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银纳米线诱导自噬:纳米复合薄膜生物相容性评估的一个新方面。

Autophagy induction by silver nanowires: a new aspect in the biocompatibility assessment of nanocomposite thin films.

机构信息

Institute of Molecular Medicine, Trinity College Dublin, Ireland.

出版信息

Toxicol Appl Pharmacol. 2012 Nov 1;264(3):451-61. doi: 10.1016/j.taap.2012.08.023. Epub 2012 Aug 31.

DOI:10.1016/j.taap.2012.08.023
PMID:22959926
Abstract

Nanomaterials and their enabled products have increasingly been attracting global attention due to their unique physicochemical properties. Among these emerging products, silver nanowire (AgNW)-based thin films are being developed for their promising applications in next generation nanoelectronics and nanodevices. However, serious concerns remain about possible health and safety risks they may pose. Here, we employed a multi-modal systematic biocompatibility assessment of thin films incorporating AgNW. To represent the possible routes of nanomaterial entry during occupational or environmental exposure, we employed four different cell lines of epithelial, endothelial, gastric, and phagocytic origin. Utilizing a cell-based automated image acquisition and analysis procedure in combination with real-time impedance sensing, we observed a low level of cytotoxicity of AgNW, which was dependent on cell type, nanowire lengths, doses and incubation times. Similarly, no major cytotoxic effects were induced by AgNW-containing thin films, as detected by conventional cell viability and imaging assays. However, transmission electron microscopy and Western immunoblotting analysis revealed AgNW-induced autophasosome accumulation together with an upregulation of the autophagy marker protein LC3. Autophagy represents a crucial mechanism in maintaining cellular homeostasis, and our data for the first time demonstrate triggering of such mechanism by AgNW in human phagocytic cells. Finally, atomic force microscopy revealed significant changes in the topology of cells attaching and growing on these films as substrates. Our findings thus emphasize the necessity of comprehensive biohazard assessment of nanomaterials in modern applications and devices and a thorough analysis of risks associated with their possible contact with humans through occupational or environmental exposure.

摘要

由于具有独特的物理化学性质,纳米材料及其衍生产品越来越受到全球关注。在这些新兴产品中,基于银纳米线(AgNW)的薄膜因其在下一代纳米电子学和纳米器件中的应用前景而得到了广泛的研究。然而,人们对它们可能带来的健康和安全风险仍存在严重担忧。在这里,我们采用多模式系统的方法评估了含有 AgNW 的薄膜的生物相容性。为了模拟纳米材料在职业或环境暴露期间进入人体的可能途径,我们使用了四种不同的上皮细胞、内皮细胞、胃细胞和吞噬细胞系。我们利用基于细胞的自动图像采集和分析程序结合实时阻抗传感,观察到 AgNW 的低细胞毒性,其毒性取决于细胞类型、纳米线长度、剂量和孵育时间。同样,通过传统的细胞活力和成像检测,我们没有观察到含 AgNW 的薄膜引起明显的细胞毒性。然而,透射电子显微镜和 Western 免疫印迹分析显示,AgNW 可诱导自噬小体的积累,并上调自噬标志物蛋白 LC3。自噬是维持细胞内环境稳定的关键机制,我们的数据首次证明了 AgNW 在人吞噬细胞中触发了这种机制。最后,原子力显微镜揭示了这些薄膜作为基底时,附着和生长的细胞拓扑结构发生了显著变化。因此,我们的研究结果强调了对现代应用和设备中的纳米材料进行全面生物危害评估的必要性,并需要对它们可能通过职业或环境暴露与人接触相关的风险进行深入分析。

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