Nadph Oxidase-Like Nanozyme for High-Efficiency Tumor Therapy Through Increasing Glutathione Consumption and Blocking Glutathione Regeneration.

To counteract the high level of reactive oxygen species (ROS) caused by rapid growth, tumor cells resist oxidative stress by accelerating the production and regeneration of intracellular glutathione (GSH). Numerous studies have focused on the consumption of GSH, but the regeneration of GSH will enhance the reduction level of tumor cells to resist oxidative stress. Therefore, inhibiting the regeneration of GSH while consuming GSH is of great significance for breaking the redox balance of tumor cells. Herein, a simple termed MnO x -coated Au (AMO) nanoflower as a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) nanoenzyme is reported for efficient tumor therapy. Au nanoparticles exhibit the capability to catalyze the oxidation of NADPH, hindering GSH regeneration while concurrently functioning as a photothermal agent. During the process of eliminating intracellular GSH, MnO x releases Mn 2+ that subsequently engage in Fenton-like reaction, ultimately facilitating the implementation of chemodynamic therapy (CDT). Overall, this NOX enzyme-based nanoplatform enhances ROS generation and disrupts the state of reduction equilibrium, inducing apoptosis and ferroptosis by blocking GSH regeneration and increasing GSH consumption, thereby achieving collaborative treatments involving PTT, CDT, and catalytic therapy. This research contributes to NADPH and GSH targeted tumor therapy and showcases the potential of nanozymes. This article is protected by copyright. All rights reserved.