Han Gao, Da Pan, Hélder A. Santos
Ischemic heart disease (IHD) remains the foremost cause of mortality worldwide, characterized by extensive myocardial injury following infarction with limited regenerative capacity of the adult mammalian heart. RNA interference (RNAi) nanotechnology is revolutionizing cardiac therapy by leveraging the sequence-oriented gene regulation that can overcome the obstacles hindering conventional therapeutic approaches. Here, we outline the evolving landscape of RNAi nanomedicine for cardiac repair, with an emphasis on therapeutic advances in myocardial infarction and atherosclerosis. We further discuss design considerations for constructing effective nanosystems, underscoring the critical principles by bridging mechanistic insights with material engineering. Finally, we delineate the translational pathway from bench to bedside, detailing current challenges and highlighting prospective opportunities for advancing RNAi therapeutics in cardiovascular therapy.