potential as a result of their small size, robust nature, excellent biocompatibility and optical properties. However, the application of GNPs as medical nanodevices it is necessary to know the biodegradation, biocompatibility, and development of surface coating which avoid the accumulation of nanoparticles. In this study, we carry out an in vitro toxicity and in vivo gene expression study using two kinds of GNPs. We found that GNPs toxicity is dependent on the dose or size administrated after the injected GNPs into the brain, and small particle size GNPs appeared more nestin expression compared to large particle size at short term implantation. These findings of toxicity of GNPs may play an important role in development of in vivo tools for the safety of GNPs.

  9. The influence of polycaprolactone coating on the internalization and cytotoxicity of gold nanoparticles.

    PubMed

    Mao, Zhengwei; Wang, Bo; Ma, Lie; Gao, Changyou; Shen, Jiacong

    2007-09-01

    The interaction between mesoscopic colloids and cells is largely dependent on the particle size and surface properties. Under a mild reaction condition, gold particles with an average diameter of approximately 100 nm were prepared by incubating poly(dimethylsiloxane) film in HAuCl4/acetic acid solution. The particles were then transferred into a polycaprolactone (PCL) film by thermal pressing. Bare and PCL-coated particles were obtained by control over the extent of rinsing. The bare and PCL-coated gold particles were co-cultured with ECV-304 cells to examine the particle internalization and their influence on the cell morphology and cytotoxicity. Transmission electron microcopy observed the subcellular distribution of the gold particles, which were found in the cell compartments (endosomes or lysosomes), cytoplasm, nucleic envelope, and even nucleus regardless of the existence of PCL coating. However, scanning electron microscopy and beta-tubulin staining revealed a significant change in terms of the cell morphology and cytoskeleton caused by the bare gold particles. Higher cytotoxicity was also determined for the bare gold particles. By contrast, no significant difference of the cell morphology and cytoskeleton change was caused by the PCL-coated gold particles, which have also shown lower cytotoxicity.

  10. Benzothiazole derivatives bearing amide moiety: potential cytotoxic and apoptosis-inducing agents against cervical cancer.

    PubMed

    Singh, Meenakshi; Modi, Arusha; Narayan, Gopeshwar; Singh, Sushil K

    2016-07-01

    Cervical cancer is a major cause of morbidity and mortality in women worldwide. In recent years, benzothiazole analogues have attracted considerable attention in anticancer research. Therefore, in this study, the earlier reported amide series of benzothiazole derivatives were investigated for their antiproliferative activity. The activity of amide derivatives was evaluated using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometric analysis, apoptosis assay, and DNA fragmentation on two human cervical cancer cell lines: SiHa and C33-A. The data reported from this investigation indicated that benzothiazole derivatives show pronounced cytotoxicity in the HPV16-positive SiHa cells compared with HPV-negative C-33A cells. The in-vitro cytotoxicity of the compounds on the HEK-293 noncancer cell line was evaluated to establish selectivity. Cells treated with benzothiazole derivatives showed prominent morphological features as evidenced by cell shrinkage, membrane blebbing, apoptotic nuclei, and DNA fragmentation. The benzothiazole derivatives show accumulation of cells in the sub-G1 and S-phase of the cell cycle in SiHa and C33-A, respectively. In addition, these derivatives exert their beneficial effect by inducing apoptosis, in the chemoprevention of cervical cancer cells, and were further ascertained using a DNA fragmentation assay. The compounds studied showed potent cytotoxic and apoptotic properties against SiHa and C33-A cancer cell lines and thus represent an excellent starting point for further optimization of therapeutically effective anticancer drugs.

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

    PubMed Central

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

    2015-01-01

    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

  12. Transcriptomic and functional pathways analysis of ascorbate-induced cytotoxicity and resistance of Burkitt lymphoma.

