An in Vivo miRNA Delivery System for Restoring Infarcted Myocardium.
Huaxiao YangXulei QinHuiyuan WangXin ZhaoYonggang LiuHung-Ta WoChun LiuMasataka NishigaHaodong ChenJing GeNazish SayedOscar J AbilezDan DingSarah C HeilshornKai LiPublished in: ACS nano (2019)
A major challenge in myocardial infarction (MI)-related heart failure treatment using microRNA is the efficient and sustainable delivery of miRNAs into myocardium to achieve functional improvement through stimulation of intrinsic myocardial restoration. In this study, we established an in vivo delivery system using polymeric nanoparticles to carry miRNA (miNPs) for localized delivery within a shear-thinning injectable hydrogel. The miNPs triggered proliferation of human embryonic stem cell-derived cardiomyocytes and endothelial cells (hESC-CMs and hESC-ECs) and promoted angiogenesis in hypoxic conditions, showing significantly lower cytotoxicity than Lipofectamine. Furthermore, one injected dose of hydrogel/miNP in MI rats demonstrated significantly improved cardiac functions: increased ejection fraction from 45% to 64%, reduced scar size from 20% to 10%, and doubled capillary density in the border zone compared to the control group at 4 weeks. As such, our results indicate that this injectable hydrogel/miNP composite can deliver miRNA to restore injured myocardium efficiently and safely.
Keyphrases
- endothelial cells
- hyaluronic acid
- ejection fraction
- drug delivery
- tissue engineering
- left ventricular
- heart failure
- wound healing
- high glucose
- aortic stenosis
- vascular endothelial growth factor
- cancer therapy
- cardiac resynchronization therapy
- signaling pathway
- drug release
- atrial fibrillation
- acute heart failure
- gestational age
- combination therapy
- smoking cessation