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未经涂覆和聚乙二醇化的单壁碳纳米管在神经元 PC12 细胞中的机制毒性评价。

Mechanistic toxicity evaluation of uncoated and PEGylated single-walled carbon nanotubes in neuronal PC12 cells.

机构信息

National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, Arkansas 72079, USA.

出版信息

ACS Nano. 2011 Sep 27;5(9):7020-33. doi: 10.1021/nn2016259. Epub 2011 Sep 7.

DOI:10.1021/nn2016259
PMID:21866971
Abstract

We investigated and compared the concentration-dependent cytotoxicity of single-walled carbon nanotubes (SWCNTs) and SWCNTs functionalized with polyethylene glycol (SWCNT-PEGs) in neuronal PC12 cells at the biochemical, cellular, and gene expressional levels. SWCNTs elicited cytotoxicity in a concentration-dependent manner, and SWCNT-PEGs exhibited less cytotoxic potency than uncoated SWCNTs. Reactive oxygen species (ROS) were generated in both a concentration- and surface coating-dependent manner after exposure to these nanomaterials, indicating different oxidative stress mechanisms. More specifically, gene expression analysis showed that the genes involved in oxidoreductases and antioxidant activity, nucleic acid or lipid metabolism, and mitochondria dysfunction were highly represented. Interestingly, alteration of the genes is also surface coating-dependent with a good correlation with the biochemical data. These findings suggest that surface functionalization of SWCNTs decreases ROS-mediated toxicological response in vitro.

摘要

我们在生物化学、细胞和基因表达水平上研究和比较了单壁碳纳米管 (SWCNTs) 和聚乙二醇 (SWCNT-PEGs) 功能化的单壁碳纳米管 (SWCNTs) 在神经元 PC12 细胞中的浓度依赖性细胞毒性。SWCNTs 以浓度依赖性方式引起细胞毒性,而 SWCNT-PEGs 的细胞毒性比未涂层的 SWCNTs 弱。暴露于这些纳米材料后,活性氧 (ROS) 的产生呈浓度依赖性和表面涂层依赖性,表明存在不同的氧化应激机制。更具体地说,基因表达分析表明,参与氧化还原酶和抗氧化活性、核酸或脂质代谢以及线粒体功能障碍的基因高度表达。有趣的是,基因的改变也依赖于表面涂层,与生化数据有很好的相关性。这些发现表明,SWCNTs 的表面功能化降低了体外 ROS 介导的毒理学反应。

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