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@MnO 2 ) was constructed by modifying manganese dioxide (MnO 2 ) nanoflowers on the S. oneidensis MR‐1 surface. The biohybrid Bac@MnO 2 uses decorated MnO 2 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 MnO 2 nanoflowers can also catalyze the conversion of endogenous hydrogen peroxide (H 2 O 2 ) into generate oxygen (O 2 ), 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@MnO 2 could significantly inhibit tumor progression by coupling bacteria respiration with tumor metabolism.