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

Nanotoxicology. 2020 Mar;14(2):145-161. doi: 10.1080/17435390.2019.1668067. Epub 2019 Sep 25.


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; endothelial cell; zinc oxide.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Endoplasmic Reticulum Stress / drug effects*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity*
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Solubility
  • Surface Properties
  • Zinc Oxide / chemistry*
  • Zinc Oxide / toxicity*


  • Reactive Oxygen Species
  • Zinc Oxide