Enhancing Cardioprotection Through Neutrophil-Mediated Delivery of 18β-Glycyrrhetinic Acid in Myocardial Ischemia/Reperfusion Injury.
Dongjian HanFuhang WangQingjiao JiangZhentao QiaoYuansong ZhuangQuanxu AnYuhang LiYazhe TangChenyao LiDeliang ShenPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)
Myocardial 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 (H 2 O 2 ), 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.
Keyphrases
- reactive oxygen species
- oxidative stress
- ischemia reperfusion injury
- hydrogen peroxide
- dna damage
- diabetic rats
- cell death
- high glucose
- endothelial cells
- pet ct
- cancer therapy
- left ventricular
- nitric oxide
- acute myocardial infarction
- cystic fibrosis
- heart failure
- escherichia coli
- acute coronary syndrome
- coronary artery disease
- biofilm formation
- vascular endothelial growth factor