Nitroreductase-instructed supramolecular assemblies for microbiome regulation to enhance colorectal cancer treatments.

Abstract

The development of human microbiome has collectively correlated the sophisticated interactions between <i>Fusobacterium nucleatum</i> 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 <i>F. nucleatum</i>-infected tumors, here, we developed the nitroreductase-instructed supramolecular self-assembly. The designed assembly precursors underwent enzymatic transformation to form assemblies, which agglutinated <i>F. nucleatum</i> and eradicated the targeted bacteria. These assemblies with anti-<i>F. nucleatum</i> activity could further alleviate the bacteria-induced drug resistance effect, thus sensitizing CRC cells against chemo-drugs. Eventually, in mice bearing <i>F. nucleatum</i>-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 <i>F. nucleatum</i> to eliminate its contribution to CRC drug resistance and ameliorate chemotherapy outcomes.