Elimination of Fusobacterium nucleatum With Biomimetic Nanoparticles to Reverse Tumor Immunosuppression and Enhance Colorectal Cancer Therapy.

Tumor-associated microbes like Fusobacterium nucleatum (F. nucleatum) critically contribute to immunosuppression and hinder cancer therapy. To overcome this challenge, we developed a microbe-targeted immune reprogramming strategy utilizing tumor cell membrane-camouflaged Ag@MSN-PpIX nanoparticles (M-MAP). Under ultrasound irradiation, M-MAP specifically eliminates intratumoral F. nucleatum, thereby directly reversing F. nucleatum-mediated immunosuppression while preserving gut microbiota homeostasis. Crucially, the killed F. nucleatum acts as an immunostimulant, promoting robust activation of antigen-presenting cells (APCs) and enhancing infiltration of cytotoxic T lymphocytes (CTLs) within the tumor. This dual action-elimination of suppressive bacteria and immunogenic activation by bacterial remnants-effectively reprograms the immunosuppressive tumor microenvironment (TME) in colorectal cancer. This work proposes a therapeutic strategy for cancer that targets tumor-associated bacteria to reprogram the TME, paving the way for more effective cancer treatments.