Specific “Unlocking” of a Nanozyme‐Based Butterfly Effect To Break the Evolutionary Fitness of Chaotic Tumors

Abstract

Chaos and the natural evolution of tumor systems can lead to the failure of tumor therapies. Herein, we demonstrate that iridium oxide nanoparticles (IrO_x ) possess acid-activated oxidase and peroxidase-like functions and wide pH-dependent catalase-like properties. The integration of glucose oxidