The researchers synthesized an atypical NTR-responsive motif by introducing additional hydrophilic carboxyl group to the nitrobenzene moiety. The conjugation of the NTR-responsive motif to a suitable peptide sequence yielded an assembly precursor. The precursors underwent NTR catalyzed transformation and formed ordered nanofibers both in vitro and in living systems. These nanofibers rather than the individual molecules exhibited antibacterial activity against F. nucleatum. The local introduction of NTR-instructed assemblies significantly alleviated bacteria-induced oxaliplatin (OXA) resistance effect and efficiently inhibit the tumor growth eventually. 

Then, the researchers confirmed that the inhibition of F. nucleatum contributed to the enhanced chemotherapy outcomes. They declared that supramolecular self-assembly could serve as an abiotic strategy to interrupt bacteria-mammalian cell interactions and enhance CRC therapy. 

"Such a strategy should be applicable to improve other cancer therapies if the tumors bearing the risk of microbial infections,” said GAO. Taking E. coli associated drug-resistant pancreatic cancer as an example, in such a model, E. coli will metabolize the anticancer drug Gemcitabine into its inactive form, resulting in the failure of chemotherapy against pancreatic cancer. 

Schematics showing the NTR-instructed peptidic nanofibers with antibacterial activity to inhibit bacterial growth and result in efficient anticancer therapy. (Image by GAO Yuan et al.)