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1

Gold Nanoparticles Cytotoxicity  

NASA Astrophysics Data System (ADS)

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

Mironava, Tatsiana

2

Amyloid fibrils enhance transport of metal nanoparticles in living cells and induced cytotoxicity.  

PubMed

Amyloid protein fibrils occur in vivo as pathological agents, in the case of neurodegenerative diseases, or as functional amyloids, when playing biologically vital roles. Here we show how amyloid fibrils generated from a food protein, ?-lactoglobulin, can be used as nanoreactors for the synthesis of metal nanoparticles and demonstrate that the resulting hybrids can play a central role in the internalization of nanoparticles into living cells, with up to 3-fold-enhanced transport properties over pristine nanoparticles. We conjugate gold, silver, and palladium nanoparticles onto amyloid fibrils by chemical reduction, and we study their effect on dendritic and MCF7 breast cancer cells. Transmission electron microscopy indicates localization of nanoparticles inside vesicles of the cells. Flow cytometry reveals that silver nanoparticle-amyloid hybrids are cytotoxic, while gold and palladium nanoparticle-amyloid hybrids produce no notable effect on cell viability and activation status. PMID:24941321

Bolisetty, Sreenath; Boddupalli, Chandra Sekhar; Handschin, Stephan; Chaitanya, Krishna; Adamcik, Jozef; Saito, Yasuyuki; Manz, Markus G; Mezzenga, Raffaele

2014-07-14

3

Cytotoxic effects of fucoidan nanoparticles against osteosarcoma.  

PubMed

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

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

2013-11-01

4

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

PubMed

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-?, an inhibitor of p53 transcriptional activity, enhanced CuONP-induced viability loss. Nutlin-3?, a p53 stabilizer, prevented CuONP-induced viability loss in HaCaT cells, but not in MEF cells, due to the inherent toxicity of nutlin-3? 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

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

2014-01-01

5

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

PubMed Central

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-?, an inhibitor of p53 transcriptional activity, enhanced CuONP-induced viability loss. Nutlin-3?, a p53 stabilizer, prevented CuONP-induced viability loss in HaCaT cells, but not in MEF cells, due to the inherent toxicity of nutlin-3? 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

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

2014-01-01

6

Are diamond nanoparticles cytotoxic?  

PubMed

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

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

2007-01-11

7

Cytotoxic Potential of Silver Nanoparticles  

PubMed Central

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

Zhang, Tianlu; Wang, Liming

2014-01-01

8

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

PubMed Central

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

Liu, Min; Zhao, Yunxue; Zhang, Xiumei

2015-01-01

9

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

PubMed

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

Liu, Min; Zhao, Yunxue; Zhang, Xiumei

2015-01-01

10

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

PubMed

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

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

2014-08-01

11

Cytotoxicity and ion release of alloy nanoparticles.  

PubMed

It is well-known that nanoparticles could cause toxic effects in cells. Alloy nanoparticles with yet unknown health risk may be released from cardiovascular implants made of Nickel-Titanium or Cobalt-Chromium due to abrasion or production failure. We show the bio-response of human primary endothelial and smooth muscle cells exposed to different concentrations of metal and alloy nanoparticles. Nanoparticles having primary particle sizes in the range of 5-250 nm were generated using laser ablation in three different solutions avoiding artificial chemical additives, and giving access to formulations containing nanoparticles only stabilized by biological ligands. Endothelial cells are found to be more sensitive to nanoparticle exposure than smooth muscle cells. Cobalt and Nickel nanoparticles caused the highest cytotoxicity. In contrast, Titanium, Nickel-Iron, and Nickel-Titanium nanoparticles had almost no influence on cells below a nanoparticle concentration of 10 ?M. Nanoparticles in cysteine dissolved almost completely, whereas less ions are released when nanoparticles were stabilized in water or citrate solution. Nanoparticles stabilized by cysteine caused less inhibitory effects on cells suggesting cysteine to form metal complexes with bioactive ions in media. PMID:22448125

Hahn, Anne; Fuhlrott, Jutta; Loos, Anneke; Barcikowski, Stephan

2012-01-01

12

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

PubMed

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 ?g/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 ?g/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. PMID:25437066

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

13

Hydroxyl radicals ( OH) are associated with titanium dioxide (TiO 2) nanoparticle-induced cytotoxicity and oxidative DNA damage in fish cells  

Microsoft Academic Search

TiO2 nanoparticles (<100nm diameter) have been reported to cause oxidative stress related effects, including inflammation, cytotoxicity and genomic instability, either alone or in the presence of UVA irradiation in mammalian studies. Despite the fact that the aquatic environment is often the ultimate recipient of all contaminants there is a paucity of data pertaining to the potential detrimental effects of nanoparticles

James F. Reeves; Simon J. Davies; Nicholas J. F. Dodd; Awadhesh N. Jha

2008-01-01

14

Experimental considerations on the cytotoxicity of nanoparticles  

PubMed Central

Engineered nanoparticles are one of the leading nanomaterials currently under investigation due to their applicability in various fields, including drug and gene delivery, biosensors, cancer treatment and diagnostic tools. Moreover, the number of commercial products containing nanoparticles released on the market is rapidly increasing. Nanoparticles are already widely distributed in air, cosmetics, medicines and even in food. Therefore, the unintended adverse effect of nanoparticle exposure is a growing concern both academically and socially. In this context, the toxicity of nanoparticles has been extensively studied; however, several challenges are encountered due to the lack of standardized protocols. In order to improve the experimental conditions of nanoparticle toxicity studies, serious consideration is critical to obtain reliable and realistic data. The cell type must be selected considering the introduction route and target organ of the nanoparticle. In addition, the nanoparticle dose must reflect the realistic concentration of nanoparticles and must be loaded as a well-dispersed form to observe the accurate size- and shape-dependent effect. In deciding the cytotoxicity assay method, it is important to choose the appropriate method that could measure the toxicity of interest without the false-negative or -positive misinterpretation of the toxicity result. PMID:21793681

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

2011-01-01

15

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

PubMed

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

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

2015-04-01

16

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

NASA Astrophysics Data System (ADS)

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

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

2012-10-01

17

Cytotoxicity of silica nanoparticles on HaCaT cells.  

PubMed

Despite the widespread use of silica nanoparticles (SiO2 NPs) in biological and medical fields, their adverse effects have not been clearly elucidated. In this study, spherical SiO2 NPs with a 50 nm diameter were used to study their interaction with HaCaT cells. SiO2 NPs were found to be readily internalized into HaCaT cells and localized in the cytoplasm, lysosomes and autophagosomes. Decreased cell viability and damaged cell membrane integrity showed the cytotoxicity of SiO2 NPs. Significant glutathione depletion and reactive oxygen species generation, which reduced the cellular antioxidant level, could be the major factor of cytotoxicity induced by SiO2 NPs. PMID:24155225

Liang, Hao; Jin, Chan; Tang, Ying; Wang, Fude; Ma, Chunwang; Yang, Yongji

2014-04-01

18

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

PubMed

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. PMID:25797930

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

2015-07-15

19

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

PubMed Central

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

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

2015-01-01

20

Nanoparticle incorporation of melittin reduces sperm and vaginal epithelium cytotoxicity.  

PubMed

Melittin is a cytolytic peptide component of bee venom which rapidly integrates into lipid bilayers and forms pores resulting in osmotic lysis. While the therapeutic utility of free melittin is limited by its cytotoxicity, incorporation of melittin into the lipid shell of a perfluorocarbon nanoparticle has been shown to reduce its toxicity in vivo. Our group has previously demonstrated that perfluorocarbon nanoparticles containing melittin at concentrations <10 µM inhibit HIV infectivity in vitro. In the current study, we assessed the impact of blank and melittin-containing perfluorocarbon nanoparticles on sperm motility and the viability of both sperm and vaginal epithelial cells. We found that free melittin was toxic to sperm and vaginal epithelium at concentrations greater than 2 µM (p<0.001). However, melittin nanoparticles were not cytotoxic to sperm (p?=?0.42) or vaginal epithelium (p?=?0.48) at an equivalent melittin concentration of 10 µM. Thus, nanoparticle formulation of melittin reduced melittin cytotoxicity fivefold and prevented melittin toxicity at concentrations previously shown to inhibit HIV infectivity. Melittin nanoparticles were toxic to vaginal epithelium at equivalent melittin concentrations ?20 µM (p<0.001) and were toxic to sperm at equivalent melittin concentrations ?40 µM (p<0.001). Sperm cytotoxicity was enhanced by targeting of the nanoparticles to the sperm surface antigen sperm adhesion molecule 1. While further testing is needed to determine the extent of cytotoxicity in a more physiologically relevant model system, these results suggest that melittin-containing nanoparticles could form the basis of a virucide that is not toxic to sperm and vaginal epithelium. This virucide would be beneficial for HIV serodiscordant couples seeking to achieve natural pregnancy. PMID:24748389

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

2014-01-01

21

Nanoparticle Incorporation of Melittin Reduces Sperm and Vaginal Epithelium Cytotoxicity  

PubMed Central

Melittin is a cytolytic peptide component of bee venom which rapidly integrates into lipid bilayers and forms pores resulting in osmotic lysis. While the therapeutic utility of free melittin is limited by its cytotoxicity, incorporation of melittin into the lipid shell of a perfluorocarbon nanoparticle has been shown to reduce its toxicity in vivo. Our group has previously demonstrated that perfluorocarbon nanoparticles containing melittin at concentrations <10 µM inhibit HIV infectivity in vitro. In the current study, we assessed the impact of blank and melittin-containing perfluorocarbon nanoparticles on sperm motility and the viability of both sperm and vaginal epithelial cells. We found that free melittin was toxic to sperm and vaginal epithelium at concentrations greater than 2 µM (p<0.001). However, melittin nanoparticles were not cytotoxic to sperm (p?=?0.42) or vaginal epithelium (p?=?0.48) at an equivalent melittin concentration of 10 µM. Thus, nanoparticle formulation of melittin reduced melittin cytotoxicity fivefold and prevented melittin toxicity at concentrations previously shown to inhibit HIV infectivity. Melittin nanoparticles were toxic to vaginal epithelium at equivalent melittin concentrations ?20 µM (p<0.001) and were toxic to sperm at equivalent melittin concentrations ?40 µM (p<0.001). Sperm cytotoxicity was enhanced by targeting of the nanoparticles to the sperm surface antigen sperm adhesion molecule 1. While further testing is needed to determine the extent of cytotoxicity in a more physiologically relevant model system, these results suggest that melittin-containing nanoparticles could form the basis of a virucide that is not toxic to sperm and vaginal epithelium. This virucide would be beneficial for HIV serodiscordant couples seeking to achieve natural pregnancy. PMID:24748389

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

2014-01-01

22

Cytotoxicity of selenium nanoparticles in rat dermal fibroblasts  

PubMed Central

Background: Ventilator-associated pneumonia is a deadly nosocomial infection caused by contaminated endotracheal tubes. It has been shown that polyvinyl chloride (PVC, the endotracheal tube substrate) coated with elemental selenium nanoparticles reduces bacterial adherence and proliferation on PVC by over 99%. However, it is not known if selenium nanoparticles elicit a cytotoxic effect in vitro. The purpose of this study was to investigate the cytotoxic effects of PVC coated with selenium nanoparticles on fibroblasts, which are mammalian cells central to endotracheal tube intubation. Methods: Different concentrations of selenium nanoparticles were precipitated onto the PVC surface by reduction of selenium salts using glutathione. Characterization of PVC coated with selenium nanoparticles was done by scanning electron microscopy, energy dispersive x-ray, and contact angle measurements. For the cytotoxicity experiments, fibroblasts were seeded at a density of 5000 cm2 onto PVC coated with three different concentrations of selenium nanoparticles (high, medium, low) and incubated for 4 hours (adhesion) as well as for 24 hours and 72 hours (proliferation). The half-maximal inhibitory concentration (IC50) value was determined after 72 hours using an ultrahigh concentration. MTT assays were used to assess cell viability at the indicated time points. Results: The three concentrations of selenium nanoparticles did not elicit a cytotoxic effect after 72 hours (P < 0.01, n = 3). It was found that the IC50value was at the ultrahigh concentration of selenium nanoparticles. The nanoparticulate elemental selenium concentration previously shown to decrease the function of bacteria was shown not to cause a cytotoxic effect on fibroblasts in vitro. Conclusion: These findings demonstrate great selectivity between bacteria and healthy cells, and are a viable option for coating endotracheal tubes in order to prevent ventilator-associated pneumonia. PMID:22915842

Ramos, Joseph F; Webster, Thomas J

2012-01-01

23

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

PubMed

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

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

2014-01-15

24

Cytotoxicity and therapeutic effect of irinotecan combined with selenium nanoparticles.  

PubMed

Although chemotherapeutic drugs are widely applied for clinic tumor treatment, severe toxicity restricts their therapeutic efficacy. In this study, we reported a new form of selenium, selenium nanoparticles (Nano Se) which have significant lower toxicity and acceptable bioavailability. We investigated Nano Se as chemotherapy preventive agent to protect against toxicities of anticancer drug irinotecan and synergistically enhance the anti-tumor treatment effect in vitro and in vivo. The underlying mechanisms were also investigated. The combination of Nano Se and irinotecan showed increased cytotoxic effect with HCT-8 tumor cells likely by p53 mediated apoptosis. Nano Se inhibited growth of HCT-8 tumor cells partially through caspases mediated apoptosis. In vivo experiment showed Nano Se at a dose of 4 mg/kg/day significantly alleviated adverse effects induced by irinotecan (60 mg/kg) treatment. Nano Se alone treatment did not induce any toxic manifestations. The combination of Nano Se and irinotecan dramatically inhibited tumor growth and significantly induced apoptosis of tumor cells in HCT-8 cells xenografted tumor. Tumor inhibition rate was about 17.2%, 48.6% and 62.1% for Nano Se, irinotecan and the combination of Nano Se and irinotecan, respectively. The beneficial effects of Nano Se for tumor therapy were mainly ascribed to selectively regulating Nrf2-ARE (antioxidant responsive elements) pathway in tumor tissues and normal tissues. Our results suggest Nano Se is a promising selenium species with potential application in cancer treatment. PMID:25064805

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

2014-10-01

25

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

PubMed

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

Yordanov, Georgi; Skrobanska, Ralica; Evangelatov, Alexander

2013-01-01

26

Modulation of arsenic induced cytotoxicity by tea.  

PubMed

Arsenic, a naturally ocurring chemical element, is considered hazardous to human health. Inorganic arsenic compounds were found to induce cytotoxicity in Chinese hamster V-79 cells in culture. The arsenite form was more toxic than arsenate. Extracts of green and two varieties of black tea, as well as their principal polyphenols, (-)-epigallocatechingallate and theaflavin, efficiently counteracted the cytotoxic effects of arsenic compounds. On the basis of the amount of tea extract that afforded 50% protection to the cells from arsenic induced cytotoxicity, black tea was found to be as effective as green tea. The protective effect was attributable to the contents of not only (-)-epigallocatechingallate but also of theaflavin, the latter being a predominant polyphenol present in black tea. PMID:14507244

Sinha, Dona; Roy, Madhumita; Dey, Subhabrata; Siddiqi, M; Bhattacharya, R K

2003-01-01

27

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

PubMed Central

Microsomal glutathione transferase 1 (MGST1) is an antioxidant enzyme located predominantly in the mitochondrial outer membrane and endoplasmic reticulum and has been shown to protect cells from lipid peroxidation induced by a variety of cytostatic drugs and pro-oxidant stimuli. We hypothesized that MGST1 may also protect against nanomaterial-induced cytotoxicity through a specific effect on lipid peroxidation. We evaluated the induction of cytotoxicity and oxidative stress by TiO2, CeO2, SiO2, and ZnO in the human MCF-7 cell line with or without overexpression of MGST1. SiO2 and ZnO nanoparticles caused dose- and time-dependent toxicity, whereas no obvious cytotoxic effects were induced by nanoparticles of TiO2 and CeO2. We also noted pronounced cytotoxicity for three out of four additional SiO2 nanoparticles tested. Overexpression of MGST1 reversed the cytotoxicity of the main SiO2 nanoparticles tested and for one of the supplementary SiO2 nanoparticles but did not protect cells against ZnO-induced cytotoxic effects. The data point toward a role of lipid peroxidation in SiO2 nanoparticle-induced cell death. For ZnO nanoparticles, rapid dissolution was observed, and the subsequent interaction of Zn2+ with cellular targets is likely to contribute to the cytotoxic effects. A direct inhibition of MGST1 by Zn2+ could provide a possible explanation for the lack of protection against ZnO nanoparticles in this model. Our data also showed that SiO2 nanoparticle-induced cytotoxicity is mitigated in the presence of serum, potentially through masking of reactive surface groups by serum proteins, whereas ZnO nanoparticles were cytotoxic both in the presence and in the absence of serum. PMID:22303956

2012-01-01

28

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

PubMed

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

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

2015-02-01

29

In Vitro Cytotoxicity of Nanoparticles in Mammalian Germline Stem Cells  

PubMed Central

Gametogenesis is a complex biological process that is particularly sensitive to environmental insults such as chemicals. Many chemicals have a negative impact on the germline, either by directly affecting the germ cells, or indirectly through their action on the somatic nursing cells. Ultimately, these effects can inhibit fertility, and they may have negative consequences for the development of the offspring. Recently, nanomaterials such as nanotubes, nanowires, fullerene derivatives (buckyballs), and quantum dots have received enormous national attention in the creation of new types of analytical tools for biotechnology and the life sciences. Despite the wide application of nanomaterials, there is a serious lack of information concerning their impact on human health and the environment. Thus, there are limited studies available on toxicity of nanoparticles for risk assessment of nanomaterials. The purpose of this study was to assess the suitability of a mouse spermatogonial stem cell line as a model to assess nanotoxicity in the male germline in vitro. The effects of different types of nanoparticles on these cells were evaluated by light microscopy, and by cell proliferation and standard cytotoxicity assays. Our results demonstrate a concentration-dependent toxicity for all types of particles tested, whereas the corresponding soluble salts had no significant effect. Silver nanoparticles were the most toxic while molybdenum trioxide (MoO3) nanoparticles were the least toxic. Our results suggest that this cell line provides a valuable model with which to assess the cytotoxicity of nanoparticles in the germ line in vitro. PMID:16014736

Braydich-Stolle, Laura; Hussain, Saber; Schlager, John J.; Hofmann, Marie-Claude

2010-01-01

30

The mechanism of asbestos-induced cytotoxicity  

SciTech Connect

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

Goodglick, L.A.

1988-01-01

31

Heparin nanoparticles for ? amyloid binding and mitigation of ? amyloid associated cytotoxicity.  

PubMed

Accumulation of ? amyloid (A?) 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 A? 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 A? induced cytotoxicity. These results suggest that heparin nanoparticles can be a very useful tool for A? studies. PMID:25498198

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

2015-03-20

32

Synthesis and Cytotoxicity of Y2O3 Nanoparticles of Various Morphologies  

PubMed Central

As the field of nanotechnology continues to grow, evaluating the cytotoxicity of nanoparticles is important in furthering their application within biomedicine. Here, we report the synthesis, characterization, and cytotoxicity of nanoparticles of different morphologies of yttrium oxide, a promising material for biological imaging applications. Nanoparticles of spherical, rod-like, and platelet morphologies were synthesized via solvothermal and hydrothermal methods and characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), light scattering, surface area analysis, thermogravimetric analysis (TGA), and zeta potential measurements. Nanoparticles were then tested for cytotoxicity with human foreskin fibroblast (HFF) cells, with the goal of elucidating nanoparticle characteristics that influence cytotoxicity. Cellular response was different for the different morphologies, with spherical particles exhibiting no cytotoxicity to HFF cells, rod-like particles increasing cell proliferation, and platelet particles markedly cytotoxic. However, due to differences in the nanoparticle chemistry as determined through the characterization techniques, it is difficult to attribute the cytotoxicity responses to the particle morphology. Rather, the cytotoxicity of the platelet sample appears due to the stabilizing ligand, oleylamine, which was present at higher levels in this sample. This study demonstrates the importance of nanoparticle chemistry on in vitro cytotoxicity, and highlights the general importance of thorough nanoparticle characterization as a prerequisite to understanding nanoparticle cytotoxicity. PMID:20672046

2010-01-01

33

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

PubMed

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

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

2014-09-22

34

Intracellular mechanisms of aminoglycoside-induced cytotoxicity  

PubMed Central

Since introduction into clinical practice over 60 years ago, aminoglycoside antibiotics remain important drugs in the treatment of bacterial infections, cystic fibrosis and tuberculosis. However, the ototoxic and nephrotoxic properties of these drugs are still a major clinical problem. Recent advances in molecular biology and biochemistry have begun to uncover the intracellular actions of aminoglycosides that lead to cytotoxicity. In this review, we discuss intracellular binding targets of aminoglycosides, highlighting specific aminoglycoside-binding proteins (HSP73, calreticulin and CLIMP-63) and their potential for triggering caspases and Bcl-2 signalling cascades that are involved in aminoglycoside-induced cytotoxicity. We also discuss potential strategies to reduce aminoglycoside cytotoxicity, which are necessary for greater bactericidal efficacy during aminoglycoside pharmacotherapy. PMID:21799993

Karasawa, Takatoshi; Steyger, Peter S.

2013-01-01

35

Reducing ZnO nanoparticle cytotoxicity by surface modification  

NASA Astrophysics Data System (ADS)

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

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

2014-05-01

36

Cytotoxicity of monodispersed chitosan nanoparticles against the Caco-2 cells  

SciTech Connect

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

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

2012-08-01

37

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

PubMed Central

In this study, the effects of the size and Chinese traditional processing (including elutriation, water cleaning, acid cleaning, alkali cleaning) on realgar nanoparticles (RN)-induced antitumor activity in human osteosarcoma cell lines (MG-63) and hepatoma carcinoma cell lines (HepG-2) were investigated. The human normal liver cell line (L-02) was used as control. RN was prepared by high-energy ball milling technology. The results showed that with the assistance of sodium dodecyl sulfate, the size of realgar could be reduced to 127 nm after 12 hours’ ball milling. The surface charge was decreased from 0.83 eV to ?17.85 eV and the content of As2O3 clearly increased. Except for elutriation, the processing methods did not clearly change the size of the RN, but the content of As2O3 was reduced dramatically. In vitro MTT tests indicated that in the two cancer cell lines, RN cytotoxicity was more intense than that of the coarse realgar nanoparticles, and cytotoxicity was typically time- and concentration-dependent. Also, RN cytotoxicities in the HepG-2 and L-02 cells all increased with increasing milling time. Due to the reduction of the As2O3 content, water cleaning, acid cleaning, and alkali cleaning decreased RN cytotoxicity in HepG-2, but RN after elutriation, with the lowest As2O3 (3.5 mg/g) and the smallest size (109.3 nm), showed comparable cytotoxicity in HepG-2 to RN without treatment. Meanwhile, RN-induced cytotoxicity in L-02 cells was clearly reduced. Therefore, it can be concluded that RN may provide a strong antiproliferation effect in the MG-63 and HepG-2 cells. Elutriation processing is a suitable approach to limit the dangerous side-effects of As2O3, while maintaining the effectiveness of RN. PMID:21845047

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

2011-01-01

38

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

PubMed Central

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

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

2014-01-01

39

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

PubMed

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

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

2014-08-01

40

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

PubMed Central

Background Photocopiers emit nanoparticles with complex chemical composition. Short-term exposures to modest nanoparticle concentrations triggered upper airway inflammation and oxidative stress in healthy human volunteers in a recent study. To further understand the toxicological properties of copier-emitted nanoparticles, we studied in-vitro their ability to induce cytotoxicity, pro-inflammatory cytokine release, DNA damage, and apoptosis in relevant human cell lines. Methods Three cell types were used: THP-1, primary human nasal- and small airway epithelial cells. Following collection in a large volume photocopy center, nanoparticles were extracted, dispersed and characterized in the cell culture medium. Cells were doped at 30, 100 and 300 ?g/mL administered doses for up to 24 hrs. Estimated dose delivered to cells, was ~10% and 22% of the administered dose at 6 and 24 hrs, respectively. Gene expression analysis of key biomarkers was performed using real time quantitative PCR (RT-qPCR) in THP-1 cells at 5 ?g nanoparticles/mL for 6-hr exposure for confirmation purposes. Results Multiple cytokines, GM-CSF, IL-1?, IL-6, IL-8, IFN?, MCP-1, TNF-? and VEGF, were significantly elevated in THP-1 cells in a dose-dependent manner. Gene expression analysis confirmed up-regulation of the TNF-? gene in THP-1 cells, consistent with cytokine findings. In both primary epithelial cells, cytokines IL-8, VEGF, EGF, IL-1?, TNF-?, IL-6 and GM-CSF were significantly elevated. Apoptosis was induced in all cell lines in a dose-dependent manner, consistent with the significant up-regulation of key apoptosis-regulating genes P53 and Casp8 in THP-1 cells. No significant DNA damage was found at any concentration with the comet assay. Up-regulation of key DNA damage and repair genes, Ku70 and Rad51, were also observed in THP-1 cells, albeit not statistically significant. Significant up-regulation of the key gene HO1 for oxidative stress, implicates oxidative stress induced by nanoparticles. Conclusions Copier-emitted nanoparticles induced the release of pro-inflammatory cytokines, apoptosis and modest cytotoxicity but no DNA damage in all three-human cell lines. Taken together with gene expression data in THP-1 cells, we conclude that these nanoparticles are directly responsible for inflammation observed in human volunteers. Further toxicological evaluations of these nanoparticles, including across different toner formulations, are warranted. PMID:23968360

2013-01-01

41

Cytotoxicity of TiO2 nanoparticles towards freshwater sediment microorganisms at low exposure concentrations.  

PubMed

There is a persistent need to assess the effects of TiO2 nanoparticles on the aquatic ecosystem owing to their increasing usage in consumer products and risk of environmental release. The current study is focused on TiO2 nanoparticle-induced acute toxicity at sub-ppm level (?1ppm) 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. PMID:25462683

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

2014-11-01

42

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

PubMed

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

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

2014-05-01

43

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

PubMed

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

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

2013-11-01

44

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

PubMed

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

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

2014-11-01

45

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

PubMed Central

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

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

2014-01-01

46

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

PubMed Central

Background Reproducibly high transfection rates with low methodology-induced cytotoxic side effects are essential to attain the required effect on targeted cells when exogenous DNA is transfected. Different approaches and modifications such as the use of nanoparticles (NPs) are being evaluated to increase transfection efficiencies. Several studies have focused on the attained transfection efficiency after NP-mediated approaches. However, data comparing toxicity of these novel approaches with conventional methods is still rare. Transfection efficiency and methodology-induced cytotoxicity were analysed after transfection with different NP-mediated and conventional approaches. Two eukaryotic DNA-expression-plasmids were used to transfect the mammalian cell line MTH53A applying six different transfection protocols: conventional transfection reagent (FuGENE HD, FHD), FHD in combination with two different sizes of stabilizer-free laser-generated AuNPs (PLAL-AuNPs_S1,_S2), FHD and commercially available AuNPs (Plano-AuNP), and two magnetic transfection protocols. 24 h post transfection efficiency of each protocol was analysed using fluorescence microscopy and GFP-based flow cytometry. Toxicity was assessed measuring cell proliferation and percentage of propidium iodide (PI%) positive cells. Expression of the respective recombinant proteins was evaluated by immunofluorescence. Results The addition of AuNPs to the transfection protocols significantly increased transfection efficiency in the pIRES-hrGFPII-eIL-12 transfections (FHD: 16%; AuNPs mean: 28%), whereas the magnet-assisted protocols did not increase efficiency. Ligand-free PLAL-AuNPs had no significant cytotoxic effect, while the ligand-stabilized Plano-AuNPs induced a significant increase in the PI% and lower cell proliferation. For pIRES-hrGFPII-rHMGB1 transfections significantly higher transfection efficiency was observed with PLAL-AuNPs (FHD: 31%; PLAL-AuNPs_S1: 46%; PLAL-AuNPs_S2: 50%), while the magnet-assisted transfection led to significantly lower efficiencies than the FHD protocol. With PLAL-AuNPs_S1 and _S2 the PI% was significantly higher, yet no consistent effect of these NPs on cell proliferation was observed. The magnet-assisted protocols were least effective, but did result in the lowest cytotoxic effect. Conclusions This study demonstrated that transfection efficiency of DNA-expression-plasmids was significantly improved by the addition of AuNPs. In some combinations the respective cytotoxicity was increased depending on the type of the applied AuNPs and the transfected DNA construct. Consequently, our results indicate that for routine use of these AuNPs the specific nanoparticle formulation and DNA construct combination has to be considered. PMID:22014272

2011-01-01

47

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

NASA Astrophysics Data System (ADS)

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

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

2006-02-01

48

The role of surface functionality in determining nanoparticle cytotoxicity  

PubMed Central

CONSPECTUS Surface properties dictate the behavior of nanomaterials in vitro, in vivo and in the environment. Such properties include surface charge and hydrophobicity. Also key are more complex supramolecular interactions like aromatic stacking and hydrogen bonding, and even surface topology from the structural to the atomic level. Surface functionalization of nanoparticles (NPs) provides an effective way to control the interface between nanomaterials and the biological systems they are designed to interact with. In medicine, for instance, proper control of surface properties can maximize therapeutic or imaging efficacy while minimizing unfavorable side effects. Meanwhile, in environmental science, thoughtful choice of particle coating can minimize the impact of manufactured nanomaterials on the environment. A thorough knowledge of how NP surfaces with various properties effect biological systems is essential for creating NPs with such useful therapeutic and imaging properties as low toxicity, stability, biocompatibility, favorable distribution throughout cells or tissues, and favorable pharmacokinetic profiles--and for reducing the potential environmental impact of manufactured nanomaterials, which are becoming increasingly prominent in the marketplace. In this Account, we discuss our research and that of others into how NP surface properties control interactions with biomolecules and cells at many scales, including the role the particle surface plays in determining in vivo behavior of nanomaterials. These interactions can be benign, beneficial, or lead to dysfunction in proteins, genes and cells, resulting in cytotoxic and genotoxic responses. Understanding these interactions and their consequences helps us to design minimally invasive imaging and delivery agents. We also highlight in this Account how we have fabricated nanoparticles to act as therapeutic agents via tailored interactions with biomacromolecules. These particles offer new therapeutic directions from traditional small molecule therapies, and with potentially greater versatility than is possible with proteins and nucleic acids. PMID:23294365

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

2013-01-01

49

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

PubMed

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

Ghosh, Manosij; Chakraborty, Anirban; Mukherjee, Anita

2013-10-01

50

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

PubMed Central

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

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

2015-01-01

51

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

PubMed Central

Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely utilized for the diagnosis and therapy of specific diseases, as magnetic resonance imaging (MRI) contrast agents and drug-delivery carriers, due to their easy transportation to targeted areas by an external magnetic field. For such biomedical applications, SPIONs must have multifunctional characteristics, including optimized size and modified surface. However, the biofunctionality and biocompatibility of SPIONs with various surface functional groups of different sizes have yet to be elucidated clearly. Therefore, it is important to carefully monitor the cytotoxicity and genotoxicity of SPIONs that are surfaced-modified with various functional groups of different sizes. In this study, we evaluated SPIONs with diameters of approximately 10 nm and 100~150 nm, containing different surface functional groups. SPIONs were covered with ?O? groups, so-called bare SPIONs. Following this, they were modified with three different functional groups – hydroxyl (?OH), carboxylic (?COOH), and amine (?NH2) groups – by coating their surfaces with tetraethyl orthosilicate (TEOS), (3-aminopropyl)trimethoxysilane (APTMS), TEOS-APTMS, or citrate, which imparted different surface charges and sizes to the particles. The effects of SPIONs coated with these functional groups on mitochondrial activity, intracellular accumulation of reactive oxygen species, membrane integrity, and DNA stability in L-929 fibroblasts were determined by water-soluble tetrazolium, 2?,7?-dichlorodihydrofluorescein, lactate dehydrogenase, and comet assays, respectively. Our toxicological observations suggest that the functional groups and sizes of SPIONs are critical determinants of cellular responses, degrees of cytotoxicity and genotoxicity, and potential mechanisms of toxicity. Nanoparticles with various surface modifications and of different sizes induced slight, but possibly meaningful, changes in cell cytotoxicity and genotoxicity, which would be significantly valuable in further studies of bioconjugation and cell interaction for drug delivery, cell culture, and cancer-targeting applications. PMID:22238510

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

2011-01-01

52

Phagocytic uptake and ROS-mediated cytotoxicity in human hepatic cell line of amphiphilic polyphosphazene nanoparticles.  

