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

California NanoSystems Institute, University of California, Los Angeles, California 90095-1680, USA.
ACS Nano (Impact Factor: 12.88). 04/2012; 6(5):4349-68. DOI: 10.1021/nn3010087
Source: PubMed

ABSTRACT 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 (-4.12 to -4.84 eV) was strongly correlated to the ability of Co(3)O(4), Cr(2)O(3), Ni(2)O(3), Mn(2)O(3), 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. Co(3)O(4), Ni(2)O(3), Mn(2)O(3), 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-activity 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.

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Available from: Xiang Wang, Sep 25, 2015
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    • "Cells have multiple 103 pathways to limit ROS build-up (D'Autréaux and Toledano, 2007), but loss of cellular function 104 can occur when this capacity is exhausted. As summarized in Fig. 1d and 1f, metal and metal- 105 oxide NPs can induce ROS outside the cell, at the cell membrane, and inside the cell (when NPs 106 are internalized) by direct interaction with biomolecules in the environmental medium, the 107 cell/outer membrane, and organic cytoplasmic components, respectively, or via similar 108 interactions of dissolved metal ions with biomacromolecules (Park et al., 2009; Cabiscol et al., 109 2010; Dutta et al., 2012); recent studies of metal-oxide NPs have attempted to correlate 110 conduction band-edge positioning with respect to cellular redox potential and the resulting ability 111 to generate ROS (Zhang et al., 2012; Kaweeteerawat et al., 2015). "
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    • "Their conclusion was in a good agreement with the results of Burello and Worth (2011b), who found that the conduction band energy of oxide NPs is related to their toxicity. Similar findings have also been reported by Zhang et al. (2012), who indicated that the oxidative stress induced by MO-NPs could be linked to their conduction and valance band energies. More recently, Singh and Gupta (2014) attempted to build classification and regression nano-(Q)SAR models using ensemble methods such as decision tree forest (DTF) and decision tree boost (DTB). "
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