Department of Medicine-Division of NanoMedicine, University of California, Los Angeles, California, California NanoSystems Institute at University of California, Los Angeles, California, IWT Foundation Institute of Materials Science, Department of Production Engineering, University of Bremen, Germany, Earth Sciences Division,
ACS Nano, 2010, 4 (1), pp 15–29 DOI: 10.1021/nn901503q Publication Date (Web): December 31, 2009 Copyright © 2009 American Chemical Society
Lawrence Berkeley National Laboratory, Berkeley, California, University of Bremen, Institute for Solid State Physics, Bremen, Germany, #Molecular Shared Screening Resources, University of California, Los Angeles, California, and Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles,California. OEThese authors contributed equally to this work.
By Saji George, Suman Pokhrel, Tian Xia, Benjamin Gilbert, Zhaoxia Ji, Marco Schowalter, Andreas Rosenauer, Robert Damoiseaux, Kenneth A. Bradley, Lutz Madler, and Andre E. Ne
ABSTRACT The establishment of verifiably safe nanotechnology requires the development of assessment tools to identify hazardous nanomaterial properties that could be modified to improve nanomaterial safety. While there is a lot of debate of what constitutes appropriate safety screening methods, one approach is to use the assessment of cellular injury pathways to collect knowledge about hazardous material properties that could lead to harm to humans and the environment. We demonstrate the use of a multiparameter cytotoxicity assay that evaluates toxic oxidative stress to compare the effects of titanium dioxide (TiO2), cerium oxide (CeO2), and zinc oxide (ZnO) nanoparticles in bronchial epithelial and macrophage cell lines. The nanoparticles were chosen on the basis of their volume of production and likelihood of spread to the environment. Among the materials, dissolution of ZnO nanoparticles and Zn2 release were capable of ROS generation and activation of an integrated cytotoxic pathway that includes intracellular calcium flux, mitochondrial depolarization, and plasma membrane leakage. These responses were chosen on the basis of the compatibility of the fluorescent dyes that contemporaneously assess their response characteristics by a semiautomated epifluorescence procedure. Purposeful reduction of ZnO cytotoxicity was achieved by iron doping, which changed the material matrix to slow Zn2+ release. In summary, we demonstrate the utility of a rapid throughput, integrated biological oxidative stress response pathway to performhazard ranking of a small batch of metal oxide nanoparticles, in addition to showing how this assay can be used to improve nanosafety by decreasing ZnO dissolution through Fe doping.