    PubMed

    Pei, Zenglin; Zhang, Xuan; Ji, Chunxia; Liu, Song-Mei; Wang, Jin

    2016-09-27

    Ascorbate is a pro-oxidant that generates hydrogen peroxide-dependent cytotoxity in cancer cells without adversely affecting normal cells. To determine the mechanistic basis for this phenotype, we selected Burkitt lymphoma cells resistant to ascorbate (JLPR cells) and their ascorbate-sensitive parental cells (JLPS cells). Compared with JLPS cells, the increased glucose uptake in JLPR cells (with upregulated glucose transporters, increased antioxidant enzyme activity, and altered cell cycling) conferred ascorbate-induced cytotoxicity and resistance. Transcriptomic profiles and function pathway analysis identified differentially expressed gene signatures for JLPR cells and JLPS cells, which differential expression levels of five genes (ATF5, CD79B, MHC, Myosin, and SAP18) in ascorbate-resistant cells were related to phosphoinositide 3 kinase, cdc42, DNA methylation and transcriptional repression, polyamine regulation, and integrin-linked kinase signaling pathways. These results suggested that coordinated changes occurred in JLPR cells to enable their survival when exposed to the cytotoxic pro-oxidant stress elicited by pharmacologic ascorbate treatment.

  13. Cytotoxicity and morphological effects induced by carvacrol and thymol on the human cell line Caco-2.

    PubMed

    Llana-Ruiz-Cabello, María; Gutiérrez-Praena, Daniel; Pichardo, Silvia; Moreno, F Javier; Bermúdez, José María; Aucejo, Susana; Cameán, Ana María

    2014-02-01

    Essential oils used as additives in the food industry due to its flavour, antimicrobial and antioxidant properties. Therefore, human can be exposed orally to these compounds through the ingestion of foods. In this sense, the present work aims to assess toxicological effects of oregano essential oil on the digestive tract. In concrete, the cytotoxic effects of two components of the oregano essential oils, carvacrol and thymol, and their mixture, on the intestinal cells line Caco-2 after 24 and 48 h of exposure are studied. The basal cytotoxicity endpoints assayed (total protein content, neutral red uptake and the tetrazolium salt reduction) and the annexin/propidium iodide staining indicated that carvacrol and the mixture carvacrol/thymol induced toxic effects. Moreover, a morphological study was performed in order to determine the ultrastructural cellular damages caused by these substances. The main morphological alterations were vacuolated cytoplasm, altered organelles and finally cell death. In addition, although no cytotoxic effects were recorded for thymol at any concentration and time of exposure, ultrastructural changes evidenced cellular damage such as lipid degeneration, mitochondrial damage, nucleolar segregation and apoptosis.

  14. Transcriptomic and functional pathways analysis of ascorbate-induced cytotoxicity and resistance of Burkitt lymphoma

    PubMed Central

    Ji, Chunxia; Liu, Song-Mei; Wang, Jin

    2016-01-01

    Ascorbate is a pro-oxidant that generates hydrogen peroxide–dependent cytotoxity in cancer cells without adversely affecting normal cells. To determine the mechanistic basis for this phenotype, we selected Burkitt lymphoma cells resistant to ascorbate (JLPR cells) and their ascorbate-sensitive parental cells (JLPS cells). Compared with JLPS cells, the increased glucose uptake in JLPR cells (with upregulated glucose transporters, increased antioxidant enzyme activity, and altered cell cycling) conferred ascorbate–induced cytotoxicity and resistance. Transcriptomic profiles and function pathway analysis identified differentially expressed gene signatures for JLPR cells and JLPS cells, which differential expression levels of five genes (ATF5, CD79B, MHC, Myosin, and SAP18) in ascorbate-resistant cells were related to phosphoinositide 3 kinase, cdc42, DNA methylation and transcriptional repression, polyamine regulation, and integrin-linked kinase signaling pathways. These results suggested that coordinated changes occurred in JLPR cells to enable their survival when exposed to the cytotoxic pro-oxidant stress elicited by pharmacologic ascorbate treatment. PMID:27590508

