Engineered Bacterial Bioreactor for Tumor Therapy via Fenton-Like Reaction with Localized H2O2 Generation

Synthetic biology based on bacteria has been displayed in antitumor therapy and shown good performance. In this study, an engineered bacterium Escherichia coli MG1655 is designed with NDH-2 enzyme (respiratory chain enzyme II) overexpression (Ec-pE), which can colonize in tumor regions and increase localized H2O2 generation. Following from this, magnetic Fe3O4 nanoparticles are covalently linked to bacteria to act as a catalyst for a Fenton-like reaction, which converts H2O2 to toxic hydroxyl radicals (center dot OH) for tumor therapy. In this constructed bioreactor, the Fenton-like reaction occurs with sustainably synthesized H2O2 produced by engineered bacteria, and severe tumor apoptosis is induced via the produced toxic center dot OH. These results show that this bioreactor can achieve effective tumor colonization, and realize a self-supplied therapeutic Fenton-like reaction without additional H2O2 provision.