PubMed

The pH-responsive amphiphilic polyphosphazenes bearing N,N-diisopropylethylenediamine (DPA) have been proven to be promising nanovehicles for drug antitumor therapy. To further modify these amphiphilic polyphosphazenes with fluorescent labeling agent or other biochemical functional groups, serine methyl ester containing active chemical group ?NH(2) was chosen to be introduced to get a novel polymer [NP(PEG)(0.24) (DPA)(0.5)(SME)(1.26) (n) (PDS-NH(2) ). Considering the possible toxic effect of -NH(2) group, the biocompatibility in bloodstream and nanotoxicity on human normal hepatic L-02 cells was evaluated in this study. The polymer [NP(PEG)(0.24)(DPA)(0.5)(SME-BOC)(1.26)](n) (PDS-BOC) linked with tert-butyloxycarbonyl groups to protect and hide -NH(2) group was applied as the comparison. First, the bovine serum albumin (BSA) adsorption and phagocytic uptake behavior in human THP-1 macrophages were performed. The results suggested that only a minor percentage of the nanoparticles were involved in BSA binding and phagocytic uptake as the result of PEGylation on the particulate surface. To determine the nanotoxicity on human normal hepatic L-02 cells, we measured cell viability, apoptosis and necrosis, reactive oxygen species generation, the loss of mitochondrial membrane potential, and the levels of the apoptotic signaling proteins in L-02 cells after the cells being exposed to nanoparticles of different concentrations (0.1, 0.2, and 0.5 mg/mL) for 24 h. Our data indicated that the two nanoparticles induced cytotoxicity in a dose-dependent manner; PDS-NH(2) caused more cytotoxicity than PDS-BOC as a result of -NH(2) exposure. The increased expression of caspase-3 and caspase-9 suggested that they triggered apoptosis through mitochondria-dependent pathways in L-02 cells. PMID:22969066

Qiu, Liyan; Chen, Yue; Gao, Menghua; Zheng, Cheng; Zhao, Qinghe

2013-01-01

53

A Role for Orexin in Cytotoxic Chemotherapy-Induced Fatigue  

PubMed Central

Fatigue is the most common symptom related to cytotoxic chemotherapeutic treatment of cancer. Peripheral inflammation associated with cytotoxic chemotherapy is likely a causal factor of fatigue. The neural mechanisms by which cytotoxic chemotherapy associated inflammation induces fatigue behavior are not known. This lack of knowledge hinders development of interventions to reduce or prevent this disabling symptom. Infection induced fatigue/lethargy in rodents is mediated by suppression of hypothalamic orexin activity. Orexin is critical for maintaining wakefulness and motivated behavior. Though there are differences between infection and cytotoxic chemotherapy in some symptoms, both induce peripheral inflammation and fatigue. Based on these similarities we hypothesized that cytotoxic chemotherapy induces fatigue by disrupting orexin neuron activity. We found that a single dose of a cytotoxic chemotherapy cocktail (cyclophosphamide, adriamycin, 5-fluorouracil—CAF) induced fatigue/lethargy in mice and rats as evidenced by a significant decline in voluntary locomotor activity measured by telemetry. CAF induced inflammatory gene expression—IL-1R1 (p<0.001), IL-6 (p<0.01), TNF? (p<0.01), and MCP-1 (p<0.05) —in the rodent hypothalamus 6 to 24 hours after treatment during maximum fatigue/lethargy. CAF decreased orexin neuron activity as reflected by decreased nuclear cFos localization in orexin neurons 24 hours after treatment (p<0.05) and by decreased orexin-A in cerebrospinal fluid 16 hours after treatment (p<0.001). Most importantly, we found that central administration of1 ?g orexin-A restored activity in CAF-treated rats (p<0.05). These results demonstrate that cytotoxic chemotherapy induces hypothalamic inflammation and that suppression of hypothalamic orexin neuron activity has a causal role in cytotoxic chemotherapy-induced fatigue in rodents. PMID:24216337

Weymann, K. B.; Wood, L. J.; Zhu, X.; Marks, D. L.

2014-01-01

54

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

PubMed Central

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

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

2013-01-01

55

Synergistic cytotoxicity induced by ?-solanine and ?-chaconine.  

PubMed

?-Solanine and ?-chaconine are well-known potato toxins, but the mechanism of the synergistic cytotoxic effect of these alkaloids has been little clarified. This study confirmed their synergistic cytotoxic effects on C6 rat glioma cells by three different cell viability tests, namely WST-1 (water-soluble tetrazolium) assay sensitive to intracellular NADH concentration, menadione-catalysed chemiluminescent assay depending on both NAD(P)H concentration and NAD(P)H:quinone reductase activity, and LDH (lactate dehydrogenase) assay sensitive to the release of LDH from damaged cells. The maximum cytotoxic effect was observed at a ratio of 1:1 between ?-solanine and ?-chaconine at micromolar concentrations. The cytotoxic effects of these alkaloids were observed immediately after incubation and were constant after 30min, suggesting that rapid damage of plasma membrane causes the lethal disorder of metabolism. PMID:23790833

Yamashoji, Shiro; Matsuda, Takako

2013-11-15

56

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

PubMed Central

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

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

2014-01-01

57

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

PubMed

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. Environ. Mol. Mutagen. 56:125-148, 2015. © 2014 Wiley Periodicals, Inc. PMID:25209650

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

2015-03-01

58

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

NASA Astrophysics Data System (ADS)

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

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

2011-07-01

59

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

NASA Astrophysics Data System (ADS)

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 ?g/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.

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

2015-03-01

60

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

PubMed Central

Background Surface charge and oxidative stress are often hypothesized to be important factors in cytotoxicity of nanoparticles. However, the role of these factors is not well understood. Hence, the aim of this study was to systematically investigate the role of surface charge, oxidative stress and possible involvement of mitochondria in the production of intracellular reactive oxygen species (ROS) upon exposure of rat macrophage NR8383 cells to silicon nanoparticles. For this aim highly monodisperse (size 1.6 ± 0.2 nm) and well-characterized Si core nanoparticles (Si NP) were used with a surface charge that depends on the specific covalently bound organic monolayers: positively charged Si NP-NH2, neutral Si NP-N3 and negatively charged Si NP-COOH. Results Positively charged Si NP-NH2 proved to be more cytotoxic in terms of reducing mitochondrial metabolic activity and effects on phagocytosis than neutral Si NP-N3, while negatively charged Si NP-COOH showed very little or no cytotoxicity. Si NP-NH2 produced the highest level of intracellular ROS, followed by Si NP-N3 and Si NP-COOH; the latter did not induce any intracellular ROS production. A similar trend in ROS production was observed in incubations with an isolated mitochondrial fraction from rat liver tissue in the presence of Si NP. Finally, vitamin E and vitamin C induced protection against the cytotoxicity of the Si NP-NH2 and Si NP-N3, corroborating the role of oxidative stress in the mechanism underlying the cytotoxicity of these Si NP. Conclusion Surface charge of Si-core nanoparticles plays an important role in determining their cytotoxicity. Production of intracellular ROS, with probable involvement of mitochondria, is an important mechanism for this cytotoxicity. PMID:20831820

2010-01-01

61

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

PubMed

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

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

62

Antibacterial and non-cytotoxic effect of nanocomposites based in polyethylene and copper nanoparticles.  

PubMed

In this study, an antibacterial, but not cytotoxic nanomaterial based on polyethylene and copper nanoparticles was prepared by in situ polymerization. PE-CuNps nanocomposites against Escherichia coli, completely suppressed the number of live bacteria after 12 h incubation compared to neat PE. TEM images showed that nanocomposites damage the plasma membrane of the bacteria, revealing a bacteriolytic effect. Toxic effects of copper nanoparticles on viability of neuroblastoma line cell also was evaluated, revealing a non cytotoxic effect for the doses used, showing that this nanocomposite is a ideal material for medical devices. PMID:25693677

Tamayo, L A; Zapata, P A; Rabagliati, F M; Azócar, M I; Muñoz, L A; Zhou, X; Thompson, G E; Páez, M A

2015-03-01

63

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

PubMed

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 4.1×10(3)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. PMID:25668698

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

2015-04-15

64

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

NASA Astrophysics Data System (ADS)

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

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

2014-11-01

65

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

SciTech Connect

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

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

2012-01-01

66

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

PubMed

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

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

2013-06-01

67

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

PubMed Central

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

Varshosaz, Jaleh; Sadeghi Aliabadi, Hojatollah

2014-01-01

68

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

PubMed

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

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

2014-01-01

69

Randomization of amyloid-?-peptide(1-42) conformation by sulfonated and sulfated nanoparticles reduces aggregation and cytotoxicity.  

PubMed

The amyloid-? peptide (A?) plays a central role in the mechanism of Alzheimer's disease, being the main constituent of the plaque deposits found in AD brains. A? amyloid formation and deposition are due to a conformational switching to a ?-enriched secondary structure. Our strategy to inhibit A? aggregation involves the re-conversion of A? conformation by adsorption to nanoparticles. NPs were synthesized by sulfonation and sulfation of polystyrene, leading to microgels and latexes. Both polymeric nanostructures affect the conformation of A? inducing an unordered state. Oligomerization was delayed and cytotoxicity reduced. The proper balance between hydrophilic moieties and hydrophobic chains seems to be an essential feature of effective NPs. PMID:20480510

Saraiva, Ana M; Cardoso, Isabel; Saraiva, Maria João; Tauer, Klaus; Pereira, M Carmo; Coelho, Manuel A N; Möhwald, Helmuth; Brezesinski, Gerald

2010-10-01

70

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

PubMed

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

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

1999-01-01

71

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

PubMed Central

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

2014-01-01

72

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

NASA Astrophysics Data System (ADS)

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

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

2011-07-01

73

Uptake and cytotoxicity of chitosan nanoparticles in human liver cells  

SciTech Connect

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

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

2010-12-01

74

Heparin and Carboxymethylchitosan Metal Nanoparticles: An Evaluation of Their Cytotoxicity  

PubMed Central

In the search for noninvasive diagnostic techniques and new therapies, “nanosystems”, which are capable of binding and targeting bioactive molecules, are becoming increasingly important. In this context, biocompatible coatings are gaining interest, not only for their biological effects but also because they are considered capable to mask nanoparticle toxicity. In this work, we have compared the toxicity of nanoparticles coated with heparin and carboxymethylchitosan in the SKOV-3 cell line. Our results indicate that heparin and carboxymethylchitosan coatings do not guarantee the decrease of nanoparticle intrinsic toxicity which is often envisaged. Nonetheless, these coatings provide the opportunity for further functionalization with a variety of biomolecules for their use in theranostics. PMID:23509708

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

2013-01-01

75

Heparin and carboxymethylchitosan metal nanoparticles: an evaluation of their cytotoxicity.  

PubMed

In the search for noninvasive diagnostic techniques and new therapies, "nanosystems", which are capable of binding and targeting bioactive molecules, are becoming increasingly important. In this context, biocompatible coatings are gaining interest, not only for their biological effects but also because they are considered capable to mask nanoparticle toxicity. In this work, we have compared the toxicity of nanoparticles coated with heparin and carboxymethylchitosan in the SKOV-3 cell line. Our results indicate that heparin and carboxymethylchitosan coatings do not guarantee the decrease of nanoparticle intrinsic toxicity which is often envisaged. Nonetheless, these coatings provide the opportunity for further functionalization with a variety of biomolecules for their use in theranostics. PMID:23509708

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

2013-01-01

76

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

PubMed Central

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

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

2015-01-01

77

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

NASA Astrophysics Data System (ADS)

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

Nabeshi, Hiromi; Yoshikawa, Tomoaki; Arimori, Akihiro; Yoshida, Tokuyuki; Tochigi, Saeko; Hirai, Toshiro; Akase, Takanori; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-Ichi; Itoh, Norio; Yoshioka, Yasuo; Tsutsumi, Yasuo

2011-12-01

78

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

PubMed

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

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

2013-04-17

79

Cytotoxicity, permeability, and inflammation of metal oxide nanoparticles in human cardiac microvascular endothelial cells: cytotoxicity, permeability, and inflammation of metal oxide nanoparticles.  

PubMed

Wide applications and extreme potential of metal oxide nanoparticles (NPs) increase occupational and public exposure and may yield extraordinary hazards for human health. Exposure to NPs has a risk for dysfunction of the vascular endothelial cells. The objective of this study was to assess the cytotoxicity of six metal oxide NPs to human cardiac microvascular endothelial cells (HCMECs) in vitro. Metal oxide NPs used in this study included zinc oxide (ZnO), iron(III) oxide (Fe(2)O(3)), iron(II,III) oxide (Fe(3)O(4)), magnesium oxide (MgO), aluminum oxide (Al(2)O(3)), and copper(II) oxide (CuO). The cell viability, membrane leakage of lactate dehydrogenase, intracellular reactive oxygen species, permeability of plasma membrane, and expression of inflammatory markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, macrophage cationic peptide-1, and interleukin-8 in HCMECs were assessed under controlled and exposed conditions (12-24 h and 0.001-100 ?g/ml of exposure). The results indicated that Fe(2)O(3), Fe(3)O(4), and Al(2)O(3) NPs did not have significant effects on cytotoxicity, permeability, and inflammation response in HCMECs at any of the concentrations tested. ZnO, CuO, and MgO NPs produced the cytotoxicity at the concentration-dependent and time-dependent manner, and elicited the permeability and inflammation response in HCMECs. These results demonstrated that cytotoxicity, permeability, and inflammation in vascular endothelial cells following exposure to metal oxide nanoparticles depended on particle composition, concentration, and exposure time. PMID:21681618

Sun, Jing; Wang, Shaochuang; Zhao, Dong; Hun, Fei Han; Weng, Lei; Liu, Hui

2011-10-01

80

Mapping Genes that Contribute to Daunorubicin-Induced Cytotoxicity  

PubMed Central

Daunorubicin is an anthracycline antibiotic agent used in the treatment of hematopoietic malignancies. Toxicities associated with this agent include myelosuppression and cardiotoxicity; however, the genes or genetic determinants that contribute to these toxicities are unknown. We present an unbiased genome-wide approach that incorporates heritability, whole-genome linkage analysis, and linkage-directed association to uncover genetic variants contributing to the sensitivity to daunorubicin-induced cytotoxicity. Cell growth inhibition in 324 Centre d’ Etude du Polymorphisme Humain lymphoblastoid cell lines (24 pedigrees) was evaluated following treatment with daunorubicin for 72 h. Heritability analysis showed a significant genetic component contributing to the cytotoxic phenotypes (h2 = 0.18–0.63at 0.0125, 0.025, 0.05, 0.1, 0.2, and 1.0 µmol/L daunorubicin and at the IC50, the dose required to inhibit 50% cell growth). Whole-genome linkage scans at all drug concentrations and IC50 uncovered 11 regions with moderate peak LOD scores (>1.5), including 4q28.2 to 4q32.3 with a maximum LOD score of 3.18. The quantitative transmission disequilibrium tests were done using 31,312 high-frequency single-nucleotide polymorphisms (SNP) located in the 1 LOD confidence interval of these 11 regions. Thirty genes were identified as significantly associated with daunorubicin-induced cytotoxicity (P ? 2.0 × 10?4, false discovery rate ? 0.1). Pathway and functional gene ontology analysis showed that these genes were overrepresented in the phosphatidylinositol signaling system, axon guidance pathway, and GPI-anchored proteins family. Our findings suggest that a proportion of susceptibility to daunorubicin-induced cytotoxicity may be controlled by genetic determinants and that analysis using linkage-directed association studies with dense SNP markers can be used to identify the genetic variants contributing to cytotoxicity. PMID:17545624

Duan, Shiwei; Bleibel, Wasim K.; Huang, Rong Stephanie; Shukla, Sunita J.; Wu, Xiaolin; Badner, Judith A.; Dolan, M. Eileen

2009-01-01

81

Cytotoxicity and antibacterial activity of gold-supported cerium oxide nanoparticles  

PubMed Central

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 ?M except for Au at >100 ?M. 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 ?M. 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 enteritidis, Escherichia coli, and Staphylococcus aureus, while, in coculture tests with Lactobacillus plantarum, S. aureus was inhibited to a greater extent than the other bacteria. Conclusion Gold-supported CeO2 nanoparticles may be a potential nanomaterial for in vivo application owing to their biocompatible and antibacterial properties. PMID:25473288

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

2014-01-01

82

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

PubMed Central

The biosynthesis of nanoparticles has been proposed as a cost effective environmental friendly alternative to chemical and physical methods. Microbial synthesis of nanoparticles is under exploration due to wide biomedical applications, research interest in nanotechnology and microbial biotechnology. In the present study, an ecofriendly process for the synthesis of nanoparticles using a novel Nocardiopsis sp. MBRC-1 has been attempted. We used culture supernatant of Nocardiopsis sp. MBRC-1 for the simple and cost effective green synthesis of silver nanoparticles. The reduction of silver ions occurred when silver nitrate solution was treated with the Nocardiopsis sp. MBRC-1 culture supernatant at room temperature. The nanoparticles were characterized by UV-visible, TEM, FE-SEM, EDX, FTIR, and XRD spectroscopy. The nanoparticles exhibited an absorption peak around 420?nm, a characteristic surface plasmon resonance band of silver nanoparticles. They were spherical in shape with an average particle size of 45 ± 0.15?nm. The EDX analysis showed the presence of elemental silver signal in the synthesized nanoparticles. The FTIR analysis revealed that the protein component in the form of enzyme nitrate reductase produced by the isolate in the culture supernatant may be responsible for reduction and as capping agents. The XRD spectrum showed the characteristic Bragg peaks of 1 2 3, 2 0 4, 0 4 3, 1 4 4, and 3 1 1 facets of the face centered cubic silver nanoparticles and confirms that these nanoparticles are crystalline in nature. The prepared silver nanoparticles exhibited strong antimicrobial activity against bacteria and fungi. Cytotoxicity of biosynthesized AgNPs against in vitro human cervical cancer cell line (HeLa) showed a dose-response activity. IC50 value was found to be 200??g/mL of AgNPs against HeLa cancer cells. Further studies are needed to elucidate the toxicity and the mechanism involved with antimicrobial and anticancer activity of the synthesized AgNPs as nanomedicine. PMID:23936787

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

2013-01-01

83

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

PubMed

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

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

2010-05-01

84

Cytotoxicity induced by nanobacteria and nanohydroxyapatites in human choriocarcinoma cells  

PubMed Central

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

2014-01-01

85

Cytotoxicity induced by nanobacteria and nanohydroxyapatites in human choriocarcinoma cells  

NASA Astrophysics Data System (ADS)

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.

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

2014-11-01

86

Enhanced growth inhibition of osteosarcoma by cytotoxic polymerized liposomal nanoparticles targeting the alcam cell surface receptor.  

PubMed

Osteosarcoma is the most common primary malignancy of bone in children, adolescents, and adults. Despite extensive surgery and adjuvant aggressive high-dose systemic chemotherapy with potentially severe bystander side effects, cure is attainable in about 70% of patients with localized disease and only 20%-30% of those patients with metastatic disease. Targeted therapies clearly are warranted in improving our treatment of this adolescent killer. However, a lack of osteosarcoma-associated/specific markers has hindered development of targeted therapeutics. We describe a novel osteosarcoma-associated cell surface antigen, ALCAM. We, then, create an engineered anti-ALCAM-hybrid polymerized liposomal nanoparticle immunoconjugate (?-AL-HPLN) to specifically target osteosarcoma cells and deliver a cytotoxic chemotherapeutic agent, doxorubicin. We have demonstrated that ?-AL-HPLNs have significantly enhanced cytotoxicity over untargeted HPLNs and over a conventional liposomal doxorubicin formulation. In this way, ?-AL-HPLNs are a promising new strategy to specifically deliver cytotoxic agents in osteosarcoma. PMID:23024593

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

2012-01-01

87

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

NASA Astrophysics Data System (ADS)

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

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

2011-07-01

88

Human Cell Line-Dependent WC-Co Nanoparticle Cytotoxicity and Genotoxicity: A Key Role of ROS Production.  

PubMed

Although tungsten carbide-cobalt (WC-Co) nanoparticles (NPs) have been widely used because of their robustness, their risk to human health remains poorly studied, despite the International Agency for Research on Cancer (IARC) classifying them as "probably carcinogenic" for humans (Group 2A) in 2006. Our current study aimed at defining the cytotoxicity and genotoxicity of one set of commercially available 60-nm diameter WC-Co NPs on three human cell lines representative of potential target organs: A549 (lung), Hep3B (liver), and Caki-1 (kidney). The cytotoxicity of WC-Co NPs was determined by evaluating cell impedance (xCELLigence), cell survival/death, and cell cycle checkpoints. Flow cytometry was used to not only evaluate cell cycle checkpoints, but to also estimate reactive oxygen species (ROS) generation. In addition, ?-H2Ax foci detection (confocal microscopy), considered to be the most sensitive technique for studying DNA double-strand breaks, was utilized to evaluate genotoxicity. As a final part of this study, we assessed the cellular incorporation of WC-Co NPs, first byflow cytometry (side scatter), and then by confocal microscopy (light reflection) to ensure that the NPs had entered cells. Overall, our current findings demonstrate that WC-Co NPs induce cell mortality, DNA double-strand breaks, and cell cycle arrest in human renal (Caki-1) and liver (Hep3B) cell lines, but do not induce significant cytotoxic effects in A549 lung cells. Interestingly, although WC-Co NPs effectively entered the cells in all 3 lines tested, ROS were detected in Caki-1 and Hep3B, but not in A549. This may explain the great differences in the cytotoxic and genotoxic effects we observed between these lines. PMID:25398624

Paget, V; Moche, H; Kortulewski, T; Grall, R; Irbah, L; Nesslany, F; Chevillard, S

2015-02-01

89

Enhancement effect of cytotoxicity response of silver nanoparticles combined with thermotherapy on C6 rat glioma cells.  

PubMed

The present studies reveal that silver nanoparticles (AgNPs) can induce apoptosis and enhance radio-sensitivity on cancer cells. In this paper, we mainly investigated the effect of AgNPs on rat glioma C6 cells upon the combination treatment of hyperthermia treatment (HTT). AgNPs were synthesized by a polyol process and the mean size was 15 nm. The particles showed dose-dependent cytotoxicity on C6 cells from the experimental data. Besides, we found that heating cells could enhance the contents of cell uptake of AgNPs. From the survival curves, AgNPs showed the ability to enhance thermo-sensitivity on C6 cells. Our results revealed that AgNPs could have a potential application in enhancing effect on HTT induced killing of glioma cells. PMID:23862417

Wang, Rui; Chen, Chunmei; Yang, Weizhong; Shi, Songsheng; Wang, Chunhua; Chen, Jing

2013-06-01

90

Cytotoxicity of organic surface coating agents used for nanoparticles synthesis and stability.  

PubMed

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 explored 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?M. Two exposure time points, 2h and 24h, 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

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

2015-06-01

91

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

PubMed

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 ?g/mL for 24 hours) resulted in a dose-dependent inhibition of cell growth, as determined by (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Similar promising results were observed for reducing bacteria functions. In this manner, this study demonstrated that sulphated zirconia nanoparticles with Brønsted acidic sites should be further studied for a wide range of anticancer and antibacterial applications. PMID:25632233

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

92

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

PubMed Central

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 ?g/mL for 24 hours) resulted in a dose-dependent inhibition of cell growth, as determined by (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Similar promising results were observed for reducing bacteria functions. In this manner, this study demonstrated that sulphated zirconia nanoparticles with Brønsted acidic sites should be further studied for a wide range of anticancer and antibacterial applications. PMID:25632233

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

93

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

PubMed

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

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

2013-01-01

94

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

PubMed Central

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

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

2013-01-01

95

Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles.  

PubMed

Cerium oxide nanoparticles (nanoceria) have shown great potential as antioxidant and radioprotective agents for applications in cancer therapy. Recently, various polymer-coated nanoceria preparations have been developed to improve their aqueous solubility and allow for surface functionalization of these nanoparticles. However, the interaction of polymer-coated nanoceria with cells, their uptake mechanism, and subcellular localization are poorly understood. Herein, we engineered polymer-coated cerium oxide nanoparticles with different surface charges (positive, negative, and neutral) and studied their internalization and toxicity in normal and cancer cell lines. The results showed that nanoceria with a positive or neutral charge enters most of the cell lines studied, while nanoceria with a negative charge internalizes mostly in the cancer cell lines. Moreover, upon entry into the cells, nanoceria is localized to different cell compartments (e.g., cytoplasm and lysosomes) depending on the nanoparticle's surface charge. The internalization and subcellular localization of nanoceria plays a key role in the nanoparticles' cytotoxicity profile, exhibiting significant toxicity when they localize in the lysosomes of the cancer cells. In contrast, minimal toxicity is observed when they localize into the cytoplasm or do not enter the cells. Taken together, these results indicate that the differential surface-charge-dependent localization of nanoceria in normal and cancer cells plays a critical role in the nanoparticles' toxicity profile. PMID:20690607

Asati, Atul; Santra, Santimukul; Kaittanis, Charalambos; Perez, J Manuel

2010-09-28

96

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

SciTech Connect

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

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

2012-11-15

97

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

NASA Astrophysics Data System (ADS)

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

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

2014-08-01

98

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

PubMed

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 ?-cyclodextrin (?-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 (??m). Results indicated that capping AgNPs with ?-CD improved their efficacy against S. epidermidis CSF 41498, reduced biofilm formation and their cytotoxicity. The study concluded that ?-CD is an effective capping and stabilising agent that reduces toxicity of AgNPs against the mammalian cell while enhancing their antibiofilm activity. PMID:25596861

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

2015-01-01

99

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

PubMed

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. PMID:25083742

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

2014-09-21

100

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

SciTech Connect

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

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

2012-08-15

101

Lipid peroxidation and cytotoxicity induced by respirable volcanic ash.  

PubMed

This paper reports that the main component of respirable volcanic ash, allophane, induces lipid peroxidation (LP), the oxidative degradation of lipids in cell membranes, and cytotoxicity in murin monocyle/macrophage cells. Naturally-occurring allophane collected from New Zealand, Japan, and Ecuador was studied. The quantification of LP was conducted using the Thiobarbituric Acid Reactive Substances (TBARS) assay. The cytotoxic effect was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide colorimetric assay. Electron-Paramagnetic Resonance (EPR) determinations of naturally-occurring allophane confirmed the incorporation in the structure and clustering of structural Fe(3+), and nucleation and growth of small-sized Fe (oxyhydr)oxide or gibbsite. LP induced by allophane varied with time, and solid concentration and composition, reaching 6.7 ± 0.2 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%. PMID:24793297

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

2014-06-15

102

Dihydrolipoic Acid Induces Cytotoxicity in Mouse Blastocysts through Apoptosis Processes  

PubMed Central

?-Lipoic acid (LA) is a thiol with antioxidant properties that protects against oxidative stress-induced apoptosis. LA is absorbed from the diet, taken up by cells and tissues, and subsequently reduced to dihydrolipoic acid (DHLA). In view of the recent application of DHLA as a hydrophilic nanomaterial preparation, determination of its biosafety profile is essential. In the current study, we examined the cytotoxic effects of DHLA on mouse embryos at the blastocyst stage, subsequent embryonic attachment and outgrowth in vitro, in vivo implantation by embryo transfer, and early embryonic development in an animal model. Blastocysts treated with 50 ?M DHLA exhibited significantly increased apoptosis and a corresponding decrease in total cell number. Notably, the implantation success rates of blastocysts pretreated with DHLA were lower than that of their control counterparts. Moreover, in vitro treatment with 50 ?M DHLA was associated with increased resorption of post-implantation embryos and decreased fetal weight. Data obtained using an in vivo mouse model further disclosed that consumption of drinking water containing 100 ?M DHLA led to decreased early embryo development, specifically, inhibition of development to the blastocyst stage. However, it appears that concentrations of DHLA lower than 50 ?M do not exert a hazardous effect on embryonic development. Our results collectively indicate that in vitro and in vivo exposure to concentrations of DHLA higher than 50 ?M DHLA induces apoptosis and retards early pre- and post-implantation development, and support the potential of DHLA to induce embryonic cytotoxicity. PMID:22489194

Houng, Wei-Li; Lin, Cheng-An J.; Shen, Ji-Lin; Yeh, Hung-I; Wang, Hsueh-Hsiao; Chang, Walter H.; Chan, Wen-Hsiung

2012-01-01

103

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

NASA Astrophysics Data System (ADS)

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.

