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

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.