期刊
NANO TODAY
卷 41, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.nantod.2021.101329
关键词
Colorectal cancer; Gut microbiota; Chemotherapy; Combination therapy; Intestinal perfusion
资金
- National Natural Science Foundation of China [52003205, 51873162, 51833007, 51690152]
- China Postdoctoral Science Foundation [211000140]
A tumor-triggered release drug delivery gel was developed to inhibit colorectal cancer cell growth in situ. The gel combines modulation of gut microbiota and chemotherapy drugs to efficiently suppress CRC growth and metastasis, providing a potential enhanced strategy for CRC treatment.
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. (c) 2021 Elsevier Ltd. All rights reserved.
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