Oral oncolytic magnetotactic bacteria elicit anti-colorectal tumor immunity and reprogram microbiota metabolism

last updated: 2025-10-10
TitleOral oncolytic magnetotactic bacteria elicit anti-colorectal tumor immunity and reprogram microbiota metabolism
Publication TypePapers in Scientific Journals
Year of Publication2025
AuthorsJiang A., Li B., Zu M., Chen L., Zhao C., Tian J., Reis R. L., Kundu S. C., Xiao B., and Shi X.
Abstract

Therapeutic outcomes of colorectal cancer (CRC) are influenced by intestinal microbiota and metabolites. To leverage the tumor-tropism and microbiota-regulating properties of bacteria, we developed oncolytic magnetotactic bacteria (MSR-CPT/APPs) loaded with camptothecin (CPT) and anti-PD-L1 peptide (APP) for targeted chemo-magnetothermal immunotherapy of CRC. To further achieve oral delivery, MSR-CPT/APPs were coated with mulberry leaf lipids and Pluronic F127 (LPs). When exposed to an alternating magnetic field, MSR-CPT/ APP@LPs penetrated colonic mucus and reached deep-seated tumors. They elevated proinflammatory cytokine secretion, prolonged T cell recruitment, and reduced immunosuppressive cell proportions by activating the cGAS-STING pathway, inducing immunogenic cell death, and facilitating macrophage polarization to M1 phenotype. Oral MSR-CPT/APP@LPs increased the relative abundances of crucial commensal microorganisms (e. g., Lachnospiraceae family and Alistipes) and influenced their metabolites, like elevating beneficial metabolites (short-chain fatty acids and citrulline) levels and decreasing harmful metabolites (L-glutamine and kynurenic acid) amounts, thereby remodeling the tumor immune microenvironment. Overall, MSR-CPT/APP@LPs foster a supportive intestinal environment and mitigate immunosuppression, achieving the eradication of both primary and distant colorectal tumors.

JournalBioactive Materials
Volume51
Pagination909-923
Date Published2025-06-29
PublisherElsevier
ISSN2452-199X
DOI10.1016/j.bioactmat.2025.06.046
URLhttps://www.sciencedirect.com/science/article/pii/S2452199X25002816?via%3Dihub
KeywordsAntitumor immunity, Bacterial metabolism, Gut Microbiota, Magnetotactic bacteria, Oral administration
RightsembargoedAccess (6 Months)
Peer reviewedyes
Statuspublished

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