Use of Metal Oxide Nanoparticle Band Gap To Develop a Predictive Paradigm for Oxidative Stress and Acute Pulmonary Inflammation

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• 作者：Haiyuan Zhang ; Zhaoxia Ji ; Tian Xia ; Huan Meng ; Cecile Low-Kam ; Rong Liu ; Suman Pokhrel ; Sijie Lin ; Xiang Wang ; Yu-Pei Liao ; Meiying Wang ; Linjiang Li ; Robert Rallo ; Robert Damoiseaux ; Donatello Telesca ; Lutz M盲dler ; Yoram Cohen ; Jeffrey I. Zink ; Andre E. Nel
• 刊名：ACS Nano
• 出版年：2012
• 出版时间：May 22, 2012
• 年：2012
• 卷：6
• 期：5
• 页码：4349-4368
• 全文大小：1127K
• 年卷期：v.6,no.5(May 22, 2012)
• ISSN：1936-086X

文摘

We demonstrate for 24 metal oxide (MOx) nanoparticles that it is possible to use conduction band energy levels to delineate their toxicological potential at cellular and whole animal levels. Among the materials, the overlap of conduction band energy (E_c) levels with the cellular redox potential (鈭?.12 to 鈭?.84 eV) was strongly correlated to the ability of Co₃O₄, Cr₂O₃, Ni₂O₃, Mn₂O₃, and CoO nanoparticles to induce oxygen radicals, oxidative stress, and inflammation. This outcome is premised on permissible electron transfers from the biological redox couples that maintain the cellular redox equilibrium to the conduction band of the semiconductor particles. Both single-parameter cytotoxic as well as multi-parameter oxidative stress assays in cells showed excellent correlation to the generation of acute neutrophilic inflammation and cytokine responses in the lungs of C57 BL/6 mice. Co₃O₄, Ni₂O₃, Mn₂O₃, and CoO nanoparticles could also oxidize cytochrome c as a representative redox couple involved in redox homeostasis. While CuO and ZnO generated oxidative stress and acute pulmonary inflammation that is not predicted by E_c levels, the adverse biological effects of these materials could be explained by their solubility, as demonstrated by ICP-MS analysis. These results demonstrate that it is possible to predict the toxicity of a large series of MOx nanoparticles in the lung premised on semiconductor properties and an integrated in vitro/in vivo hazard ranking model premised on oxidative stress. This establishes a robust platform for modeling of MOx structure鈥揳ctivity relationships based on band gap energy levels and particle dissolution. This predictive toxicological paradigm is also of considerable importance for regulatory decision-making about this important class of engineered nanomaterials.

Keywords:

metal oxide nanoparticles; band gap energy; surface dissolution; oxidative stress; in vitro and in vivo toxicity