title: Use of metal oxide nanoparticle band gap to develop a predictive paradigm for oxidative stress and acute pulmonary inflammation.
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.
authors.affiliation: California NanoSystems Institute, University of California, Los Angeles, California 90095-1680, USA.
authors.forename: Haiyuan
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Ji
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.forename: Huan
authors.initials: H
authors.lastname: Meng
authors.forename: Cecile
authors.initials: C
authors.lastname: Low-Kam
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Suman
authors.initials: S
authors.lastname: Pokhrel
authors.forename: Sijie
authors.initials: S
authors.lastname: Lin
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Yu-Pei
authors.initials: YP
authors.lastname: Liao
authors.forename: Meiying
authors.initials: M
authors.lastname: Wang
authors.forename: Linjiang
authors.initials: L
authors.lastname: Li
authors.forename: Robert
authors.initials: R
authors.lastname: Rallo
authors.forename: Robert
authors.initials: R
authors.lastname: Damoiseaux
authors.forename: Donatello
authors.initials: D
authors.lastname: Telesca
authors.forename: Lutz
authors.initials: L
authors.lastname: Mädler
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Zink
authors.forename: Andre E
authors.initials: AE
authors.lastname: Nel
mesh_terms: D000208:Acute Disease; D000818:Animals; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D011014:Pneumonia / Q000378:metabolism*