Fusobacterium nucleatum-mimicking nanovehicles to overcome chemoresistance for breast cancer treatment by eliminating tumor-colonizing bacteria
作者：
Linfu Chen1#,
单位：
1Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, P.R. China
2Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
3Department of Gynecologic Oncology, the International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, P.R. China
4Central Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, P.R. China
5School of Materials Science and Engineering, Tongji University, Shanghai 201804, P.R. China
摘要：
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.
