Self-homing TGF-β1 traps: Engineered vasorin vesicles as smart biomaterials for targeted anti-fibrotic therapy after myocardial infarction

Haomiao Bai; Guiling Wu; Xinghua Qin; Qilong Yang; Zhihui Yao; Wei Zhang; Jing Wang; Wengang Dong; Lantian Wang; Xing Zhang; Ke Zhou; Jie Deng; Guodong Yang; Jia Li; Bo Peng

doi:10.1016/j.jpha.2026.101560

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Haomiao Bai, Guiling Wu, Xinghua Qin, Qilong Yang, Zhihui Yao, Wei Zhang, Jing Wang, Wengang Dong, Lantian Wang, Xing Zhang, Ke Zhou, Jie Deng, Guodong Yang, Jia Li, Bo Peng. Self-homing TGF-β1 traps: Engineered vasorin vesicles as smart biomaterials for targeted anti-fibrotic therapy after myocardial infarction[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101560

Citation:

Haomiao Bai, Guiling Wu, Xinghua Qin, Qilong Yang, Zhihui Yao, Wei Zhang, Jing Wang, Wengang Dong, Lantian Wang, Xing Zhang, Ke Zhou, Jie Deng, Guodong Yang, Jia Li, Bo Peng. Self-homing TGF-β1 traps: Engineered vasorin vesicles as smart biomaterials for targeted anti-fibrotic therapy after myocardial infarction[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101560

Citation:

Haomiao Bai, Guiling Wu, Xinghua Qin, Qilong Yang, Zhihui Yao, Wei Zhang, Jing Wang, Wengang Dong, Lantian Wang, Xing Zhang, Ke Zhou, Jie Deng, Guodong Yang, Jia Li, Bo Peng. Self-homing TGF-β1 traps: Engineered vasorin vesicles as smart biomaterials for targeted anti-fibrotic therapy after myocardial infarction[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101560

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Self-homing TGF-β1 traps: Engineered vasorin vesicles as smart biomaterials for targeted anti-fibrotic therapy after myocardial infarction

doi: 10.1016/j.jpha.2026.101560

a. Key Laboratory of Aerospace Medicine of the Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi’an, 710032, China;
b. School of Life Sciences, Northwestern Polytechnical University, Xi’an, 710072, China;
c. Department of Cardiology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China;
d. Key Laboratory of Hazard Assessment and Control in Special Operational Environment of the Ministry of Education, Fourth Military Medical University, Xi’an, 710032, China;
e. Department of Emergency Surgery, Shaanxi Provincial People’s Hospital, Xi’an, 710068, China;
f. Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, 710032, China;
g. School of Physical Education, Henan University, Kaifeng, Henan, 475001, China;
h. State Key Laboratory of Flexible Electronics (LoFE) & Institute of Flexible Electronics (IFE), Northwestern Polytechnical University, Xi'an, 710072, China

Funds:

This work was supported by the grants from the National Natural Science Foundation of China (Grant Nos.: 32271150, 32400951, and 62475216), the Fundamental and Interdisciplinary Plan of the Ministry of Education of China (Grant No.: JYB2025XDXM605), the National Key R&

D Program of China (Grant No.: 2024YFC3016400), Shaanxi Social Development Funding, China (Grant No.: 2024SF2-GJHX-12), and the project program of Fourth Military Medical University, China (Project No.: 2022JBGS005).

Received Date: Sep. 10, 2025
Accepted Date: Jan. 22, 2026
Rev Recd Date: Jan. 20, 2026
Available Online: Jan. 23, 2026

Abstract

Abstract

Cardiac fibrosis is a critical pathological process following myocardial infarction (MI), predominantly mediated by transforming growth factor-β1 (TGF-β1), for which effective targeted therapies remain limited. Vasorin is a cell membrane glycoprotein that functions as an endogenous antagonist of TGF-β1. To enhance its binding efficiency, we engineered vasorin variants incorporating site-specific fluorosulfate-L-tyrosine (FSY) through genetic code expansion. This chemical modification enables sulfur-fluoride exchange (SuFEx) reactions and covalent trapping of TGF-β1, thereby improving target selectivity. For lesion-specific delivery, hybrid membrane vesicles (HM-MVP) were constructed by fusing FSY-modified, vasorin-anchored HEK293T cell membranes with thrombus-homing platelet (PLT) membranes. In murine MI models, HM-MVP selectively accumulated within infarcted myocardial tissue and exhibited superior TGF-β1 binding affinity, resulting in more pronounced anti-fibrotic effects compared to native vasorin vesicles. This targeted therapeutic approach was associated with significantly improved cardiac structural preservation and functional recovery post-MI, highlighting favorable drug-like characteristics. Collectively, these findings reveal, for the first time, the cardioprotective and anti-fibrotic potential of vasorin, and elucidate a novel therapeutic paradigm by synergizing FSY-engineered vasorin with biomimetic vesicle delivery to address maladaptive TGF-β1 signaling in cardiac fibrosis.
- Myocardial infarction,
- TGF-β1,
- Cardiac fibrosis,
- Vasorin

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References(34)

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