The use of transcriptomics to explore the mechanism of silver nanoparticle in inducing the dysregulation of cholesterol metabolism in human neural progenitor cells

Owing to their exceptional antibacterial properties, silver nanoparticles (SNPs) are the most widely used nanoparticles in commercial products. However, this prevalence also heightens the risk of human exposure and raises concerns regarding their adverse environmental effects and potential toxicity to organs, especially the brain. Thus, the aim of this study was to explore the effects and underlying mechanisms of noncytotoxic and cytotoxic SNPs on cholesterol metabolism in a human neural progenitor cell (hNPC) model. The SNPs were synthesized via the sodium borohydride reduction of silver nitrate, and the MTT assay and live/dead cell viability assay were used to compare the effects of different concentrations of SNPs on cell proliferation and death rate. Subsequently, RNA sequencing was performed to analyze the impact of noncytotoxic (5 μM) and cytotoxic (100/200 μM) SNPs on gene expression profiles in hNPCs after 24 hours of exposure, with differentially expressed genes identified and subjected to bioinformatic analysis. The results revealed that both noncytotoxic and cytotoxic SNPs affect cellular lipid homeostasis, with fewer cholesterol metabolism-related hub genes identified in the 5 μM SNP group than in the 100/200 μM SNP groups. Validation experiments indicated that SNPs significantly increase total cholesterol content and trigger negative feedback mechanisms to maintain cholesterol homeostasis. The greater impact of cytotoxic SNPs than noncytotoxic SNPs on cholesterol metabolism might be related to the differential expression of hub genes.