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Sample records for nanoparticles induced cytotoxicity

  1. 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.

  2. 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

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

    PubMed Central

    Glazer, Evan S.; Curley, Steven A.

    2010-01-01

    Background Non-ionizing radiation, such as radiofrequency (RF) field and near infrared laser, induces thermal cytotoxicity in cancer cells treated with gold nanoparticles (AuNP). Quantum dots (QD) are fluorescent semiconducting nanoparticles that we hypothesize will induce similar injury following RF field irradiation. Methods AuNP and two types of QD (cadmium-selenide and indium-gallium-phosphide) conjugated to cetuximab (C225), a monoclonal antibody against human epidermal growth factor receptor (EGFR-1), demonstrated concentration-dependent heating in a RF field. We investigated the effect of RF field exposure after targeted nanoparticle treatment in a co-culture of two human cancer cell lines that have differential EGFR-1 expression (a high expressing pancreatic carcinoma, Panc-1, and a low expressing breast carcinoma, Cama-1). Results RF exposed Panc-1 or Cama-1 cells not containing AuNP or QD had a viability greater than 92%. The viability of Panc-1 cells exposed to the RF field after treatment with 50 nM Au-C225 was 39.4% ± 8.3% without injury to bystander Cama-1 cells (viability was 93.7% ± 1.0%, p ~ 0.0006). Panc-1 cells treated with targeted Cd-Se QD were only 47.5% viable after RF field exposure (p < 0.0001 compared to RF only Panc-1 control cells). Targeted InGaP QD decreased Panc-1 viability to 58.2% ± 3.4% after RF field exposure (p ~ 0.0004 compared to Cama-1 and Panc-1 controls). Conclusion We selectively induced RF field cytotoxicity in Panc-1 cells without injury to bystander Cama-1 cells utilizing EGFR-1 targeted nanoparticles, and demonstrated an interesting bifunctionality of fluorescent nanoparticles as agents for both cancer cell imaging and treatment. PMID:20564640

  4. Assessment of cytotoxicity and oxidative stress induced by titanium oxide nanoparticles on Chinook salmon cells.

    PubMed

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

    2015-10-01

    Titanium oxide nanoparticles (TiO2 NPs) have received wide attention in diverse application, but the potential impact of these nanomaterials on the environment, aquatic life and especially on fish cell lines is lacking. The present study aimed to investigate the cytotoxicity and oxidative stress induced by TiO2 NPs on Chinook salmon cells derived from Oncorhynchus tshawytscha embryos (CHSE-214). The The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] and neutral red (NR) assays in CHSE-214 cells exposed to TiO2 NPs revealed concentration-dependent cytotoxic effect in the range of 10 to 60 μg/ml for 24 h. CHSE-214 cells exposed to TiO2 NPs (10-60 μg/ml) exhibited significant decline in superoxide dismutase (SOD), catalase (CAT) glutathione (GSH) content and increased lipid peroxidation (LPO) in a concentration-dependent manner. TiO2 NPs induced cytotoxicity and oxidative stress in CHSE-214 cells which serve as a base line studies for future studies. PMID:26013742

  5. 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

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

    PubMed

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

    2015-08-14

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

  7. Aluminium oxide nanoparticles induced morphological changes, cytotoxicity and oxidative stress in Chinook salmon (CHSE-214) cells.

    PubMed

    Srikanth, Koigoora; Mahajan, Amit; Pereira, Eduarda; Duarte, Armando Costa; Venkateswara Rao, Janapala

    2015-10-01

    Aluminium oxide nanoparticles (Al2 O3 NPs) are increasingly used in diverse applications that has raised concern about their safety. Recent studies suggested that Al2 O3 NPs induced oxidative stress may be the cause of toxicity in algae, Ceriodaphnia dubia, Caenorhabditis elegans and Danio rerio. However, there is paucity on the toxicity of Al2 O3 NPs on fish cell lines. The current study was aimed to investigate Al2 O3 NPs induced cytotoxicity, oxidative stress and morphological abnormality of Chinnok salmon cells (CHSE-214). A dose-dependent decline in cell viability was observed in CHSE-214 cells exposed to Al2 O3 NPs. Oxidative stress induced by Al2 O3 NPs in CHSE-214 cells has resulted in the significant reduction of superoxide dismutase, catalase and glutathione in a dose-dependent manner. However, a significant increase in glutathione sulfo-transferase and lipid peroxidation was observed in CHSE-214 cells exposed to Al2 O3 NPs in a dose-dependent manner. Significant morphological changes in CHSE-214 cells were observed when exposed to Al2 O3 NPs at 6, 12 and 24 h. The cells started to detach and appear spherical at 6 h followed by loss of cellular contents resulting in the shrinking of the cells. At 24 h, the cells started to disintegrate and resulted in cell death. Our data demonstrate that Al2 O3 NPs induce cytotoxicity and oxidative stress in a dose-dependent manner in CHSE-214 cells. Thus, our current work may serve as a base-line study for future evaluation of toxicity studies using CHSE-214 cells. PMID:25875951

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

    PubMed

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

    2016-12-01

    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.

  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. PMID:26925725

  11. 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.

  12. 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

  13. 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.

  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. Noninvasive radiofrequency field-induced hyperthermic cytotoxicity in human cancer cells using cetuximab-targeted gold nanoparticles.

    PubMed

    Curley, Steven A; Cherukuri, Paul; Briggs, Katrina; Patra, Chitta Ranjan; Upton, Mark; Dolson, Elisa; Mukherjee, Priyabrata

    2008-01-01

    Shortwave (MHz range) radiofrequency (RF) energy is nonionizing, penetrates deeply into biologic tissues with no adverse side effects, and heats gold nanoparticles efficiently. Targeted delivery of gold nanoparticles to cancer cells should result in hyperthermic cytotoxicity upon exposure to a focused, noninvasive RF field. In this report we demonstrate that gold nanoparticles conjugated with cetuximab (C225) are quickly internalized by Panc-1 (pancreatic adenocarcinoma) and Difi (colorectal adenocarcinoma) cancer cells overexpressing epidermal growth factor receptor (EGFR). Panc-1 or Difi cells treated with naked gold nanoparticles or nonspecific IgG-conjugated gold nanoparticles demonstrated minimal intracellular uptake of gold nanoparticles by transmission electron microscopy (TEM). In contrast, there were dense concentrations of cytoplasmic vesicles containing gold nanoparticles following treatment with cetuximab-conjugated gold nanoparticles. Exposure of cells to a noninvasive RF field produced nearly 100% cytotoxicity in cells treated with the cetuximab-conjugated gold nanoparticles, but significantly lower levels of cytotoxicity in the two control groups (P < 0.00012). Treatment of a breast cancer cell line (CAMA-1) that does not express EGFR with cetuximab-conjugated gold nanoparticles produced no enhanced cytotoxicity following treatment in the RF field. Conjugation of cancer cell-directed targeting agents to gold nanoparticles may represent an effective and cancer-specific therapy to treat numerous types of human malignant disease using noninvasive RF hyperthermia. PMID:19227011

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

    PubMed Central

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

    2015-01-01

    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. PMID:26834855

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

    PubMed

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

    2015-08-01

    Gold nanoparticles (AuNP) have been widely used for many applications, including as biological carriers. A better understanding concerning AuNP safety on muscle cells is crucial, since it could be a potential tool in the nanomedicine field. Here, we describe the impact of polyethylene glycol-coated gold nanoparticles (PEG-AuNP) interaction with differentiated skeletal muscle C2C12 cells on cell viability, mitochondria function, cell signaling related to survival, cytokine levels and susceptibility to apoptosis. Intracellular localization of 4.5 nm PEG-AuNP diameter size was evidenced by STEM-in-SEM in myotube cells. Methods for cytotoxicity analysis showed that PEG-AuNP did not affect cell viability, but intracellular ATP levels and mitochondrial membrane potential increased. Phosphorylation of ERK was not altered but p-AKT levels reduced (p<0.01). Pre-treatment of cells with PEG-AuNP followed by staurosporine induction increased the caspases-3/7 activity. Indeed, cytokines analysis revealed a sharp increase of IFN-γ and TGF-β1 levels after PEG-AuNP treatment, suggesting that inflammatory and fibrotic phenotypes process were activated. These data demonstrate that PEG-AuNP affect the myotube physiology leading these cells to be more susceptible to death stimuli in the presence of staurosporine. Altogether, these results present evidence that PEG-AuNP affect the susceptibility to apoptosis of muscle cells, contributing to development of safer strategies for intramuscular delivery. PMID:25790728

  18. The Protective Effect of Bafilomycin A1 Against Cobalt Nanoparticle-Induced Cytotoxicity and Aseptic Inflammation in Macrophages In Vitro.

    PubMed

    Wang, Songhua; Liu, Fan; Zeng, Zhaoxun; Yang, Huilin; Jiang, Haitao

    2016-01-01

    Co ions released due to corrosion of Co nanoparticles (CoNPs) in the lysosomes of macrophages may be a factor in the particle-induced cytotoxicity and aseptic inflammation accompanying metal-on-metal (MOM) hip prosthesis failure. Here, we show that CoNPs are easily dissolved under a low pH, simulating the acidic lysosomal environment. We then used bafilomycin A1 to change the pH inside the lysosome to inhibit intracellular corrosion of CoNPs and then investigated its protective effects against CoNP-induced cytotoxicity and aseptic inflammation on murine macrophage RAW264.7 cells. XTT {2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide} assays revealed that bafilomycin A1 can significantly decrease CoNP-induced cytotoxicity in RAW264.7 cells. Enzyme-linked immunosorbent assays showed that bafilomycin A1 can significantly decrease the subtoxic concentration of CoNP-induced levels of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), but has no effect on anti-inflammatory cytokines (transforming growth factor-β and interleukin-10) in RAW264.7 cells. We studied the protective mechanism of bafilomycin A1 against CoNP-induced effects in RAW264.7 cells by measuring glutathione/oxidized glutathione (GSH/GSSG), superoxide dismutase, catalase, and glutathione peroxidase levels and employed scanning electron microscopy, transmission electron microscopy, and energy dispersive spectrometer assays to observe the ultrastructural cellular changes. The changes associated with apoptosis were assessed by examining the pAKT and cleaved caspase-3 levels using Western blotting. These data strongly suggested that bafilomycin A1 can potentially suppress CoNP-induced cytotoxicity and aseptic inflammation by inhibiting intracellular corrosion of CoNPs and that the reduction in Co ions released from CoNPs may play an important role in downregulating oxidative stress in RAW264.7 cells.

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

    PubMed

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

    2013-11-01

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

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

    PubMed

    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

  1. 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

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

    PubMed

    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.

  3. Are diamond nanoparticles cytotoxic?

    PubMed

    Schrand, Amanda M; Huang, Houjin; Carlson, Cataleya; Schlager, John J; Omacr Sawa, Eiji; Hussain, Saber M; Dai, Liming

    2007-01-11

    Finely divided carbon particles, including charcoal, lampblack, and diamond particles, have been used for ornamental and official tattoos since ancient times. With the recent development in nanoscience and nanotechnology, carbon-based nanomaterials (e.g., fullerenes, nanotubes, nanodiamonds) attract a great deal of interest. Owing to their low chemical reactivity and unique physical properties, nanodiamonds could be useful in a variety of biological applications such as carriers for drugs, genes, or proteins; novel imaging techniques; coatings for implantable materials; and biosensors and biomedical nanorobots. Therefore, it is essential to ascertain the possible hazards of nanodiamonds to humans and other biological systems. We have, for the first time, assessed the cytotoxicity of nanodiamonds ranging in size from 2 to 10 nm. Assays of cell viability such as mitochondrial function (MTT) and luminescent ATP production showed that nanodiamonds were not toxic to a variety of cell types. Furthermore, nanodiamonds did not produce significant reactive oxygen species. Cells can grow on nanodiamond-coated substrates without morphological changes compared to controls. These results suggest that nanodiamonds could be ideal for many biological applications in a diverse range of cell types.

  4. Are diamond nanoparticles cytotoxic?

    PubMed

    Schrand, Amanda M; Huang, Houjin; Carlson, Cataleya; Schlager, John J; Omacr Sawa, Eiji; Hussain, Saber M; Dai, Liming

    2007-01-11

    Finely divided carbon particles, including charcoal, lampblack, and diamond particles, have been used for ornamental and official tattoos since ancient times. With the recent development in nanoscience and nanotechnology, carbon-based nanomaterials (e.g., fullerenes, nanotubes, nanodiamonds) attract a great deal of interest. Owing to their low chemical reactivity and unique physical properties, nanodiamonds could be useful in a variety of biological applications such as carriers for drugs, genes, or proteins; novel imaging techniques; coatings for implantable materials; and biosensors and biomedical nanorobots. Therefore, it is essential to ascertain the possible hazards of nanodiamonds to humans and other biological systems. We have, for the first time, assessed the cytotoxicity of nanodiamonds ranging in size from 2 to 10 nm. Assays of cell viability such as mitochondrial function (MTT) and luminescent ATP production showed that nanodiamonds were not toxic to a variety of cell types. Furthermore, nanodiamonds did not produce significant reactive oxygen species. Cells can grow on nanodiamond-coated substrates without morphological changes compared to controls. These results suggest that nanodiamonds could be ideal for many biological applications in a diverse range of cell types. PMID:17201422

  5. 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.

  6. 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. PMID:27536098

  7. 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

  8. Folate-Modified Chitosan Nanoparticles Coated Interferon-Inducible Protein-10 Gene Enhance Cytotoxic T Lymphocytes' Responses to Hepatocellular Carcinoma.

    PubMed

    Duan, Siliang; Song, Mongkhoune; He, Jian; Zhou, Nuo; Zhou, Sufang; Zhao, Jing; Fang, Yuan; Yi, Peng; Huang, Xianing; Luo, Guorong; Lai, Chunhui; Yu, Xia; Zhang, Zhiyong; Xie, Yuan; Zhao, Yongxiang; Lu, Xiaoling

    2016-04-01

    Adoptive therapy using tumor antigen-specific cytotoxic T lymphocytes (CTLs) is a promising approach for treatment of human cancers. Due to immune suppression in cancer patients, it is difficult for tumor antigen-specific CTLs to arrive at tumor tissues. Interferon-inducible protein-10 (IP-10) is a powerful chemokine that effectively attracts CTLs to tumor tissues and improves their anti-tumor activity. Increase over expression of IP-10 in tumor tissues can efficiently promote efficacy of adoptive therapy. Folate-modified chitosan nanoparticles coating the human IP-10 gene (FA-CS-hIP-10) were therefore developed in this study. The FA-CS-hIP-10 nanoparticles were specifically bound to folate receptors on hepatoma cells and promoted the expression of IP-10, to improve the activity of pMAGE-A1(278-286) specific CTLs. Combination of the FA-CS-hIP-10 and pMAGE-A1(278-286) specific CD8+ CTLs efficiently increased secretion of IFN-γ, inhibited tumor growth and extended survival of nude mice with subcutaneously transplanted human hepatocellular carcinoma. Our results demonstrated that the mechanism behind this novel therapeutic approach involved inhibition of angiogenesis and proliferation, and also promoted apoptosis of tumor cells. Our study provides a potentially novel approach for treatment of human hepatocellular carcinoma by improving the activity of tumor antigen-specific CTLs. PMID:27301196

  9. 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.

  10. Knockdown of Glutamate Cysteine Ligase Catalytic Subunit by siRNA Causes the Gold Nanoparticles-Induced Cytotoxicity in Lung Cancer Cells

    PubMed Central

    Liu, Min; Zhao, Yunxue; Zhang, Xiumei

    2015-01-01

    Gold nanoparticles (GNPs) have shown promising medical applications in cancer treatment involved in the regulation of intracellular redox balance. Previously, we have reported that GNPs can trigger apoptosis and necrosis in human lung cancer cells (A549) when L-buthionine-sulfoximine (BSO) was used to decrease the expression of intracellular glutathione (GSH). Herein, we investigated the cytotoxicity of GNPs toward lung cancer cells under the glutamate cysteine ligase catalytic subunit (GCLC) was silenced by siRNA. Our results showed that GNPs cause apoptosis and necrosis in cells transfected with GCLC siRNA by elevating intracellular reactive oxygen species (ROS). These findings demonstrated that the regulation of glutathione synthesis by GCLC siRNA in A549 cells can initiate the gold nanoparticles-induced cytotoxicity. PMID:25789740

  11. 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.

  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. 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.

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

    PubMed

    Clar, Justin G; Li, Xuan; Impellitteri, Christopher A; Bennett-Stamper, Christina; Luxton, Todd P

    2016-09-01

    With the inclusion of engineered nanomaterials in industrial processes and consumer products, wastewater treatment plants (WWTPs) could 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 through nitrification. This study examined the potential toxicity of uncoated and polyvinylpyrrolidone (PVP)-coated CuO, and Cu2O nanoparticles, as well as Cu ions to microbial communities responsible for nitrification 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 analysis 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 intermediated by reduced Cu(I) species. PMID:27466862

  15. 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.

  16. 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.

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

    PubMed

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

    2013-11-28

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

  18. 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. PMID:26911730

  19. Cytotoxicity and apoptosis induced by silver nanoparticles in human liver HepG2 cells in different dispersion media.

    PubMed

    Xue, Yuying; Zhang, Ting; Zhang, Bangyong; Gong, Fan; Huang, Yanmei; Tang, Meng

    2016-03-01

    Silver nanoparticles (Ag NPs) have been widely used in medical and healthcare products owing to their unique antibacterial activities. However, their safety for humans and the environment has not yet been established. This study evaluated the cellular proliferation and apoptosis of Ag NPs suspended in different solvents using human liver HepG2 cells. The ionization of Ag NPs in different dispersion media [deionized water, phosphate-buffered saline (PBS), saline and cell culture] was measured using an Ag ion selective electrode. The MTT assay was used to examine the cell proliferation activities. The effects of Ag NPs on cell cycle, induction of apoptosis, production of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were analyzed using flow cytometry. The degree of Ag NPs ionization differed with dispersion media, with the concentrations of silver ions in deionized water being the highest in all suspensions. Ag NPs could inhibit the viability of HepG2 cells in a time- and concentration-dependent manner. Ag NPs (40, 80 and 160 µg ml(-1)) exposure could cause cell-cycle arrest in the G2/M phase, significantly increasing the apoptosis rate and ROS generation, and decreasing the MMP in HepG2 cells more sensitive to deionized water than in cell culture. These results suggested that the cellular toxicological mechanism of Ag NPs might be related to the oxidative stress of cells by the generation of ROS, leading to mitochondria injury and induction of apoptosis. It also implies that it is important to assess the physicochemical properties of NPs in the media where the biological toxicity tests are performed. PMID:26198703

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Heparin nanoparticles for β amyloid binding and mitigation of β amyloid associated cytotoxicity.

    PubMed

    Wang, Peng; Kouyoumdjian, Hovig; Zhu, David C; Huang, Xuefei

    2015-03-20

    Accumulation of β amyloid (Aβ) in the brain is believed to play a key role in the pathology of Alzheimer's disease. Glycosaminoglycans on surface of neuronal cells can serve as nucleation sites to promote plaque formation on cell surface. To mimic this process, magnetic nanoparticles coated with heparin have been synthesized. The heparin nanoparticles were demonstrated to bind with Aβ through a variety of techniques including enzyme-linked immunosorbent assay, gel electrophoresis, and thioflavin T assay. The nanoparticle exhibited little toxicity to neuronal cells and at the same time can effectively protect them from Aβ induced cytotoxicity. These results suggest that heparin nanoparticles can be a very useful tool for Aβ studies.

  5. The cytotoxicity of NiO nanoparticle with borate capping.

    PubMed

    Liu, Zunjing; Wang, Yongjing; Pan, Danmei; Chen, Zhi; Pan, Xiaohong; Wang, Yonghao; Lin, Zhang

    2011-11-01

    The impact of surface capping on cytotoxicity of NiO nanoparticle was investigated with Escherichia coil (E.coli) in this work. The NiO nanoparticle and NiO nanoparticle capped by borate (denoted as NiO-borate) were synthesized by hydrothermal method. The average size of both nanoparticles is about 4.0 nm. The plate experiments demonstrated that NiO-borate nanoparticles show lower cytotoxicity than NiO nanopaticles. Further spectrophotometric analysis revealed that the concentration of both extracellular and intercellular Ni2+ in NiO-borate system were lower than that of uncapped one. Intracellular ICP-AES analysis also showed the concentration of Ni element was higher than Ni2+, suggesting the NiO nanoparticles might penetrate into the cellular interior. Comprehensive AFM, SEM and TEM observation illustrated both NiO-borate and NiO nanoparticles lead to the collapse of cellular body, the convex on the cell wall and the damage of cell wall ultimately. In summary, the surface capping with borate on NiO nanopaticles will suppress the release of the Ni2+ ions and impede the contact between the NiO nanoparticle and cell wall, which ultimately decreased the cytotoxicity of NiO nanoparticles.

  6. Cell-specific cytotoxicity of dextran-stabilized magnetite nanoparticles.

    PubMed

    Ding, Jing; Tao, Ke; Li, Jiyu; Song, Sheng; Sun, Kang

    2010-08-01

    Cytotoxicity of dextran-hybridized magnetite nanoparticles which were prepared by a novel polyol method was evaluated by incubation with four different kinds of cells, including rat liver cells BRL 3A, renal cells NRK, astrocyte and periphery blood mononuclear cells (PBMC). The study was designed not only to evaluate their cytotoxicity but also to reflect the interaction between nanoparticles and related cells in their circulation processes. By fluorescent-activated cell sorting technique, it was found that the cytotoxicity of the nanoparticles is cell-specific. Under the concentrations in our study (0-128 mg/mL), the nanoparticles lead to the apoptosis of PBMC in a concentration-dependant manner, but have almost no influence on the other kinds of cells. TEM images demonstrate that the nanoparticles were endocytosed by BRL 3A, NRK and astrocyte, and result in the apoptosis of PBMC without the observation of the uptaking process. The results suggest that the related cells in nanoparticles cycling process should also be concerned for the cytotoxicity evaluation.

  7. Titanium Dioxide Nanoparticles are not Cytotoxic or Clastogenic in Human Skin Cells

    PubMed Central

    Browning, Cynthia L; The, Therry; Mason, Michael D; Wise, John Pierce

    2015-01-01

    The application of nanoparticle technology is rapidly expanding. The reduced dimensionality of nanoparticles can give rise to changes in chemical and physical properties, often resulting in altered toxicity. People are exposed dermally to titanium dioxide (TiO2) nanoparticles in industrial and residential settings. The general public is increasingly exposed to these nanoparticles as their use in cosmetics, sunscreens and lotions expands. The toxicity of TiO2 nanoparticles towards human skin cells is unclear and understudied. We used a human skin fibroblast cell line to investigate the cytotoxicity and clastogenicity of TiO2 nanoparticles after 24 h exposure. In a clonogenic survival assay, treatments of 10, 50 and 100 μg/cm2 induced 97.8, 88.8 and 84.7% relative survival, respectively. Clastogenicity was assessed using a chromosomal aberration assay in order to determine whether TiO2 nanoparticles induced serious forms of DNA damage such as chromatid breaks, isochromatid lesions or chromatid exchanges. Treatments of 0, 10, 50 and 100 μg/cm2 induced 3.3, 3.0, 3.0 and 2.7% metaphases with damage, respectively. No isochromatid lesions or chromatid exchanges were detected. These data show that TiO2 nanoparticles are not cytotoxic or clastogenic to human skin cells. PMID:26568896

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-09-01

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

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

    PubMed

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

    2015-09-01

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

  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. Unraveling the cytotoxic potential of Temozolomide loaded into PLGA nanoparticles

    PubMed Central

    2014-01-01

    Background Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells. Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry. Results PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility. Conclusion PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity. PMID:24410831

  13. 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.

  14. 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.

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

    PubMed Central

    2009-01-01

    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. PMID:20652105

  16. 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.

  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. PMID:26200209

  18. 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.

  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. PMID:27398446

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

    PubMed

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

    2013-03-01

    Engineered nanomaterials have become prevalent in our everyday life. While the popularity of using nanomaterials in consumer products continues to rise, increasing awareness of nanotoxicology has also fuelled efforts to accelerate our understanding of the ill effects that different nanomaterials can bring to biological systems. In this study, we investigated the potential cytotoxicity and genotoxicity of three nanoparticles: titanium dioxide (TiO(2)), terbium-doped gadolinium oxide (Tb-Gd(2)O(3)), and poly(lactic-co-glycolic acid) (PLGA). To evaluate nanoparticle-induced genotoxicity more realistically, a human skin fibroblast cell line (BJ) with less mutated genotype compared with cancer cell line was used. The nanoparticles were first characterized by size, morphology, and surface charge. Cytotoxicity effects of the nanoparticles were then evaluated by monitoring the proliferation of treated BJ cells. Genotoxic influence was ascertained by profiling DNA damage via detection of γH2AX expression. Our results suggested that both TiO(2) and Tb-Gd(2)O(3) nanoparticles induced cytotoxicity in a dose dependent way on BJ cells. These two nanomaterials also promoted genotoxicity via DNA damage. On the contrary, PLGA nanoparticles did not induce significant cytotoxic or genotoxic effects on BJ cells. PMID:22927021

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

    PubMed

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

    2013-03-01

    Engineered nanomaterials have become prevalent in our everyday life. While the popularity of using nanomaterials in consumer products continues to rise, increasing awareness of nanotoxicology has also fuelled efforts to accelerate our understanding of the ill effects that different nanomaterials can bring to biological systems. In this study, we investigated the potential cytotoxicity and genotoxicity of three nanoparticles: titanium dioxide (TiO(2)), terbium-doped gadolinium oxide (Tb-Gd(2)O(3)), and poly(lactic-co-glycolic acid) (PLGA). To evaluate nanoparticle-induced genotoxicity more realistically, a human skin fibroblast cell line (BJ) with less mutated genotype compared with cancer cell line was used. The nanoparticles were first characterized by size, morphology, and surface charge. Cytotoxicity effects of the nanoparticles were then evaluated by monitoring the proliferation of treated BJ cells. Genotoxic influence was ascertained by profiling DNA damage via detection of γH2AX expression. Our results suggested that both TiO(2) and Tb-Gd(2)O(3) nanoparticles induced cytotoxicity in a dose dependent way on BJ cells. These two nanomaterials also promoted genotoxicity via DNA damage. On the contrary, PLGA nanoparticles did not induce significant cytotoxic or genotoxic effects on BJ cells.

  2. 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). PMID:25463851

  3. Nanomaterial Induced Immune Responses and Cytotoxicity.

    PubMed

    Ali, Ashraf; Suhail, Mohd; Mathew, Shilu; Shah, Muhammad Ali; Harakeh, Steve M; Ahmad, Sultan; Kazmi, Zulqarnain; Alhamdan, Mohammed Abdul Rahman; Chaudhary, Adeel; Damanhouri, Ghazi Abdullah; Qadri, Ishtiaq

    2016-01-01

    Nanomaterials are utilized in a wide array of end user products such as pharmaceuticals, electronics, clothes and cosmetic products. Due to its size (< 100 nm), nanoparticles have the propensity to enter through the airway and skin, making its path perilous with the potential to cause damages of varying severity. Once within the body, these particles have unconstrained access to different tissues and organs including the brain, liver, and kidney. As a result, nanomaterials may cause the perturbation of the immune system eliciting an inflammatory response and cytotoxicity. This potential role is dependent on many factors such as the characteristics of the nanomaterials, presence or absence of diseases, and genetic predisposition. Cobalt and nickel nanoparticles, for example, were shown to have inflammogenic properties, while silver nanoparticles were shown to reduce allergic inflammation. Just as asbestos fibers, carbon nanotubes were shown to cause lungs damage. Some nanomaterials were shown, based on animal studies, to result in cell damage, leading to the formation of pre-cancerous lesions. This review highlights the impact of nanomaterials on immune system and its effect on human health with toxicity consideration. It recommends the development of suitable animal models to study the toxicity and bio-clearance of nanomaterials and propose safety guidelines.

