Engineered Bacterial Bioreactor for Tumor Therapy via Fenton-Like Reaction with Localized H₂ O₂ Generation.

Abstract

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 H₂ O₂ generation. Following from this, magnetic Fe₃ O₄ nanoparticles are covalently linked to bacteria to act as a catalyst for a Fenton-like reaction, which converts H₂ O₂ to toxic hydroxyl radicals (•OH) for tumor therapy. In this constructed bioreactor, the Fenton-like reaction occurs with sustainably synthesized H₂ O₂ produced by engineered bacteria, and severe tumor apoptosis is induced via the produced toxic •OH. These results show that this bioreactor can achieve effective tumor colonization, and realize a self-supplied therapeutic Fenton-like reaction without additional H₂ O₂ provision.