Delivery of HDAC1 siRNA by Mn-Doped ZnSe Quantum Dots to Induce Human Mesenchymal Stem Cells Differentiation Into Cardiomyocytes

摘要

Cell-based therapies for cardiac repair have great promise for cardiovascular disease. The ability of human stem cells to differentiate into cardiomyocytes has attracted great attention in tissue engineering and other biochemical fields. In this study, we developed Poly-allylamine hydrochloride (PAH) coated Mn-doped ZnSe quantum dots (Mn:ZnSe QDs) as gene nanocarriers to deliver small interfering RNA (siRNA) against Histone deacetylase 1 (HDAC1) in human mesenchymal stem cells (human MSCs). Under the treatment of 5-azacytidine, the ablation of HDAC1 could significantly promote the differentiation of MSCs into cardiomyocytes in vitro. To further study the mechanism, we tested the sternness and differentiation genes and found that these genes had been changed by the down-regulation of HDAC1 in human MSCs. It is worth noting that Mn:ZnSe QDs can not only be served as the siRNA delivery platform, but the fluorescence from Mn:ZnSe QDs can also be applied as probes for tracking siRNA or chemotherapeutic drugs in cells or tissues. In conclusion, our results suggest for the first time use of Mn:ZnSe QDs as nanocarriers of delivery HDAC1 siRNA to induce the differentiation of human MSCs into cardiomyocytes for cardiovascular therapy, which may be clinically used to treat cardiovascular disease.