A role of ZnO nanoparticle electrostatic properties in cancer cell cytotoxicity

Denise Wingett,1–3 Panagiota Louka,1 Catherine B Anders,2 Jianhui Zhang,4 Alex Punnoose2,41Department of Biological Sciences, 2Biomolecular Sciences PhD Program, Boise State University, Boise, ID, 3Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washin...

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Autores principales:	Wingett D, Louka P, Anders CB, Zhang J, Punnoose A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	nanotechnology metal oxide cancer toxicity reactive oxygen species Medical technology R855-855.5 Chemical technology TP1-1185
Acceso en línea:	https://doaj.org/article/5e85f05299324f34b2724b43ed5fd427
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spelling	oai:doaj.org-article:5e85f05299324f34b2724b43ed5fd4272021-12-02T04:20:40ZA role of ZnO nanoparticle electrostatic properties in cancer cell cytotoxicity1177-8903https://doaj.org/article/5e85f05299324f34b2724b43ed5fd4272016-07-01T00:00:00Zhttps://www.dovepress.com/a-role-of-zno-nanoparticle-electrostatic-properties-in-cancer-cell-cyt-peer-reviewed-article-NSAhttps://doaj.org/toc/1177-8903Denise Wingett,1–3 Panagiota Louka,1 Catherine B Anders,2 Jianhui Zhang,4 Alex Punnoose2,41Department 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 speciesWingett DLouka PAnders CBZhang JPunnoose ADove Medical Pressarticlenanotechnologymetal oxidecancertoxicityreactive oxygen speciesMedical technologyR855-855.5Chemical technologyTP1-1185ENNanotechnology, Science and Applications, Vol 2016, Iss Issue 1, Pp 29-45 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanotechnology metal oxide cancer toxicity reactive oxygen species Medical technology R855-855.5 Chemical technology TP1-1185
spellingShingle	nanotechnology metal oxide cancer toxicity reactive oxygen species Medical technology R855-855.5 Chemical technology TP1-1185 Wingett D Louka P Anders CB Zhang J Punnoose A A role of ZnO nanoparticle electrostatic properties in cancer cell cytotoxicity
description	Denise Wingett,1–3 Panagiota Louka,1 Catherine B Anders,2 Jianhui Zhang,4 Alex Punnoose2,41Department 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
format	article
author	Wingett D Louka P Anders CB Zhang J Punnoose A
author_facet	Wingett D Louka P Anders CB Zhang J Punnoose A
author_sort	Wingett D
title	A role of ZnO nanoparticle electrostatic properties in cancer cell cytotoxicity
title_short	A role of ZnO nanoparticle electrostatic properties in cancer cell cytotoxicity
title_full	A role of ZnO nanoparticle electrostatic properties in cancer cell cytotoxicity
title_fullStr	A role of ZnO nanoparticle electrostatic properties in cancer cell cytotoxicity
title_full_unstemmed	A role of ZnO nanoparticle electrostatic properties in cancer cell cytotoxicity
title_sort	role of zno nanoparticle electrostatic properties in cancer cell cytotoxicity
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/5e85f05299324f34b2724b43ed5fd427
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A role of ZnO nanoparticle electrostatic properties in cancer cell cytotoxicity

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