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, Fe₃ O₄ @MnO₂ , 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 H₂ O₂ in an acidic extracellular microenvironment, following which the MnO₂ shell reacts with H₂ O₂ to generate O₂ and overcome hypoxia. Concurrently, intracellular glutathione (GSH)-which limits the effects of radiotherapy (RT)-can be oxidized by the MnO₂ shell while the latter is reduced to Mn²⁺ for T₁ -weighed MRI. The core Fe₃ O₄ , with its good magnetic targeting ability, can be utilized for T₂ -weighed MRI. In summary, the work demonstrates that Fe₃ O₄ @MnO₂ , as a dual T₁ - and T₂ -weighed MRI contrast agent with strong biocompatibility, exhibits striking potential for radiation enhancement under magnetic targeting.