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This research work, reported by Mei Lin, Shuotong Mei, Lin Yaoxin from the National Nanotechnology Center of Beijing Anding Medical University and the Chinese Academy of Medical Sciences Biomedical Engineering Institute, and Zhang Fan from the same institutions, focuses on a long-standing unresolved core issue in inflammatory bowel disease (IBD):
?? How to truly restore immune tolerance while suppressing inflammation, instead of experiencing "suppress for a while, then rebound for a while".
The authors have developed a highly biomimetic nanotherapeutic platform called PrEXO-a23:
It is not a single nanoparticle, but a heterologous nanovacuum formed by Treg-derived exosomes and platelet membranes, and on its surface, the anti-IL-23 antibody is precisely loaded through a MMP-cleavable linker.
This design simultaneously addresses three major challenges:
1️⃣ Precise targeting to the lesion site: The platelet membrane endows it with high shear adhesion ability to intestinal injury vessels and inflammatory sites;
2️⃣ Release in response to the inflammatory microenvironment: The high expression of MMP in IBD lesions triggers the in situ release of the antibody, avoiding systemic immunosuppression;
3️⃣ Immunoreprogramming rather than simple blockade: The Treg exosomes themselves can induce the expansion of tolerogenic dendritic cells and Tregs, fundamentally correcting the Th17/Treg imbalance.
In various mouse IBD models, PrEXO-a23 not only significantly alleviates acute intestinal inflammation symptoms, but also reduces the risk of intestinal fibrosis and inflammatory-related colorectal cancer (CAC) over the long term, and its anti-tumor protective effect is partially dependent on the p53 signaling pathway.
The related research was published in Nature Communications under the title "Engineered exosome nanovesicles for delivery of antibodies to treat inflammatory bowel disease".
