2. Academic Validation
  3. Cardiac and skeletal muscle delivery of biotherapeutics with a blood vessel epicardial substance-targeting peptide

Cardiac and skeletal muscle delivery of biotherapeutics with a blood vessel epicardial substance-targeting peptide

  • Biomaterials. 2026 Jun:329:123986. doi: 10.1016/j.biomaterials.2026.123986.
Biaobiao Wang 1,  Jiahui Cao 2,  Jingqiao Wu 1,  Yiwen Zhao 1,  Yao Zhang 1,  Frank Abendroth 3,  Caorui Lin 1,  Li Zhong 1,  Huanan Yu 1,  Yiqi Seow 4,  Meitong Ou 2,  Olalla Vázquez 5,  Lin Mei 2,  HaiFang Yin 6,  Gang Han 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & Division of Medical Technology & Department of Cell Biology, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin, 300070, China.
  • 2 State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Tianjin Institute of Health Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 301600, China.
  • 3 Department of Chemistry, Marburg University, Marburg, 35043, Germany.
  • 4 Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A∗STAR), 60 Biopolis Street, Genome, Singapore 138672, Republic of Singapore; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A∗STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore.
  • 5 Department of Chemistry, Marburg University, Marburg, 35043, Germany; Center for Synthetic Microbiology (SYNMIKRO), Marburg, 35043, Germany.
  • 6 State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & Division of Medical Technology & Department of Cell Biology, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin, 300070, China. Electronic address: haifangyin@tmu.edu.cn.
  • 7 State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & Division of Medical Technology & Department of Cell Biology, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin, 300070, China. Electronic address: hangang@tmu.edu.cn.
PMID: 41506143 DOI: 10.1016/j.biomaterials.2026.123986
Abstract

Although peptide-based delivery strategies show promise for muscle and heart diseases, delivery of biotherapeutics to both skeletal and cardiac muscles remains challenging. Here, we identified a muscle-homing peptide (BV2) against blood vessel epicardial substance (BVES) by phage display. BV2 shows high binding affinity to BVES and is internalized primarily via caveolae-mediated endocytosis. Importantly, BV2 enables efficient delivery of Duchenne Muscular Dystrophy (DMD) phosphorodiamidate morpholino oligomer (PMO), mCherry protein and exosomes to skeletal muscle and heart in vivo. BV2-mCherry protein and BV2-E31R anti-myostatin peptide were effectively delivered to muscle layers when microneedles loaded with these biotherapeutics were implanted on hindlimbs of mice. Muscle mass and myofiber size also significantly increased in muscle atrophy mice grafted with BV2-E31R microneedles. Moreover, significantly enhanced restoration of Dystrophin protein was achieved in peripheral and cardiac muscles of dystrophin-deficient mdx and Dystrophin/utrophin double-knockout mice when exosomes simultaneously modified with BV2 and PMO. These findings highlight the potency of BV2 in directing targeted delivery of diverse biotherapeutics to muscle and heart, thus providing an effective tool for DMD and Other muscular and cardiac disorders.

Keywords

Blood vessel epicardial substance (BVES); Duchenne muscular dystrophy; Exon-skipping; Muscle-homing peptide (BV2); Muscle-targeted delivery.

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