Novel modifications of small extracellular vesicles to enhance cardiac-specific delivery of siPKA RNA and edaravone against ischemia-reperfusion cardiac injury
8 affiliations
- 1Department of Biopharmaceuticals and Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China; Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, 300134, China
- 2Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin, 300052, China; Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, International Joint Laboratory of Ocular Diseases, School of Pharmacy, School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, 300070, China
- 3Department of Biopharmaceuticals and Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China; Corresponding authors.
- 4Department of Biopharmaceuticals and Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China
- 5Department of Ophthalmology, Laboratory of Molecular Ophthalmology and Tianjin Key Laboratory of Ocular Trauma, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin Institute of Eye Health and Eye Diseases, China-UK ''Belt and Road'' Ophthalmology Joint Laboratory, Tianjin Medical University General Hospital, Tianjin, 300052, China
- 6Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, 300052, China
- 7Tianjin Key Laboratory of Metabolic Diseases, Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China; Corresponding authors.
- 8Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, International Joint Laboratory of Ocular Diseases, School of Pharmacy, School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, 300070, China; Corresponding authors.
Abstract
Relative tight endothelium in the heart may be a barrier for drugs in the large molecule and nanoparticle formats to act on cardiomyocytes. We hypothesize that enhanced binding of large molecules or nanoparticles to the cardiac capillary endothelial cells can increase the transendothelial transport of these drugs to exert their effects on the cardiomyocytes beneath the endothelium. CD36 is densely localized on the membrane of myocardial endothelial cells and thus we engineered small extracellular vesicles (sEVs) to be coated with an analog of CD36 ligand fatty acids, KOdiA-PC. Further to trap more therapeutic sEVs in the myocardium, we conjugated the sEVs with ischemic myocardium- targeting peptide (IMT). These dual-modifications of sEVs resulted in markedly enhanced fluorescent retention in the MIRI heart, indicating the potential of this system as a promising drug delivery platform for ischemic myocardium. Thus we loaded the dually-modified sEVs with edaravone (EDV) and siPKA RNA to dampen the ROS and inhibit overactivated PKA in myocardium subjected to ischemia/reperfusion injury, making a multistage-targeting and multifunctional sEVs delivery system (KI-sEVs/siPKA/EDV). The results showed that KOdiA-PC modification significantly enhanced sEVs transendothelial transport efficiency, and dual-targeting modification dramatically increased the accumulation of sEVs in the heart. Intravenous injection of KI-sEVs/siPKA/EDV significantly decreased myocardial infarction size, improved cardiac function and reduced cardiac fibrosis in animals subjected to MIRI or MI. KI-sEVs/siPKA/EDV also showed good biocompatibility and low toxicity. Our study provides an innovative cardiac-targeting delivery strategy and offers a promising method for MIRI and Persistent coronary occlusion MI treatment.
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BibTeX
@article{pei2026novel,
title = {{Novel modifications of small extracellular vesicles to enhance cardiac-specific delivery of siPKA RNA and edaravone against ischemia-reperfusion cardiac injury}},
author = {Xing Pei and Rui Li and Yingyu Bai and Qiumei Yan and Xiangyang Qi and Wenhui Jiao and Xiaohong Wang and Hua Yan and Qing Yang and Yi Zhu and Huining He and Xiongwen Chen},
journal = {Materials Today Bio},
year = {2026},
month = oct,
doi = {10.1016/j.mtbio.2026.103760},
url = {https://doi.org/10.1016/j.mtbio.2026.103760},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Novel modifications of small extracellular vesicles to enhance cardiac-specific delivery of siPKA RNA and edaravone against ischemia-reperfusion cardiac injury
AU - Xing Pei
AU - Rui Li
AU - Yingyu Bai
AU - Qiumei Yan
AU - Xiangyang Qi
AU - Wenhui Jiao
AU - Xiaohong Wang
AU - Hua Yan
AU - Qing Yang
AU - Yi Zhu
AU - Huining He
AU - Xiongwen Chen
PY - 2026
DA - 2026/10/19
JO - Materials Today Bio
DO - 10.1016/j.mtbio.2026.103760
UR - https://doi.org/10.1016/j.mtbio.2026.103760
AB - Relative tight endothelium in the heart may be a barrier for drugs in the large molecule and nanoparticle formats to act on cardiomyocytes. We hypothesize that enhanced binding of large molecules or nanoparticles to the cardiac capillary endothelial cells can increase the transendothelial transport of these drugs to exert their effects on the cardiomyocytes beneath the endothelium. CD36 is densely localized on the membrane of myocardial endothelial cells and thus we engineered small extracellular vesicles (sEVs) to be coated with an analog of CD36 ligand fatty acids, KOdiA-PC. Further to trap more therapeutic sEVs in the myocardium, we conjugated the sEVs with ischemic myocardium- targeting peptide (IMT). These dual-modifications of sEVs resulted in markedly enhanced fluorescent retention in the MIRI heart, indicating the potential of this system as a promising drug delivery platform for ischemic myocardium. Thus we loaded the dually-modified sEVs with edaravone (EDV) and siPKA RNA to dampen the ROS and inhibit overactivated PKA in myocardium subjected to ischemia/reperfusion injury, making a multistage-targeting and multifunctional sEVs delivery system (KI-sEVs/siPKA/EDV). The results showed that KOdiA-PC modification significantly enhanced sEVs transendothelial transport efficiency, and dual-targeting modification dramatically increased the accumulation of sEVs in the heart. Intravenous injection of KI-sEVs/siPKA/EDV significantly decreased myocardial infarction size, improved cardiac function and reduced cardiac fibrosis in animals subjected to MIRI or MI. KI-sEVs/siPKA/EDV also showed good biocompatibility and low toxicity. Our study provides an innovative cardiac-targeting delivery strategy and offers a promising method for MIRI and Persistent coronary occlusion MI treatment.
SN - 2590-0064
ER -