Single-cell RNA transcriptome landscape of murine liver following systemic administration of mesoporous silica nanoparticles.

ABSTRACT

Due to the unique physicochemical properties, mesoporous silica nanoparticles (MONs) have been widely utilized in biomedical fields for drug delivery, gene therapy, disease diagnosis and imaging. With the extensive applications and large-scale production of MONs, the potential effects of MONs on human health are gaining increased attention. To better understand the cellular and molecular mechanisms underlying the effects of MONs on the mouse liver, we profiled the transcriptome of 63,783 single cells from mouse livers following weekly intravenous administration of MONs for 2 weeks. The results showed that the proportion of endothelial cells and CD4+ T cells was increased, whereas that of Kupffer cells was decreased, in a dose-dependent manner after MONs treatment in the mouse liver. We also observed that the proportion of inflammation-related Kupffer cell subtype and wound healing-related hepatocyte subtype were elevated, but the number of hepatocytes with detoxification characteristics was reduced after MONs treatment. The cell-cell communication network revealed that there was more crosstalk between cholangiocytes and Kupffer cells, liver capsular macrophages, hepatic stellate cells, and endothelial cells following MONs treatment. Furthermore, we identified key ligand-receptor pairs between crucial subtypes after MONs treatment that are known to promote liver fibrosis. Collectively, our study explored the effects of MONs on mouse liver at a single-cell level and provides comprehensive information on the potential hepatotoxicity of MONs.