Enhancing Cardioprotection Through Neutrophil‐Mediated Delivery of 18β‐Glycyrrhetinic Acid in Myocardial Ischemia/Reperfusion Injury

Dongjian Han; Fuhang Wang; Qingjiao Jiang; Zhentao Qiao; Yuansong Zhuang; Quanxu An; Yuhang Li; Yazhe Tang; Chenyao Li; Deliang Shen

doi:10.1002/advs.202406124

journal article Open Access Sep 12, 2024

Enhancing Cardioprotection Through Neutrophil‐Mediated Delivery of 18β‐Glycyrrhetinic Acid in Myocardial Ischemia/Reperfusion Injury

Dongjian Han

Fuhang Wang Qingjiao Jiang Zhentao Qiao Yuansong Zhuang Quanxu An Yuhang Li

Yazhe Tang Chenyao Li Deliang Shen

Advanced Science Vol. 11 No. 42 · Wiley

View at Publisher Save 10.1002/advs.202406124

Abstract

AbstractMyocardial ischemia/reperfusion injury (MI/RI) generates reactive oxygen species (ROS) and initiates inflammatory responses. Traditional therapies targeting specific cytokines or ROS often prove inadequate. An innovative drug delivery system (DDS) is developed using neutrophil decoys (NDs) that encapsulate 18β‐glycyrrhetinic acid (GA) within a hydrolyzable oxalate polymer (HOP) and neutrophil membrane vesicles (NMVs). These NDs are responsive to hydrogen peroxide (H2O2), enabling controlled GA release. Additionally, NDs adsorb inflammatory factors, thereby reducing inflammation. They exhibit enhanced adhesion to inflamed endothelial cells (ECs) and improved penetration. Once internalized by cardiomyocytes through clathrin‐mediated endocytosis, NDs protect against ROS‐induced damage and inhibit HMGB1 translocation. In vivo studies show that NDs preferentially accumulate in injured myocardium, reducing infarct size, mitigating adverse remodeling, and enhancing cardiac function, all while maintaining favorable biosafety profiles. This neutrophil‐based system offers a promising targeted therapy for MI/RI by addressing both inflammation and ROS, holding potential for future clinical applications.

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Published: Sep 12, 2024
Vol/Issue: 11(42)
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Dongjian Han