Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties.
Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties.
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DOI：
10.1021/nn800511k
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发表时间：
2008-10-28
期刊：
影响因子：
17.1
通讯作者：
Nel, Andre E.
中科院分区：
文献类型：
--
作者：
Xia, Tian;Kovochich, Michael;Liong, Monty;Maedler, Lutz;Gilbert, Benjamin;Shi, Haibin;Yeh, Joanne I.;Zink, Jeffrey I.;Nel, Andre E.
纳米材料（NM）表现出新的物理化学性质，决定了它们与生物基质和过程的相互作用。采用火焰喷雾热解法合成了目前产量较高的三种金属氧化物纳米粒子TiO2、ZnO和CeO2，并在一项机制研究中进行了比较，以阐明决定细胞摄取、亚细胞定位和毒性作用的物理化学特性，该实验最初是为RAW 264.7和BEAS-2B细胞系的氧化应激和细胞毒性而开发的。氧化锌在两种细胞中均诱导毒性，导致活性氧（ROS）的产生、氧化损伤、炎症的激发和细胞死亡。利用ICP-MS和荧光标记氧化锌，发现氧化锌在培养基和内体中均有溶解。未溶解的ZnO纳米颗粒在BEAS-2B细胞中进入小泡，但在RAW 264.7细胞中进入溶酶体，较小的颗粒残留物溶解在溶酶体中。相比之下，在BEAS-2B和RAW 264.7细胞中，荧光标记的CeO2纳米颗粒分别被完整地摄取到小窝蛋白-1和LAMP-1阳性的内体腔室中，没有炎症或细胞毒性。相反，CeO2抑制ROS的产生并诱导细胞抵抗外源氧化应激。荧光标记的TiO2通过与CeO2相同的摄取途径处理，但没有引起任何不良或保护作用。这些结果表明，金属氧化物纳米颗粒诱导了一系列从细胞毒性到细胞保护性的生物反应，只能通过使用分层测试策略来正确理解，例如我们为氧化应激开发的分层测试策略，并适用于研究纳米颗粒毒性的其他方面。
Nanomaterials (NM) exhibit novel physicochemical properties that determine their interaction with biological substrates and processes. Three metal oxides nanoparticles that are currently being produced in high tonnage, TiO2, ZnO and CeO2, were synthesized by flame spray pyrolysis process and compared in a mechanistic study to elucidate the physicochemical characteristics that determine cellular uptake, subcellular localization, and toxic effects based on a test paradigm that was originally developed for oxidative stress and cytotoxicity in RAW 264.7 and BEAS-2B cell lines. ZnO induced toxicity in both cells, leading to the generation of reactive oxygen species (ROS), oxidant injury, excitation of inflammation and cell death. Using ICP-MS and fluorescent-labeled ZnO, it is found that ZnO dissolution could happen in culture medium and endosomes. Non-dissolved ZnO nanoparticles enter caveolae in BEAS-2B, but enter lysosomes in RAW 264.7 cells in which smaller particle remnants dissolve. In contrast, fluorescent-labeled CeO2 nanoparticles were taken up intact into caveolin-1 and LAMP-1 positive endosomal compartments, respectively, in BEAS-2B and RAW 264.7 cells, without inflammation or cytotoxicity. Instead, CeO2 suppressed ROS production and induced cellular resistance to an exogenous source of oxidative stress. Fluorescent-labeled TiO2 was processed by the same uptake pathways as CeO2 but did not elicit any adverse or protective effects. These results demonstrate that metal oxide nanoparticles induce a range of biological responses that vary from cytotoxic to cytoprotective and can only be properly understood by using a tiered test strategy such as we developed for oxidative stress and adapted to study other aspects of nanoparticle toxicity.
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影响因子：
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通讯作者：
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