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

104

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

PubMed

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

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

2014-11-01

105

Removal of Nanoparticles With Laser Induced Plasma  

Microsoft Academic Search

A review of the recent progress in the understanding of the laser induced plasma (LIP) technique utilized for nanoparticle removal is presented. LIP nanoparticle removal technique has been successfully demonstrated for removal of 10–60 nm polystyrene latex (PSL) particles from silicon substrates. The motivation for LIP technique stems from the requirement for defect-free cleaning of wafers and lithography photomasks in

Ivin Varghese; M. D. Murthy Peri; Thomas Dunbar; Brian Maynard; Derek A. Thomas; Cetin Cetinkaya

2008-01-01

106

Effect of Crystal Size and Surface Functionalization on the Cytotoxicity of Silicalite1 Nanoparticles  

Microsoft Academic Search

In this report, we describe the synthesis and characterization of nanocrystalline silicalite (the purely siliceous form of the zeolite, ZSM-5) of defined crystal size and surface functionalization and determine the effect on the type and degree of cytotoxicity induced in two distinct model cell lines. The silicalite materials were characterized by powder X-ray diffraction, dynamic light scattering andpotential, solid state

Anton Petushkov; Janjira Intra; Jessica B. Graham; Sarah C. Larsen; Aliasger K. Salem

2009-01-01

107

Physiological changes induced in cardiac myocytes by cytotoxic T lymphocytes  

SciTech Connect

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

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

1987-01-01

108

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

NASA Astrophysics Data System (ADS)

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.

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

2014-11-01

109

Green synthesized silver nanoparticles using Nelumbonucifera root extract for efficient protein binding, antioxidant and cytotoxicity activities.  

PubMed

Silver nanoparticles (AgNPs) with a mean particle size of ? 16.7 nm were synthesized using an eco-friendly reducing material, aqueous Nelumbo nucifera root extract. Rapid reduction resulted in the formation of polydispersed nanoparticles. The formation of AgNPs was characterized by surface plasmon resonance, which was determined by ultraviolet-visible (UV-Vis) spectroscopy (band at 412 nm), Fourier transform infrared spectroscopy, scanning electron microscopy-energy dispersive X-ray spectroscopy, transmission electron microscopy and X-ray diffraction. The interaction of the green synthesized AgNPs with Bovine Serum Albumin (BSA) at various temperatures was investigated. Fluorescence quenching, synchronous and resonance light scattering spectroscopy along with UV-Vis absorption studies revealed the efficient binding between BSA and the AgNPs. In addition, the AgNPs exhibited moderate antioxidant and cytotoxicity activities against HeLa cell lines. PMID:25463656

Sreekanth, T V M; Ravikumar, Sambandam; Eom, In-Yong

2014-12-01

110

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

PubMed

It is expected that the number and variety of engineered nanoparticles will increase rapidly over the next few years, and there is a need for new methods to quickly test the potential toxicity of these materials. Because experimental evaluation of the safety of chemicals is expensive and time-consuming, computational methods have been found to be efficient alternatives for predicting the potential toxicity and environmental impact of new nanomaterials before mass production. Here, we show that the quantitative structure-activity relationship (QSAR) method commonly used to predict the physicochemical properties of chemical compounds can be applied to predict the toxicity of various metal oxides. Based on experimental testing, we have developed a model to describe the cytotoxicity of 17 different types of metal oxide nanoparticles to bacteria Escherichia coli. The model reliably predicts the toxicity of all considered compounds, and the methodology is expected to provide guidance for the future design of safe nanomaterials. PMID:21317892

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

2011-03-01

111

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

Microsoft Academic Search

In order to reveal the biocompatibility of Fe3O4 nanoparticles and bipolar surfactant tetramethylammonium 11-aminoundecanoate cytotoxicity tests were performed as a function of concentration from low (0.1 µg ml-1) to higher concentration (100 µg ml-1) using various human glia, human breast cancer and normal cell lines. Cytotoxicity tests for human glia (D54MG, G9T, SF126, U87, U251, U373), human breast cancer (MB157,

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

2010-01-01

112

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

PubMed

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

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

2013-05-01

113

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

PubMed Central

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

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

2013-01-01

114

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

PubMed

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

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

2014-11-14

115

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

PubMed Central

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.

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

2015-01-01

116

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

PubMed

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

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

2015-01-01

117

Uptake and cytotoxicity of poly( d, l-lactide- co-glycolide) nanoparticles in human colon adenocarcinoma cells  

Microsoft Academic Search

The main objectives of the present study were to evaluate the cytotoxicity and the mechanisms of uptake of biodegradable lactic acid–glycolic acid copolymer (PLGA) nanoparticle carrier systems in vitro using the human colon adenocarcinoma cell line Caco2. Nanoparticles (NPs) (PLGA 75:25) with an average diameter of 299.5nm containing bovine serum albumin labeled with fluorescein isothiocyanate (BSA-FITC) as a fluorescent model

A. Katsikari; Chr. Patronidou; C. Kiparissides; M. Arsenakis

2009-01-01

118

Assessing carbon-encapsulated iron nanoparticles cytotoxicity in Lewis lung carcinoma cells.  

PubMed

Carbon-encapsulated iron nanoparticles (CEINs) have been considered as attractive candidates for several biomedical applications. In the present study, we synthesized CEINs (the mean diameter 40-80?nm) using a carbon arc route, and the as-synthesized CEINs were characterized (scanning and transmission electron microscopy, dynamic light scattering, turbidimetry, Zeta potential) and further tested as raw and purified nanomaterials containing the carbon surface modified with acidic groups. For cytotoxicity evaluation, we applied a battery of different methods (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, lactate dehydrogenase, calcein AM/propidium iodide, annexin V/propidium iodide, JC-1, cell cycle assay, Zeta potential, TEM and inductively coupled plasma mass spectrometry) to address the strategic cytotoxic endpoints of Lewis lung carcinoma cells due to CEIN (0.0001-100?µg?ml(-1) ) exposures in vitro. Our studies evidence that incubation of Lewis lung carcinoma cells with CEINs is accompanied in substantial changes of zeta potential in cells and these effects may result in different internalization profiles. The results show that CEINs increased the mitochondrial and cell membrane cytotoxicity; however, the raw CEIN material (Fe@C/Fe) produced higher toxicities than the rest of the CEINs studied to data. The study showed that non-modified CEINs (Fe@C/Fe and Fe@C) elevated some pro-apoptotic events to a greater extent compared to that of the surface-modified CEINs (Fe@C-COOH and Fe@C-(CH2 )2 COOH). They also diminished the mitochondrial membrane potentials. In contrast to non-modified CEINs, the surface-functionalized nanoparticles caused the concentration- and time-dependent arrest of the S phase in cells. Taken all together, our results shed new light on the rational design of CEINs, as their geometry, hydrodynamic and, in particular, surface characteristics are important features in selecting CEINs as future nanomaterials for nanomedicine applications. PMID:24474239

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

2014-04-01

119

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

Microsoft Academic Search

The cytotoxicity of adriamycin (ADR)-loaded and pH-sensitive nanoparticles made of pullulan acetate (PA) and sulfonamide (sulfadimethoxine; SDM) (PA\\/SDM) conjugate to a breast tumor cell line (MCF-7) was investigated to test the feasibility of the nanoparticles in targeting acidic tumor extracellular pH (pHe). At pH 6.8, ADR loaded PA\\/SDM nanoparticles showed cytotoxicity in the cell culture experiment, comparable to that of

Kun Na; Eun Seong Lee; You Han Bae

2003-01-01

120

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

PubMed Central

Although it is hypothesized that surface (like surface charge) and physical characteristics (like particle size) play important roles in cellular interactions of nanoparticles (NPs), a systematic study probing this issue is missing. Hence, a comparative cytotoxicity study quantifying nine different cellular endpoints, was performed with a broad series of monodisperse, well characterized silicon (Si) and germanium (Ge) NPs with various surface functionalizations. Human colonic adenocarcinoma Caco-2 and rat alveolar macrophage NR8383 cells were used, to clarify the toxicity of this series of NPs. The surface coatings on the NPs appeared to dominate the cytotoxicity: the cationic NPs exhibited cytotoxicity, whereas the carboxylic acid-terminated and hydrophilic PEG- or dextran-terminated NPs did not. Within the cationic Si NPs, smaller Si NPs were more toxic than bigger ones. Manganese-doped (1 % Mn) Si NPs did not show any added toxicity, which favors their further development for bioimaging. Iron-doped (1 % Fe) Si NPs showed some added toxicity, which may be due to the leaching of Fe3+ ions from the core. A silica coating seemed to impart toxicity, in line with the reported toxicity of silica. Intracellular mitochondria seem to be a target organ for the toxic NPs since a dose-, surface charge- and size-dependent imbalance of the mitochondrial membrane potential was observed. Such imbalance led to a series of other cellular events for cationic NPs, like decreased mitochondrial membrane potential (??m) and ATP production, induction of ROS generation, increased cytoplasmic Ca2+ content, production of TNF-? and enhanced caspase-3 activity. Taken together, the results explain the toxicity of Si NPs/Ge NPs largely by their surface characteristics, provide insight in the mode of action underlying the observed cytotoxicity, and give directions on synthesizing biocompatible Si and Ge NPs, as this is crucial for bioimaging and other applications in for example the field of medicine. PMID:23619571

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

2013-01-01

121

Design of LVFFARK and LVFFARK-Functionalized Nanoparticles for Inhibiting Amyloid ?-Protein Fibrillation and Cytotoxicity.  

PubMed

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

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

2015-03-18

122

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

PubMed

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

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

2014-08-01

123

Mycoplasma pneumoniae induces cytotoxic activity in guinea pig bronchoalveolar cells  

SciTech Connect

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.

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

1985-06-01

124

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

PubMed

Superparamagnetic iron oxide nanoparticles (SPIONs) are increasingly used in medical applications, such as targeting delivery and imaging. In the future, patients are more likely to be exposed to pharmaceutical products containing such particles. The study of toxicity of SPIONs has become of great importance in recent years, although the published data in this arena is limited. The aim of the present work is to investigate the cytotoxicity of SPIONs and the effect of the particles on the cell medium components. For this purpose, uncoated and polyvinyl alcohol (PVA) coated SPIONs with narrow size distribution were synthesized via a well-known coprecipitation method. The mouse fibroblast cell line L929 was exposed to SPIONs to probe the toxicity of magnetic nanoparticles during the bio application. Changes to the cell medium caused by SPIONs were analyzed with zeta potential measurements, ultraviolet visible spectroscopy (UV/vis) and the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay. It is observed that gas vesicles are formed in SPION-treated cells. Toxicity is conventionally explained by changes in the DMEM's pH and composition due to the tendency of SPIONs to interact with biomolecules. A new procedure is proposed to examine the in vitro toxicity of nanoparticles in a more rigorous manner, which gives an improvement in the relationship between in vivo and in vitro toxicity studies. PMID:19781921

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

2010-01-01

125

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

PubMed Central

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

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

2014-01-01

126

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

PubMed Central

Objective: To evaluate the cytotoxicity of iron nanoparticles on cardiac cells and to determine whether they can modulate the biological activity of 7-ketocholesterol (7KC) involved in the development of cardiovascular diseases. Nanoparticles of iron labeled with Texas Red are introduced in cultures of nonbeating mouse cardiac cells (HL1-NB) with or without 7-ketocholesterol 7KC, and their ability to induce cell death, pro-inflammatory and oxidative effects are analyzed simultaneously. Study design: Flow cytometry (FCM), confocal laser scanning microscopy (CLSM), and subsequent factor analysis image processing (FAMIS) are used to characterize the action of iron nanoparticles and to define their cytotoxicity which is evaluated by enhanced permeability to SYTOX Green, and release of lactate deshydrogenase (LDH). Pro-inflammatory effects are estimated by ELISA in order to quantify IL-8 and MCP-1 secretions. Pro-oxidative effects are measured with hydroethydine (HE). Results: Iron Texas Red nanoparticles accumulate at the cytoplasmic membrane level. They induce a slight LDH release, and have no inflammatory or oxidative effects. However, they enhance the cytotoxic, pro-inflammatory and oxidative effects of 7KC. The accumulation dynamics of SYTOX Green in cells is measured by CLSM to characterize the toxicity of nanoparticles. The emission spectra of SYTOX Green and nanoparticles are differentiated, and corresponding factor images specify the possible capture and cellular localization of nanoparticles in cells. Conclusion: The designed protocol makes it possible to show how Iron Texas Red nanoparticles are captured by cardiomyocytes. Interestingly, whereas these fluorescent iron nanoparticles have no cytotoxic, pro-inflammatory or oxidative activities, they enhance the side effects of 7KC. PMID:20463934

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

2010-01-01

127

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

PubMed Central

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

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

2015-01-01

128

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

PubMed

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

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

2014-07-21

129

Lipid peroxidation contributes to hydrogen peroxide induced cytotoxicity in renal epithelial cells  

Microsoft Academic Search

Lipid peroxidation contributes to hydrogen peroxide induced cytotoxicity in renal epithelial cells. We have examined the role of lipid peroxidation in the cytotoxicity of H2O2 in OK cells containing markedly differing amounts of cell membrane polyunsaturated fatty acids (PUFA). In OK cells grown in a serum free medium, PUFA were undetectable. The membranes of these cells contained predominantly oleic, stearic

Alice M Sheridan; Sean Fitzpatrick; Candice Wang; David C Wheeler; Wilfred Lieberthal

1996-01-01

130

Cytotoxic lymphocytes and antibody-dependent complement-mediated cytotoxicity induced by administration of influenza vaccine.  

PubMed Central

Recently defined aspects of cellular and humoral antiviral immunity were evaluated in 10 young adults given influenza vaccines containing A/USSR/77 (H1N1) antigens. Cytotoxic lymphocytes were measured by using cryopreserved lymphocytes as effector cells and syngeneic, virus-infected lymphocytes as target cells. An assay previously developed in this laboratory was adapted for the measurement of antibody-dependent, complement-mediated cytotoxicity. Antiviral cytotoxic lymphocyte responses were detected in 5 of 10 volunteers between 3 and 10 days after the initial vaccination. These responses were found both in individuals who were previously primed and in individuals who were not primed to influenza A/USSR/77 antigens. The complement-mediated lysis assay was found to be more sensitive than the hemagglutination inhibition test and probably detected antibodies to both subtype-specific and cross-reactive antigenic determinants. These responses to influenza antigens are similar to those obtained in studies of murine influenza which indicate that cytotoxic lymphocytes and antibody-dependent, complement-mediated cytotoxicity have a role in the early response to acute infection. PMID:7439982

Quinnan, G V; Ennis, F A; Tuazon, C U; Wells, M A; Butchko, G M; Armstrong, R; McLaren, C; Manischewitz, J F; Kiley, S

1980-01-01

131

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

NASA Astrophysics Data System (ADS)

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.

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

132

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

PubMed Central

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

Fröhlich, Eleonore

2012-01-01

133

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

PubMed Central

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

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

2013-01-01

134

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

PubMed Central

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

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

2014-01-01

135

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

PubMed

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

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

2015-02-01

136

Comparative in vitro cytotoxicity study on uncoated magnetic nanoparticles: effects on cell viability, cell morphology, and cellular uptake.  

PubMed

Magnetic iron oxide nanoparticles (MIONPs) must be biocompatible, and a thorough knowledge on their potential cytotoxicity is crucial for their biomedical applications. However, the detailed study about the effects of iron oxide nanoparticles on cell viability, cell morphology, and cellular uptake of different mammalian cells is still insufficient. In this paper, comparative cytotoxicity study of uncoated magnetite nanoparticles at different concentrations was performed on human cervical cancer cell line (HeLa) and immortalized normal human retinal pigment epithelial cell line (RPE). The size, structure, and magnetic behavior of the MIONPs were characterized using transmission electron microscopy (TEM), X-ray diffractometry (XRD), and vibrating sample magnetometry (VSM) respectively. After 24-hour incubation with the MIONPs, the cell viability was determined by live/dead assay, the cell morphology at high magnification was observed under scanning electron microscopy (SEM), and the cellular uptake of MIONPs was measured under TEM and verified by energy-dispersive X-ray spectroscopy (EDX) analysis. Our results indicate that the uncoated MIONPs at a high concentration (0.40 mg/ml) were toxic to both HeLa and RPE cells. However, the cytotoxicity of uncoated MIONPs at low concentrations was cell-type specific, and RPE cells were more susceptible to these MIONPs than HeLa cells. The effects of the MIONPs on cell morphology and the nanoparticles uptake also showed different features between these two cell lines. Hence cell type should be taken into consideration in the in vitro cytotoxicity study of uncoated MIONPs. Additionally, it should be noticed that the cell morphological changes and the uptake of nanoparticles can take place even though no toxic effect of these MIONPs at low concentrations was reflected in the traditional cell viability assay. PMID:23447952

Li, L; Mak, K Y; Shi, J; Koon, H K; Leung, C H; Wong, C M; Leung, C W; Mak, C S K; Chan, N M M; Zhong, W; Lin, K W; Wu, E X; Pong, P W T

2012-12-01

137

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

PubMed

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

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

138

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

PubMed Central

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

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

2014-01-01

139

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

Microsoft Academic Search

Many viruses interfere with apoptosis of infected cells, presumably preventing cellular apoptosis as a direct response to viral infection. Since cytotoxic T lymphocytes (CTL) induce apoptosis of infected cells as part of the \\

KEITH R. JEROME; JONATHAN F. TAIT; DAVID M. KOELLE; LAWRENCE COREY

1998-01-01

140

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

PubMed

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

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

2012-01-01

141

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

PubMed Central

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

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

142

MECHANISMS OF MITOCHONDRIA-MEDIATED APOPTOSIS INDUCED BY CYTOTOXIC STRESS  

E-print Network

Defects within the apoptotic pathway are thought to contribute to tumorigenesis and therapeutic resistance. Although most cytotoxic anti-cancer drugs are thought to activate the mitochondria-mediated apoptotic pathway, the precise mechanistic...

Shelton, Shary Nicole

2010-06-04

143

cytotoxic T cells kill infected cells directly by inducing them to undergo apoptosis helper T cells help activate B cells, macrophages and cytotoxic T cells.  

E-print Network

cytotoxic T cells kill infected cells directly by inducing them to undergo apoptosis helper T cells help activate B cells, macrophages and cytotoxic T cells. Both classes of T cells express cell-surface, antibodylike receptors, encoded by genes that are assembled from multiple gene segments during T cell

Morante, Silvia

144

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

PubMed

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. PMID:23419906

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

145

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

PubMed Central

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

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

2014-01-01

146

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

NASA Astrophysics Data System (ADS)

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

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

2010-02-01

147

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

PubMed

In order to reveal the biocompatibility of Fe(3)O(4) nanoparticles and bipolar surfactant tetramethylammonium 11-aminoundecanoate cytotoxicity tests were performed as a function of concentration from low (0.1 microg ml(-1)) to higher concentration (100 microg ml(-1)) using various human glia, human breast cancer and normal cell lines. Cytotoxicity tests for human glia (D54MG, G9T, SF126, U87, U251, U373), human breast cancer (MB157, SKBR3, T47D) and normal (H184B5F5/M10, WI-38, SVGp12) cell lines exhibited almost nontoxicity and reveal biocompatibility of Fe(3)O(4) nanoparticles in the concentration range of 0.1-10 microg ml(-1), while accountable cytotoxicity can be seen at 100 microg ml(-1). The results of our studies suggest that Fe(3)O(4) nanoparticles coated with bipolar surfactant tetramethylammonium 11-aminoundecanoate are biocompatible and promising for bio-applications such as drug delivery, magnetic resonance imaging and magnetic hyperthermia. PMID:20090199

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

2010-02-19

148

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

PubMed

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 (?), the charge of the metal cation corresponding to a given oxide (?ox), 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 ?ox 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

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

2014-09-01

149

Cell-mediated cytotoxicity against rat fibroblasts induced by Actinomyces viscosus.  

PubMed Central

Cell-mediated cytotoxicity against syngeneic fetal rat fibroblasts that require in vitro exposure of effector cells to Actinomyces viscosus Ny1 fractions was investigated by measuring the uptake of radioactivity by fibroblasts during a 2-h pulse with [14C]aminoisobutyric acid after 1 to 3 days of coculture with splenic effector cells. By using splenocytes from inbred RIC-Sprague-Dawley rats as effector cells and syngeneic embryonic rat fibroblasts as target cells, strong cell-mediated cytotoxicity dependent on the in vitro exposure to an A. viscosus Ny1 fraction was observed, but only within a small range of effector-to-target cell ratios (3:1 to 10:1). Concanavalin A and lipopolysaccharide from Escherichia coli induced a comparable cytotoxicity, indicating that the effect might be connected with the mitogenic activity of the A. viscosus NY1 fraction. Splenocytes from rats immunized with A. viscosus Ny1 and from control rats induced similar levels of cytotoxicity in 72-h cytotoxicity assays. In shorter assays (24 h), however, splenocytes from immune animals induced low cytotoxicity, which was, however, significantly higher than that induced by splenocytes from control animals. We conclude that both antigen- and mitogen-dependent cell mediated effector mechanisms are operative in this system and that the two normally overlapping effects can be experimentally separated. This new system describes a fibroblast impairment in the presence of splenocytes and bacterial components and may provide a useful model for studying pathogenic mechanisms operative in periodontal disease. PMID:7118254

Gaegauf-Zollinger, R; Burckhardt, J J; Gmür, R; Guggenheim, B

1982-01-01

150

Involvement of Four Different Intracellular Sites in Chloroacetaldehyde- Induced Oxidative Stress Cytotoxicity  

PubMed Central

Chloroacetaldehyde (CAA) is a chlorination by-product in finished drinking water and a toxic metabolite of a wide variety of industrial chemicals (e.g. vinyl chloride) and chemotherapeutic agents (e.g. cyclophosphamide and ifosfamide). In this research, the cytotoxic mechanisms of CAA in freshly isolated rat hepatocytes were investigated.CAA cytotoxicity was associated with reactive oxygen species (ROS) formation and glutathione depletion suggesting that oxidative stress contributed to the CAA cytotoxic mechanism. CAA-induced oxidative stress cytotoxicity markers were significantly prevented by antioxidants, ROS scavengers, mitochondrial permeability transition (MPT) pore sealing agents, endocytosis inhibitors, ATP generators and xanthine oxidase inhibitor. In our study the hepatocyte mitochondrial membrane potential was rapidly decreased by CAA which was prevented by antioxidants and ROS scavenger indicating that mitochondrial membrane damage was a consequence of ROS formation. CAA cytotoxicity was also associated with lysosomal membrane rupture. Our findings showed that at least four different intracellular sources including: metabolic enzymes cytochrome P450 and xanthine oxidase, mitochondrial respiratory chain disruption and lysosomal Haber-weiss reaction, were involved in CAA induced ROS formation and other subsequent cytotoxic events. Our other interesting finding was that the lysosomotropic agents prevented CAA induced mitochondrial membrane potential collapse and mitochondrial MPT pore sealing agents inhibited lysosomal membrane damage caused by CAA. It can therefore be suggested that there is probably a toxic interaction (cross-talk) between mitochondrial and lysosomal oxidative stress generating systems, which potentiates each organelle damage and ROS formation in CAA- induced hepatotoxicity. PMID:24250449

Pourahmad, Jalal; Hosseini, Mir-Jamal; Eskandari, Mohammad Reza; Rahmani, Faezeh

2012-01-01

151

Laser-induced nanowelding of gold nanoparticles  

Microsoft Academic Search

Picosecond laser pulses are employed to adjoin, to hold closely, and to weld gold nanoparticles on carbon-coated copper grids. Microscopic images and profiles indicate that gold particles are well connected showing single-phased nanocontact. Our results suggest that laser-induced nanowelding can be achieved in a programmed manner to produce ohmic contact by considering the size-dependent thermodynamic, dynamic, and kinetic properties of

Seol Ji Kim; Du-Jeon Jang

2005-01-01

152

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

PubMed Central

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 (Nb?) 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% Nb?. 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 Nb?, 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

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

2014-01-01

153

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

NASA Astrophysics Data System (ADS)

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.

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

2015-03-01

154

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

PubMed

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

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

2015-02-01

155

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

PubMed

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

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

2014-08-14

156

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

PubMed

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

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

2013-09-01

157

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

PubMed

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

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

2014-11-01

158

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

NASA Astrophysics Data System (ADS)

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.

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

2015-01-01

159

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

NASA Astrophysics Data System (ADS)

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.

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

2015-02-01

160

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

NASA Astrophysics Data System (ADS)

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

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

2014-08-01

161

Butylated hydroxyanisole inhibits tumor necrosis factor-induced cytotoxicity and arachidonic acid release  

Microsoft Academic Search

The mechanisms by which the antioxidant butylated hydroxyanisole (BHA) inhibits recombinant tumor necrosis factor alpha (rTNF-?)-induced\\u000a cytotoxicity have been studied in WEHI 164 clone 13 (WEHI) and L929 fibrosarcoma cells. When BHA was added simultaneously\\u000a with rTNF-?, it completely inhibited rTNF-? cytotoxicity in the WEHI and L929 cells. BHA also inhibited the toxicity when\\u000a added 2 h after rTNF-? in

Ole-Lars Brekke; Terje Espevik; Kristian S. Bjerve

1994-01-01

162

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

PubMed

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

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

2015-02-01

163

Assessment of temporal dose-toxicity relationship of fumed silica nanoparticle in human lung A549 cells by conventional cytotoxicity and ¹H-NMR-based extracellular metabonomic assays.  

PubMed

As nanoparticles could form aggregates in biological systems, the dynamics of their dispersity drives the temporal effect of nanoparticles in vitro. To test this hypothesis, the fumed silica nanoparticles (SiNPs) that have primary sizes of 7-14 nm and form aggregates in culture medium were selected for toxicity study in human lung A549 cells. The dispersity of SiNPs was analyzed by dynamic light scattering and transmission of electron microscopy. Cytotoxicity assays including mitochondrial activity, intracellular level of reactive oxygen species (ROS), and membrane damage together with the ¹H-NMR-based extracellular metabonomic assay were conducted to determine the temporal dose-effect relationship of SiNPs. In cell culture medium, SiNPs dispersed well initially at 25-100 ?g/ml; however, they sedimented rapidly in a concentration-dependent manner. SiNPs caused a dose-dependent increase of intracellular ROS and cell membrane damage at 4 h and a loss of cell viability after 48 h. SiNPs also induced an elevation of extracellular glucose, lactate, phenylalanine, histidine, and tyrosine levels in a time- and concentration-dependent manner. The dose-effect patterns at 4 h were different from that at 12 and 24 h as assessed by both cytotoxicity and metabonomic assays. Both fitted better with polynomial regression than linear regression, implying multimode action of SiNPs at different concentrations. The early NP-cell interaction and the late sedimentation could be attributable to the temporal effects of SiNPs. The extracellular ¹H-NMR-based metabonomics demonstrated a potential as a robust nondestructive tool for monitoring the temporal effect of NPs that tend to aggregate in nature. PMID:24449423

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

2014-04-01

164

Cytotoxicity of CeO2 nanoparticles for Escherichia coli. Physico-chemical insight of the cytotoxicity mechanism.  

PubMed

The production of nanoparticles (NPs) is increasing rapidly for applications in electronics, chemistry, and biology. This interest is due to the very small size of NPs which provides them with many interesting properties such as rapid diffusion, high specific surface areas, reactivity in liquid or gas phase, and a size close to biomacromolecules. In turn, these extreme abilities might be a problem when considering a potentially uncontrolled exposure to the environment. For instance, nanoparticles might be highly mobile and rapidly transported in the environment or inside the body through a water or air pathway. Accordingly, the very fast development of these new synthetic nanomaterials raises questions about their impact on the environment and human health. We have studied the impact of a model water dispersion of nanoparticles (7 nm CeO2 oxide) on a Gram-negative bacteria (Escherichia coli). The nanoparticles are positively charged at neutral pH and thus display a strong electrostatic attraction toward bacterial outer membranes. The counting of colony forming units (CFU) after direct contact with CeO2 NPs allows for the defining of the conditions for which the contact is lethal to Escherichia coli. Furthermore, a set of experiments including sorption isotherms, TEM microscopy, and X-ray absorption spectroscopy (XAS) at cerium L3 edge is linked to propose a scenario for the observed toxic contact. PMID:17051814

Thill, Antoine; Zeyons, Ophélie; Spalla, Olivier; Chauvat, Franck; Rose, Jerôme; Auffan, Mélanie; Flank, Anne Marie

2006-10-01

165

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

PubMed Central

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

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

166

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

PubMed Central

Background Silver nanoparticles (AgNPs) are an important class of nanomaterial for a wide range of industrial and biomedical applications. AgNPs have been used as antimicrobial and disinfectant agents due their detrimental effect on target cells. The aim of our study was to determine the cytotoxic effects of biologically synthesized AgNPs using hot aqueous extracts of the mycelia of Ganoderma neo-japonicum Imazeki on MDA-MB-231 human breast cancer cells. Methods We developed a green method for the synthesis of water-soluble AgNPs by treating silver ions with hot aqueous extract of the mycelia of G. neo-japonicum. The formation of AgNPs was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction, dynamic light scattering, and transmission electron microscopy. Furthermore, the toxicity of synthesized AgNPs was evaluated using a series of assays: such as cell viability, lactate dehydrogenase leakage, reactive oxygen species generation, caspase 3, DNA laddering, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling in human breast cancer cells (MDA-MB-231). Results The ultraviolet-visible absorption spectroscopy results showed a strong resonance centered on the surface of AgNPs at 420 nm. The X-ray diffraction analysis confirmed that the synthesized AgNPs were single-crystalline, corresponding with the result of transmission electron microscopy. Treatment of MDA-MB-231 breast cancer cells with various concentrations of AgNPs (1–10 ?g/mL) for 24 hours revealed that AgNPs could inhibit cell viability and induce membrane leakage in a dose-dependent manner. Cells exposed to AgNPs showed increased reactive oxygen species and hydroxyl radical production. Furthermore, the apoptotic effects of AgNPs were confirmed by activation of caspase 3 and DNA nuclear fragmentation. Conclusion The results indicate that AgNPs possess cytotoxic effects with apoptotic features and suggest that the reactive oxygen species generated by AgNPs have a significant role in apoptosis. The present findings suggest that AgNPs could contribute to the development of a suitable anticancer drug, which may lead to the development of a novel nanomedicine for the treatment of cancers. PMID:24265551

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

2013-01-01

167

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

PubMed Central

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

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

2014-01-01

168

Comprehensive Evaluation of microRNA Expression Profiling Reveals the Neural Signaling Specific Cytotoxicity of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) through N-Methyl-D-Aspartate Receptor  

PubMed Central

Though nanomaterials are considered as drug carriers or imaging reagents targeting the central nervous system their cytotoxicity effect on neuronal cells has not been well studied. In this study, we treated PC12 cells, a model neuronal cell line, with a nanomaterial that is widely accepted for medical use, superparamagnetic iron oxide nanoparticles (SPIONs). Our results suggest that, after treated with SPIONs, the expression pattern of the cellular miRNAs changed widely in PC12 cells. As potential miRNA targets, NMDAR, one of the candidate mRNAs that were selected using GO and KEGG pathway enrichment, was significantly down regulated by SPIONs treatment. We further illustrated that SPIONs may induce cell death through NMDAR suppression. This study revealed a NMDAR neurotoxic effect of SPIONs and provides a reliable approach for assessing the neurocytotoxic effects of nanomaterials based on the comprehensive annotation of miRNA profiling. PMID:25798908

Sun, Bo; Liu, Rui; Ye, Nan; Xiao, Zhong-Dang

2015-01-01

169

Cytotoxic cells induced after Chlamydia psittaci infection in mice.  