  15. Could formaldehyde induce mutagenic and cytotoxic effects in buccal epithelial cells during anatomy classes?

    PubMed Central

    Pinheiro, Leon-Penido; Nascimento, Haniel-Serpa; Menegardo, Cristiani-Sartorio; Silva, Ronara-Gerhardt; Bautz, Willian-Grassi; Henriques, José-Fernando; Almeida-Coburn, Karla-Loureiro; da Gama-de-Souza, Letícia-Nogueira

    2017-01-01

    Background Due to increased formaldehyde exposure, carcinogenic to humans, several researches have been studying the potential toxicity and the safe levels for human beings. The aim of this study was to investigate mutagenicity and cytotoxicity in buccal epithelial exfoliated cells (BEC) of students subjected to formaldehyde (FA) during anatomy classes. Material and Methods BEC were collected periodically from 17 volunteers of undergraduate programs, who had participated in practical anatomy classes, before and after FA exposure. Cells were stained according to Feulgen method and then micronucleus test was applied. A total of 1,500 cells were assessed per individual in this study for the micronucleus frequency and other parameters of cytotoxicity. Results There was statistically significant increase in number of micronucleated BEC after FA exposure (after 1 month p=.034 and after 3.5 months p=.017). However, FA exposure caused no significant increase in other nuclear alterations closely related to cytotoxicity (p≥.05). Conclusions FA induced mutagenicity during anatomy classes. Cell death increased, but it was not statistically significant. Efforts have to be made to improve air quality and reduce exposures during anatomy classes. Key words:Carcinogens, formaldehyde, micronucleus tests, mutagenicity tests. PMID:27918743

  16. Mechanisms Underlying Cytotoxicity Induced by Engineered Nanomaterials: A Review of In Vitro Studies

    PubMed Central

    Nogueira, Daniele R.; Mitjans, Montserrat; Rolim, Clarice M. B.; Vinardell, M. Pilar

    2014-01-01

    Engineered nanomaterials are emerging functional materials with technologically interesting properties and a wide range of promising applications, such as drug delivery devices, medical imaging and diagnostics, and various other industrial products. However, concerns have been expressed about the risks of such materials and whether they can cause adverse effects. Studies of the potential hazards of nanomaterials have been widely performed using cell models and a range of in vitro approaches. In the present review, we provide a comprehensive and critical literature overview on current in vitro toxicity test methods that have been applied to determine the mechanisms underlying the cytotoxic effects induced by the nanostructures. The small size, surface charge, hydrophobicity and high adsorption capacity of nanomaterial allow for specific interactions within cell membrane and subcellular organelles, which in turn could lead to cytotoxicity through a range of different mechanisms. Finally, aggregating the given information on the relationships of nanomaterial cytotoxic responses with an understanding of its structure and physicochemical properties may promote the design of biologically safe nanostructures.

  17. The role of reactive oxygen intermediates in nonspecific monocyte cytotoxicity induced by immune complexes.

    PubMed Central

    Geffner, J R; Giordano, M; Serebrinsky, G; Isturiz, M

    1987-01-01

    Normal human monocytes were induced to lyse nonsensitized target cells when triggered by precipitating immune complexes (IC) or soluble heat-aggregated IgG (HAIgG). Catalase, azide, cyanide and three aminoacids employed as quenchers of ClO, significantly inhibited this nonspecific cytotoxicity (NSC), suggesting an important role for the myeloperoxidase (MPO) system. However, HO and/or 1O2 may also be involved in the lysis, since certain scavengers of these species such as mannitol, benzoate, ethanol and histidine, as well as superoxide dismutase (SOD), partially inhibited NSC. Moreover, cyanide and azide were unable to completely abrogate this lytic activity. When NSC was compared to antibody dependent cellular cytotoxicity (ADCC), it was found that neither catalase nor oxygen-species scavengers affected ADCC while azide and cyanide significantly enhanced it. Antibody-coated target cells were also destroyed by IC-triggered monocytes. However, kinetic analysis and studies on the capacity of catalase to inhibit the lysis demonstrated that it was mediated through a NSC-like mechanism. The cytotoxic system described in this report offers a suitable model to study in vitro alternative lytic mechanisms triggered through monocyte receptors for the Fc portion of IgG (Fc gamma R). PMID:3038442

