Multifunctional Quantum Dot Nanoparticles for Effective Differentiation and Long-Term Tracking of Human Mesenchymal Stem Cells In Vitro and In Vivo.

Human mesenchymal stem cells (hMSCs) hold great potential for regenerative medicine. Efficient induction of hMSC differentiation and better understanding of hMSCs behaviors in vitro and in vivo are essential to the clinical translation of stem cell therapy. Here a quantum dots (QDs)-based multifunctional nanoparticle (RGD-β-CD-QDs) is developed for effective enhancing differentiation and long-term tracking of hMSCs in vitro and in vivo. The RGD-β-CD-QDs are modified with β-cyclodextrin (β-CD) and Cys-Lys-Lys-Arg-Gly-Asp (CKKRGD) peptide on the surface. The β-CD can harbor hydrophobic osteogenic small molecule dexamethasone (Dex) and the RGD peptide not only facilitates the complexation of siRNA and delivers siRNA into hMSCs but also leads to cellular uptake of nanoparticles by RGD receptor. Co-delivery of Dex and siRNA by RGD-β-CD-QDs nanocarrier significantly expedites and enhances the osteogenesis differentiation of hMSCs in vitro and in vivo by combined effect of small molecule and RNAi. Furthermore, the RGD-β-CD-QDs can be labeled with hMSCs for a long-term tracking (3 weeks) in vivo to observe the behaviors of implanted hMSCs in animal level. These findings demonstrate that the RGD-β-CD-QDs nanocarrier provides a powerful tool to simultaneously enhance differentiation and long-term tracking of hMSCs in vitro and in vivo for regenerative medicine.