Reciprocal Response of Human Oral Epithelial Cells to Internalized Silica Nanoparticles

Silica nanoparticles (SiO 2 NPs) are one of the most widely used engineered nanoparticles and can been found in a wide range of consumer products. Despite their massive global production scale, little is known about their potential effects in the context of unintended exposure or ingestion. Using TR146 cells as an in vitro model of the human oral buccal mucosa, the uptake, spatial intracellular distribution, reactive oxygen species (ROS) production, infl ammatory response, and cytotoxic effects of commercial SiO 2 NPs are examined. SiO 2 NPs are shown to dock and cross the cellular mem- brane barrier in a dose-time-dependent manner. Confocal sectioning reveals translocation of SiO 2 NPs into the cell nucleus after 12 h of exposure. A concentration threshold of more than 500 ◊ 10 6 M is observed, above which SiO 2 NPs are shown to exert signifi cant oxidative stress with concomitant upregulation of infl ammatory genes IL6 and TNFA. Further analysis of the p53 pathway and a series of apoptotic and cell cycle biomarkers reveals intra- cellular accumulation of SiO 2 NPs exert marginal nanotoxicity. Collectively, this study provides important information regarding the uptake, intracellular distribution, and potential adverse cellular effects of SiO 2 NPs commonly found in consumer products in the human oral epithelium.