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

    NASA Astrophysics Data System (ADS)

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

    2011-06-01

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

  19. Human cytotoxic T-lymphocyte membrane-camouflaged nanoparticles combined with low-dose irradiation: a new approach to enhance drug targeting in gastric cancer

    PubMed Central

    Zhang, Lianru; Li, Rutian; Chen, Hong; Wei, Jia; Qian, Hanqing; Su, Shu; Shao, Jie; Wang, Lifeng; Qian, Xiaoping; Liu, Baorui

    2017-01-01

    Cell membrane-derived nanoparticles are becoming more attractive because of their ability to mimic many features of their source cells. This study reports on a biomimetic delivery platform based on human cytotoxic T-lymphocyte membranes. In this system, the surface of poly-lactic-co-glycolic acid nanoparticles was camouflaged using T-lymphocyte membranes, and local low-dose irradiation (LDI) was used as a chemoattractant for nanoparticle targeting. The T-lymphocyte membrane coating was verified using dynamic light scattering, transmission electron microscopy, and confocal laser scanning microscopy. This new platform reduced nanoparticle phagocytosis by macrophages to 23.99% (P=0.002). Systemic administration of paclitaxel-loaded T-lymphocyte membrane-coated nanoparticles inhibited the growth of human gastric cancer by 56.68% in Balb/c nude mice. Application of LDI at the tumor site significantly increased the tumor growth inhibition rate to 88.50%, and two mice achieved complete remission. Furthermore, LDI could upregulate the expression of adhesion molecules in tumor vessels, which is important in the process of leukocyte adhesion and might contribute to the localization of T-lymphocyte membrane-encapsulated nanoparticles in tumors. Therefore, this new drug-delivery platform retained both the long circulation time and tumor site accumulation ability of human cytotoxic T lymphocytes, while local LDI could significantly enhance tumor localization. PMID:28360520

  20. The prosurvival role of autophagy in Resveratrol-induced cytotoxicity in human U251 glioma cells

    PubMed Central

    2009-01-01

    Background Previous study reported that resveratrol has anti-tumor activity. In this study, we investigated the involvement of autophagy in the resveratrol-induced apoptotic death of human U251 glioma cells. Methods The growth inhibition of U251 cells induced by resveratrol was assessed with methyl thiazolyl tetrazolium (MTT). The activation of autophagy and proapoptotic effect were characterized by monodansylcadaverine labeling and Hoechst stain, respectively. Mitochondrialtransmembrane potential (ΔΨm) was measured as a function of drug treatment using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1). The role of autophagy and apoptosis in the resveratrol-induced death of U251 cells was assessed using autophagic and caspase inhibitors. Immunofluorescence, flow cytometry, and Western blot analysis were used to study the apoptotic and autophagic mechanisms. Results Methyl thiazolyl tetrazolium (MTT) assays indicated that resveratrol decreased the viability of U251 cells in a dose- and time-dependent manner. Flow cytometry analysis indicated that resveratrol increased cell population at sub-G1 phase, an index of apoptosis. Furthermore, resveratrol-induced cell death was associated with a collapse of the mitochondrial membrane potential. The pan-caspase inhibitor Z-VAD-fmk suppressed resveratrol-induced U251 cell death. Resveratrol stimulated autophagy was evidenced by punctuate monodansylcadaverine(MDC) staining and microtubule-associated protein light chain 3 (LC3) immunoreactivty. Resveratrol also increased protein levels of beclin 1 and membrane form LC3 (LC3-II). Autophagy inhibitors 3-methylademine (3-MA) and bafilomycin A1 sensitized the cytotoxicity of resveratrol. Conclusion Together, these findings indicate that resveratrol induces autophagy in human U251 glioma cells and autophagy suppressed resveratrol-induced apoptosis. This study thus suggests that autophagy inhibitors can increase the cytotoxicity of resveratrol to

