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

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)...

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Main Authors: Dongjian Han, Fuhang Wang, Qingjiao Jiang, Zhentao Qiao, Yuansong Zhuang, Quanxu An, Yuhang Li, Yazhe Tang, Chenyao Li, Deliang Shen
Format: Article
Language:English
Published: Wiley 2024-11-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202406124
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author Dongjian Han
Fuhang Wang
Qingjiao Jiang
Zhentao Qiao
Yuansong Zhuang
Quanxu An
Yuhang Li
Yazhe Tang
Chenyao Li
Deliang Shen
author_facet Dongjian Han
Fuhang Wang
Qingjiao Jiang
Zhentao Qiao
Yuansong Zhuang
Quanxu An
Yuhang Li
Yazhe Tang
Chenyao Li
Deliang Shen
author_sort Dongjian Han
collection DOAJ
description 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 (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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institution OA Journals
issn 2198-3844
language English
publishDate 2024-11-01
publisher Wiley
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series Advanced Science
spelling doaj-art-2e541b48be184aa4aa1224dddd4e02222025-08-20T01:51:14ZengWileyAdvanced Science2198-38442024-11-011142n/an/a10.1002/advs.202406124Enhancing Cardioprotection Through Neutrophil‐Mediated Delivery of 18β‐Glycyrrhetinic Acid in Myocardial Ischemia/Reperfusion InjuryDongjian Han0Fuhang Wang1Qingjiao Jiang2Zhentao Qiao3Yuansong Zhuang4Quanxu An5Yuhang Li6Yazhe Tang7Chenyao Li8Deliang Shen9Department of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 ChinaDepartment of Vascular and Endovascular Surgery The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 ChinaAbstract 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 (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.https://doi.org/10.1002/advs.202406124drug deliveryinflammationmyocardial ischemia‐reperfusion injurynanomedicineneutrophil decoys (NDs)reactive oxygen species (ROS)
spellingShingle Dongjian Han
Fuhang Wang
Qingjiao Jiang
Zhentao Qiao
Yuansong Zhuang
Quanxu An
Yuhang Li
Yazhe Tang
Chenyao Li
Deliang Shen
Enhancing Cardioprotection Through Neutrophil‐Mediated Delivery of 18β‐Glycyrrhetinic Acid in Myocardial Ischemia/Reperfusion Injury
Advanced Science
drug delivery
inflammation
myocardial ischemia‐reperfusion injury
nanomedicine
neutrophil decoys (NDs)
reactive oxygen species (ROS)
title Enhancing Cardioprotection Through Neutrophil‐Mediated Delivery of 18β‐Glycyrrhetinic Acid in Myocardial Ischemia/Reperfusion Injury
title_full Enhancing Cardioprotection Through Neutrophil‐Mediated Delivery of 18β‐Glycyrrhetinic Acid in Myocardial Ischemia/Reperfusion Injury
title_fullStr Enhancing Cardioprotection Through Neutrophil‐Mediated Delivery of 18β‐Glycyrrhetinic Acid in Myocardial Ischemia/Reperfusion Injury
title_full_unstemmed Enhancing Cardioprotection Through Neutrophil‐Mediated Delivery of 18β‐Glycyrrhetinic Acid in Myocardial Ischemia/Reperfusion Injury
title_short Enhancing Cardioprotection Through Neutrophil‐Mediated Delivery of 18β‐Glycyrrhetinic Acid in Myocardial Ischemia/Reperfusion Injury
title_sort enhancing cardioprotection through neutrophil mediated delivery of 18β glycyrrhetinic acid in myocardial ischemia reperfusion injury
topic drug delivery
inflammation
myocardial ischemia‐reperfusion injury
nanomedicine
neutrophil decoys (NDs)
reactive oxygen species (ROS)
url https://doi.org/10.1002/advs.202406124
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