Fusobacterium nucleatum-mimicking nanovehicles to overcome chemoresistance for breast cancer treatment by eliminating tumor-colonizing bacteria

Herein, we discovered that the tumor-colonized F. nucleatum is closely correlated with the expression of D-galactose-β(1-3)-N-acetyl-D-galactosamine (Gal-GalNAc) in breast cancer and would promote chemoresistance. Therefore, we designed F. nucleatum-mimicking nanovehicles by fusing the F. nucleatum cytoplasmic membrane (FM) with antibiotic-loaded liposomes and found that the obtained nanovehicles (Colistin-LipoFM) could selectively eradicate tumor-resident F. nucleatum and significantly restore chemotherapy efficacy. In addition, our F. nucleatum-mimicking nanovehicles, containing a broad-spectrum antibiotic, could interfere with other intratumoral microbiomes to inhibit the lung metastasis of breast cancer and further promote the efficacy of standard clinically used breast cancer chemotherapy, leading to complete regression of established tumors in some mice. Therefore, the F. nucleatum-mimicking nanovehicles should be an excellent targeted drug delivery carrier for tumors colonized with bacteria and provide a promising possibility to promote existing cancer therapies by selectively killing tumor-colonizing bacteria.