  4. Nanomaterial Induced Immune Responses and Cytotoxicity.

    PubMed

    Ali, Ashraf; Suhail, Mohd; Mathew, Shilu; Shah, Muhammad Ali; Harakeh, Steve M; Ahmad, Sultan; Kazmi, Zulqarnain; Alhamdan, Mohammed Abdul Rahman; Chaudhary, Adeel; Damanhouri, Ghazi Abdullah; Qadri, Ishtiaq

    2016-01-01

    Nanomaterials are utilized in a wide array of end user products such as pharmaceuticals, electronics, clothes and cosmetic products. Due to its size (< 100 nm), nanoparticles have the propensity to enter through the airway and skin, making its path perilous with the potential to cause damages of varying severity. Once within the body, these particles have unconstrained access to different tissues and organs including the brain, liver, and kidney. As a result, nanomaterials may cause the perturbation of the immune system eliciting an inflammatory response and cytotoxicity. This potential role is dependent on many factors such as the characteristics of the nanomaterials, presence or absence of diseases, and genetic predisposition. Cobalt and nickel nanoparticles, for example, were shown to have inflammogenic properties, while silver nanoparticles were shown to reduce allergic inflammation. Just as asbestos fibers, carbon nanotubes were shown to cause lungs damage. Some nanomaterials were shown, based on animal studies, to result in cell damage, leading to the formation of pre-cancerous lesions. This review highlights the impact of nanomaterials on immune system and its effect on human health with toxicity consideration. It recommends the development of suitable animal models to study the toxicity and bio-clearance of nanomaterials and propose safety guidelines. PMID:27398432

  5. 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

  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. Quercetin-induced cardioprotection against doxorubicin cytotoxicity

    PubMed Central

    2013-01-01

    Background Cancer has continually been the leading cause of death worldwide for decades. Thus, scientists have actively devoted themselves to studying cancer therapeutics. Doxorubicin is an efficient drug used in cancer therapy, but also produces reactive oxygen species (ROS) that induce severe cytotoxicity against heart cells. Quercetin, a plant-derived flavonoid, has been proven to contain potent antioxidant and anti-inflammatory properties. Thus, this in vitro study investigated whether quercetin can decrease doxorubicin-induced cytotoxicity and promote cell repair systems in cardiomyocyte H9C2 cells. Results Proteomic analysis and a cell biology assay were performed to investigate the quercetin-induced responses. Our data demonstrated that quercetin treatment protects the cardiomyocytes in a doxorubicin-induced heart damage model. Quercetin significantly facilitated cell survival by inhibiting cell apoptosis and maintaining cell morphology by rearranging the cytoskeleton. Additionally, 2D-DIGE combined with MALDI-TOF MS analysis indicated that quercetin might stimulate cardiomyocytes to repair damage after treating doxorubicin by modulating metabolic activation, protein folding and cytoskeleton rearrangement. Conclusion Based on a review of the literature, this study is the first to report detailed protective mechanisms for the action of quercetin against doxorubicin-induced cardiomyocyte toxicity based on in-depth cell biology and proteomic analysis. PMID:24359494

  8. Cytotoxicity of calcium rectorite micro/nanoparticles before and after organic modification.

    PubMed

    Liu, Yin; Deng, Hongbing; Xiao, Chunlian; Xie, Chengfeng; Zhou, Xue

    2014-08-18

    Organically modified rectorite (OREC) micro/nanoparticles can be synthesized by organic modification from calcium rectorite (Ca(2+)-REC or REC), a common form of rectorite in nature. Although REC and OREC have potential applications in food packing and drug delivery, their cytotoxicity is not clear. In the present study, we investigated and compared the cytotoxicity of REC and OREC micro/nanoparticles in Chang liver cells, the human normal hepatic cells, and human hepatoma HepG2 cells. The interlayer spacing of OREC was enlarged after organic modification. After treatment with REC or OREC for 24 h at 1 and 5 μg/mL, they were taken up by Chang liver cells. REC and OREC induced cytotoxicity in Chang liver and HepG2 cells at almost all doses (1, 2.5, 5, 7.5, and 10 μg/mL) after 6, 24, and 48 h of treatment (P < 0.05 or P < 0.01). Compared with REC, OREC was more cytotoxic. However, there was no difference in the cytotoxicity of REC and OREC between the two cell lines. After treatment with REC or OREC at 7.5 and 10 μg/mL for 24 h, the apoptotic and necrotic percentages of Chang liver cells were increased (P < 0.05 or P < 0.01). The levels of apoptosis-related proteins Bax, Bcl-2, and pro-caspase-3 were all decreased in Chang liver cells after 24 h of exposure to REC or OREC at 5, 7.5, 10 μg/mL. There was no change in the relative ratio of Bax/Bcl-2 after treatment, indicating that REC or OREC-induced apoptosis was not associated with Bax-related mitochondria-mediated apoptotic pathway. Our results suggested that OREC was more cytotoxic than REC, but the underlying mechanisms need further investigation.

  9. 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. PMID:26456245

  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. Cell outer membrane mimetic chitosan nanoparticles: preparation, characterization and cytotoxicity.

    PubMed

    Zhao, Jing; Liang, Fei; Kong, Lingheng; Zheng, Lina; Fan, Tao

    2015-01-01

    A negatively charged copolymer poly (MPC-co-AMPS) of 2-methacryloyloxyethyl phosphorylcholine (MPC) and 2-acrylamide-2-methyl propane sulfonic acid (AMPS) was designed and synthesized. Chitosan nanoparticles with cell outer membrane mimetic structure were prepared by electrostatic interaction between the sulfonic acid groups of poly (MPC-co-AMPS) and the protonated amino groups of chitosan. Effects of factors on influencing the particle size, distribution, and stability were investigated. The experimental results showed that cell membrane mimetic chitosan nanoparticles with controllable and homogeneous size ranged from 100 to 300 nm were prepared at the concentration of 0.1-2.0 mg/mL and the charge ratio of 0.5-1.1. Chitosan nanoparticles prepared can exist stably for more than 45 days when placed at 4 °C and pH < 7.5. The cytotoxicity of the chitosan nanoparticles reduced significantly after surface modification with cell membrane mimetic structure, meeting the basic requirements of biomedical materials. The results suggest cell membrane mimetic chitosan nanoparticles prepared with polyanion and polycation obtain good biological compatibility and immune stealth ability, which has important academic significance and great application prospects.

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

    PubMed

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

    2014-08-01

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

  13. 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

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

    PubMed

    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 Cu(2+) 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.

  15. 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.

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

    PubMed

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

    2014-05-01

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

  17. Rhamnose-coated superparamagnetic iron-oxide nanoparticles: an evaluation of their in vitro cytotoxicity, genotoxicity and carcinogenicity.

    PubMed

    Paolini, Alessandro; Guarch, Constança Porredon; Ramos-López, David; de Lapuente, Joaquín; Lascialfari, Alessandro; Guari, Yannick; Larionova, Joulia; Long, Jerome; Nano, Rosanna

    2016-04-01

    Tumor recurrence after the incomplete removal of a tumor mass inside brain tissue is the main reason that scientists are working to identify new strategies in brain oncologic therapy. In particular, in the treatment of the most malignant astrocytic tumor glioblastoma, the use of magnetic nanoparticles seems to be one of the most promising keys in overcoming this problem, namely by means of magnetic fluid hyperthermia (MFH) treatment. However, the major unknown issue related to the use of nanoparticles is their toxicological behavior when they are in contact with biological tissues. In the present study, we investigated the interaction of glioblastoma and other tumor cell lines with superparamagnetic iron-oxide nanoparticles covalently coated with a rhamnose derivative, using proper cytotoxic assays. In the present study, we focused our attention on different strategies of toxicity evaluation comparing different cytotoxicological approaches in order to identify the biological damages induced by the nanoparticles. The data show an intensive internalization process of rhamnose-coated iron oxide nanoparticles by the cells, suggesting that rhamnose moiety is a promising biocompatible coating in favoring cells' uptake. With regards to cytotoxicity, a 35% cell death at a maximum concentration, mainly as a result of mitochondrial damages, was found. This cytotoxic behavior, along with the high uptake ability, could facilitate the use of these rhamnose-coated iron-oxide nanoparticles for future MFH therapeutic treatments. PMID:26708321

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

    PubMed Central

    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. PMID:27274241

  19. 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.

  20. 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

  1. Cytotoxicity and physicochemical properties of hafnium oxide nanoparticles.

    PubMed

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

    2011-09-01

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

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

    PubMed Central

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

    2011-01-01

    Background The purpose of this study was to investigate the mechanism of noxious effects of amorphous silica nanoparticles on human endothelial cells. Methods Nanoparticle uptake was examined by transmission electron microscopy. Electrochemical nanosensors were used to measure the nitric oxide (NO) and peroxynitrite (ONOO−) released by a single cell upon nanoparticle stimulation. The downstream inflammatory effects were measured by an enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, and flow cytometry, and cytotoxicity was measured by lactate dehydrogenase assay. Results We found that the silica nanoparticles penetrated the plasma membrane and rapidly stimulated release of cytoprotective NO and, to a greater extent, production of cytotoxic ONOO−. The low [NO]/[ONOO−] ratio indicated increased nitroxidative/oxidative stress and correlated closely with endothelial inflammation and necrosis. This imbalance was associated with nuclear factor κB activation, upregulation of key inflammatory factors, and cell death. These effects were observed in a nanoparticle size-dependent and concentration-dependent manner. Conclusion The [NO]/[ONOO−] imbalance induced by amorphous silica nanoparticles indicates a potentially deleterious effect of silica nanoparticles on vascular endothelium. PMID:22131828

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

    PubMed Central

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

    2014-01-01

    Silver nanoparticles (AgNPs) have attracted considerable attentions due to their unique properties and diverse applications. Although it has been reported that AgNPs have acute toxic effects on a variety of cultured mammalian cells and animal models, few studies have been conducted to evaluate the associated risk of AgNPs to human health at non-cytotoxic doses. In this paper, HepG2 cells were exposed to 10 nm and 100 nm AgNPs under non-cytotoxic conditions, and cell viability was assessed. At low doses, AgNPs displayed “hormesis” effects by accelerating cell proliferation. Further studies indicated that the activation states of MAPKs were differentially regulated in this process. Specifically, by increasing the expression of downstream genes, p38 MAPK played a central role in non-cytotoxic AgNP-induced hormesis. Moreover, the treatment of HepG2 cells with silver ions (Ag+) at the same dose levels induced distinct biological effects, suggesting that different intrinsic properties exist for AgNPs and Ag+. PMID:25033410

  4. 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.

  5. 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.

  6. 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.

  7. Evaluation of Cytotoxicity and Hypoxic Effect of Nitroimidazole Embedded Nanoparticles.

    PubMed

    Sharma, Rakesh; Kwon, Soonjo

    2016-05-01

    Adenylate cyclase is a key intracellular enzyme involved in energy imbalance leading to tumor hypoxia and cytotoxicity. In this study, adenylate cyclase activities in isolated hepatocytes and Kupffer cells were compared in the presence of several metabolic stimulators. In cultured hepatocyte cells, adenylate cyclase was stimulated by guanylyl imidotriphosphate (GITP), guanosine triphosphate (GTP), progesterone and nitroimidazole embedded nanoparticle (NNP) effectors, while prostaglandin E2 and F2α were used as effectors in cultured Kupffer cells. The results showed that NNPs decreased adenylate cyclase specific activity in a dose-dependent manner after preincubation of hepatocytes with NNPs. The NNPs stimulated adenylate cyclase activities in hepatocytes were evaluated based on measurement of cyclic adenosine monophosphate (cAMP). The stimulatory effects of NNPs on adenylate cyclase were independent of the presence of GTP and may have been due to a direct effect on the catalytic subunit of adenylate cyclase. In addition, basal cAMP generation in hepatocyte cells was efficiently suppressed by the NNPs. In conclusion, NNPs exerted direct effects on the catalytic subunit of the adenylate cyclase system, and adenylate cyclase was hormone sensitive in liver cells. PMID:27483789

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

    PubMed Central

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

    2011-01-01

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

  9. 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

  10. 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

  11. 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.

  12. 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. PMID:27441588

  13. Effects of iron oxide nanoparticles: cytotoxicity, genotoxicity, developmental toxicity, and neurotoxicity.

    PubMed

    Valdiglesias, Vanessa; Kiliç, Gözde; Costa, Carla; Fernández-Bertólez, Natalia; Pásaro, Eduardo; Teixeira, João Paulo; Laffon, Blanca

    2015-03-01

    Iron oxide nanoparticles (ION) with superparamagnetic properties hold great promise for use in various biomedical applications; specific examples include use as contrast agents for magnetic resonance imaging, in targeted drug delivery, and for induced hyperthermia cancer treatments. Increasing potential applications raise concerns over their potential effects on human health. Nevertheless, very little is currently known about the toxicity associated with exposure to these nanoparticles at different levels of biological organization. This article provides an overview of recent studies evaluating ION cytotoxicity, genotoxicity, developmental toxicity and neurotoxicity. Although the results of these studies are sometimes controversial, they generally indicate that surface coatings and particle size seem to be crucial for the observed ION-induced effects, as they are critical determinants of cellular responses and intensity of effects, and influence potential mechanisms of toxicity. The studies also suggest that some ION are safe for certain biomedical applications, while other uses need to be considered more carefully. Overall, the available studies provide insufficient evidence to fully assess the potential risks for human health related to ION exposure. Additional research in this area is required including studies on potential long-term effects. PMID:25209650

  14. 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.

  15. The Role of Dextran Coatings on the Cytotoxicity Properties of Ceria Nanoparticles Toward Bone Cancer Cells

    NASA Astrophysics Data System (ADS)

    Yazici, Hilal; Alpaslan, Ece; Webster, Thomas J.

    2015-04-01

    Cerium oxide nanoparticles have demonstrated great potential as antioxidant and radioprotective agents for nanomedicine applications especially for cancer therapy. The surface chemistry of nanoparticles is an important property that has a significant effect on their performance in biological applications including cancer diagnosis, cancer treatment, and bacterial infection. Recently, various nanosized cerium oxide particles with different types of polymer coatings have been developed to improve aqueous solubility and allow for surface functionalization for distinct applications. In this study, the role of ceria nanoparticles coated with dextran on the cytotoxicity properties of bone cancer cells was shown. Specifically, 0.1 M and 0.01 M dextran-coated, <5-nm ceria nanoparticles, were synthesized. The cytotoxicity of 0.1 M and 0.01 M dextran-coated ceria nanoparticles was evaluated against osteosarcoma cells. A change in cell viability was observed when treating osteosarcoma cells with 0.1 M dextran-coated ceria nanoparticles in the 250 -1000 μg/mL concentration range. In contrast, minimal toxicity to bone cancer cells was observed for the 0.01 M dextran coating after 3 days compared with the 0.1 M dextran coating. These results indicated that surface dextran functionalization had a positive impact on the cytotoxicity of cerium oxide nanoparticles against osteosarcoma cells.

  16. 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.

  17. Zinc oxide nanoparticle and bovine serum albumin interaction and nanoparticles influence on cytotoxicity in vitro.

    PubMed

    Žūkienė, Rasa; Snitka, Valentinas

    2015-11-01

    Bovine serum albumin (BSA) and zinc oxide nanoparticles (ZnO NPs) are chosen as a model system to investigate NPs-protein corona complex formation. ZnO NPs with average size of ∼ 20 nm are coated with BSA using covalent and non-covalent conjugation at temperatures of 4 °C and 20 °C. The interaction mechanism between ZnO NPs and BSA is studied by using UV-vis absorption, fluorescence, synchronous fluorescence and Raman spectroscopy. Raman spectra of BSA in the presence of ZnO NPs are registered for the first time and confirm decreased α-helix content, increased unstructured folding and β-sheet content in BSA structure. The synchronous fluorescence spectra revealed that the hydrophobicity of the tyrosine residue is decreased and that of the tryptophan is increased. The relation of elucidated changes in BSA structure of BSA-coated ZnO NPs cytotoxicity is tested for CHO cell viability and reactive oxygen species (ROS) generation in vitro. Covalent and non-covalent binding of BSA to ZnO NPs reduces ZnO NPs cytotoxicity and ROS generation, however changes in BSA conformation makes corona less protective against ZnO NPs.

  18. Hitchhiking nanoparticles: Reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes.

    PubMed

    Wayteck, Laura; Dewitte, Heleen; De Backer, Lynn; Breckpot, Karine; Demeester, Jo; De Smedt, Stefaan C; Raemdonck, Koen

    2016-01-01

    Following intravenous injection of anti-cancer nanomedicines, many barriers need to be overcome en route to the tumor. Cell-mediated delivery of nanoparticles (NPs) is promising in terms of overcoming several of these barriers based on the tumoritropic migratory properties of particular cell types. This guided transport aims to enhance the NP accumulation in the tumor and moreover enhance the infiltration of regions that are typically inaccessible for free NPs. Within this study, cytotoxic CD8(+) T cells were selected as carriers based on both their ability to migrate to the tumor and their intrinsic cytolytic activity against tumor cells. Many anti-cancer nanomedicines require tumor cell internalization to mediate cytosolic drug delivery and enhance the anti-cancer effect. This proof-of-concept therefore reports on the reversible attachment of liposomes to the surface of cytotoxic T lymphocytes via a reduction sensitive coupling. The activation status of the T cells and the liposome composition are shown to strongly influence the loading efficiency. Loading the cells with liposomes does not compromise T cell functionalities like proliferation and cytolytic function. Additionally, the triggered liposome release is demonstrated upon the addition of glutathione. Based on this optimization using liposomes as model NPs, a small interfering RNA (siRNA)-loaded NP was developed that can be coupled to the surface of CD8(+) T cells.

  19. 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.

  20. Theiler's virus infection induces a specific cytotoxic T lymphocyte response.

    PubMed

    Pena Rossi, C; McAllister, A; Fiette, L; Brahic, M

    1991-12-01

    Theiler's virus, a murine picornavirus, persists in the central nervous system of susceptible mouse strains and causes chronic inflammation and primary demyelination. One of the current hypotheses is that demyelination is, at least in part, mediated by virus-specific cytotoxic T lymphocytes (CTL). However, it is generally assumed that picornaviruses do not induce CTL. In point of fact, their existence has only been demonstrated for Coxsackievirus B-3. To determine whether Theiler's virus induces a CTL response, we generated a murine mastocytoma cell line stably transfected with the coding region of the genome of Theiler's virus strain DA. Using these cells as targets we showed that infected DBA/2 mice, a susceptible strain, produce cytotoxic T lymphocytes. The cytotoxic activity was Theiler's-virus specific. It was for the most part mediated by CD8+ T lymphocytes and H-2 restricted. This is the first demonstration that a specific CTL response is generated during Theiler's virus infection.

  1. 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

  2. Preparation, characterization, and cytotoxic effects of liposomal nanoparticles containing cisplatin: an in vitro study.

    PubMed

    Poy, Donya; Akbarzadeh, Azim; Ebrahimi Shahmabadi, Hasan; Ebrahimifar, Meysam; Farhangi, Ali; Farahnak Zarabi, Maryam; Akbari, Azam; Saffari, Zahra; Siami, Fatemeh

    2016-10-01

    Cisplatin is a chemotherapeutic agent used for treating various malignancies. The study aimed to prepare pegylated liposomal cisplatin and evaluate its efficacy against human breast cancer cell line MCF-7. Drug-loaded nanoparticles were synthesized by reverse phase evaporation technique. The study is highlighted by extensive characterization of nanoparticles in terms of nanoparticle morphology, type of drug entrapment, cisplatin retention capability, and cytotoxicity effects. The size, size distribution, and zeta potential of nanodrug were estimated 142 nm, 0.33, and -22 mV, respectively. Drug-loading efficiency was equal to 48% that occurred physically. Furthermore, high retention capability (39% of drug was released after 72 h) with significantly enhanced cytotoxicity of nanodrug (1.75 times more than the standard drug) confirmed the potency of liposomal nanoparticles as proper cisplatin carrier. PMID:27178305

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

    PubMed

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

    2016-03-03

    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.

  4. 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

  5. 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.

  6. 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.

  7. 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

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

    PubMed

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

    2013-06-01

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

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

    PubMed Central

    Varshosaz, Jaleh; Sadeghi Aliabadi, Hojatollah

    2014-01-01

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

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

    PubMed

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

    2015-06-01

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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. Pearling of lipid vesicles induced by nanoparticles.

    PubMed

    Yu, Yan; Granick, Steve

    2009-10-14

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

  18. 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

  19. 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.

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

    PubMed Central

    2014-01-01

    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. PMID:25411570

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

    PubMed

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

    2014-01-01

    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. PMID:25411570

  2. 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. PMID:26706516

  3. Bovine Serum Albumin Nanoparticles Containing Amphotericin B: Characterization, Cytotoxicity and In Vitro Antifungal Evaluation.

    PubMed

    Casa, Diani Meza; Karam, Thaysa Ksiaskiewcz; Alves, Aline de Cristo Soares; Zgoda, Aline Aparecida; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2015-12-01

    In this study, nanoparticles based on bovine serum albumin (BSA) containing amphotericin B (AmB) were obtained by the desolvation method and characterized with respect to size, size distribution, AmB encapsulation efficiency, AmB state of aggregation, and AmB in vitro release profile. After, the effect of nanoparticles on the cytotoxicity of human erythrocytes in vitro and efficacy over strains of Candida spp. were evaluated. The mean particle size was 156 nm and the AmB encapsulation efficiency was over 82%. The in vitro release profile revealed a sustained release of approximately 48% of AmB over 5 days. AmB is present in BSA nanoparticles as monomer. AmB-loaded nanoparticles showed very low index of hemolysis (less than 8%) in 72 h of assay compared to free AmB, which presented 100% of hemolysis in 2 h of incubation. The AmB-loaded BSA nanoparticles were as effective as free AmB against Candida albicans and Candida tropicalis, considering their sustained release profile. Thus, BSA nanoparticles are potential carriers for AmB, reducing its molecular aggregation and prolonging its release, resulting in lower cytotoxicity while maintaining its antifungal activity.

  4. 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.

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

    PubMed

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

    2013-06-01

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

  6. 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.

  7. 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. PMID:25816103

  8. 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

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

    PubMed Central

    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. PMID:26491285

  10. 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.

  11. 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. PMID:26491285

  12. 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.

  13. Cytotoxicity and antibacterial activity of gold-supported cerium oxide nanoparticles

    PubMed Central

    Suresh Babu, K; Anandkumar, M; Tsai, TY; Kao, TH; Stephen Inbaraj, B; Chen, BH

    2014-01-01

    Background Cerium oxide nanoparticles (CeO2) have been shown to be a novel therapeutic in many biomedical applications. Gold (Au) nanoparticles have also attracted widespread interest due to their chemical stability and unique optical properties. Thus, decorating Au on CeO2 nanoparticles would have potential for exploitation in the biomedical field. Methods In the present work, CeO2 nanoparticles synthesized by a chemical combustion method were supported with 3.5% Au (Au/CeO2) by a deposition-precipitation method. The as-synthesized Au, CeO2, and Au/CeO2 nanoparticles were evaluated for antibacterial activity and cytotoxicity in RAW 264.7 normal cells and A549 lung cancer cells. Results The as-synthesized nanoparticles were characterized by X-ray diffraction, scanning and transmission electron microscopy, and ultraviolet-visible measurements. The X-ray diffraction study confirmed the formation of cubic fluorite-structured CeO2 nanoparticles with a size of 10 nm. All synthesized nanoparticles were nontoxic towards RAW 264.7 cells at doses of 0–1,000 μM except for Au at >100 μM. For A549 cancer cells, Au/CeO2 had the highest inhibitory effect, followed by both Au and CeO2 which showed a similar effect at 500 and 1,000 μM. Initial binding of nanoparticles occurred through localized positively charged sites in A549 cells as shown by a shift in zeta potential from positive to negative after 24 hours of incubation. A dose-dependent elevation in reactive oxygen species indicated that the pro-oxidant activity of the nanoparticles was responsible for their cytotoxicity towards A549 cells. In addition, cellular uptake seen on transmission electron microscopic images indicated predominant localization of nanoparticles in the cytoplasmic matrix and mitochondrial damage due to oxidative stress. With regard to antibacterial activity, both types of nanoparticles had the strongest inhibitory effect on Bacillus subtilis in monoculture systems, followed by Salmonella

  14. 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

  15. 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.

  16. Supercooled smectic nanoparticles: influence of the matrix composition and in vitro cytotoxicity.

    PubMed

    Kuntsche, Judith; Koch, Michel H J; Fahr, Alfred; Bunjes, Heike

    2009-10-01

    Cholesteryl nonanoate (CN), myristate (CM), palmitate (CP) and oleate (CO) alone or in combination were evaluated as matrix lipids for the preparation of supercooled smectic nanoparticles with a high stability against recrystallization during storage. The phase behavior of the cholesterol esters in the bulk was studied by polarizing light microscopy, differential scanning calorimetry (DSC) and small angle X-ray scattering (SAXS). Colloidal dispersions with pure and mixed cholesterol ester matrices were prepared by high-pressure melt homogenization and characterized by photon correlation spectroscopy, laser diffraction combined with polarizing intensity differential scattering, DSC and SAXS. The morphology of selected formulations was studied by freeze-fracture electron microscopy. All smectic nanoparticles with a mixed cholesterol ester matrix were stable against recrystallization when stored at room temperature. Nanoparticles with a pure CN and mixed CM/CN matrix with a high fraction of CN (60% of the whole lipid matrix) could even be stored at 4 degrees C for at least 18 months without any recrystallization. As smectic nanoparticles are studied especially with regard to parenteral administration of lipophilic drugs, the cytotoxicity of selected formulations was compared with that of a clinically used colloidal fat emulsion (Lipofundin MCT) in the murine fibroblast cell line L929 using the sulforhodamine B assay. The supercooled smectic nanoparticle formulations display a good overall cell compatibility although in some cases their cytotoxicity was slightly higher than that of Lipofundin MCT.

  17. Fabrication, characterization and cytotoxicity studies of ionically cross-linked docetaxel loaded chitosan nanoparticles.

    PubMed

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

    2016-02-10

    The present investigation aimed at the fabrication and characterization of ionically cross-linked docetaxel (DTX) loaded chitosan nanoparticles (DTX-CH-NP) using ionic gelation technique with sodium tripolyphosphate (TPP) as the cross-linking agent. The formulated nanoparticles were characterized in terms of particle size, drug entrapment efficiency (EE), scanning electron microscopy (SEM), in vitro release and cytotoxicity studies. Formulation factors (chitosan, TPP and drug concentration) were examined systematically for their effects on size of the nanoparticles. The average size of the nanoparticles was observed to be in the range of 159.2 ± 3.31 to 220.7 ± 2.23 nm with 78-92% encapsulation efficiency (EE). The in vitro cytotoxicity studies on breast cancer cell lines (MDA-MB-231) revealed the advantages of DTX-CH-NP over pure DTX with approximately 85% cell viability reduction. The results indicate that systematic modulation of the surface charge and particle size of ionically cross-linked nanoparticles can be readily achieved with the right control of critical processing parameters. Thus, DTX-CH-NP presents a promising delivery alternative for breast cancer treatment.

  18. Evaluation of quantum dot cytotoxicity: interpretation of nanoparticle concentrations versus intracellular nanoparticle numbers.

    PubMed

    Manshian, Bella B; Abdelmonem, Abuelmagd M; Kantner, Karsten; Pelaz, Beatriz; Klapper, Markus; Nardi Tironi, Catarina; Parak, Wolfgang J; Himmelreich, Uwe; Soenen, Stefaan J

    2016-11-01

    While substantial progress has been achieved in the design of more biocompatible nanoparticles (NP), detailed data are required on the precise interactions of NPs and their environment for more reliable interpretation of toxicity results. Therefore, this study aims to investigate the interaction of two quantum dots (QDs) of the same core material CdSe/ZnS coated with two different amphiphilic polymers, with two well-established mammalian cell lines representing possible sites of QD accumulation. Results are linked to either extracellular QD concentrations (given dose) or cellular QD levels (number of internalized particles). In this study, QD internalization, effects on cellular homeostasis, and consequent inflammatory and cytoskeletal alterations caused by these QDs were explored. Fluorescence imaging techniques, including; image-based flow cytometry, confocal microscopy and high-content imaging with the InCell analyzer were used in a multiparametric methodology to evaluate cell viability, induction of oxidative stress, mitochondrial health, cell cytoskeletal functionality and changes in cellular morphology. Gene expression arrays were also carried out on 168 key genes involved in the cytoskeletal architecture and inflammatory pathway accompanied with the analysis of focal adhesions as key markers for actin-mediated signaling. Our results show distinct differences between the PMA and PTMAEMA-stat-PLMA coated QDs, which could mainly be attributed to differences in their cellular uptake levels. The toxicity profiles of both QD types changed drastically depending on whether effects were expressed in terms of given dose or internalized particles. Both QDs triggered alterations to important but different genes, most remarkably the up-regulation of tumor suppression and necrosis genes and the down regulation of angiogenesis and metastasis genes at sub-cytotoxic concentrations of these QDs. PMID:27416974

  19. Fe3O4-nanoparticles within porous silicon: Magnetic and cytotoxicity characterization

    NASA Astrophysics Data System (ADS)

    Granitzer, P.; Rumpf, K.; Tian, Y.; Akkaraju, G.; Coffer, J.; Poelt, P.; Reissner, M.

    2013-05-01

    The magnetic properties of porous silicon/Fe3O4 composites are investigated with respect to the adjustability of the blocking temperature along with an evaluation of any size-dependent changes in cytocompatibility. Fe3O4-nanoparticles have been infiltrated within mesoporous silicon, resulting in a system with tunable magnetic properties due to the matrix-morphology, the loading of the nanoparticles, and their size. In order to provide basic information regarding its suitability as a therapeutic platform, the cytotoxicity of these composites have been investigated by a trypan blue exclusion assay with respect to human embryonic kidney 293 cells, and the results compared with cell-only and known cytotoxic controls.

