Abstract |
The development of human microbiome has collectively correlated the sophisticated interactions between Fusobacterium nucleatum and colorectal cancers ( CRCs). However, the treatment of CRC via disruption of gastrointestinal flora remains less explored. Aiming at the up-regulated activity of nitroreductase in F. nucleatum-infected tumors, here, we developed the nitroreductase-instructed supramolecular self-assembly. The designed assembly precursors underwent enzymatic transformation to form assemblies, which agglutinated F. nucleatum and eradicated the targeted bacteria. These assemblies with anti-F. nucleatum activity could further alleviate the bacteria-induced drug resistance effect, thus sensitizing CRC cells against chemo-drugs. Eventually, in mice bearing F. nucleatum-infected CRC, the local introduction of nitroreductase-instructed assemblies could efficiently inhibit the tumor growth. Overall, this study incorporated nitroreductase to broaden the toolbox of enzyme-instructed supramolecular self-assembly. The local introduction of nitroreductase-instructed assemblies could target F. nucleatum to eliminate its contribution to CRC drug resistance and ameliorate chemotherapy outcomes.
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Authors | Jiali Chen, Pai Zhang, Yan Zhao, Jie Zhao, Xiaobo Wu, Ruijia Zhang, Ruitao Cha, Qingxin Yao, Yuan Gao |
Journal | Science advances
(Sci Adv)
Vol. 8
Issue 45
Pg. eadd2789
(11 11 2022)
ISSN: 2375-2548 [Electronic] United States |
PMID | 36351016
(Publication Type: Journal Article)
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Chemical References |
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Topics |
- Humans
- Mice
- Animals
- Colorectal Neoplasms
(drug therapy, pathology)
- Fusobacterium nucleatum
(physiology)
- Gastrointestinal Microbiome
- Nitroreductases
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