Combination gut microbiota modulation and chemotherapy for orthotopic colorectal cancer therapy

Gut microbiota is closely related to the tumorigenesis and progression of colorectal cancer (CRC), especially Fusobacterium nucleatum ( Fn ) could promote colorectal tumor growth and cause chemoresistance. Here, we developed a tumor-triggered release drug delivery gel to inhibit CRC cell growth in situ by intestinal perfusion . Antibiotic metronidazole (MTZ) and 5-fluorouracil (5-FU), the first-line chemotherapy drug of CRC, are individually incorporated into metal polyphenol network-coated mesoporous silica nanoparticle (MSN), and then blended with carboxymethyl cellulose (CMC) to obtain an anti-CRC gel, AB-Gel. In vivo studies showed that AB-Gel could efficiently inhibit the growth and metastasis of CRC in an orthotopic mouse model attributing to the MTZ-induced modulation in the CRC-related microbiota. Chemotherapy efficacy against orthotopic CRC was significantly enhanced by the elimination of Fn . This strategy based on the combination of gut microbiota modulation and chemotherapy would be considered as an enhanced strategy for CRC treatment with potential use in the clinic.