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

    PubMed Central

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

    2013-01-01

    With the emergence of multidrug-resistant mycobacterial strains, better therapeutic strategies are required for the successful treatment of the infection. Although antimicrobial peptides (AMPs) and silver nanoparticles (AgNPs) are becoming one of the popular antibacterial agents, their antimycobacterial potential is not fully evaluated. In this study, we synthesized biogenic-silver nanoparticles using bacterial, fungal, and plant biomasses and analyzed their antibacterial activities in combination with AMPs against mycobacteria. Mycobacterium smegmatis was found to be more susceptible to AgNPs compared to M. marinum. We found that NK-2 showed enhanced killing effect with NP-1 and NP-2 biogenic nanoparticles at a 0.5-ppm concentration, whereas LLKKK-18 showed antibacterial activity only with NP-2 at 0.5-ppm dose against M. smegmatis. In case of M. marinum NK-2 did not show any additive activity with NP-1 and NP-2 and LLKKK-18 alone completely inhibited the bacterial growth. Both NP-1 and NP-2 also showed increased killing of M. smegmatis in combination with the antituberculosis drug rifampin. The sizes and shapes of the AgNPs were determined by transmission electron microscopy and dynamic light scattering. AgNPs showed no cytotoxic or DNA damage effects on macrophages at the mycobactericidal dose, whereas treatment with higher doses of AgNPs caused toxicity and micronuclei formation in cytokinesis blocked cells. Macrophages actively endocytosed fluorescein isothiocyanate-labeled AgNPs resulting in nitric oxide independent intracellular killing of M. smegmatis. Apoptosis and cell cycle studies showed that treatment with higher dose of AgNPs arrested macrophages at the G1-phase. In summary, our data suggest the combined effect of biogenic-AgNPs and antimicrobial peptides as a promising antimycobacterial template. PMID:23689720

  2. RB mutation and RAS overexpression induce resistance to NK cell-mediated cytotoxicity in glioma cells.

    PubMed

    Orozco-Morales, Mario; Sánchez-García, Francisco Javier; Golán-Cancela, Irene; Hernández-Pedro, Norma; Costoya, Jose A; de la Cruz, Verónica Pérez; Moreno-Jiménez, Sergio; Sotelo, Julio; Pineda, Benjamín

    2015-01-01

    Several theories aim to explain the malignant transformation of cells, including the mutation of tumor suppressors and proto-oncogenes. Deletion of Rb (a tumor suppressor), overexpression of mutated Ras (a proto-oncogene), or both, are sufficient for in vitro gliomagenesis, and these genetic traits are associated with their proliferative capacity. An emerging hallmark of cancer is the ability of tumor cells to evade the immune system. Whether specific mutations are related with this, remains to be analyzed. To address this issue, three transformed glioma cell lines were obtained (Rb(-/-), Ras(V12), and Rb(-/-)/Ras(V12)) by in vitro retroviral transformation of astrocytes, as previously reported. In addition, Ras(V12) and Rb(-/-)/Ras(V12) transformed cells were injected into SCID mice and after tumor growth two stable glioma cell lines were derived. All these cells were characterized in terms of Rb and Ras gene expression, morphology, proliferative capacity, expression of MHC I, Rae1δ, and Rae1αβγδε, mult1, H60a, H60b, H60c, as ligands for NK cell receptors, and their susceptibility to NK cell-mediated cytotoxicity. Our results show that transformation of astrocytes (Rb loss, Ras overexpression, or both) induced phenotypical and functional changes associated with resistance to NK cell-mediated cytotoxicity. Moreover, the transfer of cell lines of transformed astrocytes into SCID mice increased resistance to NK cell-mediated cytotoxicity, thus suggesting that specific changes in a tumor suppressor (Rb) and a proto-oncogene (Ras) are enough to confer resistance to NK cell-mediated cytotoxicity in glioma cells and therefore provide some insight into the ability of tumor cells to evade immune responses.

