Defect-induced electronic states amplify the cellular toxicity of ZnO nanoparticles

Abstract

Zinc oxide nanoparticles (ZnO NPs) are used in numerous applications, including sunscreens, cosmetics, textiles, and electrical devices. Increased consumer and occupational exposure to ZnO NPs potentially poses a risk for toxicity. While many studies have examined the toxicity of ZnO NPs, little is known regarding the toxicological impact of inherent defects arising from batch-to-batch variations. It was hypothesized that the presence of varying chemical defects in ZnO NPs will contribute to cellular toxicity in rat aortic endothelial cells (RAECs). Pristine and defected ZnO NPs (oxidized, reduced, and annealed) were prepared and assessed three major cellular outcomes; cytotoxicity/apoptosis, reactive oxygen species production and oxidative stress, and endoplasmic reticulum (ER) stress. ZnO NPs chemical defects were confirmed by X-ray photoelectron spectroscopy and photoluminescence. Increased toxicity was observed in defected ZnO NPs compared to the pristine NPs as measured by cell viability, ER stress, and glutathione redox potential. It was determined that ZnO NPs induced ER stress through the PERK pathway. Taken together, these results demonstrate a previously unrecognized contribution of chemical defects to the toxicity of ZnO NPs, which should be considered in the risk assessment of engineered nanomaterials.

Keywords:

• Nanotoxicity
• defects
• electronic states
• zinc oxide
• endothelial cell

Acknowledgments

The authors would like to acknowledge Kristofer Fritz and Peter Harris for their assistance with the HPLC assay for the redox potential. Electron microscopy was done at the University of Colorado, Boulder EM Services Core Facility in the Department of MCD Biology, with the technical assistance of facility staff.

Disclosure statement

Authors listed in the publication do not have any conflict of interest or benefited financially.

Additional information

Funding

This work was funded by the National Institute of Environmental Health Sciences R01 ES019311 (JMB).