Size matters: the effects of varying zinc oxide nanoparticle sizes on human cytochrome P450 enzyme activity and gene expression

Zinc oxide (ZnO) nanoparticles have sparked considerable interest in recent years due to their potential across various biomedical applications. However, their distinct physicochemical properties, including nanoscale size, high surface area-to-volume ratio, quantum confinement effects, increased reactivity, ion release, and photocatalytic activity, may result in toxicological effects or biological impacts that may not be manifest in their larger-scale counterparts. In this study, we aimed to investigate the complex interactions between ZnO nanoparticles and major drug-metabolizing cytochrome P450 (CYP) enzymes, providing insights into the physicochemical characteristics of ZnO nanoparticles and their inhibitory effects on CYP enzyme activity in vitro and gene expression in HepG2 cells. Our findings revealed that smaller ZnO nanoparticles (