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通过中性粒细胞介导的 18β-甘草次酸在心肌缺血/再灌注损伤中的递送增强心脏保护作用。

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

机构信息

Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, 450018, China.

出版信息

Adv Sci (Weinh). 2024 Nov;11(42):e2406124. doi: 10.1002/advs.202406124. Epub 2024 Sep 12.

DOI:10.1002/advs.202406124
PMID:39264272
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11558124/
Abstract

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 (HO), 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.

摘要

心肌缺血/再灌注损伤（MI/RI）会产生活性氧物种（ROS）并引发炎症反应。针对特定细胞因子或 ROS 的传统治疗方法往往效果不佳。本研究开发了一种使用中性粒细胞诱饵（NDs）的新型药物递送系统（DDS），该 DDS 将 18β-甘草次酸（GA）包裹在可水解的草酸盐聚合物（HOP）和中性粒细胞膜囊泡（NMVs）内。这些 NDs 对过氧化氢（HO）有响应，能够实现 GA 的控制释放。此外，NDs 还能吸附炎症因子，从而减轻炎症。它们对炎症内皮细胞（ECs）的黏附增强，穿透能力提高。NDs 通过网格蛋白介导的内吞作用被心肌细胞内化后，可以防止 ROS 诱导的损伤，抑制 HMGB1 易位。体内研究表明，NDs 优先聚集在受损的心肌中，减少梗死面积，减轻不良重构，增强心脏功能，同时保持良好的生物安全性。这种基于中性粒细胞的系统通过解决炎症和 ROS 两个方面，为 MI/RI 提供了一种有前途的靶向治疗方法，具有潜在的临床应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/11558124/6e601bcba4ab/ADVS-11-2406124-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2c/11558124/1a76771764b3/ADVS-11-2406124-g008.jpg
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