Nanoparticle–Patch System for Localized, Effective, and Sustained miRNA Administration into Infarcted Myocardium to Alleviate Myocardial Ischemia–Reperfusion Injury

作者：Xuerui Chen, Hang Chen, Liyun Zhu, Mengting Zeng, Tianhui Wang, Chanyuan Su, Gururaja Vulugundam, Priyanka Gokulnath, Guoping Li, Xu Wang, Jianhua Yao, Jin Li, Dragoş Crețoiu, Zhaoyang Chen, Yihua Bei · 发表于：ACS Nano · 年份：2024 · DOI：10.1021/acsnano.3c08811 · 被引用次数：21 · 研究领域：Cardiac Ischemia and Reperfusion、RNA Interference and Gene Delivery、MicroRNA in disease regulation

Timely blood reperfusion after myocardial infarction (MI) paradoxically triggers ischemia–reperfusion injury (I/RI), which currently has not been conquered by clinical treatments. Among innovative repair strategies for myocardial I/RI, microRNAs (miRNAs) are expected as genetic tools to rescue damaged myocardium. Our previous study identified that miR-30d can provide protection against myocardial apoptosis and fibrosis to alleviate myocardial injury. Although common methods such as liposomes and viral vectors have been used for miRNA transfection, their therapeutic efficiencies have struggled with inefficient in vivo delivery, susceptible inactivation, and immunogenicity. Here, we establish a nanoparticle–patch system for miR-30d delivery in a murine myocardial I/RI model, which contains ZIF-8 nanoparticles and a conductive microneedle patch. Loaded with miR-30d, ZIF-8 nanoparticles leveraging the proton sponge effect enable miR-30d to escape the endocytic pathway, thus avoiding premature degradation in lysosomes. Meanwhile, the conductive microneedle patch offers a distinct advantage by intramyocardial administration for localized, effective, and sustained miR-30d delivery, and it simultaneously releases Au nanoparticles to reconstruct electrical impulses within the infarcted myocardium. Consequently, the nanoparticle–patch system supports the consistent and robust expression of miR-30d in cardiomyocytes. Results from echocardiography and electrocardiogram (ECG) revealed imp...