Affiliation:
1. Department of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 China
2. Key Laboratory of Cardiac Injury and Repair of Henan Province Zhengzhou 450018 China
3. Department of Vascular and Endovascular Surgery The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 China
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.
Funder
National Natural Science Foundation of China