The toxicity of ZnO nanomaterials to HepG2 cells: the influence of size and shape of particles.

Understanding the possible role of physicochemical properties in determining the toxicity of ZnO nanomaterials (NMs) is crucial for the safe use of ZnO-based materials. In this study, we synthesized four types of ZnO NMs, and characterized them as ZnO nanorods (NRs; length 400-500 nm, diameter 150-200 nm), ZnO Mini-NRs (length 50-100 nm, diameter 15-20 nm), amorphous ZnO microspheres (a-ZnO MS) and crystalline ZnO MS (c-ZnO MS; the a/c-ZnO MS are nanoflowers with an extensive growth of sheet-like structures). ZnO NMs and ZnO Mini-NRs were significantly more cytotoxic than a/c-ZnO MS, and this trend was similar in both HepG2 cells and human umbilical vein endothelial cells. Intracellular reactive oxygen species was only modestly induced by c-ZnO MS, whereas intracellular Zn ions were dose-dependently increased in HepG2 cells by the exposure of all types of ZnO NMs. The expression of endoplasmic reticulum stress marker DDIT3 was induced following an order of ZnO NRs > a-ZnO MS > c-ZnO MS > ZnO Mini-NRs, and the apoptosis gene CASP12 was induced following an order of a-ZnO MS > ZnO NRs > c-ZnO MS > ZnO Mini-NRs. Combined, these results suggested that ZnO NM-induced cytotoxicity and expression of endoplasmic reticulum stress-apoptosis genes could be influenced by the size and shape of ZnO NMs.