Glutathione‐Depleting Nanoenzyme and Glucose Oxidase Combination for Hypoxia Modulation and Radiotherapy Enhancement

Abstract Nanoenzymes perceive the properties of enzyme‐like catalytic activity, thereby offering significant cancer therapy potential. In this study, Fe 3 O 4 @MnO 2 , a magnetic field (MF) targeting nanoenzyme with a core‐shell structure, is synthesized and applied to radiation enhancement with using glucose oxidase (GOX) for combination therapy. The glucose is oxidized by the GOX to produce excess H 2 O 2 in an acidic extracellular microenvironment, following which the MnO 2 shell reacts with H 2 O 2 to generate O 2 and overcome hypoxia. Concurrently, intracellular glutathione (GSH)—which limits the effects of radiotherapy (RT)—can be oxidized by the MnO 2 shell while the latter is reduced to Mn 2+ for T 1 ‐weighed MRI. The core Fe 3 O 4 , with its good magnetic targeting ability, can be utilized for T 2 ‐weighed MRI. In summary, the work demonstrates that Fe 3 O 4 @MnO 2 , as a dual T 1 ‐ and T 2 ‐weighed MRI contrast agent with strong biocompatibility, exhibits striking potential for radiation enhancement under magnetic targeting.