A comparative study of toxicity of TiO<sub>2</sub>, ZnO, and Ag nanoparticles to human aortic smooth-muscle cells

Abstract

Purpose: To evaluate the adverse vascular effects of nanoparticles (NPs) in vitro, extensive studies have investigated the toxicity of NPs on endothelial cells, but the knowledge of potential toxicity on human smooth-muscle cells (SMCs) is currently limited. Methods: This study compared the toxicity of TiO2, ZnO, and Ag NPs to human aortic SMCs. Results: Only ZnO NPs significantly induced cytotoxicity, accompanied by increased intracellular reactive oxygen species, Zn ions, and endoplasmic reticulum stress biomarkers (DDIT3 expression and p-Chop proteins). All the NPs significantly promoted the release of soluble VCAM1 and soluble sICAM1, but not IL6, which suggested that metal-based NPs might promote inflammatory responses. Furthermore, KLF4 expression (a transcription factor for SMC-phenotype switch) was significantly induced by TiO2 NPs and modestly by ZnO NPs, but the expression of CD68 remained unaltered. Conclusion: Our data indicated that ZnO NPs were more cytotoxic to human aortic SMCs than TiO2 and Ag NPs at the same mass concentrations, which might have been associated with intracellular reactive oxygen species, Zn ions, and endoplasmic reticulum stress. Keywords: metal-based nanoparticles, NPs, human aortic smooth-muscle cells, HASMCs, cytotoxicity, inflammation, endoplasmic reticulum stress, ER stress