  20. Daunomycin-loaded superparamagnetic iron oxide nanoparticles: Preparation, magnetic targeting, cell cytotoxicity, and protein delivery research.

    PubMed

    Liu, Min-Chao; Jin, Shu-Fang; Zheng, Min; Wang, Yan; Zhao, Peng-Liang; Tang, Ding-Tong; Chen, Jiong; Lin, Jia-Qi; Wang, Xia-Hong; Zhao, Ping

    2016-08-01

    The clinical use of daunomycin is restricted by dose-dependent toxicity and low specificity against cancer cells. In the present study, modified superparamagnetic iron oxide nanoparticles were employed to load daunomycin and the drug-loaded nanospheres exhibited satisfactory size and smart pH-responsive release. The cellular uptake efficiency, targeted cell accumulation, and cell cytotoxicity experimental results proved that the superparamagnetic iron oxide nanoparticle-loading process brings high drug targeting without decreasing the cytotoxicity of daunomycin. Moreover, a new concern for the evaluation of nanophase drug delivery's effects was considered, with monitoring the interactions between human serum albumin and the drug-loaded nanospheres. Results from the multispectroscopic techniques and molecular modeling calculation elucidate that the drug delivery has detectable deleterious effects on the frame conformation of protein, which may affect its physiological function. PMID:27288463

  1. 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

  2. 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

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

    PubMed

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

    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.

  4. Use of Synchrotron Radiation-Analytical Techniques To Reveal Chemical Origin of Silver-Nanoparticle Cytotoxicity.

    PubMed

    Wang, Liming; Zhang, Tianlu; Li, Panyun; Huang, Wanxia; Tang, Jinglong; Wang, Pengyang; Liu, Jing; Yuan, Qingxi; Bai, Ru; Li, Bai; Zhang, Kai; Zhao, Yuliang; Chen, Chunying

    2015-06-23

    To predict potential medical value or toxicity of nanoparticles (NPs), it is necessary to understand the chemical transformation during intracellular processes of NPs. However, it is a grand challenge to capture a high-resolution image of metallic NPs in a single cell and the chemical information on intracellular NPs. Here, by integrating synchrotron radiation-beam transmission X-ray microscopy (SR-TXM) and SR-X-ray absorption near edge structure (SR-XANES) spectroscopy, we successfully capture the 3D distribution of silver NPs (AgNPs) inside a single human monocyte (THP-1), associated with the chemical transformation of silver. The results reveal that the cytotoxicity of AgNPs is largely due to the chemical transformation of particulate silver from elemental silver (Ag(0))n, to Ag(+) ions and Ag-O-, then Ag-S- species. These results provide direct evidence in the long-lasting debate on whether the nanoscale or the ionic form dominates the cytotoxicity of silver nanoparticles. Further, the present approach provides an integrated strategy capable of exploring the chemical origins of cytotoxicity in metallic nanoparticles. PMID:25994391

  5. Internalization and cytotoxicity effects of carbon-encapsulated iron nanoparticles in murine endothelial cells: Studies on internal dosages due to loaded mass agglomerates.

    PubMed

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

    2016-08-01

    Carbon-encapsulated iron nanoparticles (CEINs) qualified as metal-inorganic hybrid nanomaterials offer a potential scope for an increasing number of biomedical applications. In this study, we have focused on the investigation of cellular fate and resulting cytotoxic effects of CEINs synthesized using a carbon arc route and studied in murine endothelial (HECa-10) cells. The CEIN samples were characterized as pristine (the mean diameter between 47 and 56nm) and hydrodynamic (the mean diameter between 270 and 460nm) forms and tested using a battery of methods to determine the cell internalization extent and cytotoxicity effects upon to the exposures (0.0001-100μg/ml) in HECa-10 cells. Our studies evidenced that the incubation with CEINs for 24h is accompanied with substantial changes of Zeta potential in cells which can be considered as a key factor for affecting the membrane transport, cellular distribution and cytotoxicity of these nanoparticles. The results demonstrate that CEINs have entered the endothelial cell through the endocytic pathway rather than by passive diffusion and they were mainly loaded as agglomerates on the cell membrane and throughout the cytoplasm, mitochondria and nucleus. The studies show that CEINs induce the mitochondrial and cell membrane cytotoxicities in a dose-dependent manner resulting from the internal dosages due to CEIN agglomerates. Our results highlight the importance of the physicochemical characterization of CEINs in studying the magnetic nanoparticle-endothelial cell interactions because the CEIN mass agglomerates can sediment more or less rapidly in culture models. PMID:27107485

  6. Cytotoxicity, intracellular localization and exocytosis of citrate capped and PEG functionalized gold nanoparticles in human hepatocyte and kidney cells.

    PubMed

    Tlotleng, Nonhlanhla; Vetten, Melissa A; Keter, Frankline K; Skepu, Amanda; Tshikhudo, Robert; Gulumian, Mary

    2016-08-01

    Surface-modified gold nanoparticles (AuNPs) are nanomaterials that hold promise in drug delivery applications. In this study, the cytotoxicity, uptake, intracellular localization, and the exocytosis of citrate-stabilized (Cit-AuNP) and polyethylene glycol (PEG)-modified gold nanoparticles with the carboxyl (COOH) terminal functional group were assessed in human embryonic kidney (HEK 293) and the human caucasian hepatocytes carcinoma (Hep G2) cell systems, representing two major accumulation sites for AuNPs. The zeta (ζ)-potential measurements confirmed the negative surface charge of the AuNPs in water and in cell growth medium. The transmission electron microscopy confirmed the size and morphology of the AuNPs. Both types of AuNPs were shown to induce cytotoxic effects in cells. The Hep G2 cells were more sensitive cell type, with the COOH-PEG-AuNPs inducing the highest toxicity at higher concentrations. Dark field microscopy and TEM images revealed that the AuNPs were internalized in cells, mostly as agglomerates. TEM micrographs further revealed that the AuNPs were confined as agglomerates inside vesicle-like compartments, likely to be endosomal and lysosomal structures as well as in the cytosol, mostly as individual particles. The AuNPs were shown to remain in cellular compartments for up to 3 weeks, but thereafter, clearance of the gold nanoparticles from the cells by exocytosis was evident. The results presented in this study may therefore give an indication on the fate of AuNPs on long-term exposure to cells and may also assist in safety evaluation of AuNPs. PMID:27184667

  7. 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. PMID:25663373

  8. 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.

  9. Protective effects of rilmenidine and AGN 192403 on oxidative cytotoxicity and mitochondrial inhibitor-induced cytotoxicity in astrocytes.

    PubMed

    Choi, Dong-Hee; Kim, Dong-Hoon; Park, Yun-Gyu; Chun, Boe-Gwun; Choi, Sang-Hyun

    2002-11-15

    Oxidative stress and mitochondrial dysfunction are important aspects of pathogenesis, particularly in the brain, which is highly dependent on oxygen, and the protection of astrocytes is essential for neuroprotection. In this context, imidazoline drugs have been reported to be neuroprotective. Our recent study showed that imidazoline drugs, including guanabenz, inhibit the naphthazarin-induced oxidative cytotoxicity associated with lysosomal destabilization. We now report on a study into the protective effects of rilmenidine and AGN 192403, which have affinity for imidazoline-1 receptors, on the cytotoxicity induced by naphthazarin and inhibitors of mitochondrial respiration in astrocytes. Cytotoxicity was measured grossly by LDH release and by measuring changes in lysosomal membrane stability and features of mitochondrial membrane permeabilization. Naphthazarin-induced cytotoxicity was evidenced by the ordered development of lysosomal acridine orange relocation, decrease in mitochondrial potential, cytochrome c release, and caspase-9 activation, and was inhibited by guanabenz, rilmenidine, and AGN 192403. Antimycin A and rotenone induced mitochondrial dysfunction primarily, and their cytotoxicities were inhibited only by AGN 192403. Rilmenidine and guanabenz may have a lysosomal stabilizing effect, which underlies their protective effects. AGN 192403 might affect the mitochondrial cell death cascades, and had a novel protective effect on the cytotoxicity associated with mitochondrial dysfunction.

  10. [Role of Monocarboxylate Transporter in Statin-induced Cytotoxicity].

    PubMed

    Kobayashi, Masaki

    2015-01-01

    Although exercise and drug therapy are important to prevent progression of arteriosclerotic disease, exercise leads to an increase in muscular disorder induced by HMG-CoA reductase inhibitors (statins). Elucidation of this mechanism is needed to prevent the occurrence of muscular disorders. Since exercise induces expression of monocarboxylate transporter (MCT) 4, we focused on the association between MCT4 function and statin-induced muscle injury. First, we examined the transport of L-lactate via MCT4 using MCT4 cRNA-injected Xenopus laevis oocytes. L-lactate uptake by MCT4-expressing oocytes was markedly reduced by alkalizing the buffer pH and saturated at higher L-lactate concentrations. On the other hand, AMP-activated protein kinase (AMPK) and protein kinase C (PKC) are activated by exercise. We next examined whether AMPK and PKC activation affects the expression and function of MCT4 in rat skeletal muscle and RD cells as an in vitro skeletal muscle model. AMPK and PKC activation increased MCT4 expression level and lactate efflux by MCT4. Finally, we examined the association between MCT4 function and statin-induced cytotoxicity. Statins inhibited transport of L-lactate via MCT4 in a concentration-dependent manner. Statin-induced cytotoxicity was associated with intracellular acidification and caspase-3/7 activation. On the other hand, bicarbonate suppressed statin-induced pH alteration, caspase activation, and morphological change. The results suggest that statin-induced muscle injury exacerbated by exercise is associated with intracellular acidification and that the effects of statins on L-lactate transport are mediated by MCT4.

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

    PubMed

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

    2015-03-01

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

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

    PubMed

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

    2015-03-01

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

  13. 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%.

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

    PubMed

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

    2012-12-17

    Increasing utilization of engineered nanoparticles in the field of electronics and biomedical applications demands an assessment of risk associated with deliberate or accidental exposure. Metal based nanoparticles are potentially most important of all the nanoparticles in terms of health risks. Microporous alumino-silicates and pure silicates named as zeolites and zeo-type materials with variety of structures, chemical compositions, particle sizes and morphologies have a significant number of industrial uses such as in catalysis, sorption and ion-exchange processes. In particular, the nanosized particles due to their unique properties are used in hybrid organic-inorganic materials for photography, photonics, electronics, labeling, imaging, and sensing. The aim of the current study is to investigate pure silica MFI-type zeolites nanoparticles with sizes of 50nm and 100nm (samples MFI-50 and MFI-100) under suspended conditions and their toxicological effects on human lung alveolar (A549) cells under in vitro conditions. Live cell imaging showed that the nanoparticles precipitated from the colloidal suspension of cell culture media as large agglomerates, coming in contact with the cell surface through sedimentation. A cellular proliferative capacity test showed the zeolite nanoparticles to exhibit no significant cytotoxicity below a concentration of 100μg/ml. However, both the MFI-50 and MFI-100 nanoparticles induced high intracellular reactive oxygen species (ROS) generation and elevated mitochondrial membrane potential in the A549 cells over the measured time period of 12h and at concentrations up to ≤50μg/ml. DNA fragmentation analysis using the comet assay showed that the MFI-50 and MFI-100 nanoparticles cause genotoxicity in a concentration dependent manner. Furthermore, the rate at which maximum genomic damage was caused by MFI-100 nanoparticles in the A549 cells was found to be high as compared to the MFI-50 nanoparticles. However, the damage caused by the

  15. Fipronil induces CYP isoforms and cytotoxicity in human hepatocytes.

    PubMed

    Das, Parikshit C; Cao, Yan; Cherrington, Nathan; Hodgson, Ernest; Rose, Randy L

    2006-12-15

    Recent studies have demonstrated the potential of pesticides to either inhibit or induce xenobiotic metabolizing enzymes in humans. Exposure of human hepatocytes to doses of fipronil (5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl) sulfinyl]-1H-pyrazole-3-carbonitrile) ranging from 0.1 to 25 microM resulted in a dose dependent increase in CYP1A1 mRNA expression (3.5 to approximately 55-fold) as measured by the branched DNA assay. In a similar manner, CYP3A4 mRNA expression was also induced (10-30-fold), although at the higher doses induction returned to near control levels. CYP2B6 and 3A5 were also induced by fipronil, although at lower levels (2-3-fold). Confirmation of bDNA results were sought through western blotting and/or enzyme activity assays. Western blots using CYP3A4 antibody demonstrated a dose responsive increase from 0.5 to 1 microM followed by decreasing responses at higher concentrations. Similar increases and decreases were observed in CYP3A4-specific activity levels as measured using 6beta-hydroxytestosterone formation following incubation with testosterone. Likewise, activity levels for a CYP1A1-specific substrate, luciferin CEE, demonstrated that CYP1A1 enzyme activities were maximally induced by 1 microM fipronil followed by dramatically declining activity measurements at 10 and 25 microM. Cytotoxic effects of fipronil and fipronil sulfone were examined using the adenylate kinase and the trypan blue exclusion assays in HepG2 cells and human hepatocytes. The results indicate both that HepG2 cells and primary human hepatocytes are sensitive to the cytotoxic effects of fipronil. The maximum induction of adenylate kinase was ca. 3-fold greater than the respective controls in HepG2 and 6-10-fold in the case of primary hepatocytes. A significant time- and dose-dependent induction of adenylate kinase activity in HepG2 cells was noted from 0.1 to 12.5 microM fipronil followed by decreasing activities at 25 and 50 microM. For

  16. 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

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

    PubMed

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

    2015-08-28

    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.

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

    Post-operatory infections in orthopedic surgeries pose a significant risk. The common approach of using antibiotics, both parenterally or embedded in bone cement (when this is employed during surgery) faces the challenge of the rising population of pathogens exhibiting resistance properties against one or more of these compounds; therefore, novel approaches need to be developed. Silver nanoparticles appear to be an exciting prospect because of their antimicrobial activity and safety at the levels used in medical applications. In this paper, a novel type of silver nanoparticles capped with tiopronin is presented. Two ratios of reagents during synthesis were tested and the effect on the nanoparticles investigated through TEM, TGA, and UV-Vis spectroscopy. Once encapsulated in bone cement, only the nanoparticles with the highest amount of inorganic fraction conferred antimicrobial activity against methicillin resistant Staphylococcus aureus (MRSA) at concentrations as low as 0.1% w/w. No other characteristics of the bone cement, such as cytotoxicity or mechanical properties, were affected by the presence of the nanoparticles. Our work presents a new type of silver nanoparticles and demonstrates that they can be embedded in bone cement to prevent infections once the synthetic conditions are tailored for such applications. PMID:23818779

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-05-01

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

  2. 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.

  3. 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. PMID:26115719

  4. 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.

  5. 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.

  6. Dual effects of β-cyclodextrin-stabilised silver nanoparticles: enhanced biofilm inhibition and reduced cytotoxicity.

    PubMed

    Jaiswal, Swarna; Bhattacharya, Kunal; McHale, Patrick; Duffy, Brendan

    2015-01-01

    The composition and mode of synthesis of nanoparticles (NPs) can affect interaction with bacterial and human cells differently. The present work describes the ability of β-cyclodextrin (β-CD) capped silver nanoparticles (AgNPs) to inhibit biofilm growth and reduce cytotoxicity. Biofilm formation of Staphylococcus epidermidis CSF 41498 was quantified by a crystal violet assay in the presence of native and capped AgNPs (Ag-10CD and Ag-20CD), and the morphology of the biofilm was observed by scanning electron microscope. The cytotoxicity of the AgNPs against HaCat cells was determined by measuring the increase in intracellular reactive oxygen species and change in mitochondrial membrane potential (ΔΨm). Results indicated that capping AgNPs with β-CD improved their efficacy against S. epidermidis CSF 41498, reduced biofilm formation and their cytotoxicity. The study concluded that β-CD is an effective capping and stabilising agent that reduces toxicity of AgNPs against the mammalian cell while enhancing their antibiofilm activity. PMID:25596861

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

    PubMed Central

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

    2013-01-01

    Owing to their radical scavenging and UV-filtering properties, ceria nanoparticles (CeO2-NPs) are currently used for various applications, including as catalysts in diesel particulate filters. Because of their ability to filter UV light, CeO2-NPs have garnered significant interest in the medical field and, consequently, are poised for use in various applications. The aim of this work was to investigate the effects of short-term (24 h) and long-term (10 days) CeO2-NP exposure to A549, CaCo2 and HepG2 cell lines. Cytotoxicity assays tested CeO2-NPs over a concentration range of 0.5 μg/mL to 5000 μg/mL, whereas genotoxicity assays tested CeO2-NPs over a concentration range of 0.5 μg/mL to 5000 μg/mL. In vitro assays showed almost no short-term exposure toxicity on any of the tested cell lines. Conversely, long-term CeO2-NP exposure proved toxic for all tested cell lines. NP genotoxicity was detectable even at 24-h exposure. HepG2 was the most sensitive cell line overall; however, the A549 line was most sensitive to the lowest concentration tested. Moreover, the results confirmed the ceria nanoparticles’ capacity to protect cells when they are exposed to well-known oxidants such as H2O2. A Comet assay was performed in the presence of both H2O2 and CeO2-NPs. When hydrogen peroxide was maintained at 25 μM, NPs at 0.5 μg/mL, 50 μg/mL, and 500 μg/mL protected the cells from oxidative damage. Thus, the NPs prevented H2O2-induced genotoxic damage. PMID:23377016

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

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

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

  10. 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.

  11. 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.

  12. 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.

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

    PubMed

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

    2014-09-21

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

  14. 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. PMID:25092048

  15. Poly(L-lactide) Nanoparticles Reduce Amphotericin B Cytotoxicity and Maintain Its In Vitro Antifungal Activity.

    PubMed

    Casa, Diani Meza; Carraro, Talita Cristina Moreira Moraes; de Camargo, Luciana Erzinger Alves; Dalmolin, Luciana Facco; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2015-01-01

    In this study, poly(L-lactide) (PLA) nanoparticles containing amphotericin B (AmB) were developed, and the in vitro cytotoxicity to human erythrocytes and efficacy on strains of Candida spp. were evaluated. The nanoparticles were prepared using an emulsion/solvent evaporation method and were characterized with respect to size, size distribution, AmB encapsulation efficiency, AmB state of aggregation, and AmB in vitro release profile. The mean particle size was 225 nm, and the AmB encapsulation efficiency was over 69%. The AmB in vitro release profile revealed a burst effect within the first 24 h, which released approximately 10% of AmB, followed by a sustained release of approximately 30% of AmB over 30 days. The AmB nanoparticles presented a very low index of hemolysis compared to free AmB, which lysed more than 80% of erythrocytes in the first 2 h of incubation. The AmB-loaded PLA nanoparticles were as effective as free AmB against strains of Candida spp., considering their sustained release profile. Thus, PLA nanoparticles can deliver AmB with reduced toxicity while maintaining its antifungal activity.

  16. 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.

  17. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  19. 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

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

    PubMed Central

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

    1983-01-01

    We have recently reported the in vivo modulation of resistance to experimental Candida albicans infection by cyclophosphamide (150 mg/kg intraperitoneally) in mice and have shown that increased resistance to the microbial challenge occurs 12 to 21 days after treatment with the drug (Bistoni et al., Infect. Immun. 40: 46-55, 1983). The event is accompanied by the appearance of a highly candidacidal cell population in the spleen and the activation of a subpopulation of natural cytotoxic effectors reactive in vitro against YAC-1 tumor cells. We now provide evidence that these anti-YAC-1 cytotoxic effectors are clearly distinct from the cyclophosphamide-induced candidacidal effectors, which seem to belong to a macrophage-monocyte lineage. The enhanced cytotoxic activity induced by cyclophosphamide was not restricted to C. albicans but was also exerted against a panel of Candida strains. PMID:6352489

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

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

    PubMed

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

    2011-03-01

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

  4. Aqueous synthesis of gold nanoparticles and their cytotoxicity in human dermal fibroblasts-fetal.

    PubMed

    Qu, Yinghua; Lü, Xiaoying

    2009-04-01

    The unique physicochemical properties of nanoparticles make them promising substrates for application in the medical area. As there are no safety regulations yet, concerns about future health problems are rising. This study was conducted to prepare approximately 20 nm gold nanoparticles (GNPs) by a chemical reduction method and evaluate their cytotoxicity by MTT assay using human dermal fibroblasts-fetal (HDF-f). 10-50 nm GNPs could be obtained in redistilled water by varying the amount of sodium citrate. MTT results showed that approximately 20 nm GNPs did not cause cell death at a maximum concentration of 300 microM but affected the morphology of HDF-f when their concentration increased. PMID:19258699

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

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  6. 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.

  7. 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.

  8. 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.

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

    PubMed

    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

  10. 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

  11. 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.

  12. Amphiphilic poly-N-vynilpyrrolidone nanoparticles: Cytotoxicity and acute toxicity study.

    PubMed

    Kuskov, A N; Kulikov, P P; Shtilman, M I; Rakitskii, V N; Tsatsakis, A M

    2016-10-01

    The aim of the present study was to evaluate the cytotoxicity against MCF-7 cells and acute intraperitoneal toxicity of amphiphilic poly-N-vinylpyrrolidone nanoparticles to confirm possibility of their application for creation of novel drug delivery systems. The effect of cellular uptake of polymeric nanoparticles on human cancer cell line MCF-7 cells was investigated by MTT assay. MTT analysis showed that tested amphiphilic polymers were essentially non-toxic. In acute toxicity studies, LD50 and other toxicity indexes were evaluated, under which no deaths or treatment related complications were observed even in high concentration treatment for 14 days of experiment. For histological analysis, organs of the animals were weighed and examined. No animal died during the study and no significant changes have been observed regarding body weight, feed consumption, organ weight or histological data. Obtained results show that amphiphilic poly-N-vinylpyrrolidone nanoparticles possessed no toxicity against cells and in animals after intraperitoneal administration. Thus, amphiphilic PVP nanoparticles demonstrate high potential as carriers for novel high-effective drug delivery systems. PMID:27539747

  13. Amphiphilic poly-N-vynilpyrrolidone nanoparticles: Cytotoxicity and acute toxicity study.

    PubMed

    Kuskov, A N; Kulikov, P P; Shtilman, M I; Rakitskii, V N; Tsatsakis, A M

    2016-10-01

    The aim of the present study was to evaluate the cytotoxicity against MCF-7 cells and acute intraperitoneal toxicity of amphiphilic poly-N-vinylpyrrolidone nanoparticles to confirm possibility of their application for creation of novel drug delivery systems. The effect of cellular uptake of polymeric nanoparticles on human cancer cell line MCF-7 cells was investigated by MTT assay. MTT analysis showed that tested amphiphilic polymers were essentially non-toxic. In acute toxicity studies, LD50 and other toxicity indexes were evaluated, under which no deaths or treatment related complications were observed even in high concentration treatment for 14 days of experiment. For histological analysis, organs of the animals were weighed and examined. No animal died during the study and no significant changes have been observed regarding body weight, feed consumption, organ weight or histological data. Obtained results show that amphiphilic poly-N-vinylpyrrolidone nanoparticles possessed no toxicity against cells and in animals after intraperitoneal administration. Thus, amphiphilic PVP nanoparticles demonstrate high potential as carriers for novel high-effective drug delivery systems.

  14. 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

  15. Encapsulation of biophenolic phytochemical EGCG within lipid nanoparticles enhances its stability and cytotoxicity against cancer.

    PubMed

    Radhakrishnan, Rasika; Kulhari, Hitesh; Pooja, Deep; Gudem, Sagarika; Bhargava, Suresh; Shukla, Ravi; Sistla, Ramakrishna

    2016-06-01

    Epigallocatechin gallate (EGCG), a green tea polyphenolic catechin, has been known to possess a variety of beneficial biological activities. The in-vitro anti-cancer activity of EGCG is well documented. However, the use of EGCG in modern therapeutics is limited due to its poor bioavailability and limited stability at physiological pH. In this study, we have investigated the stability profiles of EGCG in aqueous solutions using UV-vis spectroscopy. Stability results showed very low stability profile of EGCG at physiological pH with rapid degradation under alkaline conditions. Therefore, we have encapsulated EGCG in solid lipid nanoparticles to increase its stability and evaluated for anticancer activity. The lipid core of nanoparticles not only provides an additional structural reinforcement to the nanoparticle assembly, but also makes it biologically compatible, thereby enabling a stealth vehicle for efficient drug delivery. EGCG loaded nanoparticles (EGCG-SLN) were characterized using dynamic light scattering, Fourier transform infrared spectroscopy and differential scanning calorimetry. EGCG and EGCG-SLN were evaluated for their anticancer activities by cellular proliferation. The cytotoxicity of EGCG-SLN was found to be 8.1 times higher against MDA-MB 231 human breast cancer cells and 3.8 times higher against DU-145 human prostate cancer cells than that of the pure EGCG. PMID:27234272

  16. 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.

  17. 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. PMID:27270448

  18. In vitro cytotoxic evaluation of MgO nanoparticles and their effect on the expression of ROS genes.

    PubMed

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

    2015-01-01

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

  19. In vitro cytotoxic evaluation of MgO nanoparticles and their effect on the expression of ROS genes.

    PubMed

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

    2015-04-03

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

  20. 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

    2013-06-01

    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 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

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

    PubMed

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

    2016-01-29

    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. PMID:26656836

  2. 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.

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

    PubMed

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

    2016-01-29

    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.

  4. Cannabidiol induces intracellular calcium elevation and cytotoxicity in oligodendrocytes.

    PubMed

    Mato, Susana; Victoria Sánchez-Gómez, María; Matute, Carlos

    2010-11-01

    Heavy marijuana use has been linked to white matter histological alterations. However, the impact of cannabis constituents on oligodendroglial pathophysiology remains poorly understood. Here, we investigated the in vitro effects of cannabidiol, the main nonpsychoactive marijuana component, on oligodendrocytes. Exposure to cannabidiol induced an intracellular Ca(2+) rise in optic nerve oligodendrocytes that was not primarily mediated by entry from the extracellular space, nor by interactions with ryanodine or IP(3) receptors. Application of the mitochondrial protonophore carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP; 1 μM) completely prevented subsequent cannabidiol-induced Ca(2+) responses. Conversely, the increase in cytosolic Ca(2+) levels elicited by FCCP was reduced after previous exposure to cannabidiol, further suggesting that the mitochondria acts as the source of cannabidiol-evoked Ca(2+) rise in oligodendrocytes. n addition, brief exposure to cannabidiol (100 nM-10 μM) led to a concentration-dependent decrease of oligodendroglial viability that was not prevented by antagonists of CB(1), CB(2), vanilloid, A(2A) or PPARγ receptors, but was instead reduced in the absence of extracellular Ca(2+). The oligodendrotoxic effect of cannabidiol was partially blocked by inhibitors of caspase-3, -8 and -9, PARP-1 and calpains, suggesting the activation of caspase-dependent and -independent death pathways. Cannabidiol also elicited a concentration-dependent alteration of mitochondrial membrane potential, and an increase in reactive oxygen species (ROS) that was reduced in the absence of extracellular Ca(2+). Finally, cannabidiol-induced cytotoxicity was partially prevented by the ROS scavenger trolox. Together, these results suggest that cannabidiol causes intracellular Ca(2+) dysregulation which can lead to oligodendrocytes demise.

  5. Cytotoxicity of silica nanoparticles through exocytosis of von Willebrand factor and necrotic cell death in primary human endothelial cells.

    PubMed

    Bauer, Alexander T; Strozyk, Elwira A; Gorzelanny, Christian; Westerhausen, Christoph; Desch, Anna; Schneider, Matthias F; Schneider, Stefan W

    2011-11-01

    Nanoparticle-induced endothelial cell (EC) dysfunction, due to the induction of inflammation and/or the activation of the coagulation system, is associated with pulmonary and ischemic cardiovascular diseases. Although it is contigent on several mechanisms, involving formation of reactive oxygen species and inflammatory cytokines such as interleukin (IL)-6 and 8, the involvement of the coagulation system is not well understood. The results of toxicity assays using the tetrazolium reduction (MTT) and lactate dehydrogenase (LDH) release showed that silica NP-induced cytotoxicity depends on the size and the dose of applied NP. Moreover, propidium iodide (PI) stainings and caspase 3/7 assays identified increased necrosis in ECs. Exposing human umbilical vein endothelial cells (HUVECs) to SiO(2) NP with diameters of 304 nm and 310 nm led to significant increase of Weibel-Palade body (WPB) exocytosis, associated with the release of von Willebrand factor (VWF) and the formation of ultralarge fibers (ULVWF). High resolution microscopy techniques revealed that internalization and perinuclear localization of perylene-labeled NP with a size of 310 nm affect not only viability, but also cell migration and proliferation. In conclusion, our data indicate that NP-induced activation and dysfunction of ECs is reflected by release of VWF and necrotic cell death.

  6. 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

  7. Spectral Induced Polarization of Goethite Nanoparticles

    NASA Astrophysics Data System (ADS)

    Huisman, J. A.; Moradi, S.; Zimmermann, E.; Bosch, J.; Vereecken, H.

