Abstract
Advances in synthetic biology have enabled innovative strategies for cancer therapy, yet precise control of therapeutic expression and biosafety remain critical challenges. To address these issues, a bacterial hybrid biorobot is developed using Escherichia coli (MG1655) engineered for localized activation by microwaves. Upon activation, the biorobot expresses glucose oxidase (GOx) at tumor sites, leading to glucose depletion and hydrogen peroxide generation. Surface-attached Cu(2)O nanoparticles catalyze this hydrogen peroxide through a Fenton-like reaction, producing reactive oxygen species that drive multiple forms of tumor cell death, including apoptosis, ferroptosis, and cuproptosis. Comprehensive in vitro and in vivo studies confirm the efficacy of this approach, while transcriptomic analysis reveals disruption of glucose metabolism and robust activation of antitumor immune responses. This work demonstrates the potential of this engineered bacterial platform as a safe and versatile tool for precise, multimodal cancer treatment.