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

• Published in: Angewandte Chemie International Edition 2020-11, Vol.59 (48), p.21562-21570
• Main Authors: Chen, Qi‐Wen, Wang, Jia‐Wei, Wang, Xia‐Nan, Fan, Jin‐Xuan, Liu, Xin‐Hua, Li, Bin, Han, Zi‐Yi, Cheng, Si‐Xue, Zhang, Xian‐Zheng
• Format: Article
• Language: English
• Subjects: Animals; Bacteria; bacterial respiration; Catabolism; Cell Line, Tumor; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Coupling; Down-Regulation; Humans; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; lactate; Lactic acid; Lactic Acid - metabolism; Manganese; Manganese Compounds - chemistry; Manganese Compounds - metabolism; Manganese dioxide; Metabolism; Metabolites; Mice; Minerals; Nanoparticles - chemistry; Nanoparticles - metabolism; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Oxides - chemistry; Oxides - metabolism; Oxygen - metabolism; Particle Size; Respiration; S. oneidensis MR-1; Shewanella - metabolism; Surface Properties; tumor metabolism; tumor therapy; Tumors
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202002649

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 (H2O2) 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. MnO2 nanoflowers were modified on the cell surface of electrochemically active bacteria, S. oneidensis MR‐1. The biohybrids, which couple bacterial respiration with tumor metabolism, can catabolize intercellular lactate and prevent intracellular lactate production in the tumor, thereby inducing significant tumor inhibition.