Micro-nano microbial fuel cell-driven bioelectrochemical tumor therapy

Colorectal cancer remains one of the most challenging malignancies to treat due to its intestinal physiological barrier, extracellular interstitial barrier, and immunosuppressive tumor microenvironment. Here we develop a micro-nano microbial fuel cell system, integrating Desulfovibrio desulfuricans (Dsv) as a biological electron donor and MnO₂ as a catalytic electron acceptor, to achieve bioelectrochemical tumor modulation. The Dsv@MnO₂-NE-PEG system, featuring norepinephrine-enhanced mucosal adhesion and PEG-mediated mucus penetration, exhibits superior tumor colonization efficiency, prolonged retention, and robust anti-tumor activity. Mechanistically, this system disrupts lactate accumulation in the tumor microenvironment, catalyzes reactive oxygen species generation, and induces pyroptosis instead of apoptosis, thereby enhancing tumor antigen release and immune activation. Further investigations reveal that Mn²⁺ generated from MnO₂ reduction activates the cGAS-STING pathway, promoting dendritic cell maturation, macrophage polarization toward the M1 phenotype, and enhancing CD8⁺ T cell infiltration while reducing regulatory T cell populations, effectively converting an immunosuppressive tumor into an immunoactive environment.