PubMed Central

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. PMID:7068208

Lammert, J K

1982-01-01

170

INHIBITORS OF HYDROPEROXIDE METABOLISM ENHANCE ASCORBATE-INDUCED CYTOTOXICITY  

PubMed Central

Pharmacological ascorbate, via its oxidation, has been proposed as a pro-drug for the delivery of H2O2 to tumors. Pharmacological ascorbate decreases clonogenic survival of pancreatic cancer cells, which can be reversed by treatment with scavengers of H2O2. The goal of this study was to determine if inhibitors of intracellular hydroperoxide detoxification could enhance the cytotoxic effects of ascorbate. Human pancreatic cancer cells were treated with ascorbate alone or in combination with inhibitors of hydroperoxide removal including the glutathione disulfide reductase inhibitor 1,3 bis (2-chloroethyl)-1-nitrosurea (BCNU), siRNA targeted to glutathione disulfide reductase (siGR), and 2-deoxy-D-glucose (2DG), which inhibits glucose metabolism. Changes in the intracellular concentration of H2O2 were determined by analysis of the rate of aminotriazole-mediated inactivation of endogenous catalase activity. Pharmacological ascorbate increased intracellular H2O2 and depleted intracellular glutathione. When inhibitors of H2O2 metabolism were combined with pharmacological ascorbate the increase in intracellular H2O2 was amplified and cytotoxicity was enhanced. We conclude that inclusion of agents that inhibit cellular peroxide removal produced by pharmacological ascorbate leads to changes in the intracellular redox state resulting in enhanced cytotoxicity. PMID:23205739

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

2013-01-01

171

Cisplatin Induces Cytotoxicity through the Mitogen-Activated Protein Kinase Pathways and Activating Transcription Factor 31  

PubMed Central

The mechanisms underlying the proapoptotic effect of the chemotherapeutic agent, cisplatin, are largely undefined. Understanding the mechanisms regulating cisplatin cytotoxicity may uncover strategies to enhance the efficacy of this important therapeutic agent. This study evaluates the role of activating transcription factor 3 (ATF3) as a mediator of cisplatin-induced cytotoxicity. Cytotoxic doses of cisplatin and carboplatin treatments consistently induced ATF3 expression in five tumor-derived cell lines. Characterization of this induction revealed a p53, BRCA1, and integrated stress response-independent mechanism, all previously implicated in stress-mediated ATF3 induction. Analysis of mitogen-activated protein kinase (MAPK) pathway involvement in ATF3 induction by cisplatin revealed a MAPK-dependent mechanism. Cisplatin treatment combined with specific inhibitors to each MAPK pathway (c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38) resulted in decreased ATF3 induction at the protein level. MAPK pathway inhibition led to decreased ATF3 messenger RNA expression and reduced cytotoxic effects of cisplatin as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assay. In A549 lung carcinoma cells, targeting ATF3 with specific small hairpin RNA also attenuated the cytotoxic effects of cisplatin. Similarly, ATF3-/- murine embryonic fibroblasts (MEFs) were shown to be less sensitive to cisplatin-induced cytotoxicity compared with ATF3+/+ MEFs. This study identifies cisplatin as a MAPK pathway-dependent inducer of ATF3, whose expression influences cisplatin's cytotoxic effects. PMID:20651982

St. Germain, Carly; Niknejad, Nima; Ma, Laurie; Garbuio, Kyla; Hai, Tsonwin; Dimitroulakos, Jim

2010-01-01

172

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

NASA Astrophysics Data System (ADS)

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

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

2013-08-01

173

Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells  

PubMed Central

Background The increased use of engineered nanoparticles (NPs) has caused new concerns about the potential exposure to biological systems and the potential risk that these materials may pose on human health. Here, we examined the effects of exposure to different concentrations (0–50 ?g/mL) and incubation times (10 hours, 24 hours, or 48 hours) of yttrium oxide (Y2O3) NPs on human embryonic kidney (HEK293) cells. Changes in cellular morphology, cell viability, cell membrane integrity, reactive oxygen species levels, mitochondrial membrane potential, cell death (apoptosis and necrosis), and the DNA damage after NP exposure were compared to the effects seen following incubation with paraquat, a known toxicant. Results The 24-hour inhibitory concentration 50 (IC50) of Y2O3 NPs (41±5 nm in size) in the HEK293 cells was found to be 108 ?g/mL. Incubation with Y2O3 NPs (12.25–50 ?g/mL) increased the ratio of Bax/Bcl-2, caspase-3 expression and promoted apoptotic- and necrotic-mediated cell death in both a concentration and a time-dependent manner. Decreases in cell survivability were associated with elevations in cellular reactive oxygen species levels, increased mitochondrial membrane permeability, and evidence of DNA damage, which were consistent with the possibility that mitochondria impairment may play an important role in the cytotoxic response. Conclusion These data demonstrate that the Y2O3 NP exposure is associated with increased cellular apoptosis and necrosis in cultured HEK293 cells. PMID:24648735

Selvaraj, Vellaisamy; Bodapati, Sravanthi; Murray, Elizabeth; Rice, Kevin M; Winston, Nicole; Shokuhfar, Tolou; Zhao, Yu; Blough, Eric

2014-01-01

174

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

NASA Astrophysics Data System (ADS)

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

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

2003-05-01

175

Orthodontic cements induce genotoxicity and cytotoxicity in mammalian cells in vitro  

PubMed Central

Background: This study assessed the genotoxic and cytotoxic potential of three different glass ionomer cements used in Orthodontics (Vidrion C, OptiBand, and Band-Lok). Materials and Methods: The tested cements were exposed in vitro to mouse fibroblast cells for 1 h at 37°C. The genotoxicity and cytotoxicity were evaluated by means of the single cell gel (Comet Assay) and the trypan blue exclusion test, respectively. All data were assessed by the Kruskal–Wallis non-parametric test, followed by Dunn's test. P < 0.05 was considered for statistical significance. Results: Significant statistically differences (P < 0.05) in cytotoxicity were observed for both Vidrion C powder and liquid at the tested concentrations, with exception to the group presenting the lowest powder concentration. OptiBand similarly presented induced cellular death at the highest tested concentration for paste A (P < 0.05). Band-Lok paste B was also able to induce cytotoxicity at the highest tested concentration. Regarding the comet assay, Band-Lok paste B and OptiBand paste A resulted in increased DNA injury (P < 0.05). Conclusion: The obtained results support the thought that some glass ionomer cement components present both genotoxic and cytotoxic effects when in high concentrations. Since DNA damage and cellular death are important events during oncogenesis, this study represents relevant contribution to estimate the real risks induced by these materials upon cellular systems. PMID:23162578

Angelieri, Fernanda; Joias, Renata P.; Bresciani, Eduardo; Noguti, Juliana; Ribeiro, Daniel A.

2012-01-01

176

Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity  

PubMed Central

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 ?mol/g in hepatic tissue due to Smnps. PMID:21753880

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

2011-01-01

177

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

PubMed Central

Biofabricated metal nanoparticles are generally biocompatible, inexpensive, and ecofriendly, therefore, are used preferably in industries, medical and material science research. Considering the importance of biofabricated materials, we isolated, characterized and identified a novel bacterial strain OS4 of Stenotrophomonas maltophilia (GenBank: JN247637.1). At neutral pH, this Gram negative bacterial strain significantly reduced hexavalent chromium, an important heavy metal contaminant found in the tannery effluents and minings. Subsequently, even at room temperature the supernatant of log phase grown culture of strain OS4 also reduced silver nitrate (AgNO3) to generate nanoparticles (AgNPs). These AgNPs were further characterized by UV–visible, Nanophox particle size analyzer, XRD, SEM and FTIR. As evident from the FTIR data, plausibly the protein components of supernatant caused the reduction of AgNO3. The cuboid and homogenous AgNPs showed a characteristic UV-visible peak at 428 nm with average size of ?93 nm. The XRD spectra exhibited the characteristic Bragg peaks of 111, 200, 220 and 311 facets of the face centred cubic symmetry of nanoparticles suggesting that these nanoparticles were crystalline in nature. From the nanoparticle release kinetics data, the rapid release of AgNPs was correlated with the particle size and increasing surface area of the nanoparticles. A highly significant antimicrobial activity against medically important bacteria by the biofabricated AgNPs was also revealed as decline in growth of Staphylococcus aureus (91%), Escherichia coli (69%) and Serratia marcescens (66%) substantially. Additionally, different cytotoxic assays showed no toxicity of AgNPs to liver function, RBCs, splenocytes and HeLa cells, hence these particles were safe to use. Therefore, this novel bacterial strain OS4 is likely to provide broad spectrum benefits for curing chromium polluted sites, for biofabrication of AgNPs and ultimately in the nanoparticle based drug formulation for the treatment of infectious diseases. PMID:23555625

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

2013-01-01

178

Plasmodium falciparum: selenium-induced cytotoxicity to P. falciparum.  

PubMed

The in vitro antimalarial activity of sodium selenite (NaSe) was investigated and the mechanism of its action was studied. NaSe had antimalarial activity against both the chloroquine-susceptible strain FCR-3 and chloroquine-resistant strain K-1 of Plasmodium falciparum. The shrunken cytoplasm of the parasite was observed in a smear 12 h after treatment with NaSe. Co-treatment with copper sulfate (CuSO(4)) in culture did not affect the antimalarial activity of NaSe, but NaSe cytotoxicity against the mammalian cell line Alexander was decreased significantly. The intracellular reduced glutathione level of parasitized red blood cells was decreased significantly by treatment with NaSe, and the decrease was consistent with their mortality. Treatment with NaSe had a strong inhibitory effect on plasmodial development, and NaSe cytotoxicity to human cells was decreased by co-treatment with CuSO(4). These results suggest that co-treatment with NaSe and CuSO(4) may be useful as a new antimalarial therapy. PMID:15013789

Taguchi, Nao; Hatabu, Toshimitsu; Yamaguchi, Haruyasu; Suzuki, Mamoru; Sato, Kumiko; Kano, Shigeyuki

2004-01-01

179

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

PubMed

The air-blood barrier is a very thin membrane of about 2.2 µm thickness and therefore represents an ideal portal of entry for nanoparticles to be used therapeutically in a regenerative medicine strategy. Until now, numerous studies using cellular airway models have been conducted in vitro in order to investigate the potential hazard of NPs. However, in most in vitro studies a crucial alveolar component has been neglected. Before aspirated NPs encounter the cellular air-blood barrier, they impinge on the alveolar surfactant layer (10-20 nm in thickness) that lines the entire alveolar surface. Thus, a prior interaction of NPs with pulmonary surfactant components will occur. In the present study we explored the impact of pulmonary surfactant on the cytotoxic potential of amorphous silica nanoparticles (aSNPs) using in vitro mono- and complex coculture models of the air-blood barrier. Furthermore, different surface functionalisations (plain-unmodified, amino, carboxylate) of the aSNPs were compared in order to study the impact of chemical surface properties on aSNP cytotoxicity in combination with lung surfactant. The alveolar epithelial cell line A549 was used in mono- and in coculture with the microvascular cell line ISO-HAS-1 in the form of different cytotoxicity assays (viability, membrane integrity, inflammatory responses such as IL-8 release). At a distinct concentration (100 µg/mL) aSNP-plain displayed the highest cytotoxicity and IL-8 release in monocultures of A549. aSNP-NH2 caused a slight toxic effect, whereas aSNP-COOH did not exhibit any cytotoxicity. In combination with lung surfactant, aSNP-plain revealed an increased cytotoxicity in monocultures of A549, aSNP-NH2 caused a slightly augmented toxic effect, whereas aSNP-COOH did not show any toxic alterations. A549 in coculture did not show any decreased toxicity (membrane integrity) for aSNP-plain in combination with lung surfactant. However, a significant augmented IL-8 release was observed, but no alterations in combination with lung surfactant. The augmented aSNP toxicity with surfactant in monocultures appears to depend on the chemical surface properties of the aSNPs. Reactive silanol groups seem to play a crucial role for an augmented toxicity of aSNPs. The A549 cells in the coculture seem to be more robust towards aSNPs, which might be a result of a higher differentiation and polarization state due the longer culture period. PMID:25821694

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

2015-01-01

180

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

PubMed Central

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

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

2015-01-01

181

Magnetic nanoparticle biodistribution following intratumoral administration  

Microsoft Academic Search

Recently, heat generated by iron oxide nanoparticles (IONPs) stimulated by an alternating magnetic field (AMF) has shown promise in the treatment of cancer. To determine the mechanism of nanoparticle-induced cytotoxicity, the physical association of the cancer cells and the nanoparticles must be determined. We have used transmission electron microscopy (TEM) to define the time dependent cellular uptake of intratumorally administered

A. J. Giustini; R. Ivkov; P. J. Hoopes

2011-01-01

182

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

PubMed Central

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

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

2012-01-01

183

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

PubMed

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

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

2011-04-25

184

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

PubMed Central

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

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

2010-01-01

185

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

PubMed Central

The aim of this study was to investigate the effect of garlic constituent diallyl trisulfide (DATS) on the cell death signaling pathway in a human breast cell line (MDA-MB-231). We observed that DATS (10–100 ?M) treatment resulted in a dose- and time-dependent cytotoxicity. Treatment of MDA-MB-231 cells with a cytotoxicity inducing concentration of DATS (50–80 ?M) resulted in an increase in the intracellular level of reactive oxygen species (ROS). Data from assay with MitoSOX™ Red reagent suggest that mitochondria are the main source of ROS generation during DATS treatment. DATS-induced oxidative stress was detected through glutaredoxin (GRX), a redox-sensing molecule, and subsequently GRX was dissociated from apoptosis signal-regulating kinase 1 (ASK1). Dissociation of GRX from ASK1 resulted in the activation of ASK1. ASK1 activated a downstream signal transduction JNK (C-Jun N-terminal kinase)-Bim pathway. SP600125, a JNK inhibitor, inhibited DATS-induced Bim phosphorylation and protected cells from DATS-induced cytotoxicity. Our results indicate that the cytotoxicity caused by DATS is mediated by the generation of ROS and subsequent activation of the ASK1-JNK-Bim signal transduction pathway in human breast carcinoma MDA-MB-231 cells. PMID:21053278

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

2010-01-01

186

Biogenic-Production of SnO2 Nanoparticles and Its Cytotoxic Effect Against Hepatocellular Carcinoma Cell Line (HepG2).  

PubMed

In this paper, we have established for the first time, the terrific efficiency of aqueous extract of agricultural waste dried peel of sugar apple (Annona squamosa) in the rapid synthesis of stable SnO2 nanoparticles. In topical years, the deployment of secondary metabolites from plant extract has emerged as a novel technology for the synthesis of various nanoparticles. In this paper, we have studied the potential of SnO2 nanoparticles assembly using agricultural waste source for the first time. The synthesized nanoparticles were characterized and confirmed as SnO2 nanoparticles by using UV-visible spectroscopy, XRD, and TEM analysis. The motivation of this study was to examine cytotoxicity study of SnO2 nanoparticles against hepatocellular carcinoma cell line (HepG2). SnO2 nanoparticles inhibited the cell proliferation in a dose- and time-dependent manner with an IC50 value of 148 ?g/mL. The treated cells showed an altered morphology with increasing concentrations of SnO2 nanoparticles. Our result shows that the SnO2 nanoparticles exhibit moderate cytotoxicity towards the hepatocellular carcinoma (HepG2) at tested concentrations. PMID:25410804

Roopan, Selvaraj Mohana; Kumar, Subramanian Hari Subbish; Madhumitha, Gunabalan; Suthindhiran, Krishnamurthy

2015-02-01

187

Trichothecene-induced cytotoxicity on human cell lines.  

PubMed

Trichothecene cytotoxicity of type A (T-2 toxin and HT-2 toxin), type B (deoxynivalenol, DON, and nivalenol, NIV), and type D (satratoxins G and H) compounds was determined comparatively by using eight permanent human cell lines (Hep-G2, A549, CaCo-2, HEp-2, A204, U937, RPMI 8226, and Jurkat). Viability of cells was measured by a water-soluble tetrazolium (WST-1) reagent cell proliferation assay assessing mitochondrial metabolic activity. Toxicity was expressed as the toxin concentration inhibiting 50% of cell viability (IC50). Depending on the chemotype of the tested trichothecenes, relative cytotoxic activity differed by a factor of 100-1,000, and the corresponding IC50 values were in the range from 2.2 nmol/l (satratoxin H on Jurkat and U937 cells) to 4,900 nmol/l (deoxynivalenol on HEp-2 cells). In contrast, the specific toxicity of each individual mycotoxin towards different cell lines was within remarkable close limits, and between-cell line differences were much smaller than previously reported. For the cell lines tested, IC50 values were 4.4-10.8 nmol/l for T-2 toxin, 7.5-55.8 mol/l for HT-2 toxin, 600-4,900 nmol/l for DON, 300-2,600 nmol/l for NIV, and 2.2-18.3 nmol/l for satratoxins G/H. In addition, for the first time, the toxic activity of trichothecenes on primary cell culture of human endothelial cells (HUVEC) was tested. The susceptibility of this cell line was comparable to the other cell lines tested, with IC50 values ranging from 16.5 nmol/l (T-2 toxin) to 4,500 nmol/l (DON). The results suggest that the current focus of cytotoxicological studies on trichothecenes on lymphoid cell lines may lead to an underestimate of their potential on other target cell systems. PMID:23604982

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

2009-06-01

188

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

PubMed Central

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

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

2014-01-01

189

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

NASA Astrophysics Data System (ADS)

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

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

2013-04-01

190

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

PubMed

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

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

2015-01-25

191

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

NASA Astrophysics Data System (ADS)

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

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

2015-01-01

192

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

PubMed

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

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

2014-07-01

193

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

NASA Astrophysics Data System (ADS)

Biocompatible gold nanoparticles were synthesized by using a naturally occurring gum-Gellan Gum-as a capping and reducing agent. These were further conjugated with sophorolipids which again were accessed through a biochemical transformation of a fatty acid. The cellular uptake of sophorolipid-conjugated gellan gum reduced gold nanoparticles and their cytotoxicity on human glioma cell line LN-229 and human glioma stem cell line HNGC-2 were investigated. Quite surprisingly even the simple sophorolipid-conjugated gellan gum reduced/capped gold nanoparticles showed greater efficacy in killing the glioma cell lines and, gratifyingly, the glioma stem cell lines also. The cytotoxic effects became more prominent once the anti cancer drug doxorubicin hydrochloride was also conjugated to these gold nanoparticles.Biocompatible gold nanoparticles were synthesized by using a naturally occurring gum-Gellan Gum-as a capping and reducing agent. These were further conjugated with sophorolipids which again were accessed through a biochemical transformation of a fatty acid. The cellular uptake of sophorolipid-conjugated gellan gum reduced gold nanoparticles and their cytotoxicity on human glioma cell line LN-229 and human glioma stem cell line HNGC-2 were investigated. Quite surprisingly even the simple sophorolipid-conjugated gellan gum reduced/capped gold nanoparticles showed greater efficacy in killing the glioma cell lines and, gratifyingly, the glioma stem cell lines also. The cytotoxic effects became more prominent once the anti cancer drug doxorubicin hydrochloride was also conjugated to these gold nanoparticles. Electronic supplementary information (ESI) available: Confocal Z-stacking images of Texas Red Conjugated SL-GG-Au NPs, thermogravimetic analysis of DOX-SL-GG-Au-NPs and SL-GG-AuNPs, and time-dependent fluorescence spectra of DOX-SL-GG-Au NPs. See DOI: 10.1039/c0nr00598c

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

2011-02-01

194

Glycogen synthase kinase-3? activation mediates rotenone-induced cytotoxicity with the involvement of microtubule destabilization.  

PubMed

Rotenone, a mitochondrial complex I inhibitor, has been used to generate animal and cell culture models of Parkinson's disease. Recent studies suggest that microtubule destabilization causes selective dopaminergic neuronal loss. In this study, we investigated glycogen synthase kinase-3? (GSK3?) involvement in rotenone-induced microtubule destabilization. Rotenone-induced cytotoxicity in SH-SY5Y cells was attenuated by the GSK3? inhibitor SB216763. Tau, a microtubule-associated protein and substrate for GSK3?, has been implicated in the pathogenesis of tauopathies such as Alzheimer's disease. Rotenone induced an increase in phosphorylated tau, the effect of which was attenuated by concomitant treatment with SB216763. Rotenone treatment also decreased tau expression in the microtubule fraction and increased tau expression in the cytosol fraction. These effects were suppressed by SB216763, which suggests that rotenone reduces the capacity of tau to bind microtubules. Rotenone treatment increased the amount of free tubulin and reduced the amount of polymerized tubulin, indicating that rotenone destabilizes microtubules. Rotenone-induced microtubule destabilization was suppressed by SB216763 and taxol, a microtubule stabilizer. Taxol prevented rotenone-induced cytotoxicity and morphological changes. Taken together, these results suggest that rotenone-induced cytotoxicity is mediated by microtubule destabilization via GSK3? activation, and that microtubule destabilization is caused by reduction in the binding capacity of tau to microtubules, which is a result of tau phosphorylation via GSK3? activation. PMID:22922102

Hongo, Haruyuki; Kihara, Takeshi; Kume, Toshiaki; Izumi, Yasuhiko; Niidome, Tetsuhiro; Sugimoto, Hachiro; Akaike, Akinori

2012-09-14

195

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

PubMed Central

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

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

2013-01-01

196

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

PubMed

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

Poirier, N; Blancho, G

2008-03-01

197

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

SciTech Connect

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 palmitate/ CsA induced toxicity. ? Palmitate sensitizes cells to the toxicity induced by CsA at therapeutic exposure. ? Elevated free fatty acids may predispose the patients to CsA-induced toxicity.

Luo, Yi, E-mail: yi.luo@pfizer.com; Rana, Payal; Will, Yvonne

2012-06-01

198

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

NASA Astrophysics Data System (ADS)

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

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

2003-05-01

199

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

Microsoft Academic Search

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

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

200

Thermoresponsive nanoparticles + plasmonic nanoparticles = photoresponsive heterodimers: facile synthesis and sunlight-induced reversible clustering.  

PubMed

Magnetic nanoparticles functionalized with thermoresponsive polymers become photoresponsive when attached to plasmonic nanoparticles to form heterodimers. Under solar illumination, the plasmonic particles absorb sunlight and induce localized heating, causing collapse of the thermoresponsive polymer chain and clustering of the dimers that facilitate magnetic separation. PMID:23694849

Han, Hui; Lee, Jim Yang; Lu, Xianmao

2013-07-14

201

Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide.  

PubMed

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 ?, 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. PMID:25409153

Freudenthal, Bret D; Beard, William A; Perera, Lalith; Shock, David D; Kim, Taejin; Schlick, Tamar; Wilson, Samuel H

2015-01-29

202

Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide  

NASA Astrophysics Data System (ADS)

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 ?, 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.

Freudenthal, Bret D.; Beard, William A.; Perera, Lalith; Shock, David D.; Kim, Taejin; Schlick, Tamar; Wilson, Samuel H.

2015-01-01

203

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

PubMed Central

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

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

2014-01-01

204

Bacillus anthracis genomic DNA enhances lethal toxin¿induced cytotoxicity through TNF-¿ production.  

PubMed

Background Bacillus anthracis is the etiological agent of anthrax. Lethal toxin (LT) produced by B. anthracis is a well-known key virulence factor for anthrax because of its strong cytotoxic activity. However, little is known about the role of B. anthracis genomic DNA (BAG) in anthrax pathogenesis.ResultsWe examined the effect of BAG on TNF-¿ production and LT-mediated cytotoxicity during B. anthracis spore infection in mouse macrophage cell lines (RAW264.7 cells and J774A.1) and BALB/c mice. Infection of RAW264.7 cells with B. anthracis spores induced TNF-¿ expression in a multiplicity of infection (MOI)-dependent manner, and this enhancement was attenuated by the toll-like receptor (TLR) 9 inhibitor oligodeoxynucleotide (ODN)2088. BAG led to TNF-¿ expression in a dose- and time-dependent manner when applied to RAW264.7 cells. TNF-¿ expression induced by BAG was reduced by either pretreatment with TLR9 inhibitors (ODN2088 and chloroquine (CQ)) or transfection with TLR9 siRNA. Furthermore, BAG-induced TNF-¿ production in TLR9+/+ macrophages was completely abrogated in TLR9¿/¿ macrophages. BAG enhanced the phosphorylation of mitogen-activated protein kinases (MAPK), and BAG-induced TNF-¿ expression was attenuated by pretreatment with MAPK inhibitors. A reporter gene assay and confocal microscopy demonstrated that BAG increased NF-¿B activation, which is responsible for TNF-¿ expression. Treatment with BAG alone showed no cytotoxic activity on the macrophage cell line J774A.1, whereas LT-mediated cytotoxicity was enhanced by treatment with BAG or TNF-¿. Enhanced LT-induced lethality was also confirmed by BAG administration in mice. Furthermore, LT plus BAG-mediated lethality was significantly recovered by administration of Infliximab, an anti-TNF-¿ monoclonal antibody.ConclusionsOur results suggest that B. anthracis DNA may contribute to anthrax pathogenesis by enhancing LT activity via TLR9-mediated TNF-¿ production. PMID:25472474

Jeon, Jun; Kim, Yeon; Choi, Min; Kim, Kyung; Lee, Hae-Ri; Jang, Jeyoun; Kim, Yu-Ri; Chun, Jeong-Hoon; Eo, Seong; Kim, Tae; Rhie, Gi-Eun

2014-12-01

205

Flutamide-Induced Cytotoxicity and Oxidative Stress in an In Vitro Rat Hepatocyte System  

PubMed Central

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

Maruf, Abdullah Al; O'Brien, Peter

2014-01-01

206

Capsaicin induces cytotoxicity in pancreatic neuroendocrine tumor cells via mitochondrial action.  

PubMed

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

Skrzypski, M; Sassek, M; Abdelmessih, S; Mergler, S; Grötzinger, C; Metzke, D; Wojciechowicz, T; Nowak, K W; Strowski, M Z

2014-01-01

207

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

PubMed

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

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

2012-06-15

208

Weakly Charged Cationic Nanoparticles Induce DNA Bending and Strand Separation  

SciTech Connect

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

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

2012-01-01

209

Plasma-induced crystallization of silicon nanoparticles  

NASA Astrophysics Data System (ADS)

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

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

2014-02-01

210

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

PubMed Central

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with higher selectivity in degeneration of motor neurons. However, the molecular mechanism by which the ALS-linked mutants of human superoxide dismutase 1 (SOD1) gene induce neurotoxicity remains obscure yet. Here, we show that depletion of CIIA expression by RNA interference (RNAi) promoted cytotoxicity caused by ALS-linked G93A mutant of the SOD1 gene. The RNAi-mediated knockdown of CIIA also enhanced the SOD1(G93A)-induced interaction between ASK1 and TRAF2 as well as ASK1 activity. Furthermore, endogenous silencing of CIIA by RNAi augmented the effects of SOD1(G93A) on reduction of mitochondria membrane potential (??m), release of cytochrome c into the cytoplasm, and caspase activation. Together, our results suggest that CIIA negatively modulates ASK1-mediated cytotoxic signaling processes in a SOD1(G93A)-expressing cellular model of ALS. PMID:25018698

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

2014-01-01

211

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

PubMed

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

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

2014-11-01

212

Carnosine's Effect on Amyloid Fibril Formation and Induced Cytotoxicity of Lysozyme  

PubMed Central

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

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

213

Vitamin C Effect on Mitoxantrone-Induced Cytotoxicity in Human Breast Cancer Cell Lines  

PubMed Central

In recent years the use of natural dietary antioxidants to minimize the cytotoxicity and the damage induced in normal tissues by antitumor agents is gaining consideration. In literature, it is reported that vitamin C exhibits some degree of antineoplastic activity whereas Mitoxantrone (MTZ) is a synthetic anti-cancer drug with significant clinical effectiveness in the treatment of human malignancies but with severe side effects. Therefore, we have investigated the effect of vitamin C alone or combined with MTZ on MDA-MB231 and MCF7 human breast cancer cell lines to analyze their dose-effect on the tumor cellular growth, cellular death, cell cycle and cell signaling. Our results have evidenced that there is a dose-dependence on the inhibition of the breast carcinoma cell lines, MCF7 and MDA-MB231, treated with vitamin C and MTZ. Moreover, their combination induces: i) a cytotoxic effect by apoptotic death, ii) a mild G2/M elongation and iii) H2AX and mild PI3K activation. Hence, the formulation of vitamin C with MTZ induces a higher cytotoxicity level on tumor cells compared to a disjointed treatment. We have also found that the vitamin C enhances the MTZ effect allowing the utilization of lower chemotherapic concentrations in comparison to the single treatments. PMID:25531443

Capone, Francesca; Napolitano, Virginia; Colonna, Giovanni; Storti, Gabriella; Castello, Giuseppe; Costantini, Susan

2014-01-01

214

Preparation, characterization and in vitro cytotoxicity assay of curcumin loaded solid lipid nanoparticle in IMR32 neuroblastoma cell line.  

