Lipid nanoparticles for combined osteogenic differentiation and stem cell tracking

Original Research Article

Abstract

A major and pertinent problem in using stem cells for bone regeneration is the lack of safe and effective systems for delivering pro-osteogenic biologics and for bioimaging stem cells in vivo. This study aimed to develop a dual-component system that can deliver antimiR-138 to enhance osteogenesis while simultaneously tracking stem cells in vivo. We synthesized a dual-component lipid nanoparticles (LNP) by coating with a vitamin E derivative (TPGS) to induce cell-adhesion and penetration and encapsulating indocyanine green (ICG) for near-infrared (NIR) bio-imaging. The resulting nanoparticles (LNP-TPGS-ICG) were highly stable, with excellent optical and physicochemical properties, and achieved efficient transfection and gene silencing. The osteoblast differentiation of multipotent human mesenchymal stem/stromal cells (hMSCs) was significantly enhanced by antimiR-138 containing particles, as evidenced by increased mineralization and upregulation of ALP, RunX2, and OC. Intravenous injection of LNP-TPGS-ICG transfected hMSCs in mice demonstrated strong NIR signals in lung and liver by NIR-imaging. Finally, subcutaneously implanted stem cells were clearly detectable in mice for more than 24 h. These results suggest that the delivery system developed in this study could act as a safe and highly efficient vehicle for combined RNAi-based therapies and stem cell tracking.