An important advance in cancer therapeutics has been achieved by scientists at the Tianjin University School of Medicine, who have developed a new “microbial fuel cell” platform that integrates electrogenic bacteria with piezoelectric nanoparticles to cooperatively eradicate colorectal tumors, reverse immunosuppression, and remodel the gut microbiome.
In this study, the team constructed a bio-heterojunction by electrostatically assembling PEG-modified piezoelectric barium titanate (BaTiO₃) nanoparticles onto the surface of the sulfate-reducing bacterium Desulfovibrio desulfuricans (Dsv). The resulting construct, termed Dsv@BTO, was further encapsulated in enteric-coated chitosan capsules to enable oral, colon-targeted delivery.
Upon noninvasive ultrasound activation, the platform mounts a two-pronged attack: BaTiO₃ nanoparticles generate reactive oxygen species (ROS) and local electric fields, while the bacteria transfer metabolic electrons to enhance BTO catalysis and produce hydrogen sulfide (H₂S), which disrupts mitochondrial function. This combined action induces two distinct forms of tumor cell death—apoptosis and pyroptosis.
In an orthotopic colorectal cancer mouse model, Dsv@BTO@CS plus ultrasound achieved an ~90% tumor-inhibition rate, extended median survival beyond 30 days, and exhibited no detectable systemic toxicity. The treatment also effectively remodeled the tumor microenvironment by promoting dendritic cell maturation, reprogramming macrophages toward the anti-tumor M1 phenotype, enhancing the infiltration proportion of cytotoxic CD8⁺ T cells, and suppressing immunosuppressive Treg cells.
Moreover, 16S rRNA sequencing demonstrated that the treatment significantly reversed colorectal cancer–associated gut dysbiosis, restoring microbial diversity and beneficial taxa while suppressing pathogenic bacteria.
“This work establishes a new paradigm for treating solid tumors by creating a bio–abiotic electron-transfer interface that couples microbial metabolism with piezocatalysis,” said Prof. Xiaoyuan Ji, the corresponding author at Tianjin University. “In essence, we build a micro-nano microbial fuel cell inside the tumor. Ultrasound activates BaTiO₃ to generate local electric fields and cytotoxic species, an effect amplified by Dsv-mediated microbial electron transfer. At the same time, the therapy awakens the immune system and restores a healthy gut microbiome. For complex cancers such as colorectal cancer, this multi-pronged approach is crucial.”
The team’s structural design overcomes major limitations of conventional catalytic therapies—such as poor charge-separation efficiency and weak targeting—by leveraging bacteria’s natural hypoxia tropism and capacity for extracellular electron transfer. Ultrasound provides a remote trigger, enabling precise spatiotemporal control.
Next, the researchers plan to evaluate this platform across additional immunosuppressive, hypoxic solid-tumor models and to advance the technology toward clinical translation.
This research, titled “Bio-Heterojunction-based Micro-Nano Microbial Fuel Cell Mediated Bioelectrochemical Therapy of Cancer,” was supported by the National Natural Science Foundation of China.
Journal
Science Bulletin