Department of Pharmaceutics, Daqing Campus of Harbin Medical University, Daqing, 163319, China and School of Chemistry and Chemical Engineering, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150001, China.
Department of Pharmaceutics, Daqing Campus of Harbin Medical University, Daqing, 163319, China.
J Mater Chem B. 2020 Dec 7;8(45):10384-10391. doi: 10.1039/d0tb01821j. Epub 2020 Oct 28.
Acute and persistent myocardial ischemia is the main cause of acute myocardial infarction (AMI) and heart failure. MicroRNA-21(miR-21) contributes to the pathophysiological consequences of acute myocardial infarction by targeting downstream crucial regulators. Thus, miR-21 mimics are a promising strategy for the treatment of AMI. However, their poor stability and insufficient cellular uptake are the major challenges. Herein, we encapsulated miR-21 mimics into liposomes modified with the cardiac troponin T (cTnT) antibody for targeted delivery of miR-21(cT-21-LIPs) to the ischemic myocardium. The cT-21-LIPs exhibited enhanced targeting efficiency to hypoxia primary cardiomyocytes in vitro and improved accumulation in the ischemic heart of AMI rats after injection via the tail vein due to the specifical target to overexpressed troponin. The cT-21-LIPs could significantly improve the cardiac function and decrease the infarct size after AMI, while maintaining the viability of cardiomyocytes. This design provides a novel strategy for delivering small nucleotide drugs specifically to the infarcted heart, which may find great potential in clinics.
急性和持续性心肌缺血是急性心肌梗死 (AMI) 和心力衰竭的主要原因。 microRNA-21(miR-21) 通过靶向下游关键调节因子，导致急性心肌梗死的病理生理后果。因此，miR-21 模拟物是治疗 AMI 的一种很有前途的策略。然而，它们的稳定性差和细胞摄取不足是主要挑战。在此，我们将 miR-21 模拟物封装到心肌肌钙蛋白 T(cTnT)抗体修饰的脂质体中，用于 miR-21(cT-21-LIPs)靶向递送至缺血心肌。cT-21-LIPs 表现出增强的体外靶向缺氧原代心肌细胞的效率，并由于特异性靶向上皮细胞钙蛋白的过表达，在通过尾静脉注射后在 AMI 大鼠的缺血心脏中改善了积累。cT-21-LIPs 可显著改善 AMI 后的心脏功能并减小梗死面积，同时保持心肌细胞的活力。该设计为将小核苷酸药物特异性递送至梗死心脏提供了一种新策略，可能在临床上具有很大的潜力。
