Cytotoxicity and differentiation effects of gold nanoparticles to human bone marrow mesenchymal stem cells

摘要

Gold nanoparticles (GNPs) are widely used in chemical sensing, drug delivery, biomedical imaging, and photothermal therapy due to their strong and size-tunable surface plasmon resonance, fluorescence, and easy-surface functionalization. In this study, we investigated the effects of water-dispersed GNPs on the cytotoxicity and differentiation of human bone marrow mesenchymal stem cells (hBMSCs) and the associated death pathway. The results showed that the viability of hBMSCs was dependent upon the size of GNPs. Further, GNPs at the smallest size exhibited the highest cytotoxicity after treatment for 5 days and also substantially suppressed the number of colony-forming unit-fibroblast (CFU-F) of hBMSCs after continuous exposure for 21 days. Although large and medium sizes of GNPs had minor cytotoxicity to the cells, the sizes of CFU-F formed in the groups treated with GNPs at medium and large sizes were smaller compared to the control group. Further study of the cell death pathway using GNPs at medium size found that GNPs triggered hBMSCs necrosis, possibly by oxidative stress after GNPs were endocytosed. In addition, GNPs exerted the inhibitory effects on induced osteogenesis and adipogenesis of hBMSCs. Alkaline phosphatase (ALP) activity and calcium mineralization during osteogenic induction as well as the accumulation of triacylglycerides in adipogenic hBMSCs were repressed significantly by coculturing with GNPs at medium size. Our results suggest that the application of GNPs as long-term tracers for the activities of mesenchymal stem cells (MSCs) should be carefully evaluated.