Myocardial infarction (MI) remains the commonest cause of cardiac-related death throughout the world. In this study, we are presenting nanofiber mediated gene delivery for myocardial infarction. Branched polyethylenimine cross-linked via disulfide bonds (ssPEI) complexed with vascular endothelial growth factor (VEGF) were immobilized on the electrospun polycaprolactone (PCL)/ polyethylenimine (PEI) nanofibers for the local expression of VEGF angiogenic factor. We have studied whether the production of VEGF from myoblast cells adhering on the nanofibers has therapeutic potentials for myocardial infarction. In this method, non-specific adsorption of VEGF nanoparticles to the nanofibers occurred uniformly over all the surface area of nanofibers, resulting in increased transgene uptake and expression in more number of cells. Our results demonstrated that the delivery of therapeutic genes from biodegradable nanoparticles immobilized on the nanofiber represented minimal cytotoxicity to NIH/3T3 fibroblast cells and H9C2 myoblasts than branched PEI 25kDa did. According to luciferase assay, RT-PCR, this vector showed high transgene expression efficiency to reporter gene and VEGF gene. Surface-mediated delivery of DNA nanoparticles did not adversely affect cell growth and also facilitated the expression of transgene inside the cells. In vivo therapeutic efficacy with VEGF-embedded nanofiber will be evaluated for the treatment of myocardial infarction.