Abstract
Gold nanomaterials have garnered significant attention in biomedicine owing to their tunable size and morphology, facile surface modification capabilities, and distinctive optical properties. The surface functionalization of these nanoparticles can enhance their safety and efficacy in nanomedical applications. In this study, we examined the biological effects of gold nanoparticles (GNPs) with three distinct surface modifications (polyethylene glycol, chitosan, and polyethylenimine) in murine models, elucidating their mechanisms of action on hepatic tissue at both the transcriptomic and metabolomic levels. Our findings revealed that PEG-modified GNPs did not significantly alter any major metabolic pathway. In contrast, CS-GNPs markedly affected the metabolic pathways of retinol, arachidonic acid, linoleic acid, and glycerophospholipids (FDR < 0.05). Similarly, PEI-GNPs significantly influenced the metabolic pathways of retinol, arachidonic acid, linoleic acid, and sphingolipids (FDR < 0.05). Through a comprehensive analysis of the regulatory information within these pathways, we identified phosphatidylcholine compounds as potential biomarkers that may underlie the differential biological effects of the three functionalized GNPs. These findings provide valuable experimental data for evaluating the biological safety of functionalized GNPs.