Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery
Dashuai Zhu, Jingli Hou, Meng Qian, Dawei Jin, Hao Tian, Yanjun Pan, He Wang, Shu‐Ting Wu, Shuo Liu, Fei Wang, Lanping Wu, Yumin Zhong, Zhilu Yang, Yongzhe Che, Jie Shen, Deling Kong, Meng Yin, Qiang Zhao
Abstract
Nitric oxide (NO) is a short-lived signaling molecule that plays a pivotal role in cardiovascular system. Organic nitrates represent a class of NO-donating drugs for treating coronary artery diseases, acting through the vasodilation of systemic vasculature that often leads to adverse effects. Herein, we design a nitrate-functionalized patch, wherein the nitrate pharmacological functional groups are covalently bound to biodegradable polymers, thus transforming small-molecule drugs into therapeutic biomaterials. When implanted onto the myocardium, the patch releases NO locally through a stepwise biotransformation, and NO generation is remarkably enhanced in infarcted myocardium because of the ischemic microenvironment, which gives rise to mitochondrial-targeted cardioprotection as well as enhanced cardiac repair. The therapeutic efficacy is further confirmed in a clinically relevant porcine model of myocardial infarction. All these results support the translational potential of this functional patch for treating ischemic heart disease by therapeutic mechanisms different from conventional organic nitrate drugs.