Biomimetic “Trojan Horse” nanoparticles with biotactic behavior toward tumor-associated bacteria for targeted therapy of colorectal cancer
Wen Wu, Fanying Guo, Changzheng Wang, Xiao Qu, Qinying Wang, Yongzhi Yang, Yannan Yang, Yanlei Ma
Abstract
Tumor-associated microbiota critically drives the tumorigenesis and progression of colorectal cancer (CRC). Fusobacterium nucleatum ( F. nucleatum ) acts as a key pathogen in causing tumor progression, metastasis, and drug resistance. Herein, by cloaking colorectal cancer cell membrane (CCM) onto mesoporous silica nanoparticles (NPs) loaded with melittin (Mel), we introduced an innovative biomimetic "Trojan Horse" NP (Mel-SiO 2 @CCM). This nano-complex exhibited dual chemotactic clearance of F. nucleatum and tumor-targeting cytotoxicity, significantly suppressing tumor growth in both F. nucleatum -colonized CRC cell lines and murine subcutaneous and orthotopic models. Mechanistically, Mel-SiO 2 @CCM enhanced antigen presentation and tumor-specific immunity, amplifying F. nucleatum -colonized CRC suppression. Biosafety and biocompatibility were confirmed in healthy mouse models. Taken together, by exploiting CCM from high F. nucleatum -binding CRC cells, our strategy enables biotactic F. nucleatum targeting for CRC therapy. This "one-stone-two-bird" approach may bring inspirations to the precision treatment of F. nucleatum -positive CRC patients.