Nanocatalytic Immunotherapy Targeting Tumor-Resident Intracellular Bacteria for Triple-Negative Breast Cancer Treatment and Metastasis Suppression

Tumor-resident intracellular bacteria (TRIB) are prevalent within triple-negative breast cancer (TNBC). As integral components of the tumor pathological microenvironment, TRIB accelerate TNBC development by regulating cell proliferation, metabolism and immunosuppression. They also enhance the resistance of circulating tumor cells to mechanical stress through cytoskeletal rearrangement, boosting tumor metastasis and hindering clinical therapy. This work develops an advanced TRIB-targeted therapeutic strategy to block TNBC progression by eliminating tumor cells and intracellular bacteria, remodeling tumor immunity and suppressing metastatic colonization. We fabricate cancer cell membrane-modified narrow-bandgap FeSe2 nanosheets for enhanced ultrasound-triggered reactive oxygen species production and image-guided precise treatment. Such nanoplatforms utilize endogenous H2O2 and GSH to amplify chemodynamic effects, induce severe oxidative stress and ferroptosis in tumor cells. Combined damage-associated and pathogen-associated molecular patterns efficiently activate dendritic cells and initiate robust antigen-specific T-cell immune responses. This study provides an alternative and promising strategy for the treatment of clinically metastatic breast cancer through intratumoral microbiota intervention.