pH-Dependent Toxicity of High Aspect Ratio ZnO Nanowires in Macrophages Due to Intracellular Dissolution
pH-Dependent Toxicity of High Aspect Ratio ZnO Nanowires in Macrophages Due to Intracellular Dissolution
复制标题
DOI：
10.1021/nn101192z
复制
发表时间：
2010-11-01
期刊：
影响因子：
17.1
通讯作者：
Porter, Alexandra E.
中科院分区：
文献类型：
--
作者：
Muller, Karin H.;Kulkarni, Jaideep;Porter, Alexandra E.
在过去的几年里，高纵横比的ZnO纳米线已经成为纳米科学中最有前途的产品之一，在光学和电子学的界面上有许多应用。锌与细胞和生物体的相互作用是复杂的，锌对许多细胞过程的重要性使得研究ZnO纳米线的生物安全性势在必行，为了保证其安全的经济开发在该研究中，发现ZnO纳米线在与ZnCl 2相似的浓度下对人单核细胞巨噬细胞（HMCs）是有毒的，活细胞上的共聚焦显微镜证实在细胞死亡之前细胞内Zn 2+浓度升高。在体外，ZnO纳米线在溶酶体pH的模拟体液中非常迅速地溶解，而它们在细胞外pH下相对稳定明场透射电子显微镜（TEM）显示通过吞噬作用的ZnO纳米线聚集体的快速巨噬细胞摄取纳米线溶解发生在膜结合区室内，通过扫描电子显微镜/能量色散X射线光谱法证实溶酶体的酸性pH触发ZnO纳米线溶解。通过TEM观察到的整个ZnO纳米线结构中的致密材料可以指示细胞成分吸附到线上或局部锌诱导的蛋白质沉淀。阻碍是由于pH触发的离子Zn 2+的细胞内释放，而不是高方面的性质的电线。细胞死亡的特点，坏死以及凋亡，与线粒体显示严重的结构变化，这些发现的意义，应用氧化锌纳米线进行了讨论
High aspect ratio ZnO nanowires have become one of the most promising products in the nanosciences with the past few years with a multitude of applications at the interface of optics and electronics The interaction of zinc with cells and organisms is complex, with both deficiency and excess causing severe effects The emerging significance of zinc for many cellular processes makes it imperative to investigate the biological safety of ZnO nanowires in order to guarantee their safe economic exploitation In this study, ZnO nanowires were found to be toxic to human monocyte macrophages (HMMs) at similar concentrations as ZnCl2 Confocal microscopy on live cells confirmed a rise in intracellular Zn2+ concentrations prior to cell death In vitro, ZnO nanowires dissolved very rapidly in a simulated body fluid of lysosomal pH, whereas they were comparatively stable at extracellular pH Bright field transmission elctron microscopy (TEM) showed a rapid macrophage uptake of ZnO nanowire aggregates by phagocytosis Nanowire dissolution occurred within membrane-bound compartments, triggered by the acidic pH of the lysosomes ZnO nanowire dissolution was confirmed by scanning electron microscopy/energy dispersive X ray spectrometry Deposition of electron-dense material throughout the ZnO nanowire structures observed by TEM could indicate adsorption of cellular components onto the wires or localized Zinc induced protein precipitation Our study demonstrates that ZnO nanowire toxicity in HMMs is due to pH triggered intracellular release of ionic Zn2+ rather than the high aspect nature of the wires Cell death had features of necrosis as well as apoptosis, with mitochondna displaying severe structural changes The implications of these findings for the application of ZnO nanowires are discussed