    2014-12-01

    Goethite nanoparticles are being considered as a tool to enhance in situ remediation of aquifers contaminated with aromatic hydrocarbons. Injection of goethite nanoparticles into the plume is expected to enhance microbial iron reduction and associated beneficial oxidation of hydrocarbons in a cost-effective manner. Amongst others, current challenges associated with this novel approach are the monitoring of nanoparticle delivery and the nanoparticle and contaminant concentration dynamics over time. Obviously, non-invasive monitoring of these properties would be highly useful. In this study, we aim to evaluate whether spectral induced polarization (SIP) measurements of the complex electrical conductivity are suitable for such non-invasive characterization. In principle, this is not unreasonable because the electrical double layers of the goethite nanoparticles are expected to affect electrical polarization and thus the imaginary part of the complex electrical conductivity. In a first set of measurements, we determined the complex electrical conductivity of goethite nanoparticle suspensions with different nanoparticle concentrations, pH, and ionic strength in the mHz to kHz frequency range. In a second set of measurements, mixtures of sand and different concentrations of goethite nanoparticles and variable pH and ionic strengths were analyzed. Finally, flow experiments were monitored with SIP in a 1-m long laboratory column to investigate dynamic effects associated with goethite nanoparticle injection and delivery. The results showed that the imaginary part of the electrical conductivity was only affected in the high frequency range (Hz - kHz), which is expected from the small size of the goethite nanoparticles. Overall, we found that the goethite nanoparticles are associated with a small increase in the imaginary electrical conductivity at 1 kHz that can be measured in situ using recently improved borehole electrical impedance tomography measurement equipment that

  8. 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.

  9. 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

  10. Increased Nuclear Thioredoxin-1 Potentiates Cadmium-Induced Cytotoxicity

    PubMed Central

    Jones, Dean P.

    2013-01-01

    Cadmium (Cd) is a widely dispersed environmental agent that causes oxidative toxicity through mechanisms that are sensitive to thioredoxin-1 (Trx1). Trx1 is a cytoplasmic protein that translocates to nuclei during oxidative stress. Recent research shows that interaction of Trx1 with actin plays a critical role in cell survival and that increased nuclear Trx-1 potentiates proinflammatory signaling and death in cell and mouse models. These observations indicate that oxidative toxicity caused by low-dose Cd could involve disruption of actin-Trx1 interaction, nuclear Trx1 translocation, and potentiation of proinflammatory cell death mechanisms. In this study, we investigated the role of nuclei-localized Trx1 in Cd-induced inflammation and cytotoxicity using in vitro and in vivo models. The results show that Cd stimulated nuclear translocation of Trx1 and p65 of NF-κB. Elevation of Trx1 in nuclei in in vitro cells and kidney of transgenic mice potentiated Cd-stimulated NF-κB activation and cell death. Cd-stimulated Trx1 nuclear translocation and NF-κB activation were inhibited by cytochalasin D, an inhibitor of actin polymerization, suggesting that actin regulates Trx1 nuclear translocation and NF-κB activation by Cd. A nuclear-targeted dominant negative form of Trx1 blocked Cd-stimulated NF-κB activation and decreased cell death. Addition of zinc, known to antagonize Cd toxicity by increasing metallothionein, had no effect on Cd-stimulated nuclear translocation of Trx1 and NF-κB activation. Taken together, the results show that nuclear translocation and accumulation of redox-active Trx1 in nuclei play an important role in Cd-induced inflammation and cell death. PMID:22961094

  11. 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

  12. 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

  13. 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

  14. 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. PMID:25904210

  15. 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.

  16. 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. PMID:26148178

  17. 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

  18. 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. PMID:26653875

  19. 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.

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

    PubMed

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

    2013-01-01

    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.

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

    PubMed Central

    Fröhlich, Eleonore

    2012-01-01

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

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

    PubMed

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

    2014-09-03

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

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

    PubMed

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

    2014-09-01

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

  4. 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

  5. DNA melting and genotoxicity induced by silver nanoparticles and graphene.

    PubMed

    Ivask, Angela; Voelcker, Nicolas H; Seabrook, Shane A; Hor, Maryam; Kirby, Jason K; Fenech, Michael; Davis, Thomas P; Ke, Pu Chun

    2015-05-18

    We have revealed a connection between DNA-nanoparticle (NP) binding and in vitro DNA damage induced by citrate- and branched polyethylenimine-coated silver nanoparticles (c-AgNPs and b-AgNPs) as well as graphene oxide (GO) nanosheets. All three types of nanostructures triggered an early onset of DNA melting, where the extent of the melting point shift depends upon both the type and concentration of the NPs. Specifically, at a DNA/NP weight ratio of 1.1/1, the melting temperature of lambda DNA dropped from 94 °C down to 76 °C, 60 °C, and room temperature for GO, c-AgNPs and b-AgNPs, respectively. Consistently, dynamic light scattering revealed that the largest changes in DNA hydrodynamic size were also associated with the binding of b-AgNPs. Upon introduction to cells, b-AgNPs also exhibited the highest cytotoxicity, at the half-maximal inhibitory (IC50) concentrations of 3.2, 2.9, and 5.2 mg/L for B and T-lymphocyte cell lines and primary lymphocytes, compared to the values of 13.4, 12.2, and 12.5 mg/L for c-AgNPs and 331, 251, and 120 mg/L for GO nanosheets, respectively. At cytotoxic concentrations, all NPs elicited elevated genotoxicities via the increased number of micronuclei in the lymphocyte cells. However, b-AgNPs also induced micronuclei at subtoxic concentrations starting from 0.1 mg/L, likely due to their stronger cellular adhesion and internalization, as well as their subsequent interference with normal DNA synthesis or chromosome segregation during the cell cycle. This study facilitates our understanding of the effects of NP chemical composition, surface charge, and morphology on DNA stability and genotoxicity, with implications ranging from nanotoxicology to nanobiotechnology and nanomedicine. PMID:25781053

  6. In vitro monitoring of time and dose dependent cytotoxicity of aminated nanoparticles using Raman spectroscopy.

    PubMed

    Efeoglu, Esen; Casey, Alan; Byrne, Hugh J

    2016-09-21

    Investigation of possible adverse health effects of nanomaterials, in a rapid multi-parametric fashion, has become increasingly important, due to their increased production and potential uses in a wide range of application areas, from cosmetics to pharmaceutics. Although conventional in vitro cytotoxicological techniques provide valuable information about the particle toxicity, the importance of gaining high content information in a single assay with the analysis of multiple parameters in a non-invasive and label-free way is still one of the biggest challenges in nanotoxicology. As a vibrational spectroscopic technique, the power of Raman spectroscopy for the analysis of cells, tissues and also nanoparticle localization within cells has been shown previously. In this study, the ability of Raman spectroscopy to fingerprint the dose and time dependent cellular responses and effect of cytotoxic events on biochemical constituents of the cells is monitored. A549 human lung carcinoma cells and aminated polystyrene nanoparticles (PS-NH2) are used as a model cell line and nanoparticle, respectively. Following the determination of cellular responses in the presence of toxic PS-NH2 by using conventional cellular assays, Alamar Blue (AB) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT), and calculation of EC50 values for both assays, Raman spectroscopy was employed at response related doses and time points. Multiple point spectra from the cytoplasm, nucleus and nucleolus of 20 cells were acquired using Raman spectroscopy for each exposure dose and timepoint. Unsupervised principle components analysis (PCA) was applied to the Raman data sets for the comparison of exposed and unexposed cells as well as different exposure doses and times. The study shows the ability of Raman spectroscopy to provide information about cellular responses at different particle concentrations and exposure times with the aid of multivariate analysis. In the chosen range of

  7. Does photocatalytic activity of TiO2 nanoparticles correspond to photo-cytotoxicity? Cellular uptake of TiO2 nanoparticles is important in their photo-cytotoxicity.

    PubMed

    Horie, Masanori; Sugino, Sakiko; Kato, Haruhisa; Tabei, Yosuke; Nakamura, Ayako; Yoshida, Yasukazu

    2016-05-01

    Titanium dioxide (TiO2) nanoparticles are important industrial nano-objects with wide applications, including as photocatalysts and sunscreen components. Recently, the phototoxicity of TiO2 nanoparticles has been a concern. However, phototoxicity caused by photocatalytic activity may differ between anatase and rutile nanoparticles. In the present study, we compared the phototoxicity of anatase and rutile nanoparticles. Human keratinocyte HaCaT cells were treated with stable TiO2 nanoparticle suspensions. Without UVA irradiation, TiO2 nanoparticles did not affect mitochondrial activity or cell membranes. However, exposure to rutile nanoparticle suspensions inhibited cell growth and induced HO-1 gene expression without UVA irradiation. These effects may be explained by the hydrophobic surface of rutile nanoparticles. Next, TiO2-exposed cells were irradiated with UVA for 4 h and effects of TiO2 nanoparticles on cells were examined. The rutile nanoparticles did not show any cellular effects after UVA irradiation. However, the anatase nanoparticles caused strong phototoxicity. Decreased mitochondrial activity, cell membrane damage and the induction of oxidative stress were observed in the cells exposed to anatase nanoparticles with UVA irradiation. Cellular uptake of the nanoparticles was observed in both anatase- and rutile-exposed cells. These results suggest that internalized anatase nanoparticles are important for phototoxicity. Additionally, the exposure of a 3D skin model to TiO2 nanoparticles did not result in significant toxicity. In conclusion, rutile nanoparticles used in sunscreen did not exhibit phototoxic activity. Despite the strong phototoxic activity of anatase nanoparticles in cell cultures, they demonstrated no phototoxicity using a 3D skin model. PMID:27142467

  8. Cytotoxicity and apoptotic signalling cascade induced by chelidonine-loaded PLGA nanoparticles in HepG2 cells in vitro and bioavailability of nano-chelidonine in mice in vivo.

    PubMed

    Paul, Avijit; Das, Sreemanti; Das, Jayeeta; Samadder, Asmita; Khuda-Bukhsh, Anisur Rahman

    2013-09-12

    Poor oral bioavailability of chelidonine, a bio-active ingredient of Chelidonium majus, showing anti-cancer potentials against cancer cells with multidrug resistance, makes its optimal use rather limited. To address this problem, we encapsulated chelidonine in biodegradable poly(lactide-co-glycolide) (PLGA) polymers and evaluated nano-chelidonine's (NCs) anti-cancer efficacy vis-à-vis free chelidonine (FC) against HepG2 cells and also evaluated its bioavailability in mice. Physicochemical characteristics indicated that stable spherical NC were formed in nanometer size range (123±1.15 nm) with good yield (86.34±1.91%), better encapsulation efficiency (82.6±0.574%), negative surface charge (-19.6±2.48 mV) and ability of prolonged and sustained release of chelidonine. Fourier transform infrared analysis revealed that NC resembled similar peaks as that of FC suggesting effective encapsulation in PLGA. NC exhibited rapid cellular uptake and stronger apoptotic effect (∼46.6% reduced IC₅₀ value) than FC, blocking HepG2 cells at G2/M phase. p53, cyclin-D1, Bax, Bcl-2, cytochrome c, Apaf-1, caspase-9 and caspase-3 expressions also corroborated well to suggest greater anticancer potentials of NC. Our in vivo studies demonstrated NC to be more bio-available than FC and showed a better tissue distribution profile without inducing any toxicity (100 mg/kg bw) in mice. Unlike FC, NC could permeate into brain tissue, indicating thereby NC's better potentials for use in therapeutic oncology. PMID:23850776

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

    PubMed Central

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

    2012-01-01

    Antitumor activities have been described in selol, a hydrophobic mixture of molecules containing selenium in their structure, and also in maghemite magnetic nanoparticles (MNPs). Both selol and MNPs were co-encapsulated within poly(lactic-co-glycolic acid) (PLGA) nanocapsules for therapeutic purposes. The PLGA-nanocapsules loaded with MNPs and selol were labeled MSE-NC and characterized by transmission and scanning electron microscopy, electrophoretic mobility, photon correlation spectroscopy, presenting a monodisperse profile, and positive charge. The antitumor effect of MSE-NC was evaluated using normal (MCF-10A) and neoplastic (4T1 and MCF-7) breast cell lines. Nanocapsules containing only MNPs or selol were used as control. MTT assay showed that the cytotoxicity induced by MSE-NC was dose and time dependent. Normal cells were less affected than tumor cells. Cell death occurred mainly by apoptosis. Further exposure of MSE-NC treated neoplastic breast cells to an alternating magnetic field increased the antitumor effect of MSE-NC. It was concluded that selol-loaded magnetic PLGA-nanocapsules (MSE-NC) represent an effective magnetic material platform to promote magnetohyperthermia and thus a potential system for antitumor therapy. PMID:23055734

  11. Cytotoxic origin of copper(II) oxide nanoparticles: comparative studies with micron-sized particles, leachate, and metal salts.

    PubMed

    Gunawan, Cindy; Teoh, Wey Yang; Marquis, Christopher P; Amal, Rose

    2011-09-27

    The work investigates the source of toxicity of copper oxide nanoparticles (CuO NPs) with respect to its leaching characteristic and speciation. Complexation-mediated leaching of CuO NPs by amino acids was identified as the source of toxicity toward Escherichia coli, the model microorganism used in the current study. The leached copper-peptide complex induces a multiple-fold increase in intracellular reactive oxygen species generation and reduces the fractions of viable cells, resulting in the overall inhibition of biomass growth. The cytotoxicity of the complex leachate is however different from that of equivalent soluble copper salts (nitrates and sulfates). A pH-dependent copper speciation during the addition of copper salts gives rise to uncoordinated copper ions, which in turn result in greater toxicity and cell lysis, the latter of which was not observed for CuO NPs even at comparable pH. Since leaching did not occur with micrometer-sized CuO, no cytotoxicty effect was observed, thus highlighting the prominence of materials toxicity at the nanoscale. PMID:21812479

  12. Size-dependent cytotoxicity of europium doped NaYF ₄ nanoparticles in endothelial cells.

    PubMed

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

    2014-10-01

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

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

    PubMed

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

    2013-02-01

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

  14. 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.

  15. Nanoparticle induced self-assembly.

    PubMed

    Helgesen, G; Svåsand, E; Skjeltorp, A T

    2008-05-21

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

  16. 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.

  17. 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. PMID:27022135

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  20. 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

  1. Cytotoxicity and cytokine release in rat hepatocytes, C3A cells and macrophages exposed to gold nanoparticles--effect of biological dispersion media or corona.

    PubMed

    Brown, David M; Johnston, Helinor; Gubbins, Eva; Stone, Vicki

    2014-11-01

    The study aim was to investigate how gold nanoparticles (NPs) of different sizes (20 and 100 nm) influence primary hepatocytes, the hepatocyte cell line C3A and macrophage cytokine responses when dispersed in lung or blood relevant fluids. Gold Au NPs induced cytotoxicity in primary hepatocytes at the highest dose of 66 μg/cm2, this effect was modified by the dispersant, the effect was greater with lung lining fluid (LLF). Release of interleukin (IL)-6, Monocyte chemoattractant protein-1 (MCP-1) and IL-1β was enhanced by the Au NPs and the effects were influenced by the particle size and dispersant. In medium, the smallest particle size was most effective at inducing IL-6 release, while in LLF the largest particles were most effective at inducing IL-6 release. Both 20 nm and 100 nm particles enhanced MCP-1 and IL-1β in the presence of LLF. The Au particles had no cytotoxic effects nor did they stimulate the release of cytokines in the C3A hepatoma cell line. The Au NPs had no significant impact on macrophage viability. Particles induced IL-6 and TNF-α release. LLF and serum reduced the IL-6 response while albumin enhanced the TNF-α response compared to medium dispersed Au NPs. The Au NPs did not impact on MCP-1 release, but this cytokine was enhanced by albumin and serum, while it was depressed by LLF. The macrophage responses were lower than those evoked in primary hepatocytes. In conclusion, when assessing the cytotoxic and pro-inflammatory responses induced by Au NPs, the response is influenced by the dispersant, with different dispersants having different effects in different cell types. PMID:26000400

  2. 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.

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

    PubMed

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

    2016-01-01

    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. PMID:24949897

  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. 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.

  7. 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.

  8. 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

  9. 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.

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

    SciTech Connect

    Kaji, T.; Mishima, A.; Yamamoto, C.

    1996-04-01

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

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

    PubMed

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

    2014-11-01

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

  12. 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.

  13. 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

  14. Immobilized Silver Nanoparticles on Chitosan with Special Surface State-Enhanced Antimicrobial Efficacy and Reduced Cytotoxicity.

    PubMed

    He, Miao; Lu, Liying; Zhang, Jinchi; Li, Danzhen

    2015-09-01

    Immobilized chitosan-Ag nanoparticles (CTS-Ag NPs) with special surface state have been synthesized successfully through immobilizing Ag NPs on the amino-enriched surface of CTS by reducing Ag (I) in situ. The antimicrobial efficiency and potency of CTS-Ag NPs against Escherichia coli and Staphylococcus aureus were studied. Our results reveal that surface-immobilized CTS-Ag NPs show better antimicrobial efficacy than several other reported monodisperse colloidal Ag NPs, because the unique surface state of our CTS-Ag NPs leads to both "contact killing" and "ion mediated killing" functions. Due to the synergetic effect of CTS and Ag NPs, the immobilized CTS-Ag NPs present a broader antimicrobial spectrum and a more effective antifungal activity against Monilia albican. In addition, CTS as an environment friendly dispersant can help to reduce the cytotoxicity of Ag NPs on higher organisms. The immobilized CTS-Ag NPs are stable and can maintain good disinfection potential after 6 months' shelf-time. PMID:26716197

  15. 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

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

    PubMed

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

    2015-02-01

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

  17. 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.

  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. PMID:24755638

  20. Cytotoxic Activity of Highly Purified Silver Nanoparticles Sol Against Cells of Human Immune System.

    PubMed

    Barbasz, Anna; Oćwieja, Magdalena; Barbasz, Jakub

    2015-06-01

    The widespread use of silver nanoparticles (AgN) in the articles of common use justifies the need to investigate their effects on the human body. Nanosilver toxicity of highly purified, stable, and well-characterized Ag sol toward human immune cells at various differentiation stages has been studied. Human promyelocytic leukemia cells (HL-60) were differentiated to granulocytes using dimethyl sulfoxide and to macrophage-like cells by phorbol ester. Human monocytic cells (U-937) were differentiated to monocytes and macrophages by phorbol ester. In the presence of AgN, different changes of their survival time were observed depending on cell differentiation. Differentiated cells showed a significantly higher resistance than the non-differentiated cells, depending on the contact time and AgN concentration. In the presence of AgN at concentration of 25 mg/l, fraction of non-differentiated cells alive after 24 h was equal to 45 %; for granulocytes this number increased to 75 % and for macrophages to 65 %. The presence of AgN increases the levels of intracellular antioxidant -glutathione and of nitric oxide - one of inflammation mediators. By checking the effect caused by effluent obtained from AgN sol purification resulting at AgN sol purification, it was proved that cytotoxity should be attributed to the action of silver particles themselves.

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

    PubMed

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

    2012-08-01

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

  2. 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. PMID:26117766

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

    PubMed

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

    2012-02-01

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

  4. 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.

  5. Enhanced doxorubicin delivery and cytotoxicity in multidrug resistant cancer cells using multifunctional magnetic nanoparticles.

    PubMed

    Pilapong, Chalermchai; Keereeta, Yanee; Munkhetkorn, Samlee; Thongtem, Somchai; Thongtem, Titipun

    2014-01-01

    Carboxymethyl modified magnetic nanoparticles (CMC-MNPs) have been designed as a vehicle for drug delivery in both drug-sensitive and drug-resistant cancer cells. We have demonstrated that the CMC-MNPs were able to load doxorubicin (DOX) with a high loading efficiency while also maintaining a good colloidal stability in an aqueous solution. According to a drug release study, DOX-loaded CMC-MNPs showed that the pH-dependent drug release property had a much higher release rate in acidic pH. Compared to free DOX, the DOX-loaded CMC-MNPs showed higher DOX accumulation in drug-sensitive cancer cells and much higher accumulation in drug-resistant cancer cells. These results indicate that our nanoplatform is highly efficient as a drug delivery system in both normal cancer cells and MDR cancer cells. In addition, the DOX-loaded CMC-MNPs can also enhance cytotoxicity against drug-resistant cancer cells in comparison to free DOX. The results obtained in this research demonstrate that our nanoplatform may be a promising approach in cancer chemotherapy and for overcoming multidrug-resistant cancer cells.

  6. Cytotoxicity and genotoxicity of copper oxide nanoparticles in human skin keratinocytes cells.

    PubMed

    Alarifi, Saud; Ali, Daoud; Verma, Ankit; Alakhtani, Saad; Ali, Bahy A

    2013-07-01

    The wide scale use of copper oxide nanoparticles (CuONPs) due to their unique properties and important applications in magnetic, thermal, electrical, sensor devices, and cosmetics makes human beings more prone to the exposure of CuONPs and its potential adverse effects. Exposure to such nanoparticles is mainly through skin and inhalation. Therefore, the aim of the present study was to assess the apoptotic and genotoxic potential of CuONPs (50 nm) in the human skin epidermal (HaCaT) cells and its underlying mechanism of cellular toxicity. Significant decreases in cell viability were observed with CuONPs exposure in a dose- and time-dependent manner and also induced significant reduction in glutathione and induction in lipid peroxidation, catalase, and superoxide dismutase in HaCaT cells. A significant increase in caspase-3 activity was observed with CuONPs exposure in HaCaT cells indicating apoptosis. Apoptosis or necrosis was confirmed with fluorescent staining (acridine orange and propidium iodide). The CuONPs also induced DNA damage that was mediated by oxidative stress. This study investigating the effects of CuONPs in human skin cells has provided valuable insights into the mechanism of potential toxicity induced by CuONPs. PMID:23667135

  7. Structural dependence of in vitro cytotoxicity, oxidative stress and uptake mechanisms of poly(propylene imine) dendritic nanoparticles.

    PubMed

    Khalid, Humza; Mukherjee, Sourav Prasanna; O'Neill, Luke; Byrne, Hugh J

    2016-03-01

    The in vitro cytotoxic and intracellular oxidative stress responses to exposure to poly(propylene imine) (PPI) dendritic nanoparticles of increasing generation (number of repeated branching cycles) (G0-G4) were assessed in an immortal non-cancerous human keratinocyte cell line (HaCaT). Confocal fluorescence microscopy with organelle staining was used to explore the uptake and intracellular trafficking mechanisms. A generation- and dose-dependent cytotoxic response was observed, increasing according to generation and, therefore, number of surface amino groups. A comparison of the cytotoxic response of G4 PPI and the related G4 poly(amido amine) dendrimer indicates that the PPI with the same number of surface amino groups elicits a significantly higher cytotoxic response. The trend of cytotoxicity versus dendrimer generation and, therefore, size is discontinuous in the region of G2, however, indicating a difference in uptake mechanism for higher compared to lower generations. Whereas the higher generations elicit an oxidative stress response at short exposure times, the lower generations indicate an antioxidant response. Confocal microscopy indicates that, whereas they are prominent at early exposure times for the larger PPI dendrimers, no evidence of early stage endosomes was observed for lower generations of PPI. The results are consistent with an alternative uptake mechanism of physical diffusion across the semipermeable cell membrane for the lower generation dendrimers and are discussed in terms of their implications for predictive models for nanotoxicology and design strategies for nanomedical applications. PMID:26671548

  8. 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

  9. 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.

  10. Comparative study of respiratory tract immune toxicity induced by three sterilisation nanoparticles: silver, zinc oxide and titanium dioxide.

    PubMed

    Liu, Huanliang; Yang, Danfeng; Yang, Honglian; Zhang, Huashan; Zhang, Wei; Fang, Yanjun; Lin, Zhiqing; Tian, Lei; Lin, Bencheng; Yan, Jun; Xi, Zhuge

    2013-03-15

    Silver, zinc oxide, and titanium dioxide nanoparticles are used as sterilisation materials to enhance the performance of disinfectants. We investigated the respiratory tract immune toxicity ("immunotoxicity") of these nanoparticles in vivo and in vitro, and we explored the relationships between particle size, particle shape, chemical composition, chemical stability and the toxicological effects of these typical nanoparticles in rats. In vivo, the rats were exposed to nanoparticles by intratracheal instillation. Exposure to nanoparticles caused an increase in oxidative injury to the lungs and disorders in regulating the cytokine network, which were detected in the bronchoalveolar lavage fluid, suggesting that oxidative stress might be important for inducing the respiratory immunotoxicity of nanoparticles. In vitro, the phagocytic function of alveolar macrophages (AMs) was dose-dependently reduced by nanoparticles, and ZnO nanoparticles induced greater cytotoxicity than the silver and titanium-dioxide nanoparticles, which were coincident with the results of multiple measurements, such as a cell viability assay by WST-8 and LDH measurements. Comparative analyses demonstrated that particle composition and chemical stability most likely had a primary role in the biological effects of different nanoparticles.

  11. 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.

  12. 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. PMID:26342325

  13. 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

  14. Use of a rapid cytotoxicity screening approach to engineer a safer zinc oxide nanoparticle through iron doping.

    PubMed

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

    2010-01-26

    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 multiparameter cytotoxicity assay that evaluates toxic oxidative stress to compare the effects of titanium dioxide (TiO(2)), cerium oxide (CeO(2)), and zinc oxide (ZnO) nanoparticles in bronchial epithelial and macrophage cell lines. The nanoparticles were chosen on the basis of their volume of production and likelihood of spread to the environment. Among the materials, dissolution of ZnO nanoparticles and Zn(2+) 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 on the basis of the compatibility of the fluorescent dyes that contemporaneously assess their response characteristics by a semiautomated epifluorescence procedure. Purposeful reduction of ZnO cytotoxicity was achieved by iron doping, which changed the material matrix to slow Zn(2+) 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

  15. 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

  16. Flow-Induced Assembly of Nickel Nanoparticles

    NASA Astrophysics Data System (ADS)

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

    2008-07-01

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

  17. 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.

  18. 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. PMID:21678906

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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. PMID:26026403

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

    PubMed

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

    2011-04-25

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

  6. Layer by layer assembly of albumin nanoparticles with selective recognition of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

    PubMed

    Cui, Wei; Wang, Anhe; Zhao, Jie; Yang, Xiaoke; Cai, Peng; Li, Junbai

    2016-03-01

    Crosslinked albumin nanoparticles which loaded with doxorubicin (DOX) were fabricated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and biocompatible polysaccharide, alginate (ALG), using layer-by-layer technique. Albumin nanoparticles exhibited narrow size distribution and fluorescent property. The assembled core/shell structure of the nanoparticles can be internalized more easily with the cancer cells, which attributes to TRAIL binding with death receptors. TRAIL still hold bioactive properties after assembled onto the particles. In addition, after loaded into the albumin core nanoparticles, DOX (as the chemotherapeutics) display a synergistic cytotoxic effect on cytotoxicity in combination with TRAIL in vitro. The core/shell nanostructured nanoparticles realized in this study would be used as a promising candidate for novel drug carriers.

  7. Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity

    PubMed Central

    Das, Suvadra; Roy, Partha; Auddy, Runa Ghosh; Mukherjee, Arup

    2011-01-01

    Silymarin (Sm) is a polyphenolic component extracted from Silybum marianum. It is an antioxidant, traditionally used as an immunostimulant, hepatoprotectant, and dietary supplement. Relatively recently, Sm has proved to be a valuable chemopreventive and a useful antineoplastic agent. Medical success for Sm is, however, constrained by very low aqueous solubility and associated biopharmaceutical limitations. Sm flavonolignans are also susceptible to ion-catalyzed degradation in the gut. Proven antihepatotoxic activity of Sm cannot therefore be fully exploited in acute chemical poisoning conditions like that in paracetamol overdose. Moreover, a synchronous delivery that is required for hepatic regeneration is difficult to achieve by itself. This work is meant to circumvent the inherent limitations of Sm through the use of nanotechnology. Sm nanoparticles (Smnps) were prepared by nanoprecipitation in polyvinyl alcohol stabilized Eudragit RS100® polymer (Rohm Pharma GmbH, Darmstadt, Germany). Process parameter optimization provided 67.39% entrapment efficiency and a Gaussian particle distribution of average size 120.37 nm. Sm release from the nanoparticles was considerably sustained for all formulations. Smnps were strongly protective against hepatic damage when tested in a paracetamol overdose hepatotoxicity model. Nanoparticles recorded no animal death even when administered after an established paracetamol-induced hepatic necrosis. Preventing progress of paracetamol hepatic damage was traced for an efficient glutathione regeneration to a level of 11.3 μmol/g in hepatic tissue due to Smnps. PMID:21753880

  8. 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

  9. 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

  10. Exogenous albumin inhibits sorafenib-induced cytotoxicity in human cancer cell lines.

    PubMed

    Kanno, Syu-Ichi; Itoh, Katsuyuki; Suzuki, Naoto; Tomizawa, Ayako; Yomogida, Shin; Ishikawa, Masaaki

    2013-01-01

    Sorafenib is an orally administered multikinase inhibitor that exhibits anti-angiogenic and anti-tumor activity. Sorafenib is also known to bind to protein (>99.5%), suggesting protein binding may be involved in sorafenib pharmacokinetic variability. Albumin is a major drug-binding protein. In this study, we examined the effect of albumin on sorafenib-induced cytotoxicity using two in vitro culture cell lines, human hepatoma Huh-7 cells and androgen-independent prostate cancer PC-3 cells. The cells were cultured and incubated, and cytotoxicity was assessed. Results were confirmed by western blotting. The presence of exogenous albumin markedly blocked the sorafenib-induced cytotoxicity in the two cell lines. Albumin concentration, the change of pharmacological signal transduction as Raf-B, vascular endothelial growth factor (VEGF), and phosphorylation of MEK1/2 or ERK1/2 were found to be decreased by sorafenib. Co-incubation of warfarin, a representative coumarin anticoagulant and potent binding activity, with albumin enhanced the cytotoxic effects by sorafenib. These mechanisms depend on the high binding proper ties of sorafenib and exogenous albumin. Furthermore, we investigated the effects of endo genous albumin expression on sorafenib-induced cytotoxicity using the siRNA knockdown system or transfected expression vector assay. However, the cytotoxic effects by sorafenib showed little change either with the knockdown or overexpression of albumin. Our results suggest that particular care should be taken with albuminemia or the combined use of drugs with a high affinity for albumin, such as warfarin, and sorafenib in the treatment of cancer patients. Our findings may be useful to the cancer therapeutic strategy by sorafenib. PMID:24649118

  11. 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.

