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

ABSTRACT 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.