Inhibition of Tumor Progression through the Coupling of Bacterial Respiration with Tumor Metabolism

Abstract

By leveraging the ability of Shewanella oneidensis MR-1 (S. oneidensis MR-1) to anaerobically catabolize lactate through the transfer of electrons to metal minerals for respiration, a lactate-fueled biohybrid (Bac@MnO₂ ) was constructed by modifying manganese dioxide (MnO₂ ) nanoflowers on the S. oneidensis MR-1 surface. The biohybrid Bac@MnO₂ uses decorated MnO₂ nanoflowers as electron receptor and the tumor metabolite lactate as electron donor to make a complete bacterial respiration pathway at the tumor sites, which results in the continuous catabolism of intercellular lactate. Additionally, decorated MnO₂ nanoflowers can also catalyze the conversion of endogenous hydrogen peroxide (H₂ O₂ ) into generate oxygen (O₂ ), which could prevent lactate production by downregulating hypoxia-inducible factor-1α (HIF-1α) expression. As lactate plays a critical role in tumor development, the biohybrid Bac@MnO₂ could significantly inhibit tumor progression by coupling bacteria respiration with tumor metabolism.