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A role of ZnO nanoparticle electrostatic properties in cancer cell cytotoxicity

Authors Wingett D, Louka P, Anders C, Zhang J, Punnoose A

Received 3 November 2015

Accepted for publication 7 January 2016

Published 15 July 2016 Volume 2016:9 Pages 29—45

DOI https://doi.org/10.2147/NSA.S99747

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Haifei Xu

Peer reviewer comments 3

Editor who approved publication: Professor Israel (Rudi) Rubinstein


Denise Wingett,1–3 Panagiota Louka,1 Catherine B Anders,2 Jianhui Zhang,4 Alex Punnoose2,4

1Department of Biological Sciences, 2Biomolecular Sciences PhD Program, Boise State University, Boise, ID, 3Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Seattle, WA, 4Department of Physics, Boise State University, Boise, ID, USA

Abstract: ZnO nanoparticles (NPs) have previously been shown to exhibit selective cytotoxicity against certain types of cancerous cells suggesting their potential use in biomedical applications. In this study, we investigate the effect of surface modification of ZnO NPs on their cytotoxicity to both cancerous and primary T cells. Our results show that polyacrylic acid capping produces negatively charged ZnO NPs that are significantly more toxic compared to uncapped positively charged NPs of identical size and composition. In contrast, the greatest selectivity against cancerous cells relative to normal cells is observed with cationic NPs. In addition, differences in NP cytotoxicity inversely correlate with NP hydrodynamic size, propensity for aggregation, and dissolution profiles. The generation of reactive oxygen species (ROS) was also observed in the toxicity mechanism with anionic NPs generating higher levels of mitochondrial superoxide without appreciably affecting glutathione levels. Additional experiments evaluated the combined effects of charged ZnO NPs and nontoxic cationic or anionic CeO2 NPs. Results show that the CeO2 NPs offer protective effects against cytotoxicity from anionic ZnO NPs via antioxidant properties. Altogether, study data indicate that surface modification of NPs and resulting changes in their surface charge affect the level of intracellular ROS production, which can be ameliorated by the CeO2 ROS scavenger, suggesting that ROS generation is a dominant mechanism of ZnO NP cytotoxicity. These findings demonstrate the importance of surface electrostatic properties for controlling NP toxicity and illustrate an approach for engineering NPs with desired properties for potential use in biological applications.

Keywords: nanotechnology, metal oxide, cancer, toxicity, reactive oxygen species

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