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

Xiaoyu Liang; Yang Zhang; Changduo Wang; Huiyang Li; Quan Li; Yicong Ye; Chenchen Tu; Xiliang Zhao; Jing Yang; Yong Zeng

doi:10.1016/j.mtbio.2025.101899

Materials Today Bio (Jun 2025)

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

Xiaoyu Liang,
Yang Zhang,
Changduo Wang,
Huiyang Li,
Quan Li,
Yicong Ye,
Chenchen Tu,
Xiliang Zhao,
Jing Yang,
Yong Zeng

Affiliations

Xiaoyu Liang: Center 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, China
Yang Zhang: Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
Changduo Wang: 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
Huiyang Li: 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
Quan Li: Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
Yicong Ye: Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
Chenchen Tu: Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
Xiliang Zhao: Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
Jing Yang: 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; Corresponding author.
Yong Zeng: Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China; Corresponding author.

DOI: https://doi.org/10.1016/j.mtbio.2025.101899
Journal volume & issue: Vol. 32
p. 101899

Abstract

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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.

Published in Materials Today Bio

ISSN: 2590-0064 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: https://www.journals.elsevier.com/materials-today-bio

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