Microneedle-mediated gene delivery for the treatment of ischemic myocardial disease
Hongpeng Shi, Xue Tong, Yang Yang, Chenyu Jiang, Shixing Huang, Qi Yang, Dong Lei, Zhengwei You, Tuo Jin, Fei Wu, Qiang Zhao, Xiaofeng Ye
Abstract
Cardiovascular disorders are still the primary cause of mortality worldwide. Although intramyocardial injection can effectively deliver agents to the myocardium, this approach is limited because of its restriction to needle-mediated injection and the minor retention of agents in the myocardium. Here, we engineered phase-transition microneedles (MNs) coated with adeno-associated virus (AAV) and achieved homogeneous distribution of AAV delivery. Bioluminescence imaging revealed the successful delivery and transfection of AAV-luciferase. AAV-green fluorescent protein-transfected cardiomyocytes were homogeneously distributed on postoperative day 28. AAV-vascular endothelial growth factor (VEGF)-loaded MNs improved heart function by enhancing VEGF expression, promoting functional angiogenesis, and activating the Akt signaling pathway. The results indicated the superiority of MNs over direct muscle injection. Consequently, MNs might emerge as a promising tool with great versatility for delivering various agents to treat ischemic myocardial disease.