Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia.
Small. 2010 Sep 6;6(17):1908-17. doi: 10.1002/smll.201000032.
Sunscreens containing ZnO and TiO(2) nanoparticles (NPs) are increasingly applied to skin over long time periods to reduce the risk of skin cancer. However, long-term toxicological studies of NPs are very sparse. The in vitro toxicity of ZnO and TiO(2) NPs on keratinocytes over short- and long-term applications is reported. The effects studied are intracellular formation of radicals, alterations in cell morphology, mitochondrial activity, and cell-cycle distribution. Cellular response depends on the type of NP, concentration, and exposure time. ZnO NPs have more pronounced adverse effects on keratinocytes than TiO(2). TiO(2) has no effect on cell viability up to 100 μg mL(-1), whereas ZnO reduces viability above 15 μg mL(-1) after short-term exposure. Prolonged exposure to ZnO NPs at 10 μg mL(-1) results in decreased mitochondrial activity, loss of normal cell morphology, and disturbances in cell-cycle distribution. From this point of view TiO(2) has no harmful effect. More nanotubular intercellular structures are observed in keratinocytes exposed to either type of NP than in untreated cells. This observation may indicate cellular transformation from normal to tumor cells due to NP treatment. Transmission electron microscopy images show NPs in vesicles within the cell cytoplasm, particularly in early and late endosomes and amphisomes. Contrary to insoluble TiO(2), partially soluble ZnO stimulates generation of reactive oxygen species to swamp the cell redox defense system thus initiating the death processes, seen also in cell-cycle distribution and fluorescence imaging. Long-term exposure to NPs has adverse effects on human keratinocytes in vitro, which indicates a potential health risk.
防晒霜中含有氧化锌和二氧化钛纳米粒子（NPs），人们将其涂抹于皮肤表面，以长时间预防皮肤癌。然而，目前有关 NPs 的长期毒理学研究非常匮乏。本文报道了 ZnO 和 TiO(2) NPs 对角质形成细胞的短期和长期应用的体外毒性。研究的影响包括细胞内自由基的形成、细胞形态的改变、线粒体活性和细胞周期分布。细胞反应取决于 NP 的类型、浓度和暴露时间。与 TiO(2)相比，ZnO NPs 对角质形成细胞的负面影响更为明显。TiO(2)在 100μg/mL 以下对细胞活力没有影响，而 ZnO 在短期暴露后，浓度超过 15μg/mL 时会降低细胞活力。在 10μg/mL 的浓度下，长时间暴露于 ZnO NPs 会导致线粒体活性降低、正常细胞形态丧失和细胞周期分布紊乱。从这个角度来看，TiO(2)没有有害影响。与未经处理的细胞相比，暴露于任何一种 NP 的角质形成细胞中观察到更多的细胞间纳米管结构。这种观察可能表明由于 NP 处理，细胞从正常向肿瘤细胞发生转化。透射电子显微镜图像显示 NPs 位于细胞细胞质中的小泡中，特别是在内体和多核体中。与不溶性 TiO(2)相反，部分可溶性 ZnO 刺激活性氧的产生，从而破坏细胞的氧化还原防御系统，从而启动细胞死亡过程，这也可以从细胞周期分布和荧光成像中观察到。NP 长期暴露于体外的人角质形成细胞具有不良影响，这表明存在潜在的健康风险。
