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.

Keywords: Fenton-like reaction; bacterial bioreactor; chemodynamic therapy; synthetic biology; tumor therapy.