PubMed

Curcumin (diferuloylmethane) possesses low bioavailability due to its poor solubility, permeability and rapid metabolism. Solid Lipid Nanoparticle of curcumin was prepared by high-speed homogenization technique. Stearic acid was used as a lipid, tween 80 as surfactant and various co surfactants were used for the preparation of SLN. The prepared SLN was characterized using zeta sizer, TEM analysis and the average particle size was found to be in the range of 80 nm - 200nm. The entrapment efficiency of the SLN was ~58 to 85%. The characteristic FTIR peaks suggest that the stearic acid is compatible with curcumin. MTT assay was performed on the optimized formulation and the results are indicative that curcumin SLN showed better cytotoxicity in low dose while compared to plain curcumin. The developed Cu-SLN can find its better place in the anticancer therapy. PMID:25176384

Rahman, Mohamed Habibur; Ramanathan, Muthiah; Sankar, Veintramuthu

2014-09-01

215

Rhododendrol, a depigmentation-inducing phenolic compound, exerts melanocyte cytotoxicity via a tyrosinase-dependent mechanism.  

PubMed

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

Sasaki, Minoru; Kondo, Masatoshi; Sato, Kohji; Umeda, Mai; Kawabata, Keigo; Takahashi, Yoshito; Suzuki, Tamio; Matsunaga, Kayoko; Inoue, Shintaro

2014-09-01

216

Signaling Pathways Involved in Lunar Dust Induced Cytotoxicity  

NASA Technical Reports Server (NTRS)

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

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

2014-01-01

217

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

PubMed

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

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

2014-01-01

218

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

PubMed Central

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

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

2014-01-01

219

Cisplatin cytotoxicity: a theoretical study of induced mutations.  

PubMed

We investigate possible mutations in the genetic code induced by cisplatin with an approach combining molecular dynamics (MD) and hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. Specifically, the impact of platination on the natural tautomeric equilibrium in guanine-cytosine (GC) base pairs is assessed to disclose the possible role played by non-canonical forms in anti-tumour activity. To obtain valuable predictions, the main interactions present in a real DNA environment, namely hydration and stacking, are simultaneously taken into account. According to our results, the Pt-DNA adduct promotes a single proton transfer reaction in GC in the DNA sequence AG[combining low line]G[combining low line]C. Such rare tautomers might play an important role in the cisplatin biological activity since they meet the stability requirements necessary to promote a permanent mutation. PMID:22495492

Cerón-Carrasco, José P; Jacquemin, Denis; Cauët, Emilie

2012-09-28

220

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

PubMed Central

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

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

2011-01-01

221

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

PubMed

Core-shell iron-gold (Fe@Au) nanoparticles were synthesized by a facile reverse micelle procedure and the effect of water to surfactant molar ratio (w) on the size, size distribution and magnetic properties of the nanoparticles was studied. MTT assay was utilized to evaluate the cell toxicity of the nanoparticles. To functionalize the particles for MRI imaging and targeted drug delivery, the particles were coated by polyglycerol through capping with thiol followed by polymerization of glycidol. The characteristics of the particles were examined by X-ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FT-IR). It was found that the size and size distribution of the nanoparticles increase by increasing the water to surfactant molar ratio (w). The particles were spherical in shape with a thin layer of gold. Complementary growth of the gold shell on the iron core was noticed. Meanwhile, two types of agglomeration including magnetic beads and magnetic colloidal nanocrystals clusters were observed dependent on the w-value. The magnetic measurement studies revealed the superparamagnetic behavior of the nanoparticles. MTT assay result indicated the synthesized nanoparticles are nontoxic that will be useful for biomedical applications. PMID:20153479

Jafari, T; Simchi, A; Khakpash, N

2010-05-01

222

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

NASA Astrophysics Data System (ADS)

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

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

2011-09-01

223

Universal solvent restructuring induced by colloidal nanoparticles.  

PubMed

Colloidal nanoparticles, used for applications from catalysis and energy applications to cosmetics, are typically embedded in matrixes or dispersed in solutions. The entire particle surface, which is where reactions are expected to occur, is thus exposed. Here, we show with x-ray pair distribution function analysis that polar and nonpolar solvents universally restructure around nanoparticles. Layers of enhanced order exist with a thickness influenced by the molecule size and up to 2 nanometers beyond the nanoparticle surface. These results show that the enhanced reactivity of solvated nanoparticles includes a contribution from a solvation shell of the size of the particle itself. PMID:25593188

Zobel, Mirijam; Neder, Reinhard B; Kimber, Simon A J

2015-01-16

224

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

SciTech Connect

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

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

1990-11-01

225

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

PubMed

Gold nanoparticles (Au NPs) are used in many fields, including biomedical applications; however, no conclusive information on their potential cytotoxicity and genotoxicity mechanisms is available. For this reason, experiments in human primary lymphocytes and murine macrophages (Raw264.7) were performed exposing cells to spherical citrate-capped Au NPs with two different nominal diameters (5 nm and 15 nm). The proliferative activity, mitotic, apoptotic, and necrotic markers, as well as chromosomal damage were assessed by the cytokinesis-block micronucleus cytome assay. Fluorescence in situ hybridization with human and murine pancentromeric probes was applied to distinguish between clastogenic and aneuploidogenic effects. Our results indicate that 5 nm and 15 nm Au NPs are able to inhibit cell proliferation by apoptosis and to induce chromosomal damage, in particular chromosome mis-segregation. DNA strand breaks were detected by comet assay, and the modified protocol using endonuclease-III and formamidopyrimidine-DNA glycosylase restriction enzymes showed that pyrimidines and purines were oxidatively damaged by Au NPs. Moreover, we show a size-independent correlation between the cytotoxicity of Au NPs and their tested mass concentration or absolute number, and genotoxic effects which were more severe for Au NP 15 nm compared to Au NP 5 nm. Results indicate that apoptosis, aneuploidy, and DNA oxidation play a pivotal role in the cytotoxicity and genotoxicity exerted by Au NPs in our cell models. PMID:24855356

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

2014-01-01

226

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

PubMed

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

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

2006-12-01

227

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

NASA Astrophysics Data System (ADS)

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

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

2011-06-01

228

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

PubMed

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. PMID:21508461

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

2011-06-17

229

TiO(2) nanoparticles induce oxidative DNA damage and apoptosis in human liver cells.  

PubMed

Titanium dioxide nanoparticles (TiO(2) NPs), widely used in consumer products, paints, pharmaceutical preparations and so on, have been shown to induce cytotoxicity, genotoxicity and carcinogenic responses in vitro and in vivo. The present study revealed that TiO(2) NPs induce significant (p < 0.05) oxidative DNA damage by the Fpg-Comet assay even at 1 µg/ml concentration. A corresponding increase in the micronucleus frequency was also observed. This could be attributed to the reduced glutathione levels with concomitant increase in lipid peroxidation and reactive oxygen species generation. Furthermore, immunoblot analysis revealed an increased expression of p53, BAX, Cyto-c, Apaf-1, caspase-9 and caspase-3 and decreased the level of Bcl-2 thereby indicating that apoptosis induced by TiO(2) NPs occurs via the caspase-dependent pathway. This study systematically shows that TiO(2) NPs induce DNA damage and cause apoptosis in HepG2 cells even at very low concentrations. Hence the use of such nanoparticles should be carefully monitored. PMID:22047016

Shukla, Ritesh K; Kumar, Ashutosh; Gurbani, Deepak; Pandey, Alok K; Singh, Shashi; Dhawan, Alok

2013-02-01

230

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

PubMed

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

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

2012-11-01

231

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

PubMed

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

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

2011-01-01

232

A Signaling Network Induced by ?2 Integrin Controls the Polarization of Lytic Granulesin Cytotoxic Cells  

PubMed Central

Cytotoxic lymphocyte skill target cells by polarized release of the content of perforin-containing granules. In natural killer cells, the binding of ?2 integrin to its ligand ICAM-1 is sufficient to promote not only adhesion but also lytic granule polarization. This provided a unique opportunity to study polarization in the absence of degranulation, and ?2 integrin signaling independently of inside-out signals from other receptors. Using an unbiased proteomics approach we identified a signaling network centered on an integrin-linked kinase (ILK)–Pyk2–Paxillin core that was required for granule polarization. Downstream of ILK, the highly conserved Cdc42–Par6 signaling pathway that controls cell polarity was activated and required for granule polarization. These results delineate two connected signaling networks induced upon ?2 integrin engagement alone, which are integrated to control polarization of the microtubule organizing center and associated lytic granules toward the site of contact with target cells during cellular cytotoxicity. PMID:25292215

Zhang, Minggang; March, Michael E.; Lane, William S.; Long, Eric O.

2014-01-01

233

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

PubMed Central

With the emergence of multidrug-resistant mycobacterial strains, better therapeutic strategies are required for the successful treatment of the infection. Although antimicrobial peptides (AMPs) and silver nanoparticles (AgNPs) are becoming one of the popular antibacterial agents, their antimycobacterial potential is not fully evaluated. In this study, we synthesized biogenic-silver nanoparticles using bacterial, fungal, and plant biomasses and analyzed their antibacterial activities in combination with AMPs against mycobacteria. Mycobacterium smegmatis was found to be more susceptible to AgNPs compared to M. marinum. We found that NK-2 showed enhanced killing effect with NP-1 and NP-2 biogenic nanoparticles at a 0.5-ppm concentration, whereas LLKKK-18 showed antibacterial activity only with NP-2 at 0.5-ppm dose against M. smegmatis. In case of M. marinum NK-2 did not show any additive activity with NP-1 and NP-2 and LLKKK-18 alone completely inhibited the bacterial growth. Both NP-1 and NP-2 also showed increased killing of M. smegmatis in combination with the antituberculosis drug rifampin. The sizes and shapes of the AgNPs were determined by transmission electron microscopy and dynamic light scattering. AgNPs showed no cytotoxic or DNA damage effects on macrophages at the mycobactericidal dose, whereas treatment with higher doses of AgNPs caused toxicity and micronuclei formation in cytokinesis blocked cells. Macrophages actively endocytosed fluorescein isothiocyanate-labeled AgNPs resulting in nitric oxide independent intracellular killing of M. smegmatis. Apoptosis and cell cycle studies showed that treatment with higher dose of AgNPs arrested macrophages at the G1-phase. In summary, our data suggest the combined effect of biogenic-AgNPs and antimicrobial peptides as a promising antimycobacterial template. PMID:23689720

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

2013-01-01

234

ROS-mediated genotoxicity induced by titanium dioxide nanoparticles in human epidermal cells.  

PubMed

Titanium dioxide nanoparticles (TiO(2) NPs) are among the top five NPs used in consumer products, paints and pharmaceutical preparations. Since, exposure to such nanoparticles is mainly through the skin and inhalation, the present study was conducted in the human epidermal cells (A431). A mild cytotoxic response of TiO(2) NPs was observed as evident by the MTT and NR uptake assays after 48 h of exposure. However, a statistically significant (p<0.05) induction in the DNA damage was observed by the Fpg-modified Comet assay in cells exposed to 0.8 ?g/ml TiO(2) NPs (2.20±0.26 vs. control 1.24±0.04) and higher concentrations for 6 h. A significant (p<0.05) induction in micronucleus formation was also observed at the above concentration (14.67±1.20 vs. control 9.33±1.00). TiO(2) NPs elicited a significant (p<0.05) reduction in glutathione (15.76%) with a concomitant increase in lipid hydroperoxide (60.51%; p<0.05) and reactive oxygen species (ROS) generation (49.2%; p<0.05) after 6h exposure. Our data demonstrate that TiO(2) NPs have a mild cytotoxic potential. However, they induce ROS and oxidative stress leading to oxidative DNA damage and micronucleus formation, a probable mechanism of genotoxicity. This is perhaps the first study on human skin cells demonstrating the cytotoxic and genotoxic potential of TiO(2) NPs. PMID:21092754

Shukla, Ritesh K; Sharma, Vyom; Pandey, Alok K; Singh, Shashi; Sultana, Sarwat; Dhawan, Alok

2011-02-01

235

Cytoprotective Activity of Glycyrrhizae radix Extract Against Arsenite-induced Cytotoxicity  

PubMed Central

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

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

2008-01-01

236

Nanoparticle removal from EUV photomasks using laser induced plasma shockwaves  

Microsoft Academic Search

In recent years, it has been demonstrated that nanoparticles can be detached and removed from substrates using laser-induced plasma (LIP) shockwaves. While it was experimentally established the effectiveness of the LIP technique for removing nanoparticles in the sub-100nm range, the removal mechanisms were not well-understood. In this article, we introduce a set of particle removal mechanisms based on moment resistance

John Kadaksham; Dong Zhou; M. D. Murthy Peri; Ivin Varghese; Florence Eschbach; Cetin Cetinkaya

2006-01-01

237

Biochemical mechanisms of bornyl caffeate induced cytotoxicity in rat pheochromocytoma PC12 cells.  

PubMed

The chemopreventive and antineoplastic activities of caffeic acid derivatives are highly dependent on the chemical structures and cancer cell types. The objective of the present study was to investigate the cytotoxicity of bornyl caffeate and the underlying molecular mechanisms in rat pheochromocytoma PC12 cells. Our initial studies demonstrated that bornyl caffeate exhibited potent cytotoxicity in PC12 cells in a concentration- and time-dependent manner. By examining the cell morphology on a fluorescence microscope and detecting the cell surface phosphoserine with Annexin V-FITC, we proposed that bornyl caffeate could induce apoptosis in PC12 cells. We tested this hypothesis by investigating the effects of bornyl caffeate on several apoptosis-related biomarkers. These experiments showed that bornyl caffeate induced the up-regulation of Bax and down-regulation of Bcl-xl, the disruption of mitochondrial membrane potential, the activation of caspase 3 and the cleavage of PARP. Mechanistic studies further revealed that bornyl caffeate caused the depletion of glutathione (GSH), generation of superoxide ion and progressive activation of p38 mitogen-activate protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) in a concentration-dependent manner. In particular, GSH depletion appeared to be the most important mechanism underlying the cytotoxicity of bornyl caffeate. The preservation of the intracellular GSH contents with N-acetyl-L-cysteine (NAC), GSH and vitamin C abolished the effect of bornyl caffeate on the activation of p38 MAPK and JNK, preserved the integrity of mitochondrial membrane and ultimately rescued the cells from drug-induced cell death. These results suggest that bornyl caffeate induces apoptosis in PC12 cells via stimulating the depletion of GSH, the generation of reactive oxygen species (ROS) and the dissipation of mitochondrial transmembrane potential. PMID:24907532

Yang, Chuanbin; Zhao, Jia; Pei, Weijing; Zheng, Xiaohui; Rong, Jianhui

2014-08-01

238

Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma.  

PubMed

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 IRE1?, 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. PMID:25016296

Syed, Deeba N; Lall, Rahul K; Chamcheu, Jean Christopher; Haidar, Omar; Mukhtar, Hasan

2014-12-01

239

Toxicity of boehmite nanoparticles: impact of the ultrafine fraction and of the agglomerates size on cytotoxicity and pro-inflammatory response.  

PubMed

Boehmite (?-AlOOH) nanoparticles (NPs) are used in a wide range of industrial applications. However, little is known about their potential toxicity. This study aimed at a better understanding of the relationship between the physico-chemical properties of these NPs and their in vitro biological activity. After an extensive physico-chemical characterization, the cytotoxicity, pro-inflammatory response and oxidative stress induced by a bulk industrial powder and its ultrafine fraction were assessed using RAW264.7 macrophages. Although the bulk powder did not trigger a significant biological activity, pro-inflammatory response was highly enhanced with the ultrafine fraction. This observation was confirmed with boehmite NPs synthesized at the laboratory scale, with well-defined and tightly controlled physico-chemical features: toxicity was increased when NPs were dispersed. In conclusion, the agglomerates size of boehmite NPs has a major impact on their toxicity, highlighting the need to study not only raw industrial powders containing NPs but also the ultrafine fractions representative of respirable particles. PMID:24992651

Forest, Valérie; Pailleux, Mélanie; Pourchez, Jérémie; Boudard, Delphine; Tomatis, Maura; Fubini, Bice; Sennour, Mohamed; Hochepied, Jean-François; Grosseau, Philippe; Cottier, Michèle

2014-08-01

240

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

PubMed

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

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

2011-03-15

241

Suppression of polyglutamine-induced cytotoxicity in Saccharomyces cerevisiae by enhancement of mitochondrial biogenesis.  

PubMed

Alterations in mitochondrial metabolism have been associated with age-related neurodegenerative disorders. This is seen in diseases caused by misfolding of proteins with expanded polyglutamine (polyQ) tracts, such as Huntington's disease. Although evidence of mitochondrial impairment has been extensively documented in patients and disease models, the mechanisms involved and their relevance to the initiation of polyQ cytotoxicity and development of clinical manifestations remain controversial. We report that in yeast models of polyQ cytotoxicity, wild-type and mutant polyQ domains might associate early with the outer mitochondrial membrane. The association of mutant domains with mitochondrial membranes could contribute to induce significant changes in mitochondrial physiology, ultimately compromising the cell's ability to respire. The respiratory defect can be fully prevented by enhancing mitochondrial biogenesis by overexpression of Hap4p, the catalytic subunit of the transcriptional activator Hap2/3/4/5p complex, the master regulator of the expression of many nuclear genes encoding mitochondrial proteins in yeast. Protecting cellular respiratory capacity in this way ameliorates the effect of expanded polyQ on cellular fitness. We conclude that mitochondrial dysfunction is an important contributor to polyQ cytotoxicity. Our results suggest that therapeutic approaches enhancing mitochondrial biogenesis could reduce polyQ toxicity and delay the development of clinical symptoms in patients. PMID:20008543

Ocampo, Alejandro; Zambrano, Andrea; Barrientos, Antoni

2010-05-01

242

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

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. PMID:25229832

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

2014-09-17

243

Cytotoxicity and apoptosis induced by nanobacteria in human breast cancer cells  

PubMed Central

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

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

2014-01-01

244

Neuroprotective effects of porphyran derivatives against 6-hydroxydopamine-induced cytotoxicity is independent on mitochondria restoration  

PubMed Central

We previously reported that acetylated and phosphorylated derivatives of porphyran extracted from Porphyra haitanensis exhibit antioxidant activity in cell-free system. The aim of the present study was to investigate the neuroprotective effects of porphyran and its derivatives on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure cell viability. Changes in the mitochondrial transmembrane potential (??m) were measured by rhodamine123 using flow cytometry. The results showed that porphyran and its two derivatives, acetylated porphyran (AP) and phosphorylated porphyran (PP) (<1 mg/mL) alone did not have any toxic effects on MES23.5 cells. The cell viability decreased when cells were treated with 25 µmol/L 6-OHDA. Both AP and PP, rather than porphyran, significantly antagonized 25 µmol/L 6-OHDA-induced cytotoxicity. However, neither AP nor PP could antagonize 6-OHDA-induced mitochondrial transmembrane potential (??m) collapse. None of the three materials were effective on cell survival when cells were cotreated with 75 µmol/L 6-OHDA. These results suggest that two derivatives of porphyran, AP and PP, could antagonize the weak toxicity of 6-OHDA on MES23.5 dopaminergic cells, possessing minor neuroprotective effects independent of mitochondria restoration.

Wang, Weiwei; Song, Ning; Jia, Fengjv; Xie, Junxia; Zhang, Quanbin

2015-01-01

245

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

PubMed

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

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

2015-05-01

246

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

PubMed Central

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

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

2013-01-01

247

Evaluation of the antimicrobial activity and cytotoxicity of phytogenic gold nanoparticles  

NASA Astrophysics Data System (ADS)

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).

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

2014-09-01

248

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

PubMed Central

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

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

249

Influence of immunomodulatory drugs on the cytotoxicity induced by monoclonal antibody 17-1A and interleukin-2.  

PubMed

Patients treated with monoclonal antibodies and cytokines for cancer receive often co-medication, which may influence treatment efficacy. Therefore, we investigated with a flowcytometric cytotoxicity assay the effect of several immunomodulatory drugs on antibody dependent cellular cytotoxicity (ADCC), interleukin-2 (IL-2) induced cytotoxicity and IL-2-induced-ADCC. We found that dexamethasone markedly inhibited the IL-2 induced cytotoxicity and the IL-2-induced-ADCC. Ondansetron, a 5-HT-3 serotonin receptor antagonist augmented significantly ADCC. Clemastine, a histamine type-2 receptor antagonist augmented the IL-2-induced-ADCC. The TNF antagonist thalidomide suppressed ADCC whereas pentoxifylline proved to be ineffective. Other tested drugs namely ibuprofen and indomethacin, both prostaglandin E2 antagonists, cimetidine a histamine type-2 receptor antagonist, the opioid pethidine, prostaglandin E2 and histamine exerted minor effects or had no influence on the tested parameters. We conclude that glucocorticosteroids should be avoided with monoclonal antibody and cytokine treatment. According to our in vitro data the other drugs tested did not have a negative impact on cellular cytotoxicity and ADCC. PMID:17562330

Flieger, Dimitri; Varvenne, Michael; Kleinschmidt, Rolf; Schmidt-Wolf, Ingo G H

2007-03-01

250

Morphologic categorization of cell death induced by mild hyperthermia and comparison with death induced by ionizing radiation and cytotoxic drugs  

SciTech Connect

This paper presents a summary of the morphological categorization of cell death, results of two in vivo studies on the cell death induced by mild hyperthermia in rat small intestine and mouse mastocytoma, and a comparison of the cell death induced by hyperthermia, radiation and cytotoxic drugs. Two distinct forms of cell death, apoptosis and necrosis, can be recognized on morphologic grounds. Apoptosis appears to be a process of active cellular self-destruction to which a biologically meaningful role can usually be attributed, whereas necrosis is a passive degenerative phenomenon that results from irreversible cellular injury. Light and transmission electron microscopic studies showed that lower body hyperthermia (43 degrees C for 30 min) induced only apoptosis of intestinal epithelial cells, and of lymphocytes, plasma cells, and eosinophils. In the mastocytoma, hyperthermia (43 degrees C for 15 min) produced widespread tumor necrosis and also enhanced apoptosis of tumor cells. Ionizing radiation and cytotoxic drugs are also known to induce apoptosis in a variety of tissues. It is attractive to speculate that DNA damage by each agent is the common event which triggers the same process of active cellular self-destruction that characteristically effects selective cell deletion in normal tissue homeostasis.

Allan, D.J.; Harmon, B.V.

1986-01-01

251

Laser-induced silver nanojoining of gold nanoparticles.  

PubMed

Gold nanoparticles have been silver-joined to fabricate nanowires by irradiating gold nanospheres of 25 nm in diameter and silver nanospheres of 8 nm in diameter held together on a carbon-coated copper grid with a 30 ps laser pulse of 532 nm for 20 min at a fluence of 3.0 mJ/cm2. Laser-induced nanojoining of silver nanoparticles as well as that of gold nanoparticles has also been carried out by varying the wavelength and fluence of irradiation laser pulses. Irradiation at an optimum condition of laser fluence is essential for the proper silver nanojoining of gold nanospheres to produce gold@silver core-shell composite nanowires. The excitation of the surface plasmon resonances of the base-metallic gold nanospheres rather than the filler-metallic silver nanospheres paves the way for the silver nanojoining of gold nanoparticles. PMID:23882834

Son, Myounghee; Kim, Seol Ji; Kim, Jong-Yeob; Jang, Du-Jeon

2013-08-01

252

Disorder-induced Purcell enhancement in nanoparticle chains  

NASA Astrophysics Data System (ADS)

In this paper we report on a numerical study of plasmonic nanoparticle chains with long-range dipole-dipole interaction. We have shown that introduction of positional disorder gives a peak in the density of resonant states at the frequency of individual nanoparticle resonance. This peak is referred to as Dyson singularity in one-dimensional disordered structures and, according to our calculations, governs the spectral properties of local density of states. This provides disorder-induced Purcell enhancement that can find applications in random lasers and for surface-enhanced Raman-scattering spectroscopy. We stress that this effect relates not only to plasmonic nanoparticles but also to an arbitrary chain of nanoparticles or atoms with resonant polarizabilities.

Petrov, Mihail

2015-02-01

253

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

PubMed

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

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

2015-03-01

254

Acetaminophen-induced cytotoxicity on human normal liver L-02 cells and the protection of antioxidants.  

PubMed

In vitro cell models, which can partially mimic in vivo responses, offer potentially sensitive tools for toxicological assessment. The objective of this study was to explore the possible mechanisms of acetaminophen (AP)-induced toxicity in human normal liver L-02 cells. The expression of the CYP2E1 enzyme, which is reported to transform AP to its toxic metabolites, was higher in L-02 than in Hep3B cells. Further cell viability and reduced glutathione (GSH) depletion after AP treatment were examined. After exposure to AP for 24 h, cell viability decreased in a concentration-dependent manner. Concentration-dependent GSH depletion was also observed after AP treatment for 48 h, indicating oxidative stress had occurred in L-02 cells. The effects of D, L-buthionine-(S, R)-sulfoximine (BSO), an inhibitor of GSH biosynthesis, and N-acetylcysteine (NAC), a precursor of GSH synthesis, on the cytotoxicity induced by AP were also investigated. BSO aggravated the cytotoxicity induced by AP while NAC ameliorated such cell death. Further results showed that 10 mM AP caused cell apoptosis after 48 h treatment based on the DNA fragmentation assay and western blot of caspase-3 activation, respectively. In addition, the protective effects of various well-known antioxidants against AP-induced hepatotoxicity were observed. Taken together, these results indicate that oxidative stress and cellular apoptosis are involved in AP-induced toxicity in human normal liver L-02 cells, and this cell line is a suitable in vitro cell model for AP hepatotoxicity study. PMID:20465405

Liang, Qingning; Sheng, Yuchen; Ji, Lili; Min, Yang; Xia, Yuye; Wang, Zhengtao

2010-06-01

255

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

PubMed Central

Nitrogen-doped TiO2 (N-TiO2) nanoparticles were prepared by calcining the anatase TiO2 nanoparticles under ammonia atmosphere. The N-TiO2 showed higher absorbance in the visible region than the pure TiO2. The cytotoxicity and visible-light-induced phototoxicity of the pure- and N-TiO2 were examined for three types of cancer cell lines. No significant cytotoxicity was detected. However, the visible-light-induced photokilling effects on cells were observed. The survival fraction of the cells decreased with the increased incubation concentration of the nanoparticles. The cancer cells incubated with N-TiO2 were killed more effectively than that with the pure TiO2. The reactive oxygen species was found to play an important role on the photokilling effect for cells. Furthermore, the intracellular distributions of N-TiO2 nanoparticles were examined by laser scanning confocal microscopy. The co-localization of N-TiO2 nanoparticles with nuclei or Golgi complexes was observed. The aberrant nuclear morphologies such as micronuclei were detected after the N-TiO2-treated cells were irradiated by the visible light. PMID:21711880

2011-01-01

256

Cytotoxic Effects of Biosynthesized Zinc Oxide Nanoparticles on Murine Cell Lines  

PubMed Central

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??g/mL (4T1), 17.45?±?1.1??g/mL (CRL-1451), 11.75?±?0.8??g/mL (CT-26), and 5.6?±?0.55??g/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??g/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

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

2015-01-01

257

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

PubMed

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??g/mL (4T1), 17.45?±?1.1??g/mL (CRL-1451), 11.75?±?0.8??g/mL (CT-26), and 5.6?±?0.55??g/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??g/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

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

2015-01-01

258

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

PubMed

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

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

2013-06-01

259

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

SciTech Connect

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

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

2012-03-01

260

Polyhydroxybutyrate-coated magnetic nanoparticles for doxorubicin delivery: cytotoxic effect against doxorubicin-resistant breast cancer cell line.  

PubMed

In this study, polyhydroxybutyrate (PHB)-coated magnetic nanoparticles (MNPs) were prepared by coprecipitation of iron salts (Fe and Fe) by ammonium hydroxide. Characterizations of PHB-coated MNPs were performed by Fourier transform infrared spectroscopy, x-ray diffraction, dynamic light scattering, thermal gravimetric analysis, vibrating sample magnetometry, and transmission electron microscopy analyses. Doxorubicin was loaded onto PHB-MNPs, and the release efficiencies at different pHs were studied under in vitro conditions. The most efficient drug loading concentration was found about 87% at room temperature in phosphate-buffered saline (pH 7.2). The drug-loaded MNPs were stable up to 2 months in neutral pH for mimicking physiological conditions. The drug release studies were performed with acetate buffer (pH 4.5) that mimics endosomal pH. Doxorubicin (60%) released from PHB-MNPs within 65 hours. Doxorubicin-loaded PHB-MNPs were about 2.5-fold more cytotoxic as compared with free drug on resistant Michigan Cancer Foundation-7 (human breast adenocarcinoma, MCF-7) cell line (1 ?M doxorubicin) in vitro. Therefore, doxorubicin-loaded PHB-MNPs lead to overcome the drug resistance. PMID:25137407

Yalcin, Serap; Unsoy, Gozde; Mutlu, Pelin; Khodadust, Rouhollah; Gunduz, Ufuk

2014-01-01

261

Combined cytotoxic and anti-invasive properties of redox-active nanoparticles in tumor-stroma interactions.  

