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, Tian Hao, Yanjun Pan, He Wang, Shuting Wu, Shuo Liu, Fei Wang, Lanping Wu, Yumin Zhong, Zhilu Yang, Yongzhe Che, Jie Shen, Deling Kong, Meng Yin () and Qiang Zhao ()
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Dashuai Zhu: College of Life Sciences, Nankai University
Jingli Hou: Tianjin Medical University
Meng Qian: College of Life Sciences, Nankai University
Dawei Jin: Shanghai Jiao Tong University
Tian Hao: College of Life Sciences, Nankai University
Yanjun Pan: Shanghai Jiao Tong University
He Wang: College of Life Sciences, Nankai University
Shuting Wu: Shanghai Jiao Tong University
Shuo Liu: Nankai University
Fei Wang: College of Life Sciences, Nankai University
Lanping Wu: Shanghai Jiao Tong University
Yumin Zhong: Shanghai Jiao Tong University
Zhilu Yang: Southwest Jiaotong University
Yongzhe Che: Nankai University
Jie Shen: Nankai University
Deling Kong: College of Life Sciences, Nankai University
Meng Yin: Shanghai Jiao Tong University
Qiang Zhao: College of Life Sciences, Nankai University

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24804-3

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