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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
PubMed

Insights

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.
Keywords:
Akkermansia muciniphilabacterial vesiclesendoplasmic reticulummatrix‐penetrationsiRNA delivery

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