PubMed

Tumor-stroma interaction plays an important role in tumor progression. Myofibroblasts, pivotal for tumor progression, populate the microecosystem of reactive stroma. The formation of myofibroblasts is mediated by tumor derived transforming growth factor ?1 (TGF?1) which initiates a reactive oxygen species cell type dependent expression of alpha-smooth muscle actin, a biomarker for myofibroblastic cells. Myofibroblasts express and secrete proinvasive factors significantly increasing the invasive capacity of tumor cells via paracrine mechanisms. Although antioxidants prevent myofibroblast formation, the same antioxidants increase the aggressive behavior of the tumor cells. In this study, the question was addressed of whether redox-active polymer-coated cerium oxide nanoparticles (CNP, nanoceria) affect myofibroblast formation, cell toxicity, and tumor invasion. Herein, nanoceria downregulate both the expression of alpha-smooth muscle actin positive myofibroblastic cells and the invasion of tumor cells. Furthermore, concentrations of nanoceria being non-toxic for normal (stromal) cells show a cytotoxic effect on squamous tumor cells. The treatment with redox-active CNP may form the basis for protection of stromal cells from the dominating influence of tumor cells in tumor-stroma interaction, thus being a promising strategy for chemoprevention of tumor invasion. PMID:21269688

Alili, Lirija; Sack, Maren; Karakoti, Ajay S; Teuber, Sarah; Puschmann, Katharina; Hirst, Suzanne M; Reilly, Christopher M; Zanger, Klaus; Stahl, Wilhelm; Das, Soumen; Seal, Sudipta; Brenneisen, Peter

2011-04-01

262

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

PubMed Central

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

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

2015-01-01

263

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

NASA Astrophysics Data System (ADS)

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

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

2012-10-01

264

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

PubMed Central

Two new Ru(II) complexes, [Ru(bpy)2(FAMP)](ClO4)2 1 and 2, are synthesized and characterized by elemental analysis, electrospray mass spectrometry, and 1H nuclear magnetic resonance. The in vitro cytotoxicities and apoptosis-inducing properties of these complexes are extensively studied. Complexes 1 and 2 exhibit potent antiproliferative activities against a panel of human cancer cell lines. The cell cycle analysis shows that complexes 1 and 2 exhibit effective cell growth inhibition by triggering G0/G1 phase arrest and inducing apoptosis by mitochondrial dysfunction. The in vitro DNA binding properties of the two complexes are investigated by different spectrophotometric methods and viscosity measurements. PMID:24804832

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

2014-01-01

265

Parkinson Disease Protein DJ-1 Binds Metals and Protects against Metal-induced Cytotoxicity*  

PubMed Central

The progressive loss of motor control due to reduction of dopamine-producing neurons in the substantia nigra pars compacta and decreased striatal dopamine levels are the classically described features of Parkinson disease (PD). Neuronal damage also progresses to other regions of the brain, and additional non-motor dysfunctions are common. Accumulation of environmental toxins, such as pesticides and metals, are suggested risk factors for the development of typical late onset PD, although genetic factors seem to be substantial in early onset cases. Mutations of DJ-1 are known to cause a form of recessive early onset Parkinson disease, highlighting an important functional role for DJ-1 in early disease prevention. This study identifies human DJ-1 as a metal-binding protein able to evidently bind copper as well as toxic mercury ions in vitro. The study further characterizes the cytoprotective function of DJ-1 and PD-mutated variants of DJ-1 with respect to induced metal cytotoxicity. The results show that expression of DJ-1 enhances the cells' protective mechanisms against induced metal toxicity and that this protection is lost for DJ-1 PD mutations A104T and D149A. The study also shows that oxidation site-mutated DJ-1 C106A retains its ability to protect cells. We also show that concomitant addition of dopamine exposure sensitizes cells to metal-induced cytotoxicity. We also confirm that redox-active dopamine adducts enhance metal-catalyzed oxidation of intracellular proteins in vivo by use of live cell imaging of redox-sensitive S3roGFP. The study indicates that even a small genetic alteration can sensitize cells to metal-induced cell death, a finding that may revive the interest in exogenous factors in the etiology of PD. PMID:23792957

Björkblom, Benny; Adilbayeva, Altynai; Maple-Grødem, Jodi; Piston, Dominik; Ökvist, Mats; Xu, Xiang Ming; Brede, Cato; Larsen, Jan Petter; Møller, Simon Geir

2013-01-01

266

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

PubMed Central

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

Raza, Haider; John, Annie

2012-01-01

267

Quantification of laser local hyperthermia induced by gold plasmonic nanoparticles.  

PubMed

This paper discusses one of the key problems of laser-induced tissue/cell hyperthermia mediated by gold nanoparticles, namely, quantifying and precise prediction of the light exposure to provide a controllable local heating impact on living organisms. The distributions of such parameters as an efficiency factor of absorption, differential and integral absorbing power of a nanoparticle, temperature increment, and Arrhenius damage integral were used to quantify nanoparticle effectiveness in the two-dimensional coordinate space “laser wavelength (?) × radius of gold nanoparticles (R).” It was found that the fulfillment of required spatial and temporal characteristics of temperature fields in the vicinity of nanoparticle determines the optimal ? and R. As a result, the area in the space (? × R) with a minimal criticality to alterations of the local hyperthermia may be significantly displaced from the position of the plasmonic resonance. The aspects of generalization of the proposed methodology for the analysis of local hyperthermia using nanoparticles of different shapes (nanoshells, nanorods, nanostars) and short pulse laser radiation are discussed. PMID:25629389

Yakunin, Alexander N; Avetisyan, Yuri A; Tuchin, Valery V

2015-05-01

268

Nanoparticle removal from EUV photomasks using laser induced plasma shockwaves  

NASA Astrophysics Data System (ADS)

In recent years, it has been demonstrated that nanoparticles can be detached and removed from substrates using laser-induced plasma (LIP) shockwaves. While it was experimentally established the effectiveness of the LIP technique for removing nanoparticles in the sub-100nm range, the removal mechanisms were not well-understood. In this article, we introduce a set of particle removal mechanisms based on moment resistance of the particle-substrate bond and discuss their effectiveness and applicability in laser-induced plasma shock nanoparticle removal. The mechanical interactions between nanoparticles and shockwaves are studied by utilizing molecular dynamic simulation approach. The forces and moments acting on nanoparticles are calculated and are related to the detachment mechanisms. It is demonstrated that sub-100nm particles can be detached from various substrates. Experiments and simulations are performed to study the effect of LIP on optical and EUVL/LTEM substrates in terms of substrate damage. Initial experiments and simulations reveal the window of safe operation of LIP and the mechanisms responsible for material alterations if any at close distances of operation of LIP above the substrate.

Kadaksham, John; Zhou, Dong; Peri, M. D. Murthy; Varghese, Ivin; Eschbach, Florence; Cetinkaya, Cetin

2006-05-01

269

Identification and replication of loci involved in camptothecin-induced cytotoxicity using CEPH pedigrees.  

PubMed

To date, the Centre d'Etude Polymorphism Humain (CEPH) cell line model has only been used as a pharmacogenomic tool to evaluate which genes are responsible for the disparity in response to a single drug. The purpose of this study was demonstrate the model's ability to establish a specific pattern of quantitative trait loci (QTL) related to a shared mechanism for multiple structurally related drugs, the camptothecins, which are Topoisomerase 1 inhibitors. A simultaneous screen of six camptothecin analogues for in vitro sensitivity in the CEPH cell lines resulted in cytotoxicity profiles and orders of potency which were in agreement with the literature. For all camptothecins studied, heritability estimates for cytotoxic response averaged 23.1 ± 2.6%. Nonparametric linkage analysis was used to identify a relationship between genetic markers and response to the camptothecins. Ten QTLs on chromosomes 1, 3, 5, 6, 11, 12, 16 and 20 were identified as shared by all six camptothecin analogues. In a separate validation experiment, nine of the ten QTLs were replicated at the significant and suggestive levels using three additional camptothecin analogues. To further refine this list of QTLs, another validation study was undertaken and seven of the nine QTLs were independently replicated for all nine camptothecin analogues. This is the first study using the CEPH cell lines that demonstrates that a specific pattern of QTLs could be established for a class of drugs which share a mechanism of action. Moreover, it is the first study to report replication of linkage results for drug-induced cytotoxicity using this model. The QTLs, which have been identified as shared by all camptothecins and replicated across multiple datasets, are of considerable interest; they harbor genes related to the shared mechanism of action for the camptothecins, which are responsible for variation in response. PMID:21573211

Watson, Venita Gresham; Motsinger-Reif, Alison; Hardison, Nicholas E; Peters, Eric J; Havener, Tammy M; Everitt, Lorraine; Auman, James Todd; Comins, Daniel L; McLeod, Howard L

2011-01-01

270

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

PubMed Central

The liver has been shown to be a primary target organ for SiO2 nanoparticles in vivo, and may be highly susceptible to damage by these nanoparticles. However, until now, research focusing on the potential toxic effects of SiO2 nanoparticles on mitochondria-associated energy metabolism in hepatocytes has been lacking. In this work, SiO2 nanoparticles 20 nm in diameter were evaluated for their ability to induce dysfunction of mitochondrial energy metabolism. First, a buffalo rat liver (BRL) cell line was directly exposed to SiO2 nanoparticles, which induced cytotoxicity and mitochondrial damage accompanied by decreases in mitochondrial dehydrogenase activity, mitochondrial membrane potential, enzymatic expression in the Krebs cycle, and activity of the mitochondrial respiratory chain complexes I, III and IV. Second, the role of rat-derived Kupffer cells was evaluated. The supernatants from Kupffer cells treated with SiO2 nanoparticles were transferred to stimulate BRL cells. We observed that SiO2 nanoparticles had the ability to activate Kupffer cells, leading to release of tumor necrosis factor-?, nitric oxide, and reactive oxygen species from these cells and subsequently to inhibition of mitochondrial respiratory chain complex I activity in BRL cells. PMID:24959077

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

2014-01-01

271

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

PubMed Central

This study examines dose effects of cadmium telluride quantum dots (CdTe-QDs) from two commercial sources on model macrophages (J774A.1) and colonic epithelial cells (HT29). Effects on cellular immune signalling responses were measured following sequential exposure to QDs and Pseudomonas aeruginosa strain PA01. At CdTe-QD concentrations between 10-2 and 10 µg/ml, cells exhibited changes in metabolism and morphology. Confocal imaging revealed QD internalisation and changes in cell–cell contacts, shapes and internal organisations. QD doses below 10-2 µg/ml caused no observed effects. When QD exposures at 10-7 to 10-3 µg/ml preceded PA01 (107 bacteria/ml) challenges, there were elevated cytotoxicity (5–22%, p < 0.05) and reduced levels (two- to fivefold, p < 0.001) of nitric oxide (NO), TNF-?, KC/CXC?1 and IL-8, compared with PA01 exposures alone. These results demonstrate that exposures to sub-toxic levels of CdTe-QDs can depress cell immune-defence functions, which if occurred in vivo would likely interfere with normal neutrophil recruitment for defence against bacteria. PMID:22264036

Nguyen, Kathy C; Seligy, Vern L

2013-01-01

272

Anti-GM(2) IgM antibody-induced complement-mediated cytotoxicity in patients with dysimmune neuropathies.  

PubMed

Anti-GM2 IgM antibodies have been reported in some patients with dysimmune neuropathy or lower motor neuron syndrome. To determine whether these antibodies can induce complement-dependent cytolysis we performed a cytotoxicity assay on neuroblastoma cells with sera from seven patients with demyelinating dysimmune neuropathies and high titers of anti-GM2 IgM. As controls we used sera from seven patients with other anti-neural reactivities, six with the same neuropathies but no anti-GM2 or other anti-neural reactivity and from eight normal subjects. Of the seven positive sera tested, six induced complement-mediated cytotoxicity, while none of the controls had any relevant effect on neuroblastoma cells. Preincubation of positive sera with purified GM2 removed cytotoxic activity. Affinity purified anti-GM2 IgM had the same cytotoxic anti-GM2 effect of whole serum while serum or complement alone did not have any effect. In four anti-GM2-positive patients the percentage of cell lysis correlated with anti-GM2 titers and with IgM staining of neuroblastoma cells while in two the cytotoxic effect was higher than expected from antibody titers. Complement-mediated cell lysis induced by anti-GM2 IgM antibodies may be a possible mechanism of neural damage in patients with dysimmune neuropathy and high titers of anti-GM2 IgM antibodies. PMID:11240036

Cavanna, B; Jiang, H; Allaria, S; Carpo, M; Scarlato, G; Nobile-Orazio, E

2001-03-01

273

Cytotoxicity and immunological responses following oral vaccination of nanoencapsulated avian influenza virus H5 DNA vaccine with green synthesis silver nanoparticles.  

PubMed

DNA formulations provide the basis for safe and cost effective vaccine. Low efficiency is often observed in the delivery of DNA vaccines. In order to assess a new strategy for oral DNA vaccine formulation and delivery, plasmid encoding hemagglutinin (HA) gene of avian influenza virus, A/Ck/Malaysia/5858/04 (H5N1) (pcDNA3.1/H5) was formulated using green synthesis of sliver nanoparticles (AgNP) with polyethylene glycol (PEG). AgNP were successfully synthesized uniformly dispersed with size in the range of 4 to 18 nm with an average size of 11 nm. Cytotoxicity of the prepared AgNP was investigated in vitro and in vivo using MCF-7 cells and cytokine expression, respectively. At the concentration of -5 log??AgNP, no cytotoxic effects were detected in MCF-7 cells with 9.5% cell death compared to the control. One-day-old specific pathogen-free (SPF) chicks immunized once by oral gavage with 10 ?l of pcDNA3.1/H5 (200 ng/ml) nanoencapsulated with 40 ?l AgNP (3.7×10?² ?g of Ag) showed no clinical manifestations. PCR successfully detect the AgNP/H5 plasmid from the duodenum of the inoculated chicken as early as 1h post-immunization. Immunization of chickens with AgNP/H5 enhanced both pro inflammatory and Th1-like expressions, although no significant differences were recorded in the chickens inoculated with AgNP, AgNP/pcDNA3.1 and the control. In addition, serum samples collected from immunized chickens with AgNP/H5 showed rapidly increasing antibody against H5 on day 14 after immunization. The highest average antibody titres were detected on day 35 post-immunization at 51.2±7.5. AgNP/H5 also elicited both CD4+ and CD8+ T cells in the immunized chickens as early as day 14 after immunization, at 7.5±2.0 and 20±1.9 percentage, respectively. Hence, single oral administrations of AgNP/H5 led to induce both the antibody and cell-mediated immune responses as well as enhanced cytokine production. PMID:22549012

Jazayeri, Seyed Davoud; Ideris, Aini; Zakaria, Zunita; Shameli, Kamyar; Moeini, Hassan; Omar, Abdul Rahman

2012-07-10

274

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

PubMed Central

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

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

2014-01-01

275

Beauvericin-induced cytotoxicity via ROS production and mitochondrial damage in Caco-2 cells.  

PubMed

The cytotoxicity of beauvericin (BEA) on human colon adenocarcinoma (Caco-2) cells was studied as a function of time. Moreover, the oxidative damage and cell death endpoints were monitored after 24, 48 and 72 h. After BEA exposure, the IC?? values ranged from 1.9 ± 0.7 to 20.6 ± 6.9 ?M. A decrease in reduced glutathione (GSH; 31%) levels, as well as an increase in oxidized glutathione (GSSG, 20%) was observed. In the presence of BEA, reactive oxygen species (ROS) level was highly increased at an early stage with the highest production of 2.0-fold higher than the control that was observed at 120 min. BEA induced cell death by mitochondria-dependent apoptotic process with loss of the mitochondrial membrane potential (??m; 9% compared to the control), increase in LPO level (from 120% to 207% compared to the control) and reduced G0/G1 phase, with an arrest in G2/M, in a dose and time-dependent manner. Cell proliferation, apoptosis and ??m determined, were in a dose- time-dependent manner. Moreover, DNA damage was observed after 12.0 ?M concentration. This study demonstrated that oxidative stress is one of the mechanism involved in BEA toxicity, moreover apoptosis induction and loss of ??m contribute to its cytotoxicity in Caco-2 cells. PMID:23850777

Prosperini, A; Juan-García, A; Font, G; Ruiz, M J

2013-10-24

276

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

SciTech Connect

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

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

2010-03-19

277

Activation of p38MAPK Contributes to Expanded Polyglutamine-Induced Cytotoxicity  

PubMed Central

Background The signaling pathways that may modulate the pathogenesis of diseases induced by expanded polyglutamine proteins are not well understood. Methodologies/Principal Findings Herein we demonstrate that expanded polyglutamine protein cytotoxicity is mediated primarily through activation of p38MAPK and that the atypical PKC iota (PKC?) enzyme antagonizes polyglutamine-induced cell death through induction of the ERK signaling pathway. We show that pharmacological blockade of p38MAPK rescues cells from polyglutamine-induced cell death whereas inhibition of ERK recapitulates the sensitivity observed in cells depleted of PKC? by RNA interference. We provide evidence that two unrelated proteins with expanded polyglutamine repeats induce p38MAPK in cultured cells, and demonstrate induction of p38MAPK in an in vivo model of neurodegeneration (spinocerebellar ataxia 1, or SCA-1). Conclusions/Significance Taken together, our data implicate activated p38MAPK in disease progression and suggest that its inhibition may represent a rational strategy for therapeutic intervention in the polyglutamine disorders. PMID:18461158

Tang, Matthew Y.; Lorimer, Ian A. J.; Gray, Douglas A.

2008-01-01

278

Genotoxic and cytotoxic effects induced by aluminum in the lymphocytes of the common carp (Cyprinus carpio).  

PubMed

Few studies have been made in regard to the effect of aluminum on the molecular and cellular structure and function of aquatic organisms; therefore, in the present report we determined the genotoxic and cytotoxic effects induced by the metal on the lymphocytes of carp (Cyprinus carpio). Three groups of fish were exposed to 0.05, 120, and 239 mg/L of aluminum (Al), respectively, by using Al? (SO?)?·7H?O, and another group was included as control. The cells obtained were studied with the comet assay, flow cytometry, and the TUNEL method. With the first method we found a concentration and time dependent, significant increase in the amount of DNA damage induced by Al, and a higher damage when we evaluated the level of oxidized DNA. By applying flow cytometry we established that the metal induced a DNA content increase and ploidy modifications as well as apoptosis and disturbances of the cell cycle progression. With the last method we determined a significant increase in the amount of apoptotic cells, mainly in the 72-96 h period. Our results established that Al caused deleterious DNA and cellular effects in the tested organism, and they suggested the pertinence of evaluating toxicity induced by the metal in organisms living in contaminated water bodies. PMID:20883821

García-Medina, Sandra; Razo-Estrada, Celene; Galar-Martinez, Marcela; Cortéz-Barberena, Edith; Gómez-Oliván, Leobardo Manuel; Alvarez-González, Isela; Madrigal-Bujaidar, Eduardo

2011-01-01

279

Sodium valproate, a histone deacetylase inhibitor ameliorates cyclophosphamide-induced genotoxicity and cytotoxicity in the colon of mice.  

PubMed

Abstract Background: Cyclophosphamide (CP) is an alkylating anticancer drug used for the treatment of various cancer and noncancer disorders. Toxicity of CP is well characterized using different test systems. However, its intestinal genotoxicity and cytotoxicity are the least explored and the mechanism is not fully investigated. Valproic acid (VPA) has been reported as a histone deacetylase (HDAC) inhibitor, which modulates the cytotoxicity of anticancer drugs. The present study aimed to investigate the influence of VPA on CP-induced genotoxicity and cytotoxicity in the colon of mice. Methods: In the 16-day experiment, animals were treated with VPA alone (500 mg/kg/day), CP alone (50 mg/kg, on the 4th, 8th, 12th, and 16th days), and the combination of CP and VPA, while in the 28-day experiment, animals were treated with VPA alone (300 mg/kg/day, 5 days/week), CP alone (100 mg/kg/week), and the combination of low and high dose of VPA (VPA150+CP and VPA300+CP). Animals were sacrificed 24 h after the administration of the last dose. The influence of VPA treatment on CP-induced genotoxicity and cytotoxicity was assessed by the evaluation of oxidative stress, DNA damage, histology, and the expression of 8-hydroxy-guanosine and phosphorylated histone H2AX by immunohistochemistry. Results and conclusions: The present study's results demonstrated that VPA treatment significantly decreased the CP-induced DNA damage, cytotoxicity, and expression of ?H2AX in the colon as revealed by the comet assay and histological as well as immunohistochemical evaluation. VPA treatment significantly ameliorated the CP-induced DNA damage and cytotoxicity in the colon of mice. PMID:24468617

Khan, Sabbir; Jena, Gopabandhu

2014-01-27

280

Virus inhibition induced by polyvalent nanoparticles of different sizes  

NASA Astrophysics Data System (ADS)

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

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

2014-01-01

281

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

PubMed Central

Aim Two unexplored aspects for irinotecan and cisplatin (I&C) combination chemotherapy are (1) actively targeting both drugs to a specific diseased cell type and (2) delivering both drugs on the same vehicle to ensure their synchronized entry into the cell at a well-defined ratio. In this work we report the use of targeted polymeric nanoparticles (NPs) to co-encapsulate and deliver I&C to cancer cells expressing the Prostate Specific Membrane Antigen (PSMA). Method We prepared targeted NPs in a single-step by mixing four different precursors inside microfluidic devices. Results I&C were encapsulated in 55-nm NPs and showed an 8-fold increase in internalization by PSMA-expressing LNCaP cells compared to non-targeted NPs. NPs co-encapsulating both drugs exhibited strong synergism in LNCaP cells with a combination index of 0.2. Conclusion The strategy of co-encapsulating both irinotecan and cisplatin in a single NP targeted to a specific cell type could potentially be used to treat different types of cancer. PMID:23075285

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

2013-01-01

282

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

NASA Astrophysics Data System (ADS)

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

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

2013-03-01

283

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

PubMed

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

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

2013-08-01

284

Biosynthesis of gold nanoparticles and related cytotoxicity evaluation using A549 cells.  

PubMed

Biosynthesis of gold nanoparticles (AuNPs) has become an attractive area of research as it is environmentally benign. The toxicity of AuNPs synthesized by chemical routes has been widely studied. However, little is known about the toxicity associated with the biological synthesis of AuNPs. The present study was carried out to synthesize AuNPs using star anise (Illicium verum; a commercially available spice in abundance)and evaluate its toxicity using human epithelial lung cells (A549) in comparison with AuNPs synthesized by the traditional chemical methods (using sodium citrate and sodium borohydride). Apart from cell viability, markers of oxidative stress (reduced glutathione) and cell death (caspases) were also evaluated to understand the mechanisms of toxicity. Cell viability was observed to be 65.7 percent and 72.3 percent in cells exposed to chemically synthesized AuNPs at the highest dose (200nM) as compared to 80.2 percent for biologically synthesized AuNPs. Protective coating/capping of AuNPs by various polyphenolic compounds present in star anise extract appears to be a major contributor to lower toxicity observed in biologically synthesized AuNPs. PMID:24835429

Sathishkumar, M; Pavagadhi, S; Mahadevan, A; Balasubramanian, R

2015-04-01

285

Accumulated polymer degradation products as effector molecules in cytotoxicity of polymeric nanoparticles.  

PubMed

Polymeric nanoparticles (PNPs) are a promising platform for drug, gene, and vaccine delivery. Although generally regarded as safe, the toxicity of PNPs is not well documented. The present study investigated in vitro toxicity of poly-?-caprolactone, poly(DL-lactic acid), poly(lactide-cocaprolactone), and poly(lactide-co-glycide) NPs and possible mechanism of toxicity. The concentration-dependent effect of PNPs on cell viability was determined in a macrophage (RAW 264.7), hepatocyte (Hep G2), lung epithelial (A549), kidney epithelial (A498), and neuronal (Neuro 2A) cell lines. PNPs show toxicity at high concentrations in all cell lines. PNPs were efficiently internalized by RAW 264.7 cells and stimulated reactive oxygen species and tumor necrosis factor-alpha production. However, reactive nitrogen species and interleukin-6 production as well as lysosomal and mitochondrial stability remained unaffected. The intracellular degradation of PNPs was determined by monitoring changes in osmolality of culture medium and a novel fluorescence recovery after quenching assay. Cell death showed a good correlation with osmolality of culture medium suggesting the role of increased osmolality in cell death. PMID:23976781

Singh, Raman Preet; Ramarao, Poduri

2013-11-01

286

Anti-biofilm and cytotoxicity activity of impregnated dressings with silver nanoparticles.  

PubMed

Infections arising from bacterial adhesion and colonization on chronic wounds are a significant healthcare problem. Silver nanoparticles (AgNPs) impregnated in dressing have attracted a great deal of attention as a potential solution. The goal of the present study was to evaluate the anti-biofilm activities of AgNPs impregnated in commercial dressings against Pseudomonas aeruginosa, bacteria isolated of chronic wounds from a hospital patient. The antimicrobial activity of AgNPs was tested within biofilms generated under slow fluid shear conditions using a standard bioreactor. A 2-log reduction in the number of colony-forming units of P. aeruginosa was recorded in the reactor on exposure to dressing impregnated with 250ppm of AgNPs, diameter 9.3±1.1nm, and also showed compatibility to mammalian cells (human fibroblasts). Our study suggests that the use of dressings with AgNPs may either prevent or reduce microbial growth in the wound environment, and reducing wound bioburden may improve wound-healing outcomes. PMID:25686989

Velázquez-Velázquez, Jorge Luis; Santos-Flores, Andrés; Araujo-Meléndez, Javier; Sánchez-Sánchez, Roberto; Velasquillo, Cristina; González, Carmen; Martínez-Castañon, Gabriel; Martinez-Gutierrez, Fidel

2015-04-01

287

Cytotoxicity effects of metal oxide nanoparticles in human tumor cell lines  

NASA Astrophysics Data System (ADS)

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

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

2011-07-01

288

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

PubMed

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

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

2014-01-30

289

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

PubMed

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

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

2015-06-01

290

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

PubMed

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

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

2014-08-25

291

Enhanced reduction in cell viability by hyperthermia induced by magnetic nanoparticles.  

PubMed

Colloidal suspensions of iron oxide magnetic nanoparticles are known to dissipate energy when exposed to an oscillating magnetic field. Such energy dissipation can be employed to locally raise temperature inside a tumor between 41°C and 45°C (hyperthermia) to promote cell death, a treatment known as magnetic fluid hyperthermia (MFH). This work seeks to quantify differences between MFH and hot-water hyperthermia (HWH) in terms of reduction in cell viability using two cancer cell culture models, Caco-2 (human epithelial colorectal adenocarcinoma) and MCF-7 (human breast cancer). Magnetite nanoparticles were synthesized via the co-precipitation method and functionalized with adsorbed carboxymethyl dextran. Cytotoxicity studies indicated that in the absence of an oscillating magnetic field, cell viability was not affected at concentrations of up to 0.6 mg iron oxide/mL. MFH resulted in a significant decrease in cell viability when exposed to a magnetic field for 120 minutes and allowed to rest for 48 hours, compared with similar field applications, but with shorter resting time. The results presented here suggest that MFH most likely induces apoptosis in both cell types. When compared with HWH, MFH produced a significant reduction in cell viability, and these effects appear to be cell-type related. PMID:21499427

Rodríguez-Luccioni, Héctor L; Latorre-Esteves, Magda; Méndez-Vega, Janet; Soto, Orlando; Rodríguez, Ana R; Rinaldi, Carlos; Torres-Lugo, Madeline

2011-01-01

292

Folpet-induced short term cytotoxic and proliferative changes in the mouse duodenum.  

PubMed

Folpet, an agricultural fungicide, induces tumors in the mouse gastrointestinal tract, primarily in the duodenum. Bioassays show a threshold for tumors at ~1000 ppm dietary administration. We investigated the early histologic changes to the mouse duodenum in mice fed a diet containing 6000 ppm folpet for 28 days. Reversibility of folpet-induced changes was evaluated after treatment for 28 days and a recovery period of 17 days. Macroscopic changes in the cecum (dilatation) and duodenum (roughening) were evident by day 7, continued through day 28, then returned to normal by recovery day 17. The duodenal mucosa also appeared to be thickened. Macroscopic changes to the forestomach were also evident as a rough surface or depressions; they also decreased in incidence and severity in the recovery animals. Histologic changes of the duodenum (crypt cell hyperplasia, villous hypertrophy, numerous intraepithelial lymphocytes, and elongation of epithelial columnar cells) were evident in all treated mice by day 7 and continued and increased in severity through 28 days of administration. The incidence and severity of these findings was reduced on recovery day 17, indicating reversibility. Histologic changes (epithelial hyperplasia and hyperkeratosis) of the non-glandular squamous epithelium in the forestomach occurred later than the changes to the duodenum. The incidence and severity of these changes also lessened by recovery day 17. These early histologic changes support a non-DNA reactive mode of action for folpet carcinogenicity in mice involving the key events of mucosal cytotoxicity with consequent regenerative proliferation. Exposures that are not sufficient to produce cytotoxicity would also not lead to tumor formation. PMID:22017358

Gordon, Elliot; Cohen, Samuel M; Singh, Pramila

2012-01-01

293

D-Glucose-Induced Cytotoxic, Genotoxic, and Apoptotic Effects on Human Breast Adenocarcinoma (MCF-7) Cells  

PubMed Central

Introduction Glucose is a simple sugar that plays an important role in energy production in biological systems. However, it has been linked to many long-term health problems including the risk of heart disease and stroke, erectile dysfunction in men and pregnancy complications in women, and damage to the kidneys, nerves, eye and vision. Also, the underlying mechanisms of diabetic complications are poorly understood. Methods In the present study, D-glucose-induced cytotoxic, genotoxic, and apoptotic effects were studied using MCF-7 cells as an in vitro test model. Cell viability was determined by MTT assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet) assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay). Results The results of MTT assay indicated that D-glucose significantly reduces the viability of MCF-7 cells in a dose and time-dependent manner. Similar trend was obtained with the trypan blue exclusion test. Data obtained from the Comet assay indicated that D-glucose causes DNA damage in MCF-7 cells in a dose-dependent manner. The flow cytometry assessment (Annexin V FITC/PI) showed a strong dose-response relationship between D-glucose exposure and annexin V positive MCF-7 cells undergoing early apoptosis. Conclusion Taking together, these data provide clear evidence that D-glucose induces cytotoxic, genotoxic, and apoptotic effects on MCF-7 cells. This finding represents the basis for further studies addressing the pathophysiological mechanisms of action of glucose overdose. PMID:25506409

Tchounwou, Christine K; Yedjou, Clement G; Farah, Ibrahim; Tchounwou, Paul B

2014-01-01

294

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

PubMed Central

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

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

2013-01-01

295

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

Microsoft Academic Search

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

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

2008-01-01

296

Gold nanoparticles displaying tumor-associated self-antigens as a potential vaccine for cancer immunotherapy.  

