miR-29b-Loaded Gold Nanoparticles Targeting to the Endoplasmic Reticulum for Synergistic Promotion of Osteogenic Differentiation

Precise control of stem cells, such as human bone marrow-derived mesenchymal stem cells (hMSCs), is critical for the development of effective cellular therapies for tissue engineering and regeneration medicine. Emerging evidence suggests that several miRNAs act as key regulators of diverse biological processes, including differentiation of various stem cells. In this study, we have described a delivery system for miR-29b using PEI-capped gold nanoparticles (AuNPs) to synergistically promote osteoblastic differentiation. The cell proliferation assay revealed that AuNPs and AuNPs/miR-29b exert negligible cytotoxicity to hMSCs and MC3T3-E1 cells. With the assistance of AuNPs as a delivery vector, miR-29b could efficiently enter the cytoplasm and regulate osteogenesis. AuNPs/miR-29b more effectively promoted osteoblast differentiation and mineralization through induced the expression of osteogenesis genes (RUNX2, OPN, OCN, ALP) for the long-term, compared to the widely used commercial transfection reagent, Lipofectamine. With no obvious cytotoxicity, PEI-capped AuNPs showed great potential as an adequate miRNA vector for osteogenesis differentiation. Interestingly, we observed loading of AuNPs as well as AuNPs/miR-29b into the lumen of the endoplasmic reticulum (ER). Our findings collectively suggest that AuNPs, together with miR-29b, exert a synergistic promotory effect on osteogenic differentiation of hMSCs and MC3T3-E1 cells.