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Transplantation of gene-transfected bone marrow-derived mesenchymal stem cells (BMMSCs) is a promising strategy for ischemic myocardium repair, but current therapeutic strategy suffers from high toxicity and inefficient gene transfection in primary BMMSCs. Here we designed and synthesized molecularly organic–inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) based on nano-synthetic chemistry, which are featured with concurrent large pore size over 20 nm, small particulate size, hollow cavity and high dispersity for gene transfection in BMMSCs and subsequent in vivo cardiac repair. To efficiently create the therapeutic gene-transfected stem-cell lines, hepatocyte growth factor (HGF) gene was applied to transfect BMMSCs via biocompatible surface-engineered HMONs as a high-performance gene-delivery nanosystem. On the rat model of myocardial infarction, transplantation of HGF …