2. Academic Validation
  3. Engineered exosome nanovesicles for delivery of antibodies to treat inflammatory bowel disease

Engineered exosome nanovesicles for delivery of antibodies to treat inflammatory bowel disease

  • Nat Commun. 2026 Feb 13;17(1):2737. doi: 10.1038/s41467-026-69382-4.
Jiahui Cao 1,  Ran Luo 1,  Rourou Miao 1,  Wen Li 1,  Baisong Zhu 1,  Liu Yu 1,  Yiqiu Fu 1,  Xinyi Wang 1,  Jinxie Zhang 1,  Wenfeng Zeng 1,  Hanjie Zhang 1,  Zhuo Mao 1,  Fan Zhang 2,  Yao-Xin Lin 3 4,  Meitong Ou 5,  Lin Mei 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Beijing Key Laboratory of Key Technologies for Natural Drug Delivery and Novel Formulations, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, P. R. China.
  • 2 State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Beijing Key Laboratory of Key Technologies for Natural Drug Delivery and Novel Formulations, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, P. R. China. [email protected].
  • 3 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing, P.R. China. [email protected].
  • 4 University of Chinese Academy of Sciences, Beijing, P. R. China. [email protected].
  • 5 State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Beijing Key Laboratory of Key Technologies for Natural Drug Delivery and Novel Formulations, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, P. R. China. [email protected].
  • 6 State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Beijing Key Laboratory of Key Technologies for Natural Drug Delivery and Novel Formulations, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, P. R. China. [email protected].
PMID: 41688436 DOI: 10.1038/s41467-026-69382-4
Abstract

Inflammatory bowel disease (IBD) is characterized by chronic inflammation and impaired immune tolerance, for which current therapies provide only partial and transient relief. Here, we introduce PrEXO-a23, a biomimetic nanotherapeutic engineered by fusing regulatory T cell (Treg)-derived exosomes with platelet membrane vesicles and conjugating interleukin-23 (IL-23) antibodies via a matrix metalloproteinase (MMP)-cleavable linker. This design exploits the inherent homing ability of platelets and Tregs, enabling PrEXO-a23 to preferentially accumulate in inflamed colonic tissues in murine IBD models. At the disease site, elevated MMP activity triggers antibody release to inhibit IL-23-mediated inflammation, while exosomal cargo reprograms dendritic cells and promotes Treg expansion, thereby restoring immune tolerance. This dual-action strategy significantly alleviates IBD, prevents complications like intestinal fibrosis and colitis-associated colorectal Cancer, and shows p53-dependent efficacy in carcinogenesis prevention. These findings highlight PrEXO-a23 as a promising nanotherapeutic platform for durable immune reprogramming and long-term IBD management.

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