Microneedle-mediated gene delivery for the treatment of ischemic myocardial disease

Sci Adv. 2020 Jun 17;6(25):eaaz3621. doi: 10.1126/sciadv.aaz3621. eCollection 2020 Jun.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiomyopathies*
  • Dependovirus / genetics
  • Gene Transfer Techniques
  • Genetic Therapy / methods
  • Genetic Vectors / genetics
  • Humans
  • Myocardial Ischemia* / genetics
  • Myocardial Ischemia* / therapy
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factors / genetics

Substances

  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors