ROS-responsive death receptor 5 fusion protein nano-delivery system enhances myocardial ischemia-reperfusion injury protection

The microenvironment characterized by inflammation and oxidative stress plays a crucial role in the pathogenesis of myocardial ischemia-reperfusion (I/R) injury. The death receptor 5 fusion protein (sDR5-Fc) specifically targets and blocks the key protein-tumor necrosis factor related apoptosis indu...

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Main Authors: Xiaoyu Liang, Yang Zhang, Changduo Wang, Huiyang Li, Quan Li, Yicong Ye, Chenchen Tu, Xiliang Zhao, Jing Yang, Yong Zeng
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425004594
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author Xiaoyu Liang
Yang Zhang
Changduo Wang
Huiyang Li
Quan Li
Yicong Ye
Chenchen Tu
Xiliang Zhao
Jing Yang
Yong Zeng
author_facet Xiaoyu Liang
Yang Zhang
Changduo Wang
Huiyang Li
Quan Li
Yicong Ye
Chenchen Tu
Xiliang Zhao
Jing Yang
Yong Zeng
author_sort Xiaoyu Liang
collection DOAJ
description The microenvironment characterized by inflammation and oxidative stress plays a crucial role in the pathogenesis of myocardial ischemia-reperfusion (I/R) injury. The death receptor 5 fusion protein (sDR5-Fc) specifically targets and blocks the key protein-tumor necrosis factor related apoptosis inducing ligand (TRAIL), which is involved in cell apoptosis. This study focuses on the development of reactive oxygen species (ROS) intelligent responsive sDR5-Fc nanoparticles, aimed at improving the pathological microenvironment associated with oxidative stress and inflammatory damage, inhibiting myocardial cell apoptosis while worsening, and enhancing the bioavailability and selectivity of sDR5-Fc. The successful synthesis of 6S-PLGE-PO-PEG was verified through infrared nuclear magnetic resonance and other analytical experiments. The ROS intelligent responsive sDR5-Fc nanoparticles (DPP) were successfully constructed in vitro, exhibiting a particle size of approximately 200 nm, as well as a certain stability and H2O2 responsive release ability. DPP demonstrated good biocompatibility. The cell viability and apoptosis assays indicated that DPP significantly reduced myocardial cell damage caused by hypoxia reoxygenation and decreased cell apoptosis. In myocardial I/R rat model, the administration of DPP nanoparticle displayed superior therapeutic effects compared to the sDR5-Fc group, evidenced by the reduction in myocardial infarction area, improvement in fibrosis, decreased myocardial cell apoptosis, increased cell proliferation, enhanced angiogenesis, and inhibition of myocardial hypertrophy. The synergistic effect of ROS responsive sDR5-Fc nanoparticles in mitigating I/R injury is expected to provide a new interdisciplinary treatment approach.
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spelling doaj-art-826d0e22adf0402e896e875fc0fe2df22025-08-20T03:14:28ZengElsevierMaterials Today Bio2590-00642025-06-013210189910.1016/j.mtbio.2025.101899ROS-responsive death receptor 5 fusion protein nano-delivery system enhances myocardial ischemia-reperfusion injury protectionXiaoyu Liang0Yang Zhang1Changduo Wang2Huiyang Li3Quan Li4Yicong Ye5Chenchen Tu6Xiliang Zhao7Jing Yang8Yong Zeng9Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China; State Key Laboratory of Advanced Medical Materials and Devices, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China; Department of Heart Center, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Nankai University Affiliated Third Center Hospital, Medical College, Tianjin University, Tianjin ECMO Treatment and Training Base, Artificial Cell Engineering Technology Research Center, Institute of Hepatobiliary Disease, Tianjin, 300170, ChinaCenter for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, ChinaState Key Laboratory of Advanced Medical Materials and Devices, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, ChinaState Key Laboratory of Advanced Medical Materials and Devices, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, ChinaCenter for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, ChinaCenter for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, ChinaCenter for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, ChinaCenter for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, ChinaState Key Laboratory of Advanced Medical Materials and Devices, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China; Corresponding author.Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China; Corresponding author.The microenvironment characterized by inflammation and oxidative stress plays a crucial role in the pathogenesis of myocardial ischemia-reperfusion (I/R) injury. The death receptor 5 fusion protein (sDR5-Fc) specifically targets and blocks the key protein-tumor necrosis factor related apoptosis inducing ligand (TRAIL), which is involved in cell apoptosis. This study focuses on the development of reactive oxygen species (ROS) intelligent responsive sDR5-Fc nanoparticles, aimed at improving the pathological microenvironment associated with oxidative stress and inflammatory damage, inhibiting myocardial cell apoptosis while worsening, and enhancing the bioavailability and selectivity of sDR5-Fc. The successful synthesis of 6S-PLGE-PO-PEG was verified through infrared nuclear magnetic resonance and other analytical experiments. The ROS intelligent responsive sDR5-Fc nanoparticles (DPP) were successfully constructed in vitro, exhibiting a particle size of approximately 200 nm, as well as a certain stability and H2O2 responsive release ability. DPP demonstrated good biocompatibility. The cell viability and apoptosis assays indicated that DPP significantly reduced myocardial cell damage caused by hypoxia reoxygenation and decreased cell apoptosis. In myocardial I/R rat model, the administration of DPP nanoparticle displayed superior therapeutic effects compared to the sDR5-Fc group, evidenced by the reduction in myocardial infarction area, improvement in fibrosis, decreased myocardial cell apoptosis, increased cell proliferation, enhanced angiogenesis, and inhibition of myocardial hypertrophy. The synergistic effect of ROS responsive sDR5-Fc nanoparticles in mitigating I/R injury is expected to provide a new interdisciplinary treatment approach.http://www.sciencedirect.com/science/article/pii/S2590006425004594Myocardial ischemia-reperfusionsDR5-FcTRAILROS-ResponsiveAnti-apoptotic
spellingShingle Xiaoyu Liang
Yang Zhang
Changduo Wang
Huiyang Li
Quan Li
Yicong Ye
Chenchen Tu
Xiliang Zhao
Jing Yang
Yong Zeng
ROS-responsive death receptor 5 fusion protein nano-delivery system enhances myocardial ischemia-reperfusion injury protection
Materials Today Bio
Myocardial ischemia-reperfusion
sDR5-Fc
TRAIL
ROS-Responsive
Anti-apoptotic
title ROS-responsive death receptor 5 fusion protein nano-delivery system enhances myocardial ischemia-reperfusion injury protection
title_full ROS-responsive death receptor 5 fusion protein nano-delivery system enhances myocardial ischemia-reperfusion injury protection
title_fullStr ROS-responsive death receptor 5 fusion protein nano-delivery system enhances myocardial ischemia-reperfusion injury protection
title_full_unstemmed ROS-responsive death receptor 5 fusion protein nano-delivery system enhances myocardial ischemia-reperfusion injury protection
title_short ROS-responsive death receptor 5 fusion protein nano-delivery system enhances myocardial ischemia-reperfusion injury protection
title_sort ros responsive death receptor 5 fusion protein nano delivery system enhances myocardial ischemia reperfusion injury protection
topic Myocardial ischemia-reperfusion
sDR5-Fc
TRAIL
ROS-Responsive
Anti-apoptotic
url http://www.sciencedirect.com/science/article/pii/S2590006425004594
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