Size-dependent toxicity and cell interaction mechanisms of gold nanoparticles on mouse fibroblasts
Size-dependent toxicity and cell interaction mechanisms of gold nanoparticles on mouse fibroblasts
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DOI：
10.1016/j.toxlet.2012.11.022
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发表时间：
2013-03-13
影响因子：
3.5
通讯作者：
Rossi, Francois
中科院分区：
文献类型：
--
作者：
Coradeghini, Rosella;Gioria, Sabrina;Rossi, Francois
金纳米粒子（AuNPs）目前被用于包括生物医学应用在内的多个领域，尽管还没有关于其细胞毒性的结论性信息。出于这个原因，这项工作已经研究了金纳米颗粒在体外对Balb/3 T3小鼠成纤维细胞的影响。将细胞暴露于AuNPs 5和15 nm柠檬酸盐稳定72小时获得的结果显示，如果通过集落形成效率（CFE）测量，则仅对于浓度>= 50 μ M的AuNPs 5 nm具有细胞毒性作用。为了理解两种AuNP尺寸所观察到的细胞毒性的差异，我们研究了纳米颗粒的摄取和细胞内分布。通过TEM观察到5和15 nm的AuNP被Balb/3 T3细胞内化并位于细胞内的内体区室中。通过ICP-MS对摄取的定量显示AuNP内化甚至增强至72 h。肌动蛋白细胞骨架的破坏是明显的，细胞足迹狭窄和收缩;在暴露于5 nm AuNP的细胞中效果更显着。采用免疫细胞化学和western blot方法研究NPs细胞内化的机制。在小窝蛋白的表达水平中没有观察到显著的影响，而在暴露于金纳米颗粒72小时的细胞中观察到网格蛋白重链的表达和降解的减少。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Gold nanoparticles (AuNPs) are currently used in several fields including biomedical applications, although no conclusive information on their cytotoxicity is available. For this reason this work has investigated the effects of AuNPs in vitro on Balb/3T3 mouse fibroblasts. Results obtained exposing cells for 72 h to AuNPs 5 and 15 nm citrate stabilized, revealed cytotoxic effects only for AuNPs 5 nm at concentration >= 50 mu M if measured by colony forming efficiency (CFE). To understand the differences in cytotoxicity observed for the two AuNPs sizes, we investigated the uptake and the intracellular distribution of the nanoparticles. By TEM it was observed that 5 and 15 nm AuNPs are internalized by Balb/3T3 cells and located within intracellular endosomal compartments. Quantification of the uptake by ICP-MS showed that AuNPs internalization enhanced even up to 72 h. Disruption of the actin cytoskeleton was evident, with cell footprints narrow and contracted; effects more remarkable in cells exposed to 5 nm AuNP. The mechanism of NPs cell internalization was investigated using immunocytochemistry and western blot. No significant effect was observed in the expression level of caveolin, while reduction of the expression and degradation of the clathrin heavy chain was observed in cells exposed for 72 h to AuNPs. (C) 2012 Elsevier Ireland Ltd. All rights reserved.