  3. Cytotoxicity and cytokine expression induced by silorane and methacrylate-based composite resins

    PubMed Central

    LONGO, Daniele Lucca; PAULA-SILVA, Francisco Wanderley Garcia; FACCIOLI, Lucia Helena; GATÓN-HERNÁNDEZ, Patrícia Maria; de QUEIROZ, Alexandra Mussolino; da SILVA, Léa Assed Bezerra

    2016-01-01

    ABSTRACT The successful use of composite resins in Dentistry depends on physicochemical properties, but also on the biological compatibility of resins, because of the close association between pulp and dentin. Objective The aim of this study was to evaluate cytotoxicity and cytokine production induced by light-cured or non-light-cured methacrylate-based and silorane composite resins in RAW 264.7 macrophages. Material and Methods Cells were stimulated with the extracts from light-cured or non-light-cured composite resins. After incubation for 24 h, cytotoxicity was assessed with the lactate dehydrogenase (LDH) and methyl thiazolyl tetrazolium (MTT) assays, and total protein was quantified using the Lowry method. TNF-α detection was examined with an enzyme-linked immunosorbent assay (ELISA) conducted with cell supernatants after cell stimulation for 6, 12, and 24 h. Data were analyzed using one-way analysis of variance (ANOVA) and Tukey’s post hoc test (α=0.05). Results KaloreTM and FiltekTM Silorane were cytotoxic with or without light curing (p<0.05) after 24 h of incubation. KaloreTM stimulated the early production of TNF-α in comparison with control (p<0.05), whereas FiltekTM Silorane did not affect TNF-α levels after 6 and 12 h (p>0.05). However, after 24 h FiltekTM Silorane inhibited the production of TNF-α (p<0.05). Conclusions KaloreTM and FiltekTM Silorane were cytotoxic regardless of light curing. The extract obtained from KaloreTM after 15 days of incubation stimulated the production of TNF-α, unlike that obtained from FiltekTM Silorane. PMID:27556204

  4. Gold Nanoparticles of Diameter 13 nm Induce Apoptosis in Rabbit Articular Chondrocytes

    NASA Astrophysics Data System (ADS)

    Huang, Hao; Quan, Ying-yao; Wang, Xiao-ping; Chen, Tong-sheng

    2016-05-01

    Gold nanoparticles (AuNPs) have been widely used in biomedical science including antiarthritic agents, drug loading, and photothermal therapy. In this report, we studied the effects of AuNPs with diameters of 3, 13, and 45 nm, respectively, on rabbit articular chondrocytes. AuNPs were capped with citrate and their diameter and zeta potential were measured by dynamic light scattering (DLS). Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay after the rabbit articular chondrocytes were pre-incubated with 3, 13, and 45 nm AuNPs, respectively, for 24 h. Flow cytometry (FCM) analysis with annexin V/propidium iodide (PI) double staining and fluorescence imaging with Hoechst 33258 staining were used to determine the fashion of AuNPs-induced chondrocyte death. Further, 13 nm AuNPs (2 nM) significantly induced chondrocyte death accompanying apoptotic characteristics including mitochondrial damage, externalization of phosphatidylserine and nuclear concentration. However, 3 nm AuNPs (2 nM) and 45 nm (0.02 nM) AuNPs did not induce cytotoxicity in chondrocytes. Although 13 nm AuNPs (2 nM) increased the intracellular reactive oxygen species (ROS) level, pretreatment with Nacetyl cysteine (NAC), a ROS scavenger, did not prevent the cytotoxicity induced by 13 nm AuNPs, indicating that 13 nm AuNPs (2 nM) induced ROS-independent apoptosis in chondrocytes. These results demonstrate the size-dependent cytotoxicity of AuNPs in chondrocytes, which must be ser