Micro-nano microbial fuel cell-driven bioelectrochemical tumor therapy
Ruiyan Li, Yong Kang, Nana Ran, Gaoli Niu, Yueyue Fan, Yijing Zhang, Jiamin Ye, Yuan Xue, Jiacheng Shi, Mengbin Ding, Yuhan Zhang, Xiaoyuan Ji
Abstract
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. Colorectal cancer can be difficult to treat due to multiple biological barriers. Here, the authors report an orally delivered microbial–inorganic hybrid that combines electrogenic bacteria with MnO2 nanoparticles to disrupt tumour metabolism, trigger pyroptosis, remodel immunity, and achieve tumour-targeted therapy.