Title | Oral oncolytic magnetotactic bacteria elicit anti-colorectal tumor immunity and reprogram microbiota metabolism |
Publication Type | Papers in Scientific Journals |
Year of Publication | 2025 |
Authors | Jiang 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. |
Journal | Bioactive Materials |
Volume | 51 |
Pagination | 909-923 |
Date Published | 2025-06-29 |
Publisher | Elsevier |
ISSN | 2452-199X |
DOI | 10.1016/j.bioactmat.2025.06.046 |
URL | https://www.sciencedirect.com/science/article/pii/S2452199X25002816?via%3Dihub |
Keywords | Antitumor immunity, Bacterial metabolism, Gut Microbiota, Magnetotactic bacteria, Oral administration |
Rights | embargoedAccess (6 Months) |
Peer reviewed | yes |
Status | published |