  12. 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.

  13. Recombinant human C1-inhibitor inhibits cytotoxicity induced by allo- and xenoantibodies.

    PubMed

    Poirier, N; Blancho, G

    2008-03-01

    Antibody-mediated rejection (AMR) is usually poorly controlled, especially in the context of pretransplant immunization, and remains an unsolved issue in xenotransplantation. In order to study prevention and/or treatment of AMR through an early blockade of the complement classical pathway, we designed two strategies to test the effect of a new recombinant human C1-inhibitor that inhibits C1 esterase (rhC1-INH; Pharming, The Netherlands), in a complement-dependent cytotoxicity assay, in the contexts of pretransplant anti-donor alloimmunization and pig-to-primate combinations in order to compare the situations. RhC1-INH appeared to be efficient, in allo- and xenotransplantation settings to block cytotoxicity when given at the initiation of (preventive strategy) or during (curative strategy) the cytotoxicity assay. Importantly, we showed that a small amount of exogenous rhC1-INH was sufficient to prevent cytotoxicity induced by anti-donor alloantibody, thus possibly helping to prevent or treat AMR in preimmunized patients. These in vitro data lead to future in vivo studies in models of AMR in pigs and baboons in allotransplantation and xenotransplantation, in which cytotoxicity due to Gal and non-Gal antibodies is so detrimental.

  14. Recombinant human C1-inhibitor inhibits cytotoxicity induced by allo- and xenoantibodies.

    PubMed

    Poirier, N; Blancho, G

    2008-03-01

    Antibody-mediated rejection (AMR) is usually poorly controlled, especially in the context of pretransplant immunization, and remains an unsolved issue in xenotransplantation. In order to study prevention and/or treatment of AMR through an early blockade of the complement classical pathway, we designed two strategies to test the effect of a new recombinant human C1-inhibitor that inhibits C1 esterase (rhC1-INH; Pharming, The Netherlands), in a complement-dependent cytotoxicity assay, in the contexts of pretransplant anti-donor alloimmunization and pig-to-primate combinations in order to compare the situations. RhC1-INH appeared to be efficient, in allo- and xenotransplantation settings to block cytotoxicity when given at the initiation of (preventive strategy) or during (curative strategy) the cytotoxicity assay. Importantly, we showed that a small amount of exogenous rhC1-INH was sufficient to prevent cytotoxicity induced by anti-donor alloantibody, thus possibly helping to prevent or treat AMR in preimmunized patients. These in vitro data lead to future in vivo studies in models of AMR in pigs and baboons in allotransplantation and xenotransplantation, in which cytotoxicity due to Gal and non-Gal antibodies is so detrimental. PMID:18374134

  15. 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

  16. 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).

  17. 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

  18. 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

  19. 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. PMID:25701118

  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. 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.

  2. 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

  3. Zinc oxide nanoparticle induced genotoxicity in primary human epidermal keratinocytes.

    PubMed

    Sharma, Vyom; Singh, Suman K; Anderson, Diana; Tobin, Desmond J; Dhawan, Alok

    2011-05-01

    Zinc oxide (ZnO) nanoparticles are widely used in cosmetics and sunscreens. Human epidermal keratinocytes may serve as the first portal of entry for these nanoparticles either directly through topically applied cosmetics or indirectly through any breaches in the skin integrity. Therefore, the objective of the present study was to assess the biological interactions of ZnO nanoparticles in primary human epidermal keratinocytes (HEK) as they are the most abundant cell type in the human epidermis. Cellular uptake of nanoparticles was investigated by scanning electron microscopy using back scattered electrons imaging as well as transmission electron microscopy. The electron microscopy revealed the internalization of ZnO nanoparticles in primary HEK after 6 h exposure at 14 microg/ml concentration. ZnO nanoparticles exhibited a time (6-24 h) as well as concentration (8-20 microg/ml) dependent inhibition of mitochondrial activity as evident by the MTT assay. A significant (p < 0.05) induction in DNA damage was observed in cells exposed to ZnO nanoparticles for 6 h at 8 and 14 microg/ml concentrations compared to control as evident in the Comet assay. This is the first study providing information on biological interactions of ZnO nanoparticles with primary human epidermal keratinocytes. Our findings demonstrate that ZnO nanoparticles are internalized by the human epidermal keratinocytes and elicit a cytotoxic and genotoxic response. Therefore, caution should be taken while using consumer products containing nanoparticles as any perturbation in the skin barrier could expose the underlying cells to nanoparticles.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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. PMID:24075930

  9. 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

  10. 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.

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

    PubMed

    Yadav, Umesh C S; Ramana, K V; Srivastava, Satish K

    2013-12-01

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

  12. 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

  13. 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.

  14. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

  16. Design of LVFFARK and LVFFARK-functionalized nanoparticles for inhibiting amyloid β-protein fibrillation and cytotoxicity.

    PubMed

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

    2015-03-18

    Aggregation of amyloid β-protein (Aβ) into amyloid oligomers and fibrils is pathologically linked to Alzheimer's disease (AD). Hence, the inhibition of Aβ aggregation is essential for the prevention and treatment of AD, but the development of potent agents capable of inhibiting Aβ fibrillogenesis has posed significant challenges. Herein, we designed Ac-LVFFARK-NH2 (LK7) by incorporating two positively charged residues, R and K, into the central hydrophobic fragment of Aβ17-21 (LVFFA) and examined its inhibitory effect on Aβ42 aggregation and cytotoxicity by extensive physical, biophysical, and biological analyses. LK7 was observed to inhibit Aβ42 fibrillogenesis in a dose-dependent manner, but its strong self-assembly characteristic also resulted in high cytotoxicity. In order to prevent the cytotoxicity that resulted from the self-assembly of LK7, the peptide was then conjugated to the surface of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to fabricate a nanosized inhibitor, LK7@PLGA-NPs. It was found that LK7@PLGA-NPs had little cytotoxicity because the self-assembly of the LK7 conjugated on the NPs was completely inhibited. Moreover, the NPs-based inhibitor showed remarkable inhibitory capability against Aβ42 aggregation and significantly alleviated its cytotoxicity at a low LK7@PLGA-NPs concentration of 20 μg/mL. At the same peptide concentration, free LK7 showed little inhibitory effect. It is considered that several synergetic effects contributed to the strong inhibitory ability of LK7@PLGA-NPs, including the enhanced interactions between Aβ42 and LK7@PLGA-NPs brought on by inhibiting LK7 self-assembly, restricting conformational changes of Aβ42, and thus redirecting Aβ42 aggregation into unstructured, off-pathway aggregates. The working mechanisms of the inhibitory effects of LK7 and LK7@PLGA-NPs on Aβ42 aggregation were proposed based on experimental observations. This work provides new insights into the design and development of

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

    PubMed

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

    2011-07-01

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

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

    PubMed Central

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

    2011-01-01

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

  19. 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

  20. 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.

  1. 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. PMID:24890809

  2. The cytotoxicity of iron oxide nanoparticles with different modifications evaluated in vitro

    NASA Astrophysics Data System (ADS)

    Zavisova, Vlasta; Koneracka, Martina; Kovac, Jozef; Kubovcikova, Martina; Antal, Iryna; Kopcansky, Peter; Bednarikova, Monika; Muckova, Marta

    2015-04-01

    The toxicity of magnetite nanoparticles modified with bioavailable materials such as dextran, bovine serum albumin, polyethylene glycol, and polyvinylpyrrolidone was studied in normal and cancer cells. The size distribution and magnetic properties of the modified magnetic nanoparticles were characterized by different techniques. Transmission electron microscopy showed a nearly spherical shape of the magnetite core with diameters ranging from 4 to 11 nm. Dynamic light scattering was employed to monitor the hydrodynamic size and colloidal stability of the magnetic nanoparticles: Z-average hydrodynamic diameter was between 53 and 69 nm and zeta potential in the range from -35 to -48 mV. Saturation magnetization of the modified nanoparticles was 55-64 emu/gFe3O4. Prepared biocompatible nanoparticles had no significant toxic effect on Chinese hamster lung fibroblast cell line V79, but they substantially affected mouse melanoma B16 cell line.

  3. 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. PMID:26952466

  4. Dexamethasone-loaded Block Copolymer Nanoparticles Induce Leukemia Cell Death and Enhances Therapeutic Efficacy: A Novel Application in Pediatric Nanomedicine

    PubMed Central

    Krishnan, Vinu; Xu, Xian; Barwe, Sonali P.; Yang, Xiaowei; Czymmek, Kirk; Waldman, Scott A.; Mason, Robert W.; Jia, Xinqiao; Rajasekaran, Ayyappan K.

    2014-01-01

    Nanotechnology approaches have tremendous potential for enhancing treatment efficacy with lower doses of chemotherapeutics. Nanoparticle-based drug delivery approaches are poorly developed for childhood leukemia. Dexamethasone (Dex) is one of the most common chemotherapeutic drugs used in the treatment of childhood leukemia. In this study, we encapsulated Dex in polymeric nanoparticles and validated their anti-leukemic potential in vitro and in vivo. Nanoparticles (NPs) with an average diameter of 110 nm were assembled from amphiphilic block copolymers poly (ethylene glycol) (PEG) and poly (ε-caprolactone) (PCL) bearing pendant cyclic ketals. The blank nanoparticles were non-toxic to cultured cells in vitro and to mice in vivo. Encapsulation of Dex into the nanoparticles (Dex-NP) did not compromise the bioactivity of the drug. Dex-NPs induced glucocorticoid phosphorylation and showed cytotoxicity similar to the free Dex in leukemic cells. Studies using nanoparticles labeled with fluorescent dyes revealed leukemic cell surface binding and internalization. In vivo biodistribution studies showed NP accumulation in the liver and spleen with subsequent clearance of the particles with time. In a pre-clinical model of leukemia, Dex-NPs significantly improved the quality of life and survival of mice compared to the free drug. To our knowledge, this is the first report showing the efficacy of polymeric nanoparticles to deliver Dex to potentially treat childhood leukemia and reveals that low dose of Dex should be sufficient for inducing cell death and improve survival. PMID:23194373

  5. Neuroprotective action of genipin on tunicamycin-induced cytotoxicity in neuro2a cells.

    PubMed

    Tanaka, Masayuki; Yamazaki, Matsumi; Chiba, Kenzo

    2009-07-01

    Accumulation of unfolding or misfolded proteins within the lumen of the endoplasmic reticulum (ER) triggers ER stress, and sustained ER stress ultimately leads to cell death. Both of these events are involved in the activation of glucose-regulated protein of 78 kDa (GRP78, also known as Bip), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP, also known as growth arrest and DNA damage-inducible gene 153 (GADD153)), and caspase-12. ER stress has been shown to be involved in neurodegenerative disorders, such as Alzheimer, Parkinson, and polyglutamine diseases. We previously showed that genipin, a natural iridoid compound, has a protective effect against amyloid-beta (Abeta)-induced cytotoxicity. Here, we studied the protective effects of genipin on cytotoxicity induced in Neuro2a cells by the specific ER stress inducer tunicamycin (TM). TM treatment significantly reduced cell viability in a dose-dependent manner. Genipin dramatically rescued the cells against TM-induced cell death. In addition, genipin suppressed ER stress-induced upregulation of CHOP and GRP78. These data suggest that genipin is effective at protecting against neurodegenerative disorders.

  6. 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.

  7. 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.

  8. 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

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

    NASA Astrophysics Data System (ADS)

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

    2011-07-01

    Amorphous silica nanoparticles (nSP) have been used as a polishing agent and/or as a remineralization promoter for teeth in the oral care field. The present study investigates the effects of nSP on osteoclast differentiation and the relationship between particle size and these effects. Our results revealed that nSP exerted higher cytotoxicity in macrophage cells compared with submicron-sized silica particles. However, tartrate-resistant acid phosphatase (TRAP) activity and the number of osteoclast cells (TRAP-positive multinucleated cells) were not changed by nSP treatment in the presence of receptor activator of nuclear factor 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.

  10. 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.

  11. 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.

  12. [Detection of stimulator-induced cytotoxicity of human mononuclear cells in short-term culture].

    PubMed

    von Baehr, R; Timm, M; Fröbe, I

    1983-01-01

    A new test modification for the detection of stimulant-induced cytotoxicity of human mononuclear blood cells is described. Papain-treated human erythrocytes were used as indicator cells. The effector cells were lymphocytes. The ratio of target cells to effector cells was 10/1. Haemoglobin as a marker of lysis of the erythrocytes, released in the supernatant, was measured quantitatively in form of its pseudoperoxidase-activity. PHA, ConA and tannic acid were ascertained and tested as stimulants of cytotoxicity. The reaction was inhibitable by anti-human-lymphocyte-globulin. The test conditions were optimized in regard to incubation time, -temperature, -vessels, culture medium and target cells. The technique is easy to manipulate, has only slight pretensions to the equipment of the laboratory and appears to be very effective. We recommend to apply this method of stimulant-induced cytotoxicity within the detection of the immune state, especially in the progress of immunopathological diseases and the analysis of efficiency of immunosuppressive therapy. PMID:6224413

  13. 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.

  14. 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.

  15. 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

    2016-11-01

    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 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.

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

    PubMed

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

    2012-04-01

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

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

    SciTech Connect

    Railsback, Justin; Singh, Abhishek; Pearce, Ryan; McKnight, Timothy E; Collazo, Ramon; Sitar, Zlatko; Yingling, Yaroslava; Melechko, Anatoli Vasilievich

    2012-01-01

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

  18. Effects of ZnO nanoparticles in plants: Cytotoxicity, genotoxicity, deregulation of antioxidant defenses, and cell-cycle arrest.

    PubMed

    Ghosh, Manosij; Jana, Aditi; Sinha, Sonali; Jothiramajayam, Manivannan; Nag, Anish; Chakraborty, Anirban; Mukherjee, Amitava; Mukherjee, Anita

    2016-09-01

    Cytotoxicity, genotoxicity, and biochemical effects were evaluated in the plants Allium cepa, Nicotiana tabacum, and Vicia faba following exposure to ZnO nanoparticles (np; diameter, ∼85nm). In the root meristems of Allium cepa cells, we observed loss of membrane integrity, increased chromosome aberrations, micronucleus formation, DNA strand breaks, and cell-cycle arrest at the G2/M checkpoint. In Vicia faba and Nicotiana tabacum, we observed increased intracellular ROS production, lipid peroxidation, and activities of some antioxidant enzymes. TEM images revealed gross morphological alterations and internalization of the np. Our findings provide evidence of ZnO np toxicity, characterized by deregulation of components of ROS-antioxidant machinery, leading to DNA damage, cell-cycle arrest, and cell death. These plants, especially Allium cepa, are reliable systems for assessment of np toxicology. PMID:27542712

  19. 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.

  20. 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.

  1. 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.

  2. Structural characterization, antioxidant and in vitro cytotoxic properties of seagrass, Cymodocea serrulata (R.Br.) Asch. & Magnus mediated silver nanoparticles.

    PubMed

    Chanthini, Abdhul Basheer; Balasubramani, Govindasamy; Ramkumar, Rajendiran; Sowmiya, Rajamani; Balakumaran, Manickam Dakshinamoorthi; Kalaichelvan, Pudhupalayam Thangavelu; Perumal, Pachiappan

    2015-12-01

    The present study pertains to the synthesis, structural elucidation, antioxidant and in vitro cytotoxic properties of silver nanoparticles (AgNPs) from marine angiosperm, Cymodocea serrulata aqueous extract (CSAE). The characterization was made through UV-Visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), zeta potential and dynamic light scanning (DLS) analyses. The UV-Vis spectrum resulted in a strong surface plasmon resonance (SPR) at 430 nm. The average crystalline size of the AgNPs was predicted through XRD peaks that indicated the 2 theta values of 37.84°, 44.06°, 64.42° and 77.74° for Bragg's refraction index. The functional groups responsible for the bio-reduction of Ag(+) into Ag(0) were focused through FTIR spectrum. The FESEM images showed that the C. serrulata mediated AgNPs (CS-AgNPs) were spherical in shape. DPPH assay revealed the higher free radical scavenging activity in CS-AgNPs, when compared to CSAE. The cytotoxicity assay on the cervical cancer (HeLa) and African green monkey kidney (Vero) cells upon treatment with CSAE: 107.7 & 124.3 μgml(-1) and CS-AgNPs: 34.5 & 61.24 μgml(-1), respectively showed good inhibition rate. These findings highlight the fact that C. serrulata could be a potential source for developing potent drugs and further studies are needed.

  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 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

  5. Cytoprotective Activity of Glycyrrhizae radix Extract Against Arsenite-induced Cytotoxicity

    PubMed Central

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

    2008-01-01

    Licorice, Glycyrrhizae radix, is one of the herbal medicines in East Asia that has been commonly used for treating various diseases, including stomach disorders. This study investigated the effect of licorice on arsenite (As)-induced cytotoxicity in H4IIE cells, a rat hepatocyte-derived cell line. Cell viability was significantly diminished in As-treated H4IIE cells in a time and concentration-dependent manner. Furthermore, results from flow cytometric assay and DNA laddering in H4IIE cells showed that As treatment induced apoptotic cell death by activating caspase-3. Licorice (0.1 and 1.0 mg ml−1) treatment significantly inhibited cell death and the activity of caspase-3 in response to As exposure. These results demonstrate that licorice induced a cytoprotective effect against As-induced cell death by inhibition of caspase-3. PMID:18604262

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

    PubMed

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

    2012-11-15

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

  8. Primary WWOX phosphorylation and JNK activation during etoposide induces cytotoxicity in HEK293 cells

    PubMed Central

    Jamshidiha, M.; Habibollahi, P.; Ostad, S.N.; Ghahremani, M.H.

    2010-01-01

    Background and the purpose of the study Etoposide is an antineoplastic agent used in multiple cancers. It is known that etoposide induce cell death via interaction with topoisomerase II; however, the etopoisde cellular response is poorly understood. Upon etoposide induced DNA damage, many stress signaling pathways including JNK are activated. In response to DNA damage, it has been shown that WWOX, a recently introduced tumor suppressor, can be activated. In this study the activation of WWOX and JNK and their interaction following etoposide treatment were evaluated. Materials and Methods HEK293 cells treated with etoposide were lysed in a time course manner. The whole cell lysates were used to evaluate JNK and WWOX activation pattern using Phospho specific antibodies on western blots. The viability of cells treated with etoposide, JNK specific inhibitor and their combination was examined using MTT assay. Results Findings of this study indicate that WWOX and JNK are activated in a simultaneous way in response to DNA damage. Moreover, JNK inhibition enhances etoposide induced cytotoxicity in HEK293. Conclusion Taken together, our results indicate that etoposide induces cytotoxicity and WWOX phosphorylation and the cytotoxicty is augmented by blocking JNK pathway. PMID:22615609

  9. Changes in cardiopulmonary function induced by nanoparticles.

    PubMed

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

    2012-01-01

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

  10. 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.

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

    PubMed

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

    2014-09-01

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

  12. The cytotoxicity and cellular stress by temperature-fabricated polyshaped gold nanoparticles using marine macroalgae, Padina gymnospora.

    PubMed

    Singh, Manoj; Saurav, Kumar; Majouga, Alexander; Kumari, Mamta; Kumar, Manish; Manikandan, S; Kumaraguru, A K

    2015-01-01

    Bioreduction of metal ions for the synthesis of stable nanoparticles (NPs) in physiological environment has been a great challenge in the field of nanotechnology and its application. In the present study, well-defined biofunctionalized gold nanoparticles (AuNPs) were developed following a biomimetic approach for an enhanced anticancer activity. The fucoxanthins-capped crystalline AuNPs showed a particle size of 14 nm. The temperature-mediated biosynthesized NPs were characterized by UV-vis, dynamic light scattering, high-resolution transmission electron microscopy, and energy-dispersive X-ray spectroscopy. The cytotoxicity of the NPs was analyzed on liver (HepG2) and lung (A549) cancerous cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay infers that the biofunctionalized polyshaped AuNPs synthesized with an aqueous macroalgae extract showed a satisfactory anticancer effect on the cell lines, as evaluated by changes in cell morphology, cell viability, and metabolic activity. An altered cellular function and the morphology of cancer cell lines suggest a potential for in vivo application of AuNPs and the need to understand the interactions between nanomaterials, biomolecules, and cellular components. With continued improvements, these NPs may prove to be potential drug delivery vehicles for cancer therapy.

  13. Cytotoxic Effects of ZnO Nanoparticles on the Expression of ROS-Responsive Genes in the Human Cell Lines.

    PubMed

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

    2016-01-01

    In the present investigation, engineered ZnO nanoparticles were tested for their induced oxidative stress in T47D tumor cell lines. The expressions of reactive oxygen species (ROS) related genes, glutathione S-transferase (GST) and catalase were quantified by real time-polymerase chain reaction (RT-PCR). In addition, qualitative analysis of GST was also performed at the cell level using molecular beacon (MB) technology. The tested nanoparticles were 20 nm in size, water-dispersible and treated on human breast tumor epithelial cell lines at 20, 40, 80 µg/ml concentration with 14, 28, 48 h incubation times. Nanoparticles induced expressions of ROS responsive genes at molecular and cellular level, produces consistent results with respect to different dosage and incubation time. The experiment showed that the expression of both GST and catalase genes were maximized at 28 h with 80 µg/ml concentration. However, the toxic effect of the monodisperse ZnO nanoparticles was not significant compared with control experiments, demonstrating its high potential in the applications of nanomedicines for a diagnostic and therapeutic tool. PMID:27398447

  14. Cytotoxic Effects of ZnO Nanoparticles on the Expression of ROS-Responsive Genes in the Human Cell Lines.

    PubMed

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

    2016-01-01

    In the present investigation, engineered ZnO nanoparticles were tested for their induced oxidative stress in T47D tumor cell lines. The expressions of reactive oxygen species (ROS) related genes, glutathione S-transferase (GST) and catalase were quantified by real time-polymerase chain reaction (RT-PCR). In addition, qualitative analysis of GST was also performed at the cell level using molecular beacon (MB) technology. The tested nanoparticles were 20 nm in size, water-dispersible and treated on human breast tumor epithelial cell lines at 20, 40, 80 µg/ml concentration with 14, 28, 48 h incubation times. Nanoparticles induced expressions of ROS responsive genes at molecular and cellular level, produces consistent results with respect to different dosage and incubation time. The experiment showed that the expression of both GST and catalase genes were maximized at 28 h with 80 µg/ml concentration. However, the toxic effect of the monodisperse ZnO nanoparticles was not significant compared with control experiments, demonstrating its high potential in the applications of nanomedicines for a diagnostic and therapeutic tool.

  15. 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 seriously considered when using AuNPs for treatment of osteoarthritis (OA).

  16. Gold Nanoparticles of Diameter 13 nm Induce Apoptosis in Rabbit Articular Chondrocytes.

    PubMed

    Huang, Hao; Quan, Ying-Yao; Wang, Xiao-Ping; Chen, Tong-Sheng

    2016-12-01

    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 seriously considered when using AuNPs for treatment of osteoarthritis (OA). PMID:27178054

  17. Avermectin Confers Its Cytotoxic Effects by Inducing DNA Damage and Mitochondria-Associated Apoptosis.

    PubMed

    Zhang, Yang; Luo, Mingming; Xu, Wenping; Yang, Mingjun; Wang, Bo; Gao, Jufang; Li, Yaxiao; Tao, Liming

    2016-09-14

    Avermectin (AVM) has been widely used in agriculture and animal husbandry on the basis of its broad spectrum of effective anthelmintic activity and specificity targets. However, AVM induction of cytotoxicity through DNA damage is remains elusive. Here we investigate the cytotoxic effects of AVM in human nontarget cells in vitro. We clarify that AVM inhibited the viability of HeLa cells and enhanced apoptosis. We have used alkaline comet assay and γH2AX foci formation to detect DNA damage of HeLa cells. As expected, we found AVM caused DNA double-strand breaks in HeLa cells, as measured by significance of comet assay parameters (e.g., tail DNA) and increases of γH2AX foci in HeLa cells. Moreover, established assays of cytotoxicity were performed to characterize the mechanism of AVM toxicity on HeLa cells. The results demonstrated the collapse of mitochondrial membrane potential, and up-regulating the expression level of Bax/Bcl-2 resulted in a release of cytochrome c into cytosol as well as the activation of caspase-9/-3 and cleavage of poly(ADP-ribose) polymerase (PARP). We conclude that AVM has a potential risk to human health by inducing human cell DNA damage and mitochondria-associated apoptosis. PMID:27551889

  18. 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. PMID:26945135

  19. 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

  20. 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.

  1. 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

  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 apoptosis induced by nanobacteria in human breast cancer cells

    PubMed Central

    Zhang, Ming-jun; Liu, Sheng-nan; Xu, Ge; Guo, Ya-nan; Fu, Jian-nan; Zhang, De-chun

    2014-01-01

    Background The existing evidence that nanobacteria (NB) are closely associated with human disease is overwhelming. However, their potential toxicity against cancer cells has not yet been reported. The objective of this study was to investigate the cytotoxic effects of NB and nanohydroxyapatites (nHAPs) against human breast cancer cells and to elucidate the mechanisms of action underlying their cytotoxicity. Methodology/principal findings NB were isolated from calcified placental tissue, and nHAPs were artificially synthesized. The viability of the MDA-MB-231 human breast cancer cell line was tested by using the Kit-8 cell counting kit assay. Apoptosis was examined by transmission electron microscopy and flow cytometry. The endocytosis of NB and nHAPs by MDA-MB-231 cells was initially confirmed by microscopy. Although both NB and nHAPs significantly decreased MDA-MB-231 cell viability and increased the population of apoptotic cells, NB were more potent than nHAPs. After 72 hours, NB also caused ultrastructural changes typical of apoptosis, such as chromatin condensation, nuclear fragmentation, nuclear dissolution, mitochondrial swelling, and the formation of apoptotic bodies. Conclusion/significance In MDA-MB-231 human breast cancer cells, NB and nHAPs exerted cytotoxic effects that were associated with the induction of apoptosis. The effects exerted by NB were more potent than those induced by nHAPs. NB cytotoxicity probably emerged from toxic metabolites or protein components, rather than merely the hydroxyapatite shells. NB divided during culturing, and similar to cells undergoing binary fission, many NB particles were observed in culture by transmission electron microscopy, suggesting they are live microorganisms. PMID:24403832

  4. Human gammadelta T lymphocytes exert natural and IL-2-induced cytotoxicity to neuroblastoma cells.

    PubMed

    Schilbach, K E; Geiselhart, A; Wessels, J T; Niethammer, D; Handgretinger, R

    2000-01-01

    Human gammadelta T lymphocytes play an important role in nonadaptive reactions to infection and early tumor defense. This is the first report that freshly isolated, native gammadelta T cells of some healthy donors can kill human neuroblastoma cells to varying degrees. Their killing ability was increased and maintained during expansion and cultivation with interleukin-2 (IL-2; 400 IU/mL) for as long as 30 days (100% specific lysis at an effector-to-target cell (E:T) ratio of 20:1). gammadelta T lymphocytes without this spontaneous killing ability gained a specific cytolytic activity of 81% +/- 10.4% SD after stimulation with IL-2 for 24 hours. gammadelta cells were isolated from peripheral blood by positive enrichment (using a magnetic cell sorting system; purity, 95.2% +/- 3.2% SD, n = 21). High natural cytotoxic activity against human neuroblastoma cell lines (>50% specific lysis at an E:T ratio of 20:1) was exhibited by one of 11 donors, whereas two of 11 showed medium cytotoxicity (30% to 50% specific lysis). Eight of 11 donors showed very slight or no lytic activity against human neuroblastoma cells (<30% specific lysis). gammadelta T cells were also cytotoxic against Daudi (32.7% specific lysis at an E:T ratio of 20:1), Raji (10.3%), Colo 205 (23.1%), A 204 (54%), K 562 (100%), and SK-N-MC (100%) cells. Isolated gammadelta T cells were grown in Iscove modified Dulbecco medium with IL-2 (400 IU/mL). Increased cell proliferation (38.5% to 182%) was induced with phytohemagglutinin, IL-15, Clodronat, OKT3, or various combinations of these. Results of cold target inhibition assays suggest a natural killer-like activity of the gammadelta T-cell killing mechanism. Peptidase or papain render neuroblastoma cells unsusceptible to gammadelta T-cell killing, suggesting the involvement of antigen peptide(s) in the process of neuroblastoma cell killing. Treatment with acid phosphatase reduced specific lysis by 66.5% +/- 34.1% SD, which suggests a binding to phosphorylated

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

    PubMed

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

    2010-02-12

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

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

    PubMed

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

    2010-02-12

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

  7. Multiple biomarkers of the cytotoxicity induced by BDE-47 in human embryonic kidney cells.

    PubMed

    Wu, Huifeng; Cao, Lulu; Li, Fei; Lian, Peiwen; Zhao, Jianmin

    2015-05-01

    Polybrominated diphenyl ethers (PBDEs) are widely used as brominated flame-retardants in a variety of industrial products. Among these PBDEs, 2,2',4,4'-tetra-bromodiphenyl ether (BDE-47) is one of the most predominant congeners inducing multiple toxicities, including hepatotoxicity, neurotoxicity, cytotoxicity, genotoxicity, carcinogenecity and immunotoxicity in human body. In this study, the cytotoxicity of BDE-47 in human embryonic kidney cells (HEK293) was investigated by a set of bioassays, including cell proliferation, apoptosis, oxidative stress and metabolic responses as well as gene expressions related to apoptosis. Results showed that BDE-47 induced an inverted U-shaped curve of cell proliferation in HEK293 cells from 10(-6) to 10(-4) M. Cell apoptosis and ROS overproduction were detected at 10(-5) M of BDE-47 (p<0.05). In addition, the expressions of Bcl-2 family-encoding genes (Bad, Hrk and Bcl-2) increased significantly in 10(-4)M group (p<0.05). Metabolic responses indicated that BDE-47 mainly caused disturbance in energy metabolism marked by differentially altered ethanol, glutathione, creatine, aspartate, UDP-glucose and NAD(+). The increased lactate/alanine ratios indicated the higher reductive state induced by BDE-47 in all exposures confirmed by the overproduction of ROS. PMID:25697951

  8. Cytotoxicity induced by cypermethrin in Human Neuroblastoma Cell Line SH-SY5Y.

    PubMed

    Raszewski, Grzegorz; Lemieszek, Marta Kinga; Łukawski, Krzysztof

    2016-01-01

    The purpose of this study was to evaluate the cytotoxic potential of Cypermethrin (CM) on cultured human Neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with CM at 0-200µM for 24, 48, and 72 h, in vitro. It was found that CM induced the cell death of Neuroblastoma cells in a dose- and time-dependent manner, as shown by LDH assays. Next, some aspects of the process of cell death triggered by CM in the human SH-SY5Y cell line were investigated. It was revealed that the pan-caspase inhibitor Q-VD-OPh, sensitizes SH-SY5Y cells to necroptosis caused by CM. Furthermore, signal transduction inhibitors PD98059, SL-327, SB202190, SP600125 failed to attenuate the effect of the pesticide. Finally, it was shown that inhibition of TNF-a by Pomalidomide (PLD) caused statistically significant reduction in CM-induced cytotoxicity. Overall, the data obtained suggest that CM induces neurotoxicity in SH-SY5Y cells by necroptosis.

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

    PubMed

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

    2015-05-01

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

  10. Protective Effects of Quercetin against Dimethoate-Induced Cytotoxicity and Genotoxicity in Allium sativum Test

    PubMed Central

    Ahmad, Waseem; Shaikh, Sibhghatulla; Nazam, Nazia; Lone, Mohammad Iqbal

    2014-01-01

    The present investigation was directed to study the possible protective activity of quercetin—a natural antioxidant against dimethoate-induced cyto- and genotoxicity in meristematic cells of Allium sativum. So far there is no report on the biological properties of quercetin in plant test systems. Chromosome breaks, multipolar anaphase, stick chromosome, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Untreated control, quercetin controls (@ 5, 10 and 20 μg/mL for 3 h), and dimethoate exposed groups (@ 100 and 200 μg/mL for 3 h) were maintained. For protection against cytogenotoxicity, the root tip cells treated with dimethoate at 100 and 200 μg/mL for 3 h and quercetin treatment at 5, 10, and 20 μg/mL for 16 h, prior to dimethoate treatment, were undertaken. Quercetin was found to be neither cytotoxic nor genotoxic in Allium sativum control at these doses. A significant increase (P < 0.05) in chromosomal aberrations was noted in dimethoate treated Allium. Pretreatment of Allium sativum with quercetin significantly (P < 0.05) reduced dimethoate-induced genotoxicity and cytotoxicity in meristematic cells, and these effects were dose dependent. In conclusion, quercetin has a protective role in the abatement of dimethoate-induced cyto- and genotoxicity in the meristematic cells of Allium sativum that resides, at least in part, on its antioxidant effects. PMID:27379342

  11. Taurine, a conditionally essential amino acid, ameliorates arsenic-induced cytotoxicity in murine hepatocytes.

    PubMed

    Sinha, Mahua; Manna, Prasenjit; Sil, Parames C

    2007-12-01

    Arsenic is a potent environmental toxin. Present study has been designed to evaluate the protective role of taurine (2-aminoethanesulfonic acid) against arsenic induced cytotoxicity in murine hepatocytes. Sodium arsenite (NaAsO(2)) was chosen as the source of arsenic. Incubation of hepatocytes with the toxin (1 mM) for 2 h reduced the cell viability as well as intra-cellular antioxidant power. Increased activities of alanine transaminase (ALT) and alkaline phosphatase (ALP) due to toxin exposure confirmed membrane damage. Toxin treatment caused reduction in the activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx). In addition, the same treatment reduced the level of glutathione (GSH), elevated the level of oxidized glutathione (GSSG) and increased the extent of lipid peroxidation. Incubation of hepatocytes with taurine, both prior to and in combination with NaAsO(2), attenuated the extent of lipid peroxidation and enhanced the activities of enzymatic as well as non enzymatic antioxidants. Besides, taurine administration normalized the arsenic-induced enhanced levels of the marker enzymes ALT and ALP in hepatocytes. The cytoprotective activity of taurine against arsenic poisoning was found to be comparable to that of a known antioxidant, vitamin C. Combining all, the results suggest that taurine protects mouse hepatocytes against arsenic induced cytotoxicity.

  12. Involvement of oxidative stress in hydroquinone-induced cytotoxicity in catalase-deficient Escherichia coli mutants.

    PubMed

    Horita, Masako; Wang, Da-Hong; Tsutsui, Ken; Sano, Kuniaki; Masuoka, Noriyoshi; Kira, Shohei

    2005-10-01

    Hydroquinone is a benzene-derived metabolite. To clarify whether the reactive oxygen species (ROS) are involved in hydroquinone-induced cytotoxicity, we constructed transformants of Escherichia coli (E. coli) strains that express mammalian catalase gene derived from catalase mutant mice (Cs(b), Cs(c)) and the wild-type (Cs(a)) using a catalase-deficient E. coli UM255 as a recipient. Specific catalase activities of these tester strains were in order of Cs(a) > Cs(c) > Cs(b) > UM255, and their susceptibility to hydrogen peroxide (H2O2) showed UM255 > Cs(b) > Cs(c) > Cs(a). We found that hydroquinone exposure reduced the survival of catalase-deficient E. coli mutants in a dose-dependent manner significantly, especially in the strains with lower catalase activities. Hydroquinone toxicity was also confirmed using zone of inhibition test, in which UM255 was the most susceptible, showing the largest zone of growth inhibition, followed by Cs(b), Cs(c) and Cs(a). Furthermore, we found that hydroquinone-induced cell damage was inhibited by the pretreatment of catalase, ascorbic acid, dimethyl sulfoxide (DMSO), and ethylenediaminetetraacetic acid (EDTA), and augmented by superoxide dismutase (both CuZnSOD and MnSOD). The present results suggest that H2O2 is probably involved in hydroquinone-induced cytotoxicity in catalase-deficient E. coli mutants and catalase plays an important role in protection of the cells against hydroquinone toxicity.

  13. Cytotoxic and aryl hydrocarbon hydroxylase-inducing effects of laboratory rodent diets. A cell culture study

    SciTech Connect

    Toerroenen, R.; Pelkonen, K.; Kaerenlampi, S. )

    1991-01-01

    Extracts of several rodent diets were studied for their cytotoxic and aryl hydrocarbon hydroxylase-inducing properties by an in vitro method. The cell culture system based on a mouse hepatoma cell line (Hepa-1) was shown to be convenient and sensitive method for screening of diets for these parameters implying the presence of compounds potentially harmful in vivo. Considerable differences among diets and batches were detected. Smallest effects were observed with a semipurified diet and with the unrefined diet which - contrary to other four unrefined diets - contained no fish.

  14. Methylglyoxal-induced DNA-protein cross-links and cytotoxicity in Chinese hamster ovary cells.

    PubMed

    Brambilla, G; Sciabà, L; Faggin, P; Finollo, R; Bassi, A M; Ferro, M; Marinari, U M

    1985-05-01

    The technique of alkaline elution was applied to study the capacity of methylglyoxal to induce DNA damage and repair in Chinese hamster ovary cells. DNA cross-linking was observed after a 90-min exposure to a subtoxic dose (1.5 mM), and the cross-links were fully repaired by 24 h. The cross-linking appeared to be DNA-protein in nature, since proteinase treatment removed the effect. When the same cells were exposed to methylglyoxal in the presence of a rat liver metabolic system, both cytotoxicity and cross-linking frequency were significantly reduced.

  15. Cell death induced by AC magnetic fields and magnetic nanoparticles: current state and perspectives.

    PubMed

    Goya, Gerardo F; Asín, Laura; Ibarra, M Ricardo

    2013-12-01

    This review analyses the advances in the field of magnetically induced cell death using intracellular magnetic nanoparticles (MNPs). Emphasis has been given to in vitro research results, discussing the action of radiofrequency (RF) waves on biological systems as well as those results of thermally induced cell death in terms of MNP cell interactions. Our main goal has been to provide a unified depiction of many recent experiments and theoretical models relevant to the effect of applied electromagnetic fields on MNPs after cellular uptake and the cytotoxicity assessment of MNPs. We have addressed the effects of RF waves used for in vitro magnetic hyperthermia on eukaryotic cells regarding physical modifications of the cellular local environment and cell viability.

  16. Hydrogen peroxide sensing and cytotoxicity activity of Acacia lignin stabilized silver nanoparticles.

    PubMed

    Aadil, Keshaw Ram; Barapatre, Anand; Meena, Avtar Singh; Jha, Harit

    2016-01-01

    The study is aimed at detection of hydrogen peroxide (H2O2) using Acacia lignin mediated silver nanoparticles (AGNPs). The synthesis of AGNPs was achieved at conditions optimized as, 3 ml of 0.02% lignin and 1mM silver nitrate incubated for 30 min at 80°C and pH 9. Initial screening of AGNPs was performed by measuring the surface plasmon resonance peak at 410-430 nm using UV-vis spectrophotometer. Transmission electron microscopy, atomic force microscopy, X-ray diffraction and particle size analysis confirmed the spherical shaped face centered cubic structure and 10-50 nm size of AGNPs. The infrared spectroscopy study further revealed that the active functional groups present in lignin were responsible for the reduction of silver ions (Ag(+)) to metallic silver (Ag(0)). Lignin stabilized silver nanoparticles showed good sensitivity and a linear response over wide concentrations of H2O2 (10(-1) to 10(-6)M). Further, the in vitrocytotoxicity activity of the lignin mediated AGNPs (5-500 μg/ml) demonstrated toxicity effects in MCF-7 and A375 cell lines. Thus, lignin stabilized silver nanoparticles based optical sensor for H2O2 could be potentially applied in the determination of reactive oxygen species and toxic chemicals which further expands the importance of lignin stabilized silver nanoparticles.

  17. Hydrogen peroxide sensing and cytotoxicity activity of Acacia lignin stabilized silver nanoparticles.

    PubMed

    Aadil, Keshaw Ram; Barapatre, Anand; Meena, Avtar Singh; Jha, Harit

    2016-01-01

    The study is aimed at detection of hydrogen peroxide (H2O2) using Acacia lignin mediated silver nanoparticles (AGNPs). The synthesis of AGNPs was achieved at conditions optimized as, 3 ml of 0.02% lignin and 1mM silver nitrate incubated for 30 min at 80°C and pH 9. Initial screening of AGNPs was performed by measuring the surface plasmon resonance peak at 410-430 nm using UV-vis spectrophotometer. Transmission electron microscopy, atomic force microscopy, X-ray diffraction and particle size analysis confirmed the spherical shaped face centered cubic structure and 10-50 nm size of AGNPs. The infrared spectroscopy study further revealed that the active functional groups present in lignin were responsible for the reduction of silver ions (Ag(+)) to metallic silver (Ag(0)). Lignin stabilized silver nanoparticles showed good sensitivity and a linear response over wide concentrations of H2O2 (10(-1) to 10(-6)M). Further, the in vitrocytotoxicity activity of the lignin mediated AGNPs (5-500 μg/ml) demonstrated toxicity effects in MCF-7 and A375 cell lines. Thus, lignin stabilized silver nanoparticles based optical sensor for H2O2 could be potentially applied in the determination of reactive oxygen species and toxic chemicals which further expands the importance of lignin stabilized silver nanoparticles. PMID:26434518

  18. Biomimetic synthesis of titania nanoparticles induced by protamine.

    PubMed

    Jiang, Yanjun; Yang, Dong; Zhang, Lei; Li, Lin; Sun, Qianyun; Zhang, Yufei; Li, Jian; Jiang, Zhongyi

    2008-08-21

    Protamine, a kind of cationic protein extracted from sperm nuclei, was employed for the first time in vitro to induce the formation of a titania/protamine nanoparticle composite from a water-stable titanium precursor, titanium(IV) bis(ammonium lactato) dihydroxide (Ti-BALDH). The resulting titania/protamine nanoparticle composite was extensively characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and X-ray photoelectron spectroscopy (XPS). The titania/protamine nanoparticle composite was of amorphous structure, and exhibited a different morphology from those prepared by an alkali-catalyzed approach. The catalyzing and templating function of protamine involved in the synthesis of the nanoparticle composite is discussed, and a mechanism tentatively proposed. In addition, the effects of pH and temperature on the amount and size of as-prepared titania/protamine nanoparticle composite were systematically investigated.

  19. Physico-chemical characterization and cytotoxicity evaluation of curcumin loaded in chitosan/chondroitin sulfate nanoparticles.

    PubMed

    Jardim, Katiúscia Vieira; Joanitti, Graziella Anselmo; Azevedo, Ricardo Bentes; Parize, Alexandre Luis

    2015-11-01

    In this study, chitosan (CTS)/chondroitin sulfate (CS) nanoparticles, both pure and curcumin-loaded, were synthesized by ionic gelation. This method is simple and efficient for obtaining nanoparticles with a low polydispersity index (0.151±0.03 to 0.563±0.07) and hydrodynamic diameter in the range of 175.7±2.5 to 710.2±8.9nm, for this study. Samples have a relatively high zeta potential value, a fact that indicates that the colloidal system has good physical and chemical stabilities. The efficiency of the curcumin encapsulation in nanoparticles, which ranged from 62.4±0.61% to 68.3±0.88%, depends on the pH of the chitosan solution. The release of curcumin from the nanoparticles was enabled by a diffusion mechanism, with fast release in a phosphate buffer solution at pH6.8. The assaying of cell viability by the MTT test showed that the presence of both free curcumin and curcumin in the nanoencapsulated form leads to a statistically significant reduction in the viability of A549 cells, by comparison with the control group. The most significant reductions in cell viability of 41.1% and 60.4% (p<0.0001) were observed after 72h, by using 40μmol∙L(-1) free curcumin and curcumin encapsulated in CTS/CS nanoparticles with the chitosan solution at pH6.0, respectively.

  20. Nickel oxide nanoparticles induce inflammation and genotoxic effect in lung epithelial cells.

    PubMed

    Capasso, Laura; Camatini, Marina; Gualtieri, Maurizio

    2014-04-01

    Nickel oxide nanoparticles (NiONPs) toxicity has been evaluated in the human pulmonary epithelial cell lines: BEAS-2B and A549. The nanoparticles, used at the doses of 20, 40, 60, 80, 100 μg/ml, induced a significant reduction of cell viability and an increase of apoptotic and necrotic cells at 24h. A significant release of interleukin-6 and -8 was assessed after 24h of treatment, even intracellular ROS increased already at 45 min after exposure. The results obtained evidenced that the cytokines release was dependent on mitogen activated protein kinases (MAPK) cascade through the induction of NF-kB pathway. NiONPs induced cell cycle alteration in both the cell lines even in different phases and these modifications may be induced by the NPs genotoxic effect, suggested by the nuclear translocation of phospho-ATM and phospho-ATR. Our results confirm the cytotoxic and pro-inflammatory potential of NiONPs. Moreover their ability in inducing DNA damage responses has been demonstrated. Such effects were present in A549 cells which internalize the NPs and BEAS-2B cells in which endocytosis has not been observed. PMID:24503009

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

    PubMed Central

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

    2012-01-01

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

  2. Aggregation in charged nanoparticles solutions induced by different interactions

    NASA Astrophysics Data System (ADS)

    Abbas, S.; Kumar, Sugam; Aswal, V. K.; Kohlbrecher, J.

    2016-05-01

    Small-angle neutron scattering (SANS) has been used to study the aggregation of anionic silica nanoparticles as induced through different interactions. The nanoparticle aggregation is induced by addition of salt (NaCl), cationic protein (lysozyme) and non-ionic surfactant (C12E10) employing different kind of interactions. The results show that the interaction in presence of salt can be explained using DLVO theory whereas non-DLVO forces play important role for interaction of nanoparticles with protein and surfactant. The presence of salt screens the repulsion between charged nanoparticles giving rise to a net attraction in the DLVO potential. On the other hand, strong electrostatic attraction between nanoparticle and oppositely charged protein leads to protein-mediated nanoparticle aggregation. In case of non-ionic surfactant, the relatively long-range attractive depletion interaction is found to be responsible for the particle aggregation. Interestingly, the completely different interactions lead to similar kind of aggregate morphology. The nanoparticle aggregates formed are found to have mass fractal nature having a fractal dimension (~2.5) consistent with diffusion limited type of fractal morphology in all three cases.

  3. Complement-dependent cytotoxicity in rats bearing human adenovirus type 12-induced primary retinoblastoma-like tumor in the eye.

    PubMed

    Nishida, T; Mukai, N; Solish, S P

    1981-01-01

    Using an animal model of retinoblastoma in inbred rats and cultured human adenovirus type 12-induced retinoblastoma-like tumor cells (RAO 188), complement-dependent cytotoxicity was determined by measuring release of 3H-uridine labelled RNA. Sera from rats in which tumors did not grow after adenovirus type 12 inoculation had higher cytotoxicity against RAO 188 cells than sera from rats bearing primary adenovirus type 12-induced retinoblastoma-like tumor. These results showed that the rat which could raise antibodies against adenovirus type 12-induced retinoblastoma-like tumor cells did not allow the tumor growth in the eye after virus inoculation.

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

    PubMed

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

    2012-06-01

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

  5. Effect of population and gender on chemotherapeutic agent–induced cytotoxicity

    PubMed Central

    Huang, Rong Stephanie; Kistner, Emily O.; Bleibel, Wasim K.; Shukla, Sunita J.; Dolan, M. Eileen

    2009-01-01

    Large interindividual variance is observed in both response and toxicity associated with chemotherapy. Our goal is to identify factors that contribute to chemotherapy-induced toxicity. To this end, we used EBV-transformed B-lymphoblastoid HapMap cell lines derived from 30 Yoruban trios (African descent) and 30 Centre d' Etude du Polymorphisme Humain (CEPH) trios (European descent) to evaluate population- and gender-specific differences in cytotoxicity of carboplatin, cisplatin, daunorubicin, and etoposide using a high-throughput, short-term cytotoxicity assay. The IC50 was compared for population- and gender-specific differences for the four drugs. We observed large interindividual variance in IC50 values for carboplatin, cisplatin, daunorubicin, and etoposide for both Yoruban and CEPH populations (range from 8- to 433-fold). Statistically significant differences in carboplatin and daunorubicin IC50 were shown when comparing Yoruban cell lines (n = 89) to CEPH cell lines (n = 87; P = 0.002 and P = 0.029, respectively). This population difference in treatment induced cytotoxicity was not seen for either cisplatin or etoposide. In the Yoruban population, cell lines derived from females were less sensitive to platinating agents than males [median carboplatin IC50, 29.1 versus 24.6 μmol/L (P = 0.012); median cisplatin IC50, 7.0 versus 6.0 μmol/L (P = 0.020) in female and male, respectively]. This difference was not observed in the CEPH population. These results show that population and gender may affect risk for toxicities associated with certain chemotherapeutic agents. PMID:17237264

  6. Cytotoxicity and apoptotic gene expression in an in vitro model of the blood-brain barrier following exposure to poly(butylcyanoacrylate) nanoparticles.

    PubMed

    Hall, Andrew M; Hemmer, Ruth; Spaulding, Robert; Wetzel, Hanna N; Curcio, Joseph; Sabel, Bernhard A; Henrich-Noack, Petra; Pixley, Sarah; Hopkins, Tracy; Boyce, Richard L; Schultheis, Patrick J; Haik, Kristi L

    2016-08-01

    Background Poly(butylcyanoacrylate) (PBCA) nanoparticles (NPs) loaded with doxorubicin (DOX) and coated with polysorbate 80 (PS80) have shown efficacy in the treatment of rat glioblastoma. However, cytotoxicity of this treatment remains unclear. Purpose The purpose of this study was to investigate cytotoxicity and apoptotic gene expression using a proven in vitro co-culture model of the blood-brain barrier. Methods The co-cultures were exposed to uncoated PBCA NPs, PBCA-PS80 NPs or PBCA-PS80-DOX NPs at varying concentrations and evaluated using a resazurin-based cytotoxicity assay and an 84-gene apoptosis RT-PCR array. Results The cytotoxicity assays showed PBCA-PS80-DOX NPs exhibited a decrease in metabolic function at lower concentrations than uncoated PBCA NPs and PBCA-PS80 NPs. The apoptosis arrays showed differential expression of 18 genes in PBCA-PS80-DOX treated cells compared to the untreated control. Discussion As expected, the cytotoxicity assays demonstrated enhanced dose-dependent toxicity in the DOX loaded NPs. The differentially expressed apoptotic genes participate in both the tumor necrosis factor receptor-1 and mitochondria-associated apoptotic pathways implicated in current DOX chemotherapeutic toxicity. Conclusion The following data suggest that the cytotoxic effect may be attributed to DOX and not the NPs themselves, further supporting the use of PBCA-PS80 NPs as an effective drug delivery vehicle for treating central nervous system conditions.

  7. Sterically induced shape control of magnetite nanoparticles

    NASA Astrophysics Data System (ADS)

    Zhang, Ling; Dou, Yong-Hua; Gu, Hong-Chen

    2006-11-01

    Starlike and flowerlike Fe 3O 4 nanoparticles were synthesized by the pyrolysis method using 1- adamantanecarboxylic acid (ACA) and oleylamine (OLA), ACA and 1-adamantaneamine (AA) as the combined surfactants, respectively. XRD, TEM, HRTEM, PPMS are used to characterize the structure and magnetic property of the as-synthesized nanostructures. Control over the morphology of these nanoparticles was realized by using different surfactants under otherwise similar reaction conditions.

  8. Towards understanding mechanisms governing cytotoxicity of metal oxides nanoparticles: hints from nano-QSAR studies.

    PubMed

    Gajewicz, Agnieszka; Schaeublin, Nicole; Rasulev, Bakhtiyor; Hussain, Saber; Leszczynska, Danuta; Puzyn, Tomasz; Leszczynski, Jerzy

    2015-05-01

    The production of nanomaterials increases every year exponentially and therefore the probability these novel materials that they could cause adverse outcomes for human health and the environment also expands rapidly. We proposed two types of mechanisms of toxic action that are collectively applied in a nano-QSAR model, which provides governance over the toxicity of metal oxide nanoparticles to the human keratinocyte cell line (HaCaT). The combined experimental-theoretical studies allowed the development of an interpretative nano-QSAR model describing the toxicity of 18 nano-metal oxides to the HaCaT cell line, which is a common in vitro model for keratinocyte response during toxic dermal exposure. The comparison of the toxicity of metal oxide nanoparticles to bacteria Escherichia coli (prokaryotic system) and a human keratinocyte cell line (eukaryotic system), resulted in the hypothesis that different modes of toxic action occur between prokaryotic and eukaryotic systems.

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

    PubMed

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

    2015-08-01

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

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

    PubMed Central

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

    2013-01-01

    Objective To synthesize silver nanopaticles from leaves extract of Eucalyptus chapmaniana (E. chapmaniana) and test the antimicrobial of the nanoparticles against different pathogenic bacteria, yeast and its toxicity against human acute promyelocytic leukemia (HL-60) cell line. Methods Ten milliliter of leaves extract was mixed with 90 mL of 0.01 mmol/mL or 0.02 mmol/mL aqueous AgNO3 and exposed to sun light for 1 h. A change from yellowish to reddish brown color was observed. Characterization using UV-vis spectrophotometery and X-ray diffraction analysis were performed. Antimicrobial activity against six microorganisms was tested using well diffusion method and cytoxicity test using 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole was obtained on the human leukemia cell line (HL-60). Results UV-vis spectral analysis showed silver surface plasmon resonance band at 413 nm. X-ray diffraction showed that the particles were crystalline in nature with face centered cubic structure of the bulk silver with broad beaks at 38.50° and 44.76°. The synthesized silver nanoparticles efficiently inhibited various pathogenic organisms and reduced viability of the HL-60 cells in a dose-dependent manner. Conclusions It has been demonstrated that the extract of E. chapmaniana leaves are capable of producing silver nanoparticles extracellularly and the Ag nanoparticles are quite stable in solution. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the antimicrobial and anticancer activity of these particles. PMID:23570018

  11. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer specific cytotoxicity and tumor growth delay

    PubMed Central

    Christensen, Camilla L.; Gjetting, Torben; Poulsen, Thomas T.; Cramer, Frederik; Roth, Jack A.; Poulsen, Hans S.

    2012-01-01

    Purpose Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment and novel therapies are therefore in high demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug Experimental design The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter Insulinoma-associated 1 (INSM1). Therapeutic effect was evaluated in vitro in SCLC cell lines and in vivo in SCLC xenografted nude mice using the non-viral nanoparticle, DOTAP:Cholesterol for transgene delivery. Results INSM1-YCD/5-FC and INSM1-YCD-YUPRT/5-FC therapy induced high cytotoxicity in a range of SCLC cell lines. The highest therapeutic effect was obtained from the YCD-YUPRT fusion gene strategy. No cytotoxicity was induced after treatment of cell lines of other origin than SCLC. In addition the INSM1-YCD-YUPRT/5-FC therapy was superior to an established suicide gene system consisting of the Herpes Simplex Virus Thymidine Kinase (HSVTK) gene and prodrug Ganciclovir (GCV). The superior effect was in part due to massive bystander cytotoxicity of YCD-YUPRT-produced toxins. Finally, INSM1-YCD-YUPRT/5-FC therapy induced significant tumor growth delay in SCLC xenografts compared to control treated xenografts. Conclusions The current study is the first to test cytosine deaminase-based suicide gene therapy for SCLC and the first to demonstrate an anti-tumor effect from the delivery of suicide gene therapeutics for SCLC in vivo. PMID:20371678

  12. Role of soluble zinc in ZnO nanoparticle cytotoxicity in Daphnia magna: A morphological approach.

    PubMed

    Bacchetta, Renato; Maran, Barbara; Marelli, Marcello; Santo, Nadia; Tremolada, Paolo

    2016-07-01

    The role of soluble zinc has been determined in Daphnia magna by a morphological approach, integrating a previous paper in which the ultrastructural damages to gut epithelial cells have been studied after ZnO nanoparticles exposure. In the present paper, the toxicity and morphological effects of soluble zinc from ZnSO4 have been determined in a 48-h acute exposure test. Daphnids have been exposed to six nominal zinc concentrations (0.075, 0.15, 0.3, 0.6, 1.2, and 2.4mg Zn/L) and then fixed for microscopic analyses. Data from the acute toxicity tests gave an EC50 value of 0.99mg/L and showed that no immobilization appeared up to 0.3mg Zn/L. Ultrastructural analyses of samples from the two highest concentrations showed large vacuolar structures, swelling of mitochondria, multilamellar bodies, and a great number of autophagy vacuoles. These findings have been compared to those from our previous study, and similarities and/or differences discussed. Based on the overall results it can be concluded that dissolved zinc ions played a key role in ZnO nanoparticle toxicity and that the morphological approach is an extremely useful tool for comparing toxicological effects as well. A possible common toxic mechanism of soluble zinc and ZnO nanoparticles was also proposed. PMID:27131075

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  15. Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia Cells.

    PubMed

    Turrini, Eleonora; Calcabrini, Cinzia; Sestili, Piero; Catanzaro, Elena; de Gianni, Elena; Diaz, Anna Rita; Hrelia, Patrizia; Tacchini, Massimo; Guerrini, Alessandra; Canonico, Barbara; Papa, Stefano; Valdrè, Giovanni; Fimognari, Carmela

    2016-01-01

    Cancer chemotherapy is characterized by an elevated intrinsic toxicity and the development of drug resistance. Thus, there is a compelling need for new intervention strategies with an improved therapeutic profile. Immunogenic cell death (ICD) represents an innovative anticancer strategy where dying cancer cells release damage-associated molecular patterns promoting tumor-specific immune responses. The roots of Withania somnifera (W. somnifera) are used in the Indian traditional medicine for their anti-inflammatory, immunomodulating, neuroprotective, and anticancer activities. The present study is designed to explore the antileukemic activity of the dimethyl sulfoxide extract obtained from the roots of W. somnifera (WE). We studied its cytostatic and cytotoxic activity, its ability to induce ICD, and its genotoxic potential on a human T-lymphoblastoid cell line by using different flow cytometric assays. Our results show that WE has a significant cytotoxic and cytostatic potential, and induces ICD. Its proapoptotic mechanism involves intracellular Ca(2+) accumulation and the generation of reactive oxygen species. In our experimental conditions, the extract possesses a genotoxic potential. Since the use of Withania is suggested in different contexts including anti-infertility and osteoarthritis care, its genotoxicity should be carefully considered for an accurate assessment of its risk-benefit profile.

  16. Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia Cells

    PubMed Central

    Turrini, Eleonora; Calcabrini, Cinzia; Sestili, Piero; Catanzaro, Elena; de Gianni, Elena; Diaz, Anna Rita; Hrelia, Patrizia; Tacchini, Massimo; Guerrini, Alessandra; Canonico, Barbara; Papa, Stefano; Valdrè, Giovanni; Fimognari, Carmela

    2016-01-01

    Cancer chemotherapy is characterized by an elevated intrinsic toxicity and the development of drug resistance. Thus, there is a compelling need for new intervention strategies with an improved therapeutic profile. Immunogenic cell death (ICD) represents an innovative anticancer strategy where dying cancer cells release damage-associated molecular patterns promoting tumor-specific immune responses. The roots of Withania somnifera (W. somnifera) are used in the Indian traditional medicine for their anti-inflammatory, immunomodulating, neuroprotective, and anticancer activities. The present study is designed to explore the antileukemic activity of the dimethyl sulfoxide extract obtained from the roots of W. somnifera (WE). We studied its cytostatic and cytotoxic activity, its ability to induce ICD, and its genotoxic potential on a human T-lymphoblastoid cell line by using different flow cytometric assays. Our results show that WE has a significant cytotoxic and cytostatic potential, and induces ICD. Its proapoptotic mechanism involves intracellular Ca2+ accumulation and the generation of reactive oxygen species. In our experimental conditions, the extract possesses a genotoxic potential. Since the use of Withania is suggested in different contexts including anti-infertility and osteoarthritis care, its genotoxicity should be carefully considered for an accurate assessment of its risk–benefit profile. PMID:27187469

  17. Cytotoxicity of zinc oxide nanoparticles on antioxidant enzyme activities and mRNA expression in the cocultured C2C12 and 3T3-L1 cells.

    PubMed

    Pandurangan, Muthuraman; Veerappan, Muthuviveganandavel; Kim, Doo Hwan

    2015-02-01

    The present study was aimed to investigate the dose-dependent effect of zinc oxide (ZnO) nanoparticles on antioxidant enzyme activities and messenger RNA (mRNA) expression in the cocultured C2C12 and 3T3-L1 cells. Coculturing experiments are 3D and more reliable compared to mono-culture (2D) experiment. Even though, there are several studies on ZnO nanoparticle-mediated cytotoxicity, but there are no studies on the effect of ZnO nanoparticle on antioxidant enzyme activities and mRNA expression in the cocultured C2C12 and 3T3-L1 cells. A cytotoxicity assay was carried out to determine the effect of ZnO nanoparticles on the C2C12 and 3T3-L1 cell viability. At higher concentration of ZnO nanoparticles, C2C12 and 3T3-L1 cells almost die. ZnO nanoparticles increased reactive oxygen species (ROS) and lipid peroxidation and reduced glutathione (GSH) levels in a dose-dependent manner in the C2C12 and 3T3-L1 cells. In addition, ZnO nanoparticles increased antioxidant enzyme activities and their mRNA expression in the C2C12 and 3T3-L1 cells. In conclusion, the present study showed that ZnO nanoparticles increased oxidative stress, antioxidant enzyme activities, and their mRNA expression in the cocultured C2C12 and 3T3-L1 cells. PMID:25380643

  18. Anti-biofilm activity of chitosan gels formulated with silver nanoparticles and their cytotoxic effect on human fibroblasts.

    PubMed

    Pérez-Díaz, M; Alvarado-Gomez, E; Magaña-Aquino, M; Sánchez-Sánchez, R; Velasquillo, C; Gonzalez, C; Ganem-Rondero, A; Martínez-Castañon, G; Zavala-Alonso, N; Martinez-Gutierrez, F

    2016-03-01

    The development of multi-species biofilms in chronic wounds is a serious health problem that primarily generates strong resistance mechanisms to antimicrobial therapy. The use of silver nanoparticles (AgNPs) as a broad-spectrum antimicrobial agent has been studied previously. However, their cytotoxic effects limit its use within the medical area. The purpose of this study was to evaluate the anti-biofilm capacity of chitosan gel formulations loaded with AgNPs, using silver sulfadiazine (SSD) as a standard treatment, on strains of clinical isolates, as well as their cytotoxic effect on human primary fibroblasts. Multi-species biofilm of Staphylococcus aureus oxacillin resistant (MRSA) and Pseudomonas aeruginosa obtained from a patient with chronic wound infection were carried out using a standard Drip Flow Reactor (DFR) under conditions that mimic the flow of nutrients in the human skin. Anti-biofilm activity of chitosan gels and SSD showed a log-reduction of 6.0 for MRSA when chitosan gel with AgNPs at a concentration of 100 ppm was used, however it was necessary to increase the concentration of the chitosan gel with AgNPs to 1000 ppm to get a log-reduction of 3.3, while the SSD showed a total reduction of both bacteria in comparison with the negative control. The biocompatibility evaluation on primary fibroblasts showed better results when the chitosan gels with AgNPs were tested even in the high concentration, in contrast with SSD, which killed all the primary fibroblasts. In conclusion, chitosan gel formulations loaded with AgNPs effectively prevent the formation of biofilm and kill bacteria in established biofilm, which suggest that chitosan gels with AgNPs could be used for prevention and treatment of infections in chronic wounds. The statistic significance of the biocompatibility of chitosan gel formulations loaded with AgNPs represents an advance; however further research and development are necessary to translate this technology into therapeutic and

  19. Butachlor is cytotoxic and clastogenic and induces apoptosis in mammalian cells.

    PubMed

    Panneerselvam, N; Sinha, S; Shanmugam, G

    1999-09-01

    The ability of butachlor to induce cytotoxicity, clastogenicity and DNA damage was assessed using Chinese hamster ovary cells (CHO), Swiss mouse embryo fibroblasts (MEF) and human peripheral blood lymphocytes. A dose and time dependent loss of viability was evident upon treatment of CHO cells with butachlor. Cell killing to an extent of 50% was observed when cells were treated with 16.2 micrograms/ml of butachlor for 24 hr or with 11.5 micrograms/ml for 48 hr. The herbicide induced micronuclei significantly in cultured lymphocytes at 24 and 48 hr of treatment suggesting that it is clastogenic. To understand the mechanism of cell death caused by butachlor, its effect on DNA strand breaks was studied in MEF. A concomitant decrease in cell viability was observed with increase in DNA strand breaks. Agarose gel electrophoresis of DNA from herbicide treated CHO cells and cytochemical staining indicate the induction of apoptosis by butachlor.

  20. Characterization of the cytotoxin produced by macrophages in response to dengue virus-induced cytotoxic factor.

    PubMed Central

    Gulati, L.; Chaturvedi, U. C.; Mathur, A.

    1983-01-01

    We have observed earlier that dengue type 2 virus-induced cytotoxic factor (CF) induces macrophages to produce a cytotoxin (CF2) which kills mainly the macrophages, some of the T lymphocytes and has no effect on B-lymphocytes of normal mouse spleen. The findings of the present study show that CF2 is heat-labile, trypsin-sensitive and unstable at acid and alkaline pH. It is a low molecular weight product as it is dialysable, non-sedimentable on ultracentrifugation at 103,500 g for 3 h and passes through 0.22 micron Millipore filter. It is adsorbed onto the target normal mouse spleen cells. The properties of CF and CF2 have been compared. PMID:6849814

  1. A Comparison between the cytotoxic effects of pure curcumin and curcumin-loaded PLGA-PEG nanoparticles on the MCF-7 human breast cancer cell line.

    PubMed

    Tabatabaei Mirakabad, Fatemeh Sadat; Akbarzadeh, Abolfazl; Milani, Morteza; Zarghami, Nosratollah; Taheri-Anganeh, Mortaza; Zeighamian, Vahideh; Badrzadeh, Fariba; Rahmati-Yamchi, Mohammad

    2016-01-01

    Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women worldwide. Herbal medicines have tremendous potential as promising agents for the treatment of cancer. Curcumin is a natural polyphenol which has many anticancer effects. Because of its low aqueous solubility, low bioavailability, and quick degradation and metabolism, curcumin was released using PLGA-PEG nanoparticles. Herein, the efficiency of pure curcumin and curcumin-loaded PLGA-PEG in MCF-7 human breast cancer cell lines was studied. (1)H NMR, FT-IR and SEM demonstrated PLGA-PEG structure and curcumin loaded on nanoparticles. Subsequently, the cytotoxic effects of free curcumin and curcumin-loaded PLGA-PEG were determined via an MTT assay. Our study confirmed that curcumin-loaded PLGA-PEG has more cytotoxic effects on the MCF-7 breast cancer cell line and could be exploited as a potential source for developing novel drugs against breast cancer.

  2. Inflammatory and cytotoxic responses of an alveolar-capillary coculture model to silica nanoparticles: Comparison with conventional monocultures

    PubMed Central

    2011-01-01

    Background To date silica nanoparticles (SNPs) play an important role in modern technology and nanomedicine. SNPs are present in various materials (tyres, electrical and thermal insulation material, photovoltaic facilities). They are also used in products that are directly exposed to humans such as cosmetics or toothpaste. For that reason it is of great concern to evaluate the possible hazards of these engineered particles for human health. Attention should primarily be focussed on SNP effects on biological barriers. Accidentally released SNP could, for example, encounter the alveolar-capillary barrier by inhalation. In this study we examined the inflammatory and cytotoxic responses of monodisperse amorphous silica nanoparticles (aSNPs) of 30 nm in size on an in vitro coculture model mimicking the alveolar-capillary barrier and compared these to conventional monocultures. Methods Thus, the epithelial cell line, H441, and the endothelial cell line, ISO-HAS-1, were used in monoculture and in coculture on opposite sides of a filter membrane. Cytotoxicity was evaluated by the MTS assay, detection of membrane integrity (LDH release), and TER (Transepithelial Electrical Resistance) measurement. Additionally, parameters of inflammation (sICAM-1, IL-6 and IL-8 release) and apoptosis markers were investigated. Results Regarding toxic effects (viability, membrane integrity, TER) the coculture model was less sensitive to apical aSNP exposure than the conventional monocultures of the appropriate cells. On the other hand, the in vitro coculture model responded with the release of inflammatory markers in a much more sensitive fashion than the conventional monoculture. At concentrations that were 10-100fold less than the toxic concentrations the apically exposed coculture showed a release of IL-6 and IL-8 to the basolateral side. This may mimic the early inflammatory events that take place in the pulmonary alveoli after aSNP inhalation. Furthermore, a number of apoptosis markers

  3. Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells

    PubMed Central

    Tang, Xiang-Jun; Huang, Kuan-Ming; Gui, Hui; Wang, Jun-Jie; Lu, Jun-Ti; Dai, Long-Jun; Zhang, Li; Wang, Gang

    2016-01-01

    As one of the natural herbal flavonoids, myricetin has attracted much research interest, mainly owing to its remarkable anticancer properties and negligible side effects. It holds great potential to be developed as an ideal anticancer drug through improving its bioavailability. This study was performed to investigate the effects of Pluronic-based micelle encapsulation on myricetin-induced cytotoxicity and the mechanisms underlying its anticancer properties in human glioblastoma cells. Cell viability was assessed using a methylthiazol tetrazolium assay and a real-time cell analyzer. Immunoblotting and quantitative reverse transcriptase polymerase chain reaction techniques were used for determining the expression levels of related molecules in protein and mRNA. The results indicated that myricetin-induced cytotoxicity was highly potentiated by the encapsulation of myricetin. Mitochondrial apoptotic pathway was demonstrated to be involved in myricetin-induced glioblastoma cell death. The epidermal growth factor receptor (EGFR)/PI3K/Akt pathway located in the plasma membrane and cytosol and the RAS-ERK pathway located in mitochondria served as upstream and downstream targets, respectively, in myricetin-induced apoptosis. MiR-21 inhibitors interrupted the expression of EGFR, p-Akt, and K-Ras in the same fashion as myricetin-loaded mixed micelles (MYR-MCs) and miR-21 expression were dose-dependently inhibited by MYR-MCs, indicating the interaction of miR-21 with MYR-MCs. This study provided evidence supportive of further development of MYR-MC formulation for preferentially targeting mitochondria of glioblastoma cells. PMID:27757032

  4. Molecular Mechanism of Silver Nanoparticles-Induced Human Osteoblast Cell Death: Protective Effect of Inducible Nitric Oxide Synthase Inhibitor

    PubMed Central

    Zielinska, Ewelina; Tukaj, Cecylia; Radomski, Marek Witold; Inkielewicz-Stepniak, Iwona

    2016-01-01

    Background Silver nanoparticles (AgNPs) show strong antibacterial properties, making them excellent candidates to be used in orthopaedic repair and regeneration. However, there are concerns regarding the cytotoxicity of AgNPs and molecular mechanisms underlying AgNPs-induced bone cells toxicity have not been elucidated. Therefore, the aim of our study was to explore mechanisms of AgNPs-induced osteoblast cell death with particular emphasis on the role of nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS). Methods and Result Silver nanoparticles used in this study were 18.3±2.6 nm in size, uncoated, spherical, regular shape and their zeta potential was -29.1±2.4 mV as measured by transmission electron microscopy (TEM) and zetasizer. The release of silver (Ag) from AgNPs was measured in cell culture medium by atomic absorption spectroscopy (AAS). The exposure of human osteoblast cells (hFOB 1.19) to AgNPs at concentration of 30 or 60 μg/mL for 24 or 48 hours, respectively resulted in cellular uptake of AgNPs and changes in cell ultrastructure. These changes were associated with apoptosis and necrosis as shown by flow cytometry and lactate dehydrogenase (LDH) assay as well as increased levels of pro-apoptotic Bax and decreased levels of anti-apoptotic Bcl-2 mRNA and protein. Importantly, we have found that AgNPs elevated the levels of nitric oxide (NO) with concomitant upregulation of inducible nitric oxide synthase (iNOS) mRNA and protein. A significant positive correlation was observed between the concentration of AgNPs and iNOS at protein and mRNA level (r = 0.837, r = 0.721, respectively; p<0.001). Finally, preincubation of osteoblast cells with N-iminoethyl-l-lysine (L-NIL), a selective iNOS inhibitor, as well as treating cells with iNOS small interfering RNAs (siRNA) significantly attenuated AgNPs-induced apoptosis and necrosis. Moreover, we have found that AgNPs-induced cells death is not related to Ag dissolution is cell culture medium

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

    PubMed

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

    2013-01-01

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

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

    SciTech Connect

    Wang, Yi-Fen; Shyu, Huey-Wen; Chang, Yi-Chuang; Tseng, Wei-Chang; Huang, Yeou-Lih; Lin, Kuan-Hua; Chou, Miao-Chen; Liu, Heng-Ling; Chen, Chang-Yu

    2012-03-01

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

  7. Cytotoxic Effects of Biosynthesized Zinc Oxide Nanoparticles on Murine Cell Lines

    PubMed Central

    Namvar, Farideh; Rahman, Heshu Sulaiman; Mohamad, Rosfarizan; Azizi, Susan; Tahir, Paridah Mohd; Chartrand, Max Stanley

    2015-01-01

    The aim of this study is to evaluate the in vitro cytotoxic activity and cellular effects of previously prepared ZnO-NPs on murine cancer cell lines using brown seaweed (Sargassum muticum) aqueous extract. Treated cancer cells with ZnO-NPs for 72 hours demonstrated various levels of cytotoxicity based on calculated IC50 values using MTT assay as follows: 21.7 ± 1.3 μg/mL (4T1), 17.45 ± 1.1 μg/mL (CRL-1451), 11.75 ± 0.8 μg/mL (CT-26), and 5.6 ± 0.55 μg/mL (WEHI-3B), respectively. On the other hand, ZnO-NPs treatments for 72 hours showed no toxicity against normal mouse fibroblast (3T3) cell line. On the other hand, paclitaxel, which imposed an inhibitory effect on WEHI-3B cells with IC50 of 2.25 ± 0.4, 1.17 ± 0.5, and 1.6 ± 0.09 μg/mL after 24, 48, and 72 hours treatment, respectively, was used as positive control. Furthermore, distinct morphological changes were found by utilizing fluorescent dyes; apoptotic population was increased via flowcytometry, while a cell cycle block and stimulation of apoptotic proteins were also observed. Additionally, the present study showed that the caspase activations contributed to ZnO-NPs triggered apoptotic death in WEHI-3 cells. Thus, the nature of biosynthesis and the therapeutic potential of ZnO-NPs could prepare the way for further research on the design of green synthesis therapeutic agents, particularly in nanomedicine, for the treatment of cancer. PMID:25784947

  8. Cytotoxic effects of biosynthesized zinc oxide nanoparticles on murine cell lines.

    PubMed

    Namvar, Farideh; Rahman, Heshu Sulaiman; Mohamad, Rosfarizan; Azizi, Susan; Tahir, Paridah Mohd; Chartrand, Max Stanley; Yeap, Swee Keong

    2015-01-01

    The aim of this study is to evaluate the in vitro cytotoxic activity and cellular effects of previously prepared ZnO-NPs on murine cancer cell lines using brown seaweed (Sargassum muticum) aqueous extract. Treated cancer cells with ZnO-NPs for 72 hours demonstrated various levels of cytotoxicity based on calculated IC50 values using MTT assay as follows: 21.7 ± 1.3 μg/mL (4T1), 17.45 ± 1.1 μg/mL (CRL-1451), 11.75 ± 0.8 μg/mL (CT-26), and 5.6 ± 0.55 μg/mL (WEHI-3B), respectively. On the other hand, ZnO-NPs treatments for 72 hours showed no toxicity against normal mouse fibroblast (3T3) cell line. On the other hand, paclitaxel, which imposed an inhibitory effect on WEHI-3B cells with IC50 of 2.25 ± 0.4, 1.17 ± 0.5, and 1.6 ± 0.09 μg/mL after 24, 48, and 72 hours treatment, respectively, was used as positive control. Furthermore, distinct morphological changes were found by utilizing fluorescent dyes; apoptotic population was increased via flowcytometry, while a cell cycle block and stimulation of apoptotic proteins were also observed. Additionally, the present study showed that the caspase activations contributed to ZnO-NPs triggered apoptotic death in WEHI-3 cells. Thus, the nature of biosynthesis and the therapeutic potential of ZnO-NPs could prepare the way for further research on the design of green synthesis therapeutic agents, particularly in nanomedicine, for the treatment of cancer. PMID:25784947

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

    PubMed

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

    2015-03-01

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

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

    PubMed

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

    2015-03-01

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

  11. Antibacterial, antibiofilm and cytotoxic effects of Nigella sativa essential oil coated gold nanoparticles.

    PubMed

    Manju, Sivalingam; Malaikozhundan, Balasubramanian; Vijayakumar, Sekar; Shanthi, Sathappan; Jaishabanu, Ameeramja; Ekambaram, Perumal; Vaseeharan, Baskaralingam

    2016-02-01

    This study reports the biological synthesis of gold nanoparticles using essential oil of Nigella sativa (NsEO-AuNPs). The synthesized NsEO-AuNPs were characterized by UV-visible spectra, X-ray diffraction (XRD), FTIR and Transmission electron microscopy (TEM). UV-vis spectra of NsEO-AuNPs showed strong absorption peak at 540 nm. The X-ray diffraction analysis revealed crystalline nature of nanoparticle with distinctive facets (111, 200, 220 and 311 planes) of NsEO-AuNPs. The FTIR spectra recorded peaks at 3388, 2842, 1685, 1607, 1391 and 1018 cm(-1). TEM studies showed the spherical shape of nanoparticles and the particle size ranges between 15.6 and 28.4 nm. The antibacterial activity of NsEO-AuNPs was greater against Gram positive Staphylococcus aureus MTCC 9542 (16 mm) than Gram negative Vibrio harveyi MTCC 7771 (5 mm) at the concentration of 10 μg ml(-1). NsEO-AuNPs effectively inhibited the biofilm formation of S. aureus and V. harveyi by decreasing the hydrophobicity index (78% and 46% respectively). The in-vitro anti-lung cancer activity confirmed by MTT assay on the cell line of A549 carcinoma cells showed IC50 values of bulk Au at 87.2 μg ml(-1), N. sativa essential oil at 64.15 μg ml(-1) and NsEO-AuNPs at 28.37 μg ml(-1). The IC50 value showed that NsEO-AuNPs was highly effective in inhibiting the A549 lung cancer cells compared to bulk Au and N. sativa essential oil.

  12. Antibacterial, antibiofilm and cytotoxic effects of Nigella sativa essential oil coated gold nanoparticles.

    PubMed

    Manju, Sivalingam; Malaikozhundan, Balasubramanian; Vijayakumar, Sekar; Shanthi, Sathappan; Jaishabanu, Ameeramja; Ekambaram, Perumal; Vaseeharan, Baskaralingam

    2016-02-01

    This study reports the biological synthesis of gold nanoparticles using essential oil of Nigella sativa (NsEO-AuNPs). The synthesized NsEO-AuNPs were characterized by UV-visible spectra, X-ray diffraction (XRD), FTIR and Transmission electron microscopy (TEM). UV-vis spectra of NsEO-AuNPs showed strong absorption peak at 540 nm. The X-ray diffraction analysis revealed crystalline nature of nanoparticle with distinctive facets (111, 200, 220 and 311 planes) of NsEO-AuNPs. The FTIR spectra recorded peaks at 3388, 2842, 1685, 1607, 1391 and 1018 cm(-1). TEM studies showed the spherical shape of nanoparticles and the particle size ranges between 15.6 and 28.4 nm. The antibacterial activity of NsEO-AuNPs was greater against Gram positive Staphylococcus aureus MTCC 9542 (16 mm) than Gram negative Vibrio harveyi MTCC 7771 (5 mm) at the concentration of 10 μg ml(-1). NsEO-AuNPs effectively inhibited the biofilm formation of S. aureus and V. harveyi by decreasing the hydrophobicity index (78% and 46% respectively). The in-vitro anti-lung cancer activity confirmed by MTT assay on the cell line of A549 carcinoma cells showed IC50 values of bulk Au at 87.2 μg ml(-1), N. sativa essential oil at 64.15 μg ml(-1) and NsEO-AuNPs at 28.37 μg ml(-1). The IC50 value showed that NsEO-AuNPs was highly effective in inhibiting the A549 lung cancer cells compared to bulk Au and N. sativa essential oil. PMID:26703114

  13. Lipidoid nanoparticle mediated silencing of Mcl-1 induces apoptosis in mantle cell lymphoma.

    PubMed

    Knapp, Christopher M; He, Jia; Lister, John; Whitehead, Kathryn A

    2016-05-01

    Conventional chemo-immunotherapy fails to cure the majority of mantle cell lymphoma patients and causes substantial toxicity. Resistant mantle cell lymphoma cells commonly overexpress and are dependent on the anti-apoptotic protein, Mcl-1, for survival. In this study, we use potent lipidoid nanoparticles to deliver siRNA to silence Mcl-1 expression. Studies were conducted using two different mantle cell lymphoma cell lines, a normal (JeKo-1) and an aggressive (MAVER-1) line, to assess the ability of lipidoid nanoparticles to be used broadly in the treatment of mantle cell lymphoma. Mcl-1 mRNA silencing and protein knockdown was observed as early as one day after treatment and the lipidoid nanoparticles achieved sustained silencing of Mcl-1 mRNA for at least four days in both JeKo-1 and MAVER-1 cells. Eighty percent silencing was achieved at three days post-transfection in JeKo-1 cells while 50% silencing was achieved in MAVER-1 cells, which are more resistant to transfection. Interestingly, silencing of Mcl-1 induced apoptosis in nearly 30% of both JeKo-1 and MAVER-1 cells three days post-transfection. Additionally, Mcl-1 silencing and the resultant apoptosis in mantle cell lymphoma cells were dose dependent. These data suggest that lipidoid nanoparticles siRNA therapy targeting Mcl-1 has potential as a new treatment modality for mantle cell lymphoma and many other cancers that overexpress Mcl-1. The combination of anti-Mcl-1 lipidoid nanoparticles with other forms of targeted therapy offers hope for reducing or replacing cytotoxic chemotherapy as standard treatment for mantle cell lymphoma. PMID:27022142

  14. Nanoparticles induce raft formation in phospholipid liposomes

    NASA Astrophysics Data System (ADS)

    Wang, Bo; Zhang, Liangfang; Granick, Steve

    2007-03-01

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

  15. NMO sera down-regulate AQP4 in human astrocyte and induce cytotoxicity independent of complement.

    PubMed

    Haruki, Hiroyo; Sano, Yasuteru; Shimizu, Fumitaka; Omoto, Masatoshi; Tasaki, Ayako; Oishi, Mariko; Koga, Michiaki; Saito, Kazuyuki; Takahashi, Toshiyuki; Nakada, Tsutomu; Kanda, Takashi

    2013-08-15

    Autoantibodies against astrocyte water channel aquaporin-4 (AQP4) are highly specific for neuromyelitis optica (NMO). However, the molecular mechanism of NMO still remains unclear. The purpose of this study was to identify the possible humoral mechanisms responsible for the occurrence of astrocytic damage. Human primary astrocytes (AST) were immortalized by retroviral vectors harboring temperature-sensitive SV40 T antigen gene and AQP4 cDNA (M23), designated as hAST-AQP4. The effects of NMO sera on the content and localization of AQP4, including cytotoxicity and astrocytic morphology, were evaluated. In addition, this study examined whether the amount and localization of AQP4 protein in astrocytes were influenced by direct contact with the immortalized human brain microvascular endothelial cell line, TY09. NMO sera alone induced cytotoxicity and addition of complement had a more harmful effect on hAST-AQP4. NMO sera also decreased AQP4 mRNA and protein. NMO sera alone up-regulated TNFα and IL-6 in astrocytes and co-incubation with anti-TNFα and anti-IL-6 neutralizing antibodies blocked both the cytotoxicity and reduction of AQP4 in astrocytes. In the experiment using the in vitro BBB models, AQP4 protein mainly localized at the astrocytic membrane after co-culture with TY09, in contact with TY09. The future elucidation of factors that up-regulate AQP4 in astrocytes presumably released by blood brain barrier forming endothelial cells and that block the production of inflammatory cytokines may therefore lead to the development of a novel therapeutic strategy.

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

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

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

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

    PubMed Central

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

    2013-01-01

    The construction of nanostructures from biodegradable precursors and shell/core crosslinking have been pursued as strategies to solve the problems of toxicity and limited stability, respectively. Polyphosphoester (PPE)-based micelles and crosslinked nanoparticles with non-ionic, anionic, cationic, and zwitterionic surface characteristics for potential packaging and delivery of therapeutic and diagnostic agents, were constructed using a quick and efficient synthetic strategy, and importantly, demonstrated remarkable differences in terms of cytotoxicity, immunotoxicity, and biofouling properties, as a function of their surface characteristics and also with dependence on crosslinking throughout the shell layers. For instance, crosslinking of zwitterionic micelles significantly reduced the immunotoxicity, as evidenced from the absence of secretions of any of the 23 measured cytokines from RAW 264.7 mouse macrophages treated with the nanoparticles. The micelles and their crosslinked analogs demonstrated lower cytotoxicity than several commercially-available vehicles, and their degradation products were not cytotoxic to cells at the range of the tested concentrations. PPE-nanoparticles are expected to have broad implications in clinical nanomedicine as alternative vehicles to those involved in several of the currently available medications. PMID:24264796

  18. Streptozotocin-induced cytotoxicity, oxidative stress and mitochondrial dysfunction in human hepatoma HepG2 cells.

    PubMed

    Raza, Haider; John, Annie

    2012-01-01

    Streptozotocin (STZ) is an antibiotic often used in the treatment of different types of cancers. It is also highly cytotoxic to the pancreatic beta-cells and therefore is commonly used to induce experimental type 1 diabetes in rodents. Resistance towards STZ-induced cytotoxicity in cancer cells has also been reported. Our previous studies have reported organ-specific toxicity and metabolic alterations in STZ-induced diabetic rats. STZ induces oxidative stress and metabolic complications. The precise molecular mechanism of STZ-induced toxicity in different tissues and carcinomas is, however, unclear. We have, therefore, investigated the mechanism of cytotoxicity of STZ in HepG2 hepatoma cells in culture. Cells were treated with different doses of STZ for various time intervals and the cytotoxicity was studied by observing the alterations in oxidative stress, mitochondrial redox and metabolic functions. STZ induced ROS and RNS formation and oxidative stress as measured by an increase in the lipid peroxidation as well as alterations in the GSH-dependent antioxidant metabolism. The mitochondria appear to be a highly sensitive target for STZ toxicity. The mitochondrial membrane potential and enzyme activities were altered in STZ treated cells resulting in the inhibition of ATP synthesis. ROS-sensitive mitochondrial aconitase activity was markedly inhibited suggesting increased oxidative stress in STZ-induced mitochondrial toxicity. These results suggest that STZ-induced cytotoxicity in HepG2 cells is mediated, at least in part, by the increase in ROS/RNS production, oxidative stress and mitochondrial dysfunction. Our study may be significant for better understanding the mechanisms of STZ action in chemotherapy and drug induced toxicity. PMID:22754329

  19. Enhancement of radiation cytotoxicity by gold nanoparticles in MCF-7 breast cancer cell lines

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

    Therapy combined with metallic nanoparticles is a new way to treat cancer, in which gold nanoparticles (AuNPs) are injected through intravenous administration and bound to tumor sites. Radiotherapy aims to deliver a high therapeutic dose of ionizing radiation to the tumor without exceeding normal tissue tolerance. The use of AuNPs which is a high-atomic-number (Z) material in radiotherapy will provide a high probability for photon interaction by photoelectric effect. These provide advantages in terms of radiation dose enhancement. The high linear energy transfer and short range of photoelectric interaction products (photoelectrons, characteristic x-rays, Auger electrons) produce localized dose enhancement of the tumor. In this work, breast cancer cell lines (MCF-7) are seeded in the 96-well plate and were treated with 13 nm AuNPs before they were irradiated with 6 MV and 10 MV photon beam from a medical linear accelerator at various radiation doses. To validate the enhanced killing effect, both with and without AuNPs MCF-7 cells is irradiated simultaneously. By comparison, the results show that AuNPs significantly enhance cancer killing.

  20. Enhancement of radiation cytotoxicity by gold nanoparticles in MCF-7 breast cancer cell lines

    SciTech Connect

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

    2015-04-24

    Therapy combined with metallic nanoparticles is a new way to treat cancer, in which gold nanoparticles (AuNPs) are injected through intravenous administration and bound to tumor sites. Radiotherapy aims to deliver a high therapeutic dose of ionizing radiation to the tumor without exceeding normal tissue tolerance. The use of AuNPs which is a high-atomic-number (Z) material in radiotherapy will provide a high probability for photon interaction by photoelectric effect. These provide advantages in terms of radiation dose enhancement. The high linear energy transfer and short range of photoelectric interaction products (photoelectrons, characteristic x-rays, Auger electrons) produce localized dose enhancement of the tumor. In this work, breast cancer cell lines (MCF-7) are seeded in the 96-well plate and were treated with 13 nm AuNPs before they were irradiated with 6 MV and 10 MV photon beam from a medical linear accelerator at various radiation doses. To validate the enhanced killing effect, both with and without AuNPs MCF-7 cells is irradiated simultaneously. By comparison, the results show that AuNPs significantly enhance cancer killing.

  1. Cytotoxicity of Ultrasmall Gold Nanoparticles on Planktonic and Biofilm Encapsulated Gram-Positive Staphylococci.

    PubMed

    Boda, Sunil Kumar; Broda, Janine; Schiefer, Frank; Weber-Heynemann, Josefine; Hoss, Mareike; Simon, Ulrich; Basu, Bikramjit; Jahnen-Dechent, Willi

    2015-07-01

    The emergence of multidrug resistant bacteria, especially biofilm-associated Staphylococci, urgently requires novel antimicrobial agents. The antibacterial activity of ultrasmall gold nanoparticles (AuNPs) is tested against two gram positive: S. aureus and S. epidermidis and two gram negative: Escherichia coli and Pseudomonas aeruginosa strains. Ultrasmall AuNPs with core diameters of 0.8 and 1.4 nm and a triphenylphosphine-monosulfonate shell (Au0.8MS and Au1.4MS) both have minimum inhibitory concentration (MIC) and minimum bactericidal concentration of 25 × 10(-6) m [Au]. Disc agar diffusion test demonstrates greater bactericidal activity of the Au0.8MS nanoparticles over Au1.4MS. In contrast, thiol-stabilized AuNPs with a diameter of 1.9 nm (AuroVist) cause no significant toxicity in any of the bacterial strains. Ultrasmall AuNPs cause a near 5 log bacterial growth reduction in the first 5 h of exposure, and incomplete recovery after 21 h. Bacteria show marked membrane blebbing and lysis in biofilm-associated bacteria treated with ultrasmall AuNP. Importantly, a twofold MIC dosage of Au0.8MS and Au1.4MS each cause around 80%-90% reduction in the viability of Staphylococci enveloped in biofilms. Altogether, this study demonstrates potential therapeutic activity of ultrasmall AuNPs as an effective treatment option against staphylococcal infections. PMID:25712910

  2. The significance of nanoparticles in particle-induced pulmonary fibrosis

    PubMed Central

    Byrne, James D; Baugh, John A

    2008-01-01

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

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

    PubMed

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

    2012-08-01

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

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

    PubMed

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

    2009-04-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2010-08-15

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

  7. Morphine Attenuated the Cytotoxicity Induced by Arsenic Trioxide in H9c2 Cardiomyocytes.

    PubMed

    Amini-Khoei, Hossein; Hosseini, Mir-Jamal; Momeny, Majid; Rahimi-Balaei, Maryam; Amiri, Shayan; Haj-Mirzaian, Arya; Khedri, Mostafa; Jahanabadi, Samane; Mohammadi-Asl, Ali; Mehr, Shahram Ejtemaie; Dehpour, Ahmad Reza

    2016-09-01

    Arsenic trioxide (ATO) is an efficient drug for the treatment of the patients with acute promyelocytic leukemia (APL). Inhibition of proliferation as well as apoptosis, attenuation of migration, and induction of differentiation in tumor cells are the main mechanisms through which ATO acts against APL. Despite advantages of ATO in treatment of some malignancies, certain harmful side effects, such as cardiotoxicity, have been reported. It has been well documented that morphine has antioxidant, anti-apoptotic, and cytoprotective properties and is able to attenuate cytotoxicity. Therefore, in this study, we aimed to investigate the protective effects of morphine against ATO toxicity in H9c2 myocytes using multi-parametric assay including thiazolyl blue tetrazolium bromide (MTT) assay, reactive oxygen species (ROS) generation, caspase 3 activity, nuclear factor kappa B (NF-κB) phosphorylation assay, and expression of apoptotic markers. Our results showed that morphine (1 μM) attenuated cytotoxicity induced by ATO in H9c2 cells. Results of this study suggest that morphine may have protective properties in management of cardiac toxicity in patients who receive ATO as an anti-cancer treatment. PMID:26815588

  8. Houttuynia cordata Thunb extract induces cytotoxicity in human nasopharyngeal carcinoma cells: Raman spectroscopic studies

    NASA Astrophysics Data System (ADS)

    Chen, Weiwei; Li, Zuanfang; Yu, Yun; Lin, Duo; Huang, Hao; Shi, Hong

    2016-01-01

    The molecular mechanisms of cytotoxicity induced by Houttuynia cordata Thunb (HCT) in nasopharyngeal carcinoma (NPC) cells was investigated by Raman spectroscopy (RS). The average Raman spectra of cell groups treated with HCT (0, 62.5, 125, 250, and 500 μg ml-1) for 24 h were measured separately. Compared to the control group, the intensities of the selected bands (1002, 1338, and 1448 cm-1) related to protein, DNA, and lipid in the treatment groups decreased obviously as the concentration of HCT increased. Both cell groups treated with 250 and 500 μg ml-1 of HCT could be differentiated from the control group by principal component analysis (PCA) combined with linear discriminate analysis (LDA) with a diagnostic accuracy of 100%, suggesting that cytotoxicity occurred and that 250 μg ml-1 was the proper dose for treatment. Simultaneously, the Raman spectra of cells treated with different treatment times with 250 μg ml-1 of HCT were obtained. We can get that treatment with HCT decreased cell viability in a dose and time-dependent fashion. The results indicated that the RS combined with PCA-LDA can be used for pharmacokinetics studies of HCT in NPC cells, which could also provide useful data for clinical dosage optimization for HCT.

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

    PubMed Central

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

    2015-01-01

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

  10. Strong and Nonspecific Synergistic Antibacterial Efficiency of Antibiotics Combined with Silver Nanoparticles at Very Low Concentrations Showing No Cytotoxic Effect.

    PubMed

    Panáček, Aleš; Smékalová, Monika; Kilianová, Martina; Prucek, Robert; Bogdanová, Kateřina; Večeřová, Renata; Kolář, Milan; Havrdová, Markéta; Płaza, Grażyna Anna; Chojniak, Joanna; Zbořil, Radek; Kvítek, Libor

    2015-12-28

    The resistance of bacteria towards traditional antibiotics currently constitutes one of the most important health care issues with serious negative impacts in practice. Overcoming this issue can be achieved by using antibacterial agents with multimode antibacterial action. Silver nano-particles (AgNPs) are one of the well-known antibacterial substances showing such multimode antibacterial action. Therefore, AgNPs are suitable candidates for use in combinations with traditional antibiotics in order to improve their antibacterial action. In this work, a systematic study quantifying the synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was performed. Employing the microdilution method as more suitable and reliable than the disc diffusion method, strong synergistic effects were shown for all tested antibiotics combined with AgNPs at very low concentrations of both antibiotics and AgNPs. No trends were observed for synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs, indicating non-specific synergistic effects. Moreover, a very low amount of silver is needed for effective antibacterial action of the antibiotics, which represents an important finding for potential medical applications due to the negligible cytotoxic effect of AgNPs towards human cells at these concentration levels.

  11. Enhanced accumulation of curcumin and temozolomide loaded magnetic nanoparticles executes profound cytotoxic effect in glioblastoma spheroid model.

    PubMed

    Dilnawaz, Fahima; Sahoo, Sanjeeb Kumar

    2013-11-01

    Glioblastomas (GBMs) are highly lethal primary brain tumours. Treatment of these malignant gliomas remains ineffective as these are extremely resistant to chemotherapeutic applications. Furthermore, combination therapy for cancer treatment is becoming more popular because it generates synergistic anticancer effects, by reducing individual drug-related toxicity and associated side effects. Currently, magnetic nanoparticles (MNPs) based drug delivery system has attracted much more attention owing to its intrinsic magnetic properties and drug loading capacity. In the present study, MNPs based drug delivery approach for co-delivering of potent chemotherapeutic drugs such as Curcumin (herbal drug) and Temozolomide (DNA methylating agent) has been implemented. The dual drug loaded MNPs formulations were evaluated in two-dimensional (2-D) monolayer culture and three-dimensional (3-D) tumour spheroid culture of T-98G cells for understanding the therapeutic discrepancy. The dual drug loaded MNPs formulations demonstrated higher cytotoxic effect than single drug loaded MNPs formulations as compared to their corresponding native drugs in 2-D and 3-D culture. The combination index (CI) analysis revealed synergistic mode of action of dual drug loaded MNPs formulations, which was further confirmed by cell death induction assay mediated by acridine orange (AO)/propidium iodide (PI) staining, illustrating higher efficacy of the formulation towards GBM therapy.

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

    PubMed

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

    2015-01-01

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

  13. In vitro cytotoxicity of hydrothermally synthesized ZnO nanoparticles on human periodontal ligament fibroblast and mouse dermal fibroblast cells.

    PubMed

    Seker, Sükran; Elçin, A Eser; Yumak, Tuğrul; Sınağ, Ali; Elçin, Y Murat

    2014-12-01

    The use of metal oxide nanoparticles (NPs) in industrial applications has been expanding, as a consequence, risk of human exposure increases. In this study, the potential toxic effects of zinc oxide (ZnO) NPs on human periodontal ligament fibroblast cells (hPDLFs) and on mouse dermal fibroblast cells (mDFs) were evaluated in vitro. We synthesized ZnO NPs (particle size; 7-8 nm) by the hydrothermal method. Characterization assays were performed with atomic force microscopy, Braun-Emmet-Teller analysis, and dynamic light scattering. The hPDLFs and mDFs were incubated with the NPs with concentrations of 0.1, 1, 10, 50 and 100 μg/mL for 6, 24 and 48h. Under the control and NP-exposed conditions, we have made different types of measurements for cell viability and morphology, membrane leakage and intracellular reactive oxygen species generation. Also, we monitored cell responses to ZnO NPs using an impedance measurement system in real-time. While the morphological changes were visualized using scanning electron microscopy, the subcellular localization of NPs was investigated by transmission electron microscopy. Results indicated that ZnO NPs have significant toxic effects on both of the primary fibroblastic cells at concentrations of ∼50-100 μg/mL. The cytotoxicity of ZnO NPs on fibroblasts depended on concentration and duration of exposure.

  14. Binding analysis of carbon nanoparticles to human immunoglobulin G: Elucidation of the cytotoxicity of CNPs and perturbation of immunoglobulin conformations

    NASA Astrophysics Data System (ADS)

    Zhang, Shengrui; Yang, Haitao; Ji, Xiaohui; Wang, Qin

    2016-02-01

    The chemical compositions, sizes and fluorescent properties of synthesized carbon nanoparticles (CNPs) were characterized. Escherichia coli (E. coli) cells were used as a model to study the cytotoxicity of CNPs, and the results of the cellular uptake of CNPs yielded excellent results: the CNPs demonstrated good biocompatibility and were non-toxic to the growth of the E. coli cells. Moreover, to assess the potential toxicity of CNPs to human health, the binding behavior of CNPs with human immunoglobulin G (HIgG) was examined by fluorescence quenching spectroscopy, synchronous fluorescence spectroscopy and circular dichroism spectroscopy under physiological conditions. The fluorescence quenching constants and parameters for the interaction at different temperatures had been calculated according to Scatchard. The thermodynamic parameters, such as enthalpy change (ΔH), entropy change (ΔS) and free energy change (ΔG), were calculated, and the results indicated strong static quenching and showed that van der Waals forces, hydrogen bonds and hydrophobic interactions were the predominant intermolecular forces stabilizing the CNP-HIgG complex. Synchronous fluorescence and circular dichroism spectra provided information regarding the conformational alteration of HIgG in the presence of CNPs. These findings help to characterize the interactions between CNPs and HIgG, which may clarify the potential risks and undesirable health effects of CNPs, as well as the related cellular trafficking and systemic translocation.

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

  16. Nanoparticle-Mediated, Light-Induced Phase Separations.

    PubMed

    Neumann, Oara; Neumann, Albert D; Silva, Edgar; Ayala-Orozco, Ciceron; Tian, Shu; Nordlander, Peter; Halas, Naomi J

    2015-12-01

    Nanoparticles that both absorb and scatter light, when dispersed in a liquid, absorb optical energy and heat a reduced fluid volume due to the combination of multiple scattering and optical absorption. This can induce a localized liquid-vapor phase change within the reduced volume without the requirement of heating the entire fluid. For binary liquid mixtures, this process results in vaporization of the more volatile component of the mixture. When subsequently condensed, these two steps of vaporization and condensation constitute a distillation process mediated by nanoparticles and driven by optical illumination. Because it does not require the heating of a large volume of fluid, this process requires substantially less energy than traditional distillation using thermal sources. We investigated nanoparticle-mediated, light-induced distillation of ethanol-H2O and 1-propanol-H2O mixtures, using Au-SiO2 nanoshells as the absorber-scatterer nanoparticle and nanoparticle-resonant laser irradiation to drive the process. For ethanol-H2O mixtures, the mole fraction of ethanol obtained in the light-induced process is substantially higher than that obtained by conventional thermal distillation, essentially removing the ethanol-H2O azeotrope that limits conventional distillation. In contrast, for 1-propanol-H2O mixtures the distillate properties resulting from light-induced distillation were very similar to those obtained by thermal distillation. In the 1-propanol-H2O system, a nanoparticle-mediated, light-induced liquid-liquid phase separation was also observed. PMID:26535465

  17. Enhancement of Cytotoxicity of Three Apoptosis-inducing Agents Against Human Oral Squamous Cell Carcinoma Cell Line by Benzoxazinotropone.

    PubMed

    Tomikoshi, Yukiko; Nomura, Maki; Okudaira, Noriyuki; Sakagami, Hiroshi; Wakabayashi, Hidetsugu

    Tumor-specificity (TS) and anti-inflammatory activity of benzo[b]cyclohept[e][1,4]oxazin-6(11H)-one, generally known as benzoxazinotropone (BOT), have been reported. In order to find a new biological activity, the combination effect of BOT and three apoptosis-inducing agents was investigated. Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and five human oral normal cells (gingival fibroblasts, periodontal ligament fibroblasts, pulp cells, oral keratinocytes and primary gingival epithelial cells) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. TS was evaluated by the ratio of the mean 50% cytotoxic concentration (CC50) against normal oral cells to the one against OSCC cell lines. Synergy was evaluated by CompuSyn software program. Expression of cleaved forms of poly ADP-ribose polymerase and caspsase-3 was evaluated by western blot analysis. BOT induced activation of caspase 3, suggesting the apoptosis induction in HSC-2 OSCC cells. BOT enhanced the cytotoxicity of doxorubicin (DXR) additively and that of curcumin and resveratrol synergistically. On the other hand, BOT did not enhance, but rather inhibit the cytotoxicity of DXR against normal keratinocytes. The present study suggests that BOT may enhance the anti-tumor activity of apoptosis-inducing agents, while reducing its cytotoxicity against normal cells. PMID:27566085

  18. Cytotoxicity of synthesized Iron Oxide nanoparticles: toward novel biomarkers of colon cancer.

    PubMed

    Raji, M Ahmadzadeh; Amara, M; Amoabediny, G; Tajik, P; Barin, A; Magierowski, S; Ghafar-Zadeh, E

    2014-01-01

    In this paper we present the preliminary results of a novel biological analysis platform for early colon cancer detection using magnetic separation of magnetized markers. The platform consists of a microfluidic structure integrated with biosensors. Super-Paramagnetic Iron Oxide nanoparticles (SPIO-NPs) were functionalized with purified DNA Aptamer and their synthesis is described. In this paper, we also present the physicochemical results of the synthesized SPIO/Au-NPs characterized by TEM and XRD. Toxicity of our synthesized biomarkers on HCT116 cell line is discussed. Based on our findings, a concentration of 1mg/ml of our biomarkers added to 5 × 105 cells per well has no effect the viability of the human cells even after 24 hours.

  19. Novel hyperbranched polyamidoamine nanoparticle based gene delivery: transfection, cytotoxicity and in vitro evaluation.

    PubMed

    Zhu, Kai; Guo, Changfa; Lai, Hao; Yang, Wuli; Wang, Chunsheng

    2012-02-28

    In this study, hyperbranched polyamidoamine (hPAMAM) was developed as a novel non-viral gene vector for the first time. The hPAMAM was synthesized using a modified "one-pot" method. DNA was then bound to hPAMAM at different weight ratios (w(hPAMAM)/w(DNA)). The higher weight ratio could bring larger particle size and higher zeta potential of hPAMAM-DNA complexes. The encapsulated DNA was protected by hPAMAM from degradation for over 3h. Under the optimal condition, high gene transfection efficiency could be achieved in COS7 (47.47 ± 1.42%) and HEK293 (40.8 ± 0.98%) cell lines. And hPAMAM showed rather minor cytotoxicity in vitro (cell viability=91.38 ± 0.46% in COS7 and 92.38 ± 0.61% in HEK293). The hPAMAM mediated human vascular endothelial growth factor 165 (hVEGF(165)) gene transfected cells could express hVEGF(165) stably for 14 days, with the peak expression at day 2. In conclusion, hPAMAM based gene delivery was economical, effective and biocompatible, and may serve as a promising non-viral vehicle for gene therapy.

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

    SciTech Connect

    Liu, Xiao-Yun; Yang, Yue-Feng; Wu, Chu-Tse; Xiao, Feng-Jun; Zhang, Qun-Wei; Ma, Xiao-Ni; Li, Qing-Fang; Yan, Jun; Wang, Hua; Wang, Li-Sheng

    2010-03-19

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

  1. Transactivation of bad by vorinostat-induced acetylated p53 enhances doxorubicin-induced cytotoxicity in cervical cancer cells.

    PubMed

    Lee, Sook-Jeong; Hwang, Sung-Ook; Noh, Eun Joo; Kim, Dong-Uk; Nam, Miyoung; Kim, Jong Hyeok; Nam, Joo Hyun; Hoe, Kwang-Lae

    2014-02-14

    Vorinostat (VOR) has been reported to enhance the cytotoxic effects of doxorubicin (DOX) with fewer side effects because of the lower DOX dosage in breast cancer cells. In this study, we investigated the novel mechanism underlying the synergistic cytotoxic effects of VOR and DOX co-treatment in cervical cancer cells HeLa, CaSki and SiHa cells. Co-treatment with VOR and DOX at marginal doses led to the induction of apoptosis through caspase-3 activation, poly (ADP-ribose) polymerase cleavage and DNA micronuclei. Notably, the synergistic growth inhibition induced by the co-treatment was attributed to the upregulation of the pro-apoptotic protein Bad, as the silencing of Bad expression using small interfering RNA (siRNA) abolished the phenomenon. As siRNA against p53 did not result in an increase in acetylated p53 and the consequent upregulation of Bad, the observed Bad upregulation was mediated by acetylated p53. Moreover, a chromatin immunoprecipitation analysis showed that the co-treatment of HeLa cells with VOR and DOX increased the recruitment of acetylated p53 to the bad promoter, with consequent bad transactivation. Conversely, C33A cervical cancer cells containing mutant p53 co-treated with VOR and DOX did not exhibit Bad upregulation, acetylated p53 induction or consequent synergistic growth inhibition. Together, the synergistic growth inhibition of cervical cancer cell lines induced by co-treatment with VOR and DOX can be attributed to the upregulation of Bad, which is induced by acetylated p53. These results show for the first time that the acetylation of p53, rather than histones, is a mechanism for the synergistic growth inhibition induced by VOR and DOX co-treatments.

  2. Effective Delivery of Antigen-Encapsulin Nanoparticle Fusions to Dendritic Cells Leads to Antigen-Specific Cytotoxic T Cell Activation and Tumor Rejection.

    PubMed

    Choi, Bongseo; Moon, Hyojin; Hong, Sung Joon; Shin, Changsik; Do, Yoonkyung; Ryu, Seongho; Kang, Sebyung

    2016-08-23

    In cancer immunotherapy, robust and efficient activation of cytotoxic CD8(+) T cell immune responses is a promising, but challenging task. Dendritic cells (DCs) are well-known professional antigen presenting cells that initiate and regulate antigen-specific cytotoxic CD8(+) T cells that kill their target cells directly as well as secrete IFN-γ, a cytokine critical in tumor rejection. Here, we employed recently established protein cage nanoparticles, encapsulin (Encap), as antigenic peptide nanocarriers by genetically incorporating the OT-1 peptide of ovalbumin (OVA) protein to the three different positions of the Encap subunit. With them, we evaluated their efficacy in activating DC-mediated antigen-specific T cell cytotoxicity and consequent melanoma tumor rejection in vivo. DCs efficiently engulfed Encap and its variants (OT-1-Encaps), which carry antigenic peptides at different positions, and properly processed them within phagosomes. Delivered OT-1 peptides were effectively presented by DCs to naïve CD8(+) T cells successfully, resulting in the proliferation of antigen-specific cytotoxic CD8(+) T cells. OT-1-Encap vaccinations in B16-OVA melanoma tumor bearing mice effectively activated OT-1 peptide specific cytotoxic CD8(+) T cells before or even after tumor generation, resulting in significant suppression of tumor growth in prophylactic as well as therapeutic treatments. A large number of cytotoxic CD8(+) T cells that actively produce both intracellular and secretory IFN-γ were observed in tumor-infiltrating lymphocytes collected from B16-OVA tumor masses originally vaccinated with OT-1-Encap-C upon tumor challenges. The approaches we describe herein may provide opportunities to develop epitope-dependent vaccination systems that stimulate and/or modulate efficient and epitope-specific cytotoxic T cell immune responses in nonpathogenic diseases.

  3. The mining chemical Polydadmac is cytotoxic but does not interfere with Cu-induced toxicity in Atlantic salmon hepatocytes.

    PubMed

    Olsvik, Pål A; Berntssen, Marc H G; Waagbø, Rune; Hevrøy, Ernst; Søfteland, Liv

    2015-12-25

    To speed up sedimentation of suspended solids the mining industry often uses flocculent chemicals. In this work we evaluated the cytotoxic and mechanistic effects of Polydadmac, and its basic component Dadmac, on fish cells. Dose-response effects, temperature-dependent effects and impact of Dadmac and Polydadmac on Cu toxicity were studied in Atlantic salmon hepatocytes. We used the xCELLigence system and the MTT test for cytotoxicity assessments, and real-time RT-qPCR to evaluate molecular effects. The results showed a cytotoxic response for Polydadmac but not for Dadmac. Elevated levels of Cu were cytotoxic. Moderately cytotoxic concentrations of Cu (100-1000 μM) induced significant responses on the transcription of a number of genes in the cells, i.e. cuznsod (sod1), cat, mnsod (sod2), nfe2l2, hmox1, mta, casp3b, casp6, bclx, cyp1a, ccs, atp7a, app, mmp13, esr1, ppara, fads2 and ptgs2. A factorial PLS regression model for mnsod transcription showed a synergistic effect between Dadmac and Cu exposure in the cells, indicating an interaction effect between Dadmac and Cu on mitochondrial ROS scavenging. No interaction effects were seen for Polydadmac on Cu toxicity. In conclusion, Polydadmac is cytotoxic at elevated concentrations but appears to have low ability to interfere with Cu toxicity in Atlantic salmon liver cells.

  4. Mechanisms of silver nanoparticle-induced toxicity and important role of autophagy.

    PubMed

    Mao, Bin-Hsu; Tsai, Jui-Chen; Chen, Chun-Wan; Yan, Shian-Jang; Wang, Ying-Jan

    2016-10-01

    Safety concerns have been raised over the extensive applications of silver nanoparticles (AgNPs) because nano dimensions make them highly bioactive, being potentially harmful to the exposed humans. Surface physico-chemistry (shape, surface charge, chemical composition, etc.) that mainly dictates nano-bio interactions is relevant for influencing their biocompatibility and toxicity. Although the hazardousness of AgNPs has been demonstrated in vitro and in vivo, mechanistic understanding of the toxicity particularly at the molecular and organismal levels, in addition to oxidative stress and silver ion dissolution, has remained unclear. A growing body of research has elucidated that autophagy, being activated in response to exposure to various nanomaterials, may serve as a cellular defense mechanism against nanotoxicity. Recently, autophagy activation was shown to correlate with AgNPs exposure; however, the subsequent autophagosome-lysosome fusion was defective. As autophagy plays a crucial role in selective removal of stress-mediated protein aggregates and injured organelles, AgNPs-induced autophagic flux defect may consequently lead to aggravated cytotoxic responses. Furthermore, we suggest that p62 accumulation resulting from defective autophagy may also potentially account for AgNPs cytotoxicity. Intriguingly, AgNPs have been shown to interfere with ubiquitin modifications, either via upregulating levels of enzymes participating in ubiquitination, or through impairing the biological reactivity of ubiquitin (due to formation of AgNPs-ubiquitin corona). Ubiquitination both confers selectivity to autophagy as well as modulates stabilization, activation, and trafficking of proteins involved in autophagic clearance pathways. In this regard, we offer a new perspective that interference of AgNPs with ubiquitination may account for AgNPs-induced defective autophagy and cytotoxic effects. PMID:27240148

  5. Preparation of water-soluble hyperbranched polyester nanoparticles