<i>Geobacter sulfurreducens</i> Armed with Biosynthetic Gold Nanoparticles for Tumor-Selective Cascade Catalytic Cancer Therapy

Catalytic nanomedicine represents an attractive therapeutic approach for cancer therapy while heavily relying on the catalytic activity and tumor selectivity of the catalyst. Here, a novel catalytic biohybrid ("bacterobot") of gold nanoparticle-coated electroactive bacterium is developed for enhanced catalytic cancer therapy. The electroactive <i>G. sulfurreducens</i>, for the first time used in cancer therapy, turbocharges the multienzyme-like catalytic activities of biosynthetic gold nanoparticles via cascade catalytic reactions to produce abundant reactive oxygen species to induce apoptosis and pyroptosis of tumor cells. Distinctive tumor accumulation and a tumor inhibition rate of 68% were achieved with single-dose intravenous injection of biohybrids in 4T1 tumor-bearing mice. Overall, the bacterobot biohybrid therapy demonstrates a high degree of therapeutic selectivity to tumor tissues and consequent excellent therapeutic efficacy and systemic biosafety, signifying the potential to create a paradigm shift in the way cancers are treated.