Gold nanoparticles (AuNPs), with their excellent biocompatibility and distinctive optical properties, have been widely applied in drug delivery, imaging, and photothermal therapy. However, the potential regulatory mechanisms of different gold nanoparticle morphologies on cellular gene expression remain unclear. This study systematically evaluated the differential regulation of gene expression profiles in human cells by gold nanorods and gold nanospheres using gene set enrichment analysis (GSEA) based on public transcriptomic databases (GSE233641 and GSE181369). Results found that gold nanospheres were associated with the upregulation of multiple immune and inflammation-related pathways in both gastric cancer cells and THP-1 monocytes, accompanied by energy metabolism reprogramming and oxidative stress responses, suggesting they may trigger relatively conserved biological responses across cell types. In contrast, gold nanorods exhibited greater cell-type specificity: in gastric cancer cells, they were primarily associated with upregulation of energy metabolism, oxidative stress, and inflammatory pathways while correlating with suppression of protein synthesis and cellular stress defense mechanisms; in THP-1 monocytes, they showed minimal inhibitory effects, mainly correlating with enhanced cytotoxicity, cytokine release, and related metabolic reprogramming. This study provides insights into the morphology-dependent molecular action patterns of AuNPs, thereby offering a potential theoretical basis to guide the rational design and safety assessment of these nanomaterials for biomedical applications.
Wang et al. (Fri,) studied this question.