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Published on: January 15, 2015
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Akkermansia Muciniphila-Inspired Oral siRNA Delivery by Active Matrix-Penetration and Intracellular Endoplasmic
Chao Pan1,2, Yang Wang1,3, Min Zhang1,2,4
1State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, P. R. China.
Advanced Materials (Deerfield Beach, Fla.)
|November 18, 2025
Summary
Inspired by gut bacteria, Akkermansia muciniphila membrane vesicles (AMVs) offer a novel oral delivery method for small interfering ribonucleic acid (siRNA). This bioinspired approach enhances mucus penetration and tumor delivery, improving gene silencing and inhibiting cancer growth.
Area of Science:
- Biotechnology
- Nanomedicine
- Drug Delivery
Background:
- Oral delivery of small interfering ribonucleic acid (siRNA) faces significant challenges due to gastrointestinal and cellular barriers.
- Current delivery systems often struggle with effective mucus penetration and intracellular transport.
Purpose of the Study:
- To develop a novel, bioinspired platform for effective oral siRNA delivery.
- To leverage Akkermansia muciniphila membrane vesicles (AMVs) for enhanced therapeutic efficacy.
Main Methods:
- Utilized Akkermansia muciniphila membrane vesicles (AMVs) for siRNA encapsulation and oral delivery.
- Investigated AMV interaction with intestinal mucins for mucus penetration.
- Assessed intracellular trafficking and gene silencing efficiency in tumor cells.
- Evaluated tumor growth inhibition and biosafety in a colorectal cancer mouse model.
Main Results:
- AMVs demonstrated active mucus penetration by degrading mucins, improving intestinal barrier traversal by 4.6 times.
- AMVs significantly enhanced siRNA penetration into tumor tissues.
- AMVs facilitated siRNA accumulation in the endoplasmic reticulum, bypassing endosomal-lysosomal degradation and improving gene silencing.
- Achieved 91.6% inhibition of tumor growth in a colorectal cancer model with a favorable safety profile.
Conclusions:
- Akkermansia muciniphila membrane vesicles (AMVs) represent a promising bioinspired platform for oral siRNA delivery.
- This approach overcomes key barriers to oral nucleic acid therapeutics, enhancing efficacy and safety.
- Further development of AMV-based systems could advance oral gene silencing therapies.
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