PubMed

Golden vaccine for cancers. Gold nanoparticles enable efficient antigen delivery to dendritic cells and then activate the cells to facilitate cross-presentation, inducing antigen-specific cytotoxic T-lymphocyte responses for effective cancer therapy. PMID:24652754

Ahn, Sukyung; Lee, In-Hyun; Kang, Sukmo; Kim, Daejin; Choi, Minsuk; Saw, Phei Er; Shin, Eui-Cheol; Jon, Sangyong

2014-08-01

297

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

PubMed Central

This study aimed to compare the inhibitory effects of photosensitizers loaded in hollow silica nanoparticles and conventional photosensitizers on HepG2 human hepatoma cell proliferation and determine the underlying mechanisms. Photosensitizers (conventional Photosan-II or nanoscale Photosan-II) were administered to in vitro cultured HepG2 hepatoma cells and treated by photodynamic therapy (PDT) with various levels of light exposure. To assess photosensitizers' effects, cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, apoptotic and necrotic cells were measured by flow cytometry and the expression of caspase-3 and caspase-9 evaluated by western blot. Finally, the in vivo effects of nanoscale and conventional photosensitizers on liver cancer were assessed in nude mice. Nanoscale Photosan-II significantly inhibited hepatoma cell viability in a concentration-dependent manner and this effect was more pronounced with high laser doses. Moreover, nanoscale photosensitizers performed better than the conventional ones under the same experimental conditions (p?induced cell death was markedly increased after treatment with nanoscale Photosan-II in comparison with free Photosan-II (p?nanoparticles than free Photosan-II (p?nanoparticles containing photosensitizer more efficiently inhibited hepatoma cells than photosensitizer alone, through induction of apoptosis, both in vivo and in vitro. PMID:25024681

2014-01-01

298

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

NASA Astrophysics Data System (ADS)

This study aimed to compare the inhibitory effects of photosensitizers loaded in hollow silica nanoparticles and conventional photosensitizers on HepG2 human hepatoma cell proliferation and determine the underlying mechanisms. Photosensitizers (conventional Photosan-II or nanoscale Photosan-II) were administered to in vitro cultured HepG2 hepatoma cells and treated by photodynamic therapy (PDT) with various levels of light exposure. To assess photosensitizers' effects, cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, apoptotic and necrotic cells were measured by flow cytometry and the expression of caspase-3 and caspase-9 evaluated by western blot. Finally, the in vivo effects of nanoscale and conventional photosensitizers on liver cancer were assessed in nude mice. Nanoscale Photosan-II significantly inhibited hepatoma cell viability in a concentration-dependent manner and this effect was more pronounced with high laser doses. Moreover, nanoscale photosensitizers performed better than the conventional ones under the same experimental conditions ( p < 0.05). Flow cytometry data demonstrated that laser-induced cell death was markedly increased after treatment with nanoscale Photosan-II in comparison with free Photosan-II ( p < 0.05). Activated caspase-3 and caspase-9 levels were significantly higher in cells treated with Photosan-II loaded in silica nanoparticles than free Photosan-II ( p < 0.05). Accordingly, treatment with nanoscale photosensitizers resulted in improved outcomes (tumor volume) in a mouse model of liver cancer, in comparison with conventional photosensitizers. Hollow silica nanoparticles containing photosensitizer more efficiently inhibited hepatoma cells than photosensitizer alone, through induction of apoptosis, both in vivo and in vitro.

Liu, Zhong-Tao; Xiong, Li; Liu, Zhi-Peng; Miao, Xiong-Ying; Lin, Liang-Wu; Wen, Yu

2014-06-01

299

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

PubMed

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

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

2009-02-01

300

SIRT3 protects endothelial cells from high glucose-induced cytotoxicity.  

PubMed

Diabetes is a frequent and increasing public health problem with a large economic burden in modern society. Endothelial cells dysfunction was involved in the development of diabetes-associated diseases. Sirtuins are a conserved family of NAD-dependent deacetylases. However, the role of sirtuins in diabetes-associated endothelial cell dysfunction was relatively unknown. In this study, we focus on the intrinsic link between SIRT3, a mitochondrial sirtuin, and high glucose-induced endothelial cells dysfunction. We showed that loss of SIRT3 expression was associated with decreased viability in endothelial cells from diabetes patients. Knockdown of SIRT3 decreased viability of endothelia cells exposed to high glucose condition. Further, mechanistic study showed that SIRT3 repression results in SOD2 acetylation, leading to SOD2 inactivation, which enhanced high glucose-induced oxidative stress in endothelial cells. Our data suggested that SIRT3 protects endothelial cells from high glucose-induced cytotoxicity. Our findings are considered a significant step toward a better understanding of diabetes-associated vascular diseases. PMID:25755722

Liu, Guodong; Cao, Mingming; Xu, Ying; Li, Yanbo

2015-01-01

301

SIRT3 protects endothelial cells from high glucose-induced cytotoxicity  

PubMed Central

Diabetes is a frequent and increasing public health problem with a large economic burden in modern society. Endothelial cells dysfunction was involved in the development of diabetes-associated diseases. Sirtuins are a conserved family of NAD-dependent deacetylases. However, the role of sirtuins in diabetes-associated endothelial cell dysfunction was relatively unknown. In this study, we focus on the intrinsic link between SIRT3, a mitochondrial sirtuin, and high glucose-induced endothelial cells dysfunction. We showed that loss of SIRT3 expression was associated with decreased viability in endothelial cells from diabetes patients. Knockdown of SIRT3 decreased viability of endothelia cells exposed to high glucose condition. Further, mechanistic study showed that SIRT3 repression results in SOD2 acetylation, leading to SOD2 inactivation, which enhanced high glucose-induced oxidative stress in endothelial cells. Our data suggested that SIRT3 protects endothelial cells from high glucose-induced cytotoxicity. Our findings are considered a significant step toward a better understanding of diabetes-associated vascular diseases. PMID:25755722

Liu, Guodong; Cao, Mingming; Xu, Ying; Li, Yanbo

2015-01-01

302

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

SciTech Connect

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

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

2011-05-01

303

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

NASA Astrophysics Data System (ADS)

The effect of gold nanoparticles (AuNPs) on the polymerization of tubulin has not been examined till now. We report that interaction of weakly protected AuNPs with microtubules (MTs) could cause inhibition of polymerization and aggregation in the cell free system. We estimate that single citrate capped AuNPs could cause aggregation of ~105 tubulin heterodimers. Investigation of the nature of inhibition of polymerization and aggregation by Raman and Fourier transform-infrared (FTIR) spectroscopies indicated partial conformational changes of tubulin and microtubules, thus revealing that AuNP-induced conformational change is the driving force behind the observed phenomenon. Cell culture experiments were carried out to check whether this can happen inside a cell. Dark field microscopy (DFM) combined with hyperspectral imaging (HSI) along with flow cytometric (FC) and confocal laser scanning microscopic (CLSM) analyses suggested that AuNPs entered the cell, caused aggregation of the MTs of A549 cells, leading to cell cycle arrest at the G0/G1 phase and concomitant apoptosis. Further, Western blot analysis indicated the upregulation of mitochondrial apoptosis proteins such as Bax and p53, down regulation of Bcl-2 and cleavage of poly(ADP-ribose) polymerase (PARP) confirming mitochondrial apoptosis. Western blot run after cold-depolymerization revealed an increase in the aggregated insoluble intracellular tubulin while the control and actin did not aggregate, suggesting microtubule damage induced cell cycle arrest and apoptosis. The observed polymerization inhibition and cytotoxic effects were dependent on the size and concentration of the AuNPs used and also on the incubation time. As microtubules are important cellular structures and target for anti-cancer drugs, this first observation of nanoparticles-induced protein's conformational change-based aggregation of the tubulin-MT system is of high importance, and would be useful in the understanding of cancer therapeutics and safety of nanomaterials.The effect of gold nanoparticles (AuNPs) on the polymerization of tubulin has not been examined till now. We report that interaction of weakly protected AuNPs with microtubules (MTs) could cause inhibition of polymerization and aggregation in the cell free system. We estimate that single citrate capped AuNPs could cause aggregation of ~105 tubulin heterodimers. Investigation of the nature of inhibition of polymerization and aggregation by Raman and Fourier transform-infrared (FTIR) spectroscopies indicated partial conformational changes of tubulin and microtubules, thus revealing that AuNP-induced conformational change is the driving force behind the observed phenomenon. Cell culture experiments were carried out to check whether this can happen inside a cell. Dark field microscopy (DFM) combined with hyperspectral imaging (HSI) along with flow cytometric (FC) and confocal laser scanning microscopic (CLSM) analyses suggested that AuNPs entered the cell, caused aggregation of the MTs of A549 cells, leading to cell cycle arrest at the G0/G1 phase and concomitant apoptosis. Further, Western blot analysis indicated the upregulation of mitochondrial apoptosis proteins such as Bax and p53, down regulation of Bcl-2 and cleavage of poly(ADP-ribose) polymerase (PARP) confirming mitochondrial apoptosis. Western blot run after cold-depolymerization revealed an increase in the aggregated insoluble intracellular tubulin while the control and actin did not aggregate, suggesting microtubule damage induced cell cycle arrest and apoptosis. The observed polymerization inhibition and cytotoxic effects were dependent on the size and concentration of the AuNPs used and also on the incubation time. As microtubules are important cellular structures and target for anti-cancer drugs, this first observation of nanoparticles-induced protein's conformational change-based aggregation of the tubulin-MT system is of high importance, and would be useful in the understanding of cancer therapeutics and safety of nanomaterials. Electronic supplementary information (ESI

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

2013-05-01

304

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

PubMed

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

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

2015-02-11

305

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

PubMed

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

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

2015-03-01

306

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

PubMed Central

Human exposure to inorganic arsenic leads to various dermal disorders, including hyperkeratosis and skin cancer. Curcumin is demonstrated to induce remarkable antioxidant activity in a variety of cells and tissues. The present study aimed at identifying curcumin as a potent activator of nuclear factor erythroid 2-related factor 2 (NRF2) and demonstrating its protective effect against inorganic arsenite- (iAs3+-) induced cytotoxicity in human keratinocytes. We found that curcumin led to nuclear accumulation of NRF2 protein and increased the expression of antioxidant response element- (ARE-) regulated genes in HaCaT keratinocytes in concentration- and time-dependent manners. High concentration of curcumin (20??M) also increased protein expression of long isoforms of NRF1. Treatment with low concentrations of curcumin (2.5 or 5??M) effectively increased the viability and survival of HaCaT cells against iAs3+-induced cytotoxicity as assessed by the MTT assay and flow cytometry and also attenuated iAs3+-induced expression of cleaved caspase-3 and cleaved PARP protein. Selective knockdown of NRF2 or KEAP1 by lentiviral shRNAs significantly diminished the cytoprotection conferred by curcumin, suggesting that the protection against iAs3+-induced cytotoxicity is dependent on the activation of NRF2. Our results provided a proof of the concept of using curcumin to activate the NRF2 pathway to alleviate arsenic-induced dermal damage. PMID:23710286

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

2013-01-01

307

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

PubMed

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

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

2014-03-25

308

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

PubMed

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

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

2013-05-21

309

Renal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles via the NF-?B signaling pathway  

PubMed Central

Previous studies have indicated that the nephrotoxicity induced by mesoporous silica nanoparticles (MSNs) is closely related to inflammation. Nuclear factor kappa B (NF-?B), a common rapid transcription factor associated with inflammation, plays an important role in the process of many kidney diseases. Acute toxicity assessment with a high-dose exposure is critical for the development of nanoparticle, as a part of standardized procedures for the evaluation of their toxicity. The present study was undertaken to observe the acute toxicity, predict the potential target organs of MSNs injury, and test the hypothesis that the NF-?B pathway plays a role in mediating the acute kidney injury and renal interstitial fibrosis in mice induced by MSNs. Balb/c mice were intraperitoneally injected with MSNs at concentrations of 150, 300, or 600 mg/kg. All of the animals were euthanized 2 and 12 days after exposure, and the blood and kidney tissues were collected for further studies. In vitro, the cytotoxicity, fibrosis markers, and NF-?B pathway were measured in a normal rat kidney cell line (NRK-52E). Acute kidney injury was induced by MSNs in mice after 2 days, some renal tubules regenerated and renal interstitial fibrosis was also observed. The expression of fibrosis markers and the nuclear translocation of NF-?B p65 in the kidney homogenates increased after exposure to MSNs. The in vitro study showed that MSNs cause cytotoxicity in NRK-52E cells and increased the expression of fibrosis markers. In addition, the NF-?B pathway could be induced, and inhibition of the NF-?B pathway could alleviate the fibrosis caused by MSNs. We conclude that inflammation is a major effector of the acute kidney toxicity induced by MSNs and results in renal interstitial fibrosis, which is mediated by the NF-?B signaling pathway. PMID:25565800

Chen, Xi; Zhouhua, Wang; Jie, Zhou; Xinlu, Fu; Jinqiang, Liang; Yuwen, Qiu; Zhiying, Huang

2015-01-01

310

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

PubMed

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

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

2014-04-01

311

Light induced cytosolic drug delivery from liposomes with gold nanoparticles.  

PubMed

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

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

2015-04-10

312

Computational tool for risk assessment of nanomaterials: novel QSTR-perturbation model for simultaneous prediction of ecotoxicity and cytotoxicity of uncoated and coated nanoparticles under multiple experimental conditions.  

PubMed

Nanomaterials have revolutionized modern science and technology due to their multiple applications in engineering, physics, chemistry, and biomedicine. Nevertheless, the use and manipulation of nanoparticles (NPs) can bring serious damages to living organisms and their ecosystems. For this reason, ecotoxicity and cytotoxicity assays are of special interest in order to determine the potential harmful effects of NPs. Processes based on ecotoxicity and cytotoxicity tests can significantly consume time and financial resources. In this sense, alternative approaches such as quantitative structure-activity/toxicity relationships (QSAR/QSTR) modeling have provided important insights for the better understanding of the biological behavior of NPs that may be responsible for causing toxicity. Until now, QSAR/QSTR models have predicted ecotoxicity or cytotoxicity separately against only one organism (bioindicator species or cell line) and have not reported information regarding the quantitative influence of characteristics other than composition or size. In this work, we developed a unified QSTR-perturbation model to simultaneously probe ecotoxicity and cytotoxicity of NPs under different experimental conditions, including diverse measures of toxicities, multiple biological targets, compositions, sizes and conditions to measure those sizes, shapes, times during which the biological targets were exposed to NPs, and coating agents. The model was created from 36488 cases (NP-NP pairs) and exhibited accuracies higher than 98% in both training and prediction sets. The model was used to predict toxicities of several NPs that were not included in the original data set. The results of the predictions suggest that the present QSTR-perturbation model can be employed as a highly promising tool for the fast and efficient assessment of ecotoxicity and cytotoxicity of NPs. PMID:25384130

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

2014-12-16

313

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

PubMed Central

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

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

2013-01-01

314

Protective effect of lipoic acid against acrolein-induced cytotoxicity in IMR-90 human fibroblasts.  

PubMed

Acrolein is a highly reactive unsaturated hazardous air pollutant of human health concern, particularly as a component of cigarette smoke. In this study, the effects of acrolein on mitochondrial damage in IMR-90 (a human lung fibroblast cell line), and the reduction of this damage by R-alpha-lipoic acid were examined. Our results show that acute acrolein exposure exceeding 100 microM (24 h) in IMR-90 cells caused serious cytotoxicity, including decreases in cell viability, mitochondrial membrane potential, SOD activity, GSH and ATP levels, and acute exposure also increased in ROS levels. Pretreatment with R-alpha-lipoic acid effectively protected IMR-90 cells from acrolein toxicity. The results show that acrolein is a mitochondrial toxin in IMR-90 cells and that acrolein-induced oxidative mitochondrial dysfunction is reduced by R-alpha-lipoic acid. These experiments imply R-alpha-lipoic acid may be an effective antioxidant for reducing or preventing chronic oxidant-induced lung cells degeneration in vivo from a variety of sources, including cigarette smoke. PMID:19436138

Jia, Lihong; Zhang, Zhiyu; Zhai, Lingling; Bai, Yinglong

2009-04-01

315

Chimeric influenza virus induces neutralizing antibodies and cytotoxic T cells against human immunodeficiency virus type 1.  

PubMed Central

Expression vectors based on DNA or plus-stranded RNA viruses are being developed as vaccine carriers directed against various pathogens. Less is known about the use of negative-stranded RNA viruses, whose genomes have been refractory to direct genetic manipulation. Using a recently described reverse genetics method, we investigated whether influenza virus is able to present antigenic structures from other infectious agents. We engineered a chimeric influenza virus which expresses a 12-amino-acid peptide derived from the V3 loop of gp120 of human immunodeficiency virus type 1 (HIV-1) MN. This peptide was inserted into the loop of antigenic site B of the influenza A/WSN/33 virus hemagglutinin (HA). The resulting chimeric virus was recognized by specific anti-V3 peptide antibodies and a human anti-gp120 monoclonal antibody in both hemagglutination inhibition and neutralization assays. Mice immunized with the chimeric influenza virus produced anti-HIV antibodies which were able to bind to synthetic V3 peptide, to precipitate gp120, and to neutralize MN virus in human T-cell culture system. In addition, the chimeric virus was also capable of inducing cytotoxic T cells which specifically recognize the HIV sequence. These results suggest that influenza virus can be used as an expression vector for inducing both B- and T-cell-mediated immunity against other infectious agents. Images PMID:7692083

Li, S; Polonis, V; Isobe, H; Zaghouani, H; Guinea, R; Moran, T; Bona, C; Palese, P

1993-01-01

316

Upregulation of Twist-1 by NF-?B Blocks Cytotoxicity Induced by Chemotherapeutic Drugs?  

PubMed Central

NF-?B/Rel transcription factors are central to controlling programmed cell death (PCD). Activation of NF-?B blocks PCD induced by numerous triggers, including ligand engagement of tumor necrosis factor receptor (TNF-R) family receptors. The protective activity of NF-?B is also crucial for oncogenesis and cancer chemoresistance. Downstream of TNF-Rs, this activity of NF-?B has been linked to the suppression of reactive oxygen species and the c-Jun-N-terminal-kinase (JNK) cascade. The mechanism by which NF-?B inhibits PCD triggered by chemotherapeutic drugs, however, remains poorly understood. To understand this mechanism, we sought to identify unrecognized protective genes that are regulated by NF-?B. Using an unbiased screen, we identified the basic-helix-loop-helix factor Twist-1 as a new mediator of the protective function of NF-?B. Twist-1 is an evolutionarily conserved target of NF-?B, blocks PCD induced by chemotherapeutic drugs and TNF-? in NF-?B-deficient cells, and is essential to counter this PCD in cancer cells. The protective activity of Twist-1 seemingly halts PCD independently of interference with cytotoxic JNK, p53, and p19ARF signaling, suggesting that it mediates a novel protective mechanism activated by NF-?B. Indeed, our data indicate that this activity involves a control of inhibitory Bcl-2 phosphorylation. The data also suggest that Twist-1 and -2 play an important role in NF-?B-dependent chemoresistance. PMID:17403902

Pham, Can G.; Bubici, Concetta; Zazzeroni, Francesca; Knabb, James R.; Papa, Salvatore; Kuntzen, Christian; Franzoso, Guido

2007-01-01

317

Assessment of cytotoxicity and oxidative effect of Bismuth Ferrite (BFO) harmonic nanoparticles for localized DNA photo-interaction  

NASA Astrophysics Data System (ADS)

Bismuth Ferrite nanoparticles have been recently used to selectively interact with malignant cell DNA via in situ generated second harmonic in a novel theranostics protocol [Nanoscale 6(5), pp. 2929, 2014]. In this report, we extend the screening of biocompatibility of BFO uncoated uncoated nanoparticles and assess the nanoparticle- mediated production of reactive oxygen species as a function of excitation wavelength.

Staedler, Davide; Magouroux, Thibaud; Passemard, Solène; Ciepielewski, Daniel; Gerber-Lemaire, Sandrine; Wolf, Jean-Pierre; Bonacina, Luigi

2014-09-01

318

Green Synthesis of Silver Nanoparticles Using Extract of Oak Fruit Hull (Jaft): Synthesis and In Vitro Cytotoxic Effect on MCF-7 Cells  

PubMed Central

A green synthetic approach by using oak fruit hull (Jaft) extract for preparation of silver nanoparticles (AgNPs) was developed and optimized. Parameters affecting the synthesis of AgNPs, such as temperature, extract pH, and concentration of extract (ratio of plant sample to extraction solvent), were investigated and optimized. Optimum conditions for the synthesis of silver nanoparticles are as follows: Ag+ concentration, 1?mM; extract concentration, 40?g/L (4% w/v); pH = 9 and temperature, 45°C. Biosynthesized silver nanoparticles were characterized using UV-visible absorption spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). TEM and DLS analyses have shown the synthesized AgNPs were predominantly spherical in shape with an average size of 40?nm. The cytotoxic activity of the synthesized AgNPs and Jaft extract containing AgNPs against human breast cancer cell (MCF-7) was investigated and the half maximal inhibitory concentrations (IC50) were found to be 50 and 0.04??g/mL at 24?h incubation, respectively. This eco-friendly and cost-effective synthesis method can be potentially used for large-scale production of silver nanoparticles. PMID:25685560

Rashidipour, Marzieh

2015-01-01

319

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

Microsoft Academic Search

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

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

2000-01-01

320

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

SciTech Connect

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

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

1992-12-31

321

Neuroprotective effect of N-acyl 5-hydroxytryptamines on glutamate-induced cytotoxicity in HT-22 cells.  

PubMed

Some endocannabinoids have been known to express anti-inflammatory and antioxidant actions independent of cannabinoid receptors. In this respect, we investigated whether N-acyl 5-hydroxytryptamines (5-HTs) might prevent against glutamate-induced oxidative cytotoxicity in HT-22 cells, and attempted to elucidate the mechanism for their cytoprotective action. N-acyl 5-HTs with palmitoyl, stearoyl, arachidonoyl or docosahexaenoyl chain expressed a remarkable protective effect on glutamate-induced cytotoxicity. Additionally, glutamate-induced oxidative stress, represented by the increase of reactive oxygen species level and the reduction of glutathione level, was prevented markedly by N-acyl 5-HTs at submicromolar levels. Further, N-palmitoyl 5-HT, the most cytoprotective, enhanced antioxidant defense by up-regulating the expression of antioxidant enzymes such as heme oxygenase-1, glutamate-cysteine ligase catalytic subunit or NAD(P)H quinine oxidoreductase-1 in the presence or absence of glutamate. Consistent with this, N-palmitoyl 5-HT stimulated nuclear translocation of Nrf2 in early phase (2 h), and this effect was remarkably suppressed by inhibitors of PI3K, PDK-1, Akt or p38 MAPK. Additionally, N-palmitoyl 5-HT suppressed glutamate-induced activation of ERK in late phase (12 h), but not in early phase (2 h), presumably supporting the implication of MEK/ERK pathway in glutamate-induced cytotoxicity. Collectively, it is suggested that N-acyl 5-HTs may attenuate glutamate-induced cytotoxicity via the activation of PI3K/PDK-1/Akt- and p38 MAPK-dependent Nrf2 signaling in early phase as well as the suppression of MEK/ERK pathway in late phase. PMID:25307111

Jin, Mei Chen; Yoo, Jae-Myung; Sok, Dai-Eun; Kim, Mee Ree

2014-12-01

322

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

PubMed

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

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

2014-01-01

323

Mycobacterium tuberculosis Multidrug Resistant Strain M Induces an Altered Activation of Cytotoxic CD8+ T Cells  

PubMed Central

In human tuberculosis (TB), CD8+ T cells contribute to host defense by the release of Th1 cytokines and the direct killing of Mycobacterium tuberculosis (Mtb)-infected macrophages via granule exocytosis pathway or the engagement of receptors on target cells. Previously we demonstrated that strain M, the most prevalent multidrug-resistant (MDR) Mtb strain in Argentine, is a weak inducer of IFN-? and elicits a remarkably low CD8-dependent cytotoxic T cell activity (CTL). In contrast, the closely related strain 410, which caused a unique case of MDR-TB, elicits a CTL response similar to H37Rv. In this work we extend our previous study investigating some parameters that can account for this discrepancy. We evaluated the expressions of the lytic molecules perforin, granzyme B and granulysin and the chemokine CCL5 in CD8+ T cells as well as activation markers CD69 and CD25 and IL-2 expression in CD4+ and CD8+ T cells stimulated with strains H37Rv, M and 410. Our results demonstrate that M-stimulated CD8+ T cells from purified protein derivative positive healthy donors show low intracellular expression of perforin, granzyme B, granulysin and CCL5 together with an impaired ability to form conjugates with autologous M-pulsed macrophages. Besides, M induces low CD69 and IL-2 expression in CD4+ and CD8+ T cells, being CD69 and IL-2 expression closely associated. Furthermore, IL-2 addition enhanced perforin and granulysin expression as well as the degranulation marker CD107 in M-stimulated CD8+ T cells, making no differences with cells stimulated with strains H37Rv or 410. Thus, our results highlight the role of IL-2 in M-induced CTL activity that drives the proper activation of CD8+ T cells as well as CD4+ T cells collaboration. PMID:24836916

Geffner, Laura; Kviatcovsky, Denise; Sabio y García, Carmen; Ritacco, Viviana; López, Beatriz; Sasiain, María del Carmen; de la Barrera, Silvia

2014-01-01

324

Melatonin protects MG63 osteoblast-like cells from hydrogen peroxide-induced cytotoxicity by maintaining mitochondrial function.  

PubMed

Osteoporosis is a bone disease that has been connected with reactive oxygen species (ROS)-induced cytotoxicity. Mitochondrial dysfunction may be involved in the mechanism underlying ROS-induced cytotoxicity. It has been demonstrated that melatonin may exert cytoprotective effects by improving mitochondrial energetics and functions in several models of oxidative damage. In the present study, the MG63 osteoblast-like cell line was exposed to different concentrations of hydrogen peroxide (H2O2; 0, 100, 200, 400 or 800 µM) for 8 h, and 200 or 400 µM H2O2 for various periods of time (0.5, 4, 8 or 12 h). Results showed that H2O2 significantly reduced cell viability, increased the release of lactate dehydrogenase, increased the levels of ROS and malondialdehyde, reduced the concentration of adenosine-5'-triphosphate, disrupted the mitochondrial membrane potential (??m) and decreased the mitochondrial DNA copy number in MG63 cells. However, pretreatment with melatonin effectively decreased all of these H2O2-induced changes in cytotoxicity and mitochondrial dysfunction in MG63 cells. The protective effects of melatonin may be attributed to its ability to maintain mitochondrial function in H2O2-treated cells. This study suggests that melatonin is a potential pharmacological agent for preventing ROS-induced bone loss in diseases such as osteoporosis. PMID:24297096

She, Fei; Wang, Wenbo; Wang, Yan; Tang, Peifu; Wei, Junqiang; Chen, Hua; Zhang, Boxun

2014-02-01

325

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

PubMed

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

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

2011-07-01

326

Clostridium perfringens phospholipase C induced ROS production and cytotoxicity require PKC, MEK1 and NF?B activation.  

PubMed

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

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

2014-01-01

327

Jadomycin breast cancer cytotoxicity is mediated by a copper-dependent, reactive oxygen species–inducing mechanism  

PubMed Central

Jadomycins are natural products biosynthesized by the bacteria Streptomyces venezuelae which kill drug-sensitive and multidrug-resistant breast cancer cells in culture. Currently, the mechanisms of jadomycin cytotoxicity are poorly understood; however, reactive oxygen species (ROS)–induced DNA cleavage is suggested based on bacterial plasmid DNA cleavage studies. The objective of this study was to determine if and how ROS contribute to jadomycin cytotoxicity in drug-sensitive MCF7 (MCF7-CON) and taxol-resistant MCF7 (MCF7-TXL) breast cancer cells. As determined using an intracellular, fluorescent, ROS-detecting probe, jadomycins B, S, SPhG, and F dose dependently increased intracellular ROS activity 2.5- to 5.9-fold. Cotreatment with the antioxidant N-acetyl cysteine lowered ROS concentrations to below baseline levels and decreased the corresponding cytotoxic potency of the four jadomycins 1.9- to 3.3-fold, confirming a ROS-mediated mechanism. Addition of CuSO4 enhanced, whereas addition of the Cu(II)-chelator d-penicillamine reduced, the ROS generation and cytotoxicity of each jadomycin. Specific inhibitors of the antioxidant enzymes, superoxide dismutase 1, glutathione S-transferase, and thioredoxin reductase, but not catalase, enhanced jadomycin-mediated ROS generation and anticancer activity. In conclusion, the results indicate that jadomycin cytotoxicity involves the generation of cytosolic superoxide via a Cu(II)-jadomycin reaction, a mechanism common to all jadomycins tested and observed in MCF7-CON and drug-resistant MCF7-TXL cells. The superoxide dismutase 1, glutathione, and peroxiredoxin/thioredoxin cellular antioxidant enzyme pathways scavenged intracellular ROS generated by jadomycin treatment. Blocking these antioxidant pathways could serve as a strategy to enhance jadomycin cytotoxic potency in drug-sensitive and multidrug-resistant breast cancers. PMID:25729577

Hall, Steven R; Blundon, Heather L; Ladda, Matthew A; Robertson, Andrew W; Martinez-Farina, Camilo F; Jakeman, David L; Goralski, Kerry B

2015-01-01

328

Jadomycin breast cancer cytotoxicity is mediated by a copper-dependent, reactive oxygen species-inducing mechanism.  

PubMed

Jadomycins are natural products biosynthesized by the bacteria Streptomyces venezuelae which kill drug-sensitive and multidrug-resistant breast cancer cells in culture. Currently, the mechanisms of jadomycin cytotoxicity are poorly understood; however, reactive oxygen species (ROS)-induced DNA cleavage is suggested based on bacterial plasmid DNA cleavage studies. The objective of this study was to determine if and how ROS contribute to jadomycin cytotoxicity in drug-sensitive MCF7 (MCF7-CON) and taxol-resistant MCF7 (MCF7-TXL) breast cancer cells. As determined using an intracellular, fluorescent, ROS-detecting probe, jadomycins B, S, SPhG, and F dose dependently increased intracellular ROS activity 2.5- to 5.9-fold. Cotreatment with the antioxidant N-acetyl cysteine lowered ROS concentrations to below baseline levels and decreased the corresponding cytotoxic potency of the four jadomycins 1.9- to 3.3-fold, confirming a ROS-mediated mechanism. Addition of CuSO4 enhanced, whereas addition of the Cu(II)-chelator d-penicillamine reduced, the ROS generation and cytotoxicity of each jadomycin. Specific inhibitors of the antioxidant enzymes, superoxide dismutase 1, glutathione S-transferase, and thioredoxin reductase, but not catalase, enhanced jadomycin-mediated ROS generation and anticancer activity. In conclusion, the results indicate that jadomycin cytotoxicity involves the generation of cytosolic superoxide via a Cu(II)-jadomycin reaction, a mechanism common to all jadomycins tested and observed in MCF7-CON and drug-resistant MCF7-TXL cells. The superoxide dismutase 1, glutathione, and peroxiredoxin/thioredoxin cellular antioxidant enzyme pathways scavenged intracellular ROS generated by jadomycin treatment. Blocking these antioxidant pathways could serve as a strategy to enhance jadomycin cytotoxic potency in drug-sensitive and multidrug-resistant breast cancers. PMID:25729577

Hall, Steven R; Blundon, Heather L; Ladda, Matthew A; Robertson, Andrew W; Martinez-Farina, Camilo F; Jakeman, David L; Goralski, Kerry B

2015-03-01

329

Mechanism of trifluorothymidine potentiation of oxaliplatin-induced cytotoxicity to colorectal cancer cells.  

PubMed

Oxaliplatin (OHP) is an anticancer agent that acts by formation of Platinum-DNA (Pt-DNA) adducts resulting in DNA-strand breaks and is used for the treatment of colorectal cancer. The pyrimidine analog trifluorothymidine (TFT) forms together with a thymidine phosphorylase inhibitor (TPI) the anticancer drug formulation TAS-102, in which TPI enhances the bioavailability of TFT in vivo. In this in vitro study the combined cytotoxic effects of OHP with TFT were investigated in human colorectal cancer cells as a model for TAS-102 combinations. In a panel of five colon cancer cell lines (WiDr, H630, Colo320, SNU-C4 and SW1116) we evaluated the OHP-TFT drug combinations using the multiple drug-effect analysis with CalcuSyn software, in which the combination index (CI) indicates synergism (CI<0.9), additivity (CI=0.9-1.1) or antagonism (CI>1.1). Drug target analysis was used for WiDr, H630 and SW1116 to investigate whether there was an increase in Pt-DNA adduct formation, DNA damage induction, cell cycle delay and apoptosis. Trifluorothymidine combined with OHP resulted in synergism for all cell lines (all CI<0.9). This was irrespective of schedule in which either one of the drugs was kept at a constant concentration (using variable drug ratio) or when the two drugs were added in a 1 : 1 IC(50)-based molar ratio. Synergism could be increased for WiDr using sequential drug treatment schedules. Trifluorothymidine increased Pt-DNA adduct formation significantly in H630 and SW1116 (14.4 and 99.1%, respectively; P<0.05). Platinum-DNA adducts were retained best in SW1116 in the presence of TFT. More DNA-strand breaks were induced in SW1116 and the combination increased DNA damage induction (>20%) compared with OHP alone. Exposure to the drugs induced a clear cell-cycle S-phase arrest, but was dose schedule and cell line dependent. Trifluorothymidine (TFT) and OHP both induced apoptosis, which increased significantly for WiDr and SW1116 after TFT-OHP exposure (18.8 and 20.6% respectively; P<0.05). The basal protein levels of ERCC1 DNA repair enzyme were not related to the DNA damage that was induced in the cell lines. In conclusion, the combination of TFT with the DNA synthesis inhibitor OHP induces synergism in colorectal cancer cells, but is dependent on the dose and treatment schedule used. PMID:17242697

Temmink, O H; Hoebe, E K; van der Born, K; Ackland, S P; Fukushima, M; Peters, G J

2007-01-29

330

Preparation of membrane fraction from herpes simplex virus-infected cells which induce cytotoxic T lymphocytes.  

PubMed

The immunogenic capacity of herpes simplex virus (HSV)-infected cells and their subcellular membrane fractions was investigated by assessing the anti-HSV cytotoxic T lymphocyte (CTL) response in cultures of spleen lymphocytes from HSV-primed BALB/c mice. Methylchloranthrane-induced fibrosarcoma (Meth A) cells infected with HSV (HSV-Meth A) were fixed either with glutaraldehyde or by heating at 56 C to preserve their immunogenic competence and then used as a stimulator. Microsomes and plasma membranes were prepared from HSV-Meth A and their immunogenic activities were determined. Through the recovery of stimulatory activity in the plasma membrane fraction was half of that in the microsome fraction, the activity in the former was much more stable than in the latter and the plasma membrane fraction proved to be well qualified as an immunogen for anti-HSV CTL induction. Upon purification, the specific activity of the membrane fraction, on the basis of protein concentration, increased 43-fold. PMID:6606107

Hitsumoto, Y; Sonoda, S; Okuyama, M; Miki, Y; Utsumi, S

1983-01-01

331

A permethrin/allethrin mixture induces genotoxicity and cytotoxicity in human peripheral blood lymphocytes.  

PubMed

Two pyrethroids, permethrin and allethrin, are often combined for large-scale use in public health programs to control vector-borne diseases. In this study, the genotoxic potential of a commercial formulation of permethrin and allethrin was examined using cultured human peripheral blood lymphocytes (PBL). Genotoxicity was evaluated using the cytokinesis-block micronucleus cytome (CBMN cyt) assay by measuring the frequency of micronuclei (MN), nuclear division index (NDI), formation of nucleoplasmic bridges (NPB) and nuclear buds (NBUD), as well as apoptotic and necrotic cells. Human PBL were treated with different concentrations of a permethrin/allethrin mixture (1/0.01, 5/0.07, and 10/0.14 ?g/ml) for 24 or 36 h. The highest concentration (10/0.14 ?g/ml) of permethrin/allethrin mixture significantly increased MN frequency and percent apoptotic cells after incubations for 24 or 36 h. The NDI was markedly decreased in response to treatment with 5/0.07 or 10/0.14 ?g/ml permethrin/allethrin for both 24 and 36 h. Exposure to the permethrin/allethrin mixture did not significantly alter formation of NBUD, NPB, or percent necrotic cells. The MN frequency was significantly correlated with the number of apoptotic and necrotic cells but inversely correlated with NDI. Data demonstrated that a mixture of permethrin and allethrin induced concentration- and time-dependent cytotoxic and genotoxic damage to human PBL in vitro. PMID:25424543

Ramos-Chavez, Lucio A; Sordo, Monserrat; Calderon-Aranda, Emma; Castañeda-Saucedo, Eduardo; Ostrosky-Wegman, Patricia; Moreno-Godinez, Ma Elena

2015-01-01

332

Cotransin induces accumulation of a cytotoxic clusterin variant that cotranslationally rerouted to the cytosol  

SciTech Connect

Although clusterin (CLU) was originally identified as a secreted glycoprotein that plays cytoprotective role, several intracellular CLU variants have been recently identified in the diverse pathological conditions. The mechanistic basis of these variants is now believed to be alternative splicing and retrotranslocation. Here, we uncovered, an unglycosylated and signal sequence-unprocessed, CLU variant in the cytosol. This variant proved to be a product that cotranslationally rerouted to the cytosol during translocation. Cytosolic CLU was prone to aggregation at peri-nuclear region of cells and induced cell death. Signal sequence is shown to be an important determinant for cytosolic CLU generation and aggregation. These results provide not only a new mechanistic insight into the cytosolic CLU generation but also an idea for therapeutic mislocalization of CLU as a strategy for cancer treatment. - Highlights: ? Intracellular CLU variants have been recently identified in the diverse pathological conditions. ? Translocation of clusterin is less efficient than that of Prl. ? We identified a new cytotoxic clusterin variant whose signal sequence was unprocessed. ? This variant proved to be a product that cotranslationally rerouted to cytosol.

Choi, Ilho; Kim, Jiyeon [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Park, Joong-Yeol [Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kang, Sang-Wook, E-mail: swkang@amc.seoul.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2013-05-01

333

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

PubMed Central

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

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

2014-01-01

334

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

PubMed Central

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

Knighten, Brionna; Tchounwou, Paul

2010-01-01

335

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

PubMed

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

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

2015-02-01

336

Skin irritant-induced cytotoxicity and prostaglandin E(2) release in human skin keratinocyte cultures.  

PubMed

Damage to the skin induced by chemical irritants is associated with the release of arachidonic acid metabolites, such as prostaglandin E(2) (PGE(2)) which plays an important role in epidermal inflammation. This study investigated cytotoxicity and release of PGE(2) in human epidermal keratinocytes following an 18 hr exposure of confluent cultures to various skin irritants. The concentration-dependent release of PGE, into the extracellular medium appeared to fall into two categories, which was reflective of possible mechanisms of action. Potent skin irritants, such as phorbol-12-myristate-13-acetate, benzalkonium chloride and tributyltin chloride, elicited an increase in extracellular PGE(2) levels at concentrations that did not produce overt cell damage (uptake of neutral red at these concentrations was comparable to control levels). Non-irritants (2-methoxyethanol and 2-butoxyethyl acetate) and two less severe irritants (sodium dodecyl sulfate and acetic acid) stimulated release of PGE(2) only at concentrations that compromised cellular integrity (uptake of neutral red was at least 50% lower than that of control cultures). PMID:20654361

Lawrence, J N; Dickson, F M; Benford, D J

1997-10-01

337

Cytotoxic and apoptotic-inducing effects of purple rice extracts and chemotherapeutic drugs on human cancer cell lines.  

PubMed

Pigmented rice is mainly black, red, and dark purple, and contains a variety of flavones, tannin, polyphenols, sterols, tocopherols, ?-oryzanols, amino acids, and essential oils. The present study evaluated the cytotoxic effects of purple rice extracts (PREs) combined with chemotherapeutic drugs on human cancer cells and mechanisms of cell death. Methanolic (MeOH) and dichloromethane (DCM) extracts of three cultivars of purple rice in Thailand: Doisaket (DSK), Nan and Payao (PYO), were tested and compared with white rice (KK6). Cytotoxicity was determined by 3-(4, 5-dimethyl)-2, 5-diphenyltetrazolium bromide (MTT) assay in human hepatocellular carcinoma HepG2, prostate cancer LNCaP and murine normal fibroblast NIH3T3 cells. MeOH-PYO-PRE was the most cytotoxic and inhibited HepG2 cell growth more than that of LNCaP cells but was not toxic to NIH3T3 cells. When PREs were combined with paclitaxel or vinblastine, they showed additive cytotoxic effects on HepG2 and LNCaP cells, except for MeOH-PYO-PRE which showed synergistic effects on HepG2 cells when combined with vinblastine. MeOH-PYO-PRE plus vinblastine induced HepG2 cell apoptosis with loss of mitochondrial transmembrane potential (MTP) but no ROS production. MeOH-PYO-PRE-treated HepG2 cells underwent apoptosis via caspase-9 and-3 activation. The level of ?-oryzanol was highest in DCM-PYO-PRE (44.17 mg/g) whereas anthocyanin content was high in MeOH-PYO-PRE (5.80 mg/g). In conclusion, methanolic Payao purple rice extract was mostly toxic to human HepG2 cells and synergistically enhanced the cytotoxicity of vinblastine. Human HepG2 cell apoptosis induced by MeOH-PYO-PRE and vinblastine was mediated through a mitochondrial pathway. PMID:24377565

Banjerdpongchai, Ratana; Wudtiwai, Benjawan; Sringarm, Korawan

2014-01-01

338

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

PubMed

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

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

2012-09-01

339

Molecular mechanism of cytotoxicity induced by Hsp90-targeted Antp-TPR hybrid peptide in glioblastoma cells  

PubMed Central

Background Heat-shock protein 90 (Hsp90) is vital to cell survival under conditions of stress, and binds client proteins to assist in protein stabilization, translocation of polypeptides across cell membranes, and recovery of proteins from aggregates. Therefore, Hsp90 has emerged as an important target for the treatment of cancer. We previously reported that novel Antp-TPR hybrid peptide, which can inhibit the interaction of Hsp90 with the TPR2A domain of Hop, induces selective cytotoxic activity to discriminate between normal and cancer cells both in vitro and in vivo. Results In this study, we investigated the functional cancer-cell killing mechanism of Antp-TPR hybrid peptide in glioblastoma (GB) cell lines. It was demonstrated that Antp-TPR peptide induced effective cytotoxic activity in GB cells through the loss of Hsp90 client proteins such as p53, Akt, CDK4, and cRaf. Antp-TPR also did not induce the up-regulation of Hsp70 and Hsp90 proteins, although a small-molecule inhibitor of Hsp90, 17-AAG, induced the up-regulation of these proteins. It was also found that Antp-TPR peptide increased the endoplasmic reticulum unfolded protein response, and the cytotoxic activity of this hybrid peptide to GB cells in the endoplasmic reticulum stress condition. Conclusion These results show that targeting of Hsp90 by Antp-TPR could be an attractive approach to selective cancer-cell killing because no other Hsp90-targeted compounds show selective cytotoxic activity. Antp-TPR might provide potent and selective therapeutic options for the treatment of cancer. PMID:22913813

2012-01-01

340

Identification of potentially cytotoxic lesions induced by UVA photoactivation of DNA 4-thiothymidine in human cells.  

PubMed

Photochemotherapy-in which a photosensitizing drug is combined with ultraviolet or visible radiation-has proven therapeutic effectiveness. Existing approaches have drawbacks, however, and there is a clinical need to develop alternatives offering improved target cell selectivity. DNA substitution by 4-thiothymidine (S(4)TdR) sensitizes cells to killing by ultraviolet A (UVA) radiation. Here, we demonstrate that UVA photoactivation of DNA S(4)TdR does not generate reactive oxygen or cause direct DNA breakage and is only minimally mutagenic. In an organotypic human skin model, UVA penetration is sufficiently robust to kill S(4)TdR-photosensitized epidermal cells. We have investigated the DNA lesions responsible for toxicity. Although thymidine is the predominant UVA photoproduct of S(4)TdR in dilute solution, more complex lesions are formed when S(4)TdR-containing oligonucleotides are irradiated. One of these, a thietane/S(5)-(6-4)T:T, is structurally related to the (6-4) pyrimidine:pyrimidone [(6-4) Py:Py] photoproducts induced by UVB/C radiation. These lesions are detectable in DNA from S(4)TdR/UVA-treated cells and are excised from DNA more efficiently by keratinocytes than by leukaemia cells. UVA irradiation also induces DNA interstrand crosslinking of S(4)TdR-containing duplex oligonucleotides. Cells defective in repairing (6-4) Py:Py DNA adducts or processing DNA crosslinks are extremely sensitive to S(4)TdR/UVA indicating that these lesions contribute significantly to S(4)TdR/UVA cytotoxicity. PMID:21890905

Reelfs, Olivier; Macpherson, Peter; Ren, Xiaolin; Xu, Yao-Zhong; Karran, Peter; Young, Antony R

2011-12-01

341

Upregulation of Twist-1 by NF-kappaB blocks cytotoxicity induced by chemotherapeutic drugs.  

PubMed

NF-kappaB/Rel transcription factors are central to controlling programmed cell death (PCD). Activation of NF-kappaB blocks PCD induced by numerous triggers, including ligand engagement of tumor necrosis factor receptor (TNF-R) family receptors. The protective activity of NF-kappaB is also crucial for oncogenesis and cancer chemoresistance. Downstream of TNF-Rs, this activity of NF-kappaB has been linked to the suppression of reactive oxygen species and the c-Jun-N-terminal-kinase (JNK) cascade. The mechanism by which NF-kappaB inhibits PCD triggered by chemotherapeutic drugs, however, remains poorly understood. To understand this mechanism, we sought to identify unrecognized protective genes that are regulated by NF-kappaB. Using an unbiased screen, we identified the basic-helix-loop-helix factor Twist-1 as a new mediator of the protective function of NF-kappaB. Twist-1 is an evolutionarily conserved target of NF-kappaB, blocks PCD induced by chemotherapeutic drugs and TNF-alpha in NF-kappaB-deficient cells, and is essential to counter this PCD in cancer cells. The protective activity of Twist-1 seemingly halts PCD independently of interference with cytotoxic JNK, p53, and p19(ARF) signaling, suggesting that it mediates a novel protective mechanism activated by NF-kappaB. Indeed, our data indicate that this activity involves a control of inhibitory Bcl-2 phosphorylation. The data also suggest that Twist-1 and -2 play an important role in NF-kappaB-dependent chemoresistance. PMID:17403902

Pham, Can G; Bubici, Concetta; Zazzeroni, Francesca; Knabb, James R; Papa, Salvatore; Kuntzen, Christian; Franzoso, Guido

2007-06-01

342

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

PubMed Central

We report here results of a single-cell Raman spectroscopy study of stress effects induced by silver nanoparticles in human mesenchymal stem cells (hMSCs). A high-sensitivity, high-resolution Raman Tweezers set-up has been used to monitor nanoparticle-induced biochemical changes in optically-trapped single cells. Our micro-Raman spectroscopic study reveals that hMSCs treated with silver nanoparticles undergo oxidative stress at doping levels in excess of 2 µg/ml, with results of a statistical analysis of Raman spectra suggesting that the induced stress becomes more dominant at nanoparticle concentration levels above 3 µg/ml. PMID:22514708

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

2012-01-01

343

RBE4 cells are highly resistant to paraquat-induced cytotoxicity: studies on uptake and efflux mechanisms.  

PubMed

Paraquat (PQ) is a widely used, highly toxic and non-selective contact herbicide, which has been associated with central neurotoxic effects, namely the development of Parkinson's disease, but whose effects to the blood-brain barrier (BBB) itself have rarely been studied. This work studied the mechanisms of PQ uptake and efflux in a rat's BBB cell model, the RBE4 cells. PQ is believed to enter cells using the basic or neutral amino acid or polyamine transport systems or through the choline-uptake system. In contrast, PQ efflux from cells is reported to be mediated by P-glycoprotein. Therefore, we evaluated PQ-induced cytotoxicity and the effect of some substrates/blockers of these transporters (such as arginine, L-valine, putrescine, hemicholinium-3 and GF120918) on such cytotoxicity. RBE4 cells were shown to be extremely resistant to PQ after 24?h of exposure; even at concentrations as high as 50?mM approximately 45% of the cells remained viable. Prolonging exposure until 48?h elicited significant cytotoxicity only for PQ concentrations above 5?mM. Although hemicholinium-3, a choline-uptake system inhibitor, significantly protected cells against PQ-induced toxicity, none of the effects were observed for arginine, L-valine or putrescine. Meanwhile, inhibiting the efflux pump P-glycoprotein using GF120918 significantly enhanced PQ-induced cytotoxicity. In conclusion, PQ used the choline-uptake system, instead of the transporters for the basic or neutral amino acids or for the polyamines, to enter RBE4 cells. P-glycoprotein extrudes PQ back to the extracellular medium. However, this efflux mechanism only partially explains the observed RBE4 resistance to PQ. PMID:24105845

Vilas-Boas, V; Silva, R; Guedes-de-Pinho, P; Carvalho, F; Bastos, M L; Remião, F

2014-09-01

344

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

345

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

PubMed

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

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

2015-04-01

346

Neuroprotective effects of biochanin A against glutamate-induced cytotoxicity in PC12 cells via apoptosis inhibition.  

PubMed

L-Glutamate plays a crucial role in neuronal cell death, which is known to be associated with various neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's diseases. In this study, we investigated the protective effects of biochanin A, a phytoestrogen compound found mainly in Trifolium pratense, against L-glutamate-induced cytotoxicity in a PC12 cell line. Exposure of the cells to 10 mM L-glutamate was found to significantly increase cell viability loss and apoptosis, whereas pretreatment with various concentrations of biochanin A attenuated the cytotoxic effects of L-glutamate. Specifically, the pretreatment led to not only decreases in the release of lactate dehydrogenase, the number of apoptotic cells, and the activity of caspase-3 but also an increase in the total glutathione level in the L-glutamate-treated PC12 cells. These results indicate that biochanin A may be able to exert neuroprotective effects against L-glutamate-induced cytotoxicity. Furthermore, our findings also imply that biochanin A may act as an antiapoptotic agent in order to perform its protective function. PMID:23224778

Tan, Ji Wei; Tham, Chau Ling; Israf, Daud A; Lee, Sang Hyub; Kim, Min Kyu

2013-03-01

347

Decreased helenalin-induced cytotoxicity by flavonoids from Arnica as studied in a human lung carcinoma cell line.  

PubMed

The effect of the flavones apigenin, luteolin, hispidulin and eupafolin, and of the flavonols kaempferol, quercetin, 6-methoxykaempferol and patuletin from Arnica spp. on the cytotoxicity of the sesquiterpene lactone helenalin was studied in the human lung carcinoma cell line GLC4 using the microculture tetrazolium (MTT) assay. The tumour cells were exposed to the test compounds for 2h. Helenalin concentrations around its control IC(50) value, 0.5 ?M, were combined with flavonoid concentrations ranging from 0.01 to 20 ?M. At non-toxic concentrations, up to 10?M, all flavonoids except kaempferol significantly reduced the helenalin-induced cytotoxicity. Hispidulin and patuletin displayed their modulating effect on helenalin-induced cytotoxicity in the broadest concentration range. The strongest effect was found with 5 and 10?M hispidulin, 0.05 ?M quercetin, and 1 ?M patuletin, increasing the IC(50) value of helenalin with circa 40%. No dose-dependency was found in the concentration range tested. PMID:23196154

Woerdenbag, H J; Merfort, I; Schmidt, T J; Passreiter, C M; Willuhn, G; Van Uden, W; Pras, N; Konings, A W

1995-10-01

348

Arsenic trioxide synergizes with everolimus (Rad001) to induce cytotoxicity of ovarian cancer cells through increased autophagy and apoptosis.  

PubMed

Phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway plays a key role in the tumorigenesis of a variety of human cancers including ovarian cancer. However, inhibitors of this pathway such as Rad001 have not shown therapeutic efficacy as a single agent for this cancer. Arsenic trioxide (ATO) induces an autophagic pathway in ovarian carcinoma cells. We found that ATO can synergize with Rad001 to induce cytotoxicity of ovarian cancer cells. Moreover, we identified synergistic induction of autophagy and apoptosis as the likely underlying mechanism that is responsible for the enhanced cytotoxicity. The enhanced cytotoxicity is accompanied by decreased p-AKT levels as well as upregulation of ATG5-ATG12 conjugate and LC3-2, hallmarks of autophagy. Rad001 and ATO can also synergistically inhibit tumors in a xenograft animal model of ovarian cancer. These results thus identify and validate a novel mechanism to enhance and expand the existing targeted therapeutic agent to treat human ovarian cancer. PMID:22919067

Liu, Nan; Tai, Sheng; Ding, Boxiao; Thor, Ryan K; Bhuta, Sunita; Sun, Yin; Huang, Jiaoti

2012-10-01

349

Quercetin-3-O-?-D-glucopyranoside, a dietary flavonoid, protects PC12 cells from H?O?-induced cytotoxicity through inhibition of reactive oxygen species.  

PubMed

Since flavonols are antioxidant agents, they could in principle, beneficially affect neurodegenerative diseases where reactive oxygen species are involved. Quercetin derivatives are the most abundant dietary flavonoids, and we have investigated the capacity of quercetin-3-O-?-d-glucopyranoside (Q3G) isolated from Echinophora cinerea to protect PC12 cells from H2O2-induced cytotoxicity. Direct cytotoxic effects of H2O2 on PC12 in presence and absence of Q3G were evaluated. H2O2 induced cytotoxicity in a concentration dependent manner (IC50=118 ± 5.09 ?M, 24h). Pretreatment of cells with non-toxic concentrations of Q3G protected cells from H2O2-induced cytotoxicity, leading to a decrease in the generation of reactive oxygen species. These observations qualify Q3G as an interesting dietary compound worth further investigation as a cytoprotective agent. PMID:25148973

Shokoohinia, Yalda; Rashidi, Maryam; Hosseinzadeh, Leila; Jelodarian, Zohreh

2015-01-15

350

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

PubMed Central

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

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

2013-01-01

351

IKK? inhibitor in combination with bortezomib induces cytotoxicity in breast cancer cells  

PubMed Central

Bortezomib is a proteasome inhibitor with remarkable clinical antitumor activity in multiple myeloma (MM) and is under evaluation in clinical trials in various types of cancer including breast cancer. Although the initial rationale for its use in cancer treatment was the inhibition of NF-?B activity by blocking proteasomal degradation of I?B?, direct evidence indicating inhibition of constitutive NF-?B activity by bortezomib in tumor cells in patients has not yet been reported. Moreover, recent studies have shown that bortezomib activates constitutive NF-?B activity via stimulating the canonical pathway in MM cells. In this study, we first examined protein expression of I?B? after bortezomib treatment. We observed that bortezomib upregulated the phosphorylation and downregulated I?B? protein expression in a dose- and time-dependent manner in MCF7 and T47D cells, associated with phosphorylation of IKK?. Since I?B? is an inhibitor of nuclear translocation of NF-?B, we further examined alteration of NF-?B activity by bortezomib. Importantly, bortezomib significantly upregulates NF-?B activity in both MCF7 and T47D in a dose-dependent fashion, demonstrated by electrophoretic mobility shift analysis (EMSA). Furthermore, immunocytochemical analysis confirmed enhanced nuclear translocation of p65 NF-?B (RelA) by bortezomib treatment. Supershift assay showed supershifted bands by anti-p65 and -p50 antibodies. Taken together, these results indicate that bortezomib activates the canonical NF-?B pathway in both cell lines. Finally, we demonstrated that IKK? inhibitor enhanced cytotoxicity, associated with inhibition of NF-?B activity induced by bortezomib in MCF7 and T47D breast cancer cells. PMID:24481412

HIDESHIMA, HIROMASA; YOSHIDA, YASUHIRO; IKEDA, HIROSHI; HIDE, MAYA; IWASAKI, AKINORI; ANDERSON, KENNETH C.; HIDESHIMA, TERU

2014-01-01

352

Mitochondrial protein cyclophilin-D-mediated programmed necrosis attributes to berberine-induced cytotoxicity in cultured prostate cancer cells.  

PubMed

The prostate cancer is one of the leading causes of men's cancer mortality. The development of alternative chemotherapeutic strategies is urgent. Berberine has displayed significant anti-prostate cancer activities. The underlying mechanisms are not fully understood. In the current study, we found that berberine induced apoptosis and programmed necrosis in cultured prostate cancer cells (LNCaP and PC-82 lines), and necrosis weighted more than apoptosis in contributing berberine's cytotoxicity. We demonstrated that mitochondrial protein cyclophilin-D (Cyp-D) is required for berberine-induced programmed necrosis. Inhibition of Cyp-D by its inhibitors cyclosporin A (CSA) or sanglifehrin A (SFA), and by Cyp-D shRNA depletion alleviated berberine-induced prostate cancer cell necrosis (but not apoptosis). Our data found that in prostate cancer cells, berberine induced reactive oxygen species (ROS) production, which dictated P53 translocation to mitochondria, where it physically interacted with Cyp-D to open mitochondrial permeability transition pore (mPTP). The anti-oxidant N-acetylcysteine (NAC), the P53 inhibitor pifithrin-? (PFT?) as well as P53 siRNA knockdown suppressed berberine-induced P53 mitochondrial translocation and Cyp-D association, thus inhibiting mitochondrial membrane potential (MMP) decrease and prostate cancer cell necrosis. In summary, the results of the present study provide mechanistic evidence that both apoptosis and programmed necrosis attribute to berberine's cytotoxicity in prostate cancer cells. PMID:24946211

Zhang, Long-yang; Wu, Yan-lin; Gao, Xing-hua; Guo, Feng

2014-07-18

353

Protection against 2-chloroethyl ethyl sulfide (CEES) - induced cytotoxicity in human keratinocytes by an inducer of the glutathione detoxification pathway  

SciTech Connect

Sulfur mustard (SM or mustard gas) was first used as a chemical warfare agent almost 100 years ago. Due to its toxic effects on the eyes, lungs, and skin, and the relative ease with which it may be synthesized, mustard gas remains a potential chemical threat to the present day. SM exposed skin develops fluid filled bullae resulting from potent cytotoxicity of cells lining the basement membrane of the epidermis. Currently, there are no antidotes for SM exposure; therefore, chemopreventive measures for first responders following an SM attack are needed. Glutathione (GSH) is known to have a protective effect against SM toxicity, and detoxification of SM is believed to occur, in part, via GSH conjugation. Therefore, we screened 6 potential chemopreventive agents for ability to induce GSH synthesis and protect cultured human keratinocytes against the SM analog, 2-chloroethyl ethyl sulfide (CEES). Using NCTC2544 human keratinocytes, we found that both sulforaphane and methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) stimulated nuclear localization of Nrf2 and induced expression of the GSH synthesis gene, GCLM. Additionally, we found that treatment with CDDO-Me elevated reduced GSH content of NCTC2544 cells and preserved their viability by {approx} 3-fold following exposure to CEES. Our data also suggested that CDDO-Me may act additively with 2,6-dithiopurine (DTP), a nucleophilic scavenging agent, to increase the viability of keratinocytes exposed to CEES. These results suggest that CDDO-Me is a promising chemopreventive agent for SM toxicity in the skin. - Highlights: > CDDO-Me treatment increased intracellular GSH in human keratinocytes. > CDDO-Me increased cell viability following exposure to the half-mustard, CEES. > The cytoprotective effect of CDDO-Me was likely due to scavenging with endogenous GSH.

Abel, Erika L.; Bubel, Jennifer D.; Simper, Melissa S.; Powell, Leslie; McClellan, S. Alex [Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957 (United States); Andreeff, Michael [Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States); MacLeod, Michael C. [Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957 (United States); DiGiovanni, John, E-mail: john.digiovanni@austin.utexas.edu [Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957 (United States)

2011-09-01

354

TiO2 nanoparticles induced hippocampal neuroinflammation in mice.  

PubMed

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

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

2014-01-01

355

TiO2 Nanoparticles Induced Hippocampal Neuroinflammation in Mice  

PubMed Central

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

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

2014-01-01

356

Discrete nanoparticles induce loss of Legionella pneumophila biofilms from surfaces.  

PubMed

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

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

2014-08-01

357

Ion beam induced effects on the ferromagnetism in Pd nanoparticles  

SciTech Connect

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

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

2012-06-05

358<