Low‐Dose Silver Nanoparticle Surface Chemistry and Temporal Effects on Gene Expression in Human Liver Cells

Silver nanoparticles (AgNPs) are widely incorporated into consumer and biomedical products for their antimicrobial and plasmonic properties with limited risk assessment of low‐dose cumulative exposure in humans. To evaluate cellular responses to low‐dose AgNP exposures across time, human liver cells (HepG2) are exposed to AgNPs with three different surface charges (1.2 µg mL−1) and complete gene expression is monitored across a 24 h period. Time and AgNP surface chemistry mediate gene expression. In addition, since cells are fed, time has marked effects on gene expression that should be considered. Surface chemistry of AgNPs alters gene transcription in a time‐dependent manner, with the most dramatic effects in cationic AgNPs. Universal to all surface coatings, AgNP‐treated cells responded by inactivating proliferation and enabling cell cycle checkpoints. Further analysis of these universal features of AgNP cellular response, as well as more detailed analysis of specific AgNP treatments, time points, or specific genes, is facilitated with an accompanying application. Taken together, these results provide a foundation for understanding hepatic response to low‐dose AgNPs for future risk assessment. Low‐level nanomaterial exposure studies represent probable exposure scenarios for typical consumers. In HepG2 cells, low‐dose response to silver nanoparticles reveals that gene transcription is dependent upon both time of exposure and nanoparticle surface chemistry. Features universal to all tested silver nanoparticles are also identified. An application is provided for complete user interrogation of the data.