Cytotoxicity of Metallic Oxide Nanoparticles: New Insights into Methodological Problems and Advances in Elucidation of Underlying Mechanisms

Increasing industrial applications of metallic oxide nanoparticles have led to escalation of human exposure to these nanoparticles in occupational and other environments. Nevertheless, the health effects of exposure of human and other species to these nanoparticles have not been systematically investigated as the impact of environmental exposure to these nanoparticles has not been under regulatory control. In a systematic investigation of the cytotoxicity of various types of metallic oxide nanoparticles, we found several important methodological issues not previously addressed in the limited literature on toxicity of nanoparticles and other nanomaterials: such issues have given rise to erroneous reports of experimental data and their interpretation. In this study, we report new approaches to overcome some methodological problems associated with recent studies on cellular nanotoxicity. Our results demonstrate the acute need for awareness of such methodological issues and how this awareness leads to improved methodologies for data collection and/or interpretation in such studies. As a result of adopting new and improved methodologies, our findings lead to new insights into the cytotoxic mechanisms underlying the effects of metallic oxide nanoparticles on human cells. Consequently, our new approaches may have long-term implications and applications in the elucidation of nanotoxicity mechanisms.