Repeated intravenous mesoporous silica nanoparticle exposure increases serum total bile acids and alters hepatic bile acid-related gene expression in mice.

Mesoporous silica nanoparticles (MSNs) are promising drug-delivery materials, but their effects on hepatobiliary metabolic endpoints remain incompletely characterized. This study examined whether repeated systemic MSN exposure affects serum total bile acids (TBA) and hepatic bile acid-related gene expression in mice. Male C57BL/6J mice received intravenous MSNs at 20 mg/kg/day for 7 consecutive days. Exposure caused mild focal liver injury, shown by inflammatory cell infiltration and increased serum alanine aminotransferase. Serum TBA increased significantly, whereas alkaline phosphatase decreased, indicating that TBA elevation did not accompany a classical cholestatic enzyme pattern. Hepatic Il1b, Tnfa, and Il6 transcripts were strongly induced. MSN exposure also altered bile acid-related genes: Cyp7a1 increased at mRNA and protein levels, whereas Cyp8b1, Cyp7b1, Abcb11/Bsep, and Abcg2/Bcrp were reduced. Ostα was increased. Proteomic and metabolomic analyses provided supporting evidence of broader changes in cholesterol-related and central carbon metabolism. These findings identify TBA elevation and altered bile acid-related hepatic gene expression as early hepatobiliary-associated responses to repeated systemic MSN exposure.