Construction of size-transformable supramolecular nano-platform against drug-resistant colorectal cancer caused by Fusobacterium nucleatum

The presence of Fusobacterium nucleatum (F. nucleatum) in the community of colorectal cancer (CRC) accounts for its chemotherapy resistance. To resolve this drawback, we prepared multifaceted supramolecular nanomedicine by conjugating lauric acid (LA) and platinum (IV) oxaliplatin prodrug to hyperbranched polyglycidyl ether (PG), followed by addition of cucurbit[7]uril (CB[7]) to elicit supramolecular assembly. In principle, LA is used to eliminate the F. nucleatum, thereby enhancing chemotherapeutic efficacy of oxaliplatin. CB[7] facilitates host–guest complexation with oxaliplatin, allowing its activation specifically in the spermine-overexpressed CRC tumors. Moreover, CB[7] conduces to supramolecular assembly between the self-assembly units of PG-Pt-LA nanoparticles, representing a novel size-transformable supramolecular nanomedicine (PG-Pt-LA/CB[7]), which can address the dilemma of long circulation and deep penetration existed in nanomedicine. In F. nucleatum co-localized HT29 mouse model and CT26luc mouse model, PG-Pt-LA/CB[7] is validated to be a targeted, safe and effective nanomedicine that can substantially promote the chemotherapeutic efficacy in the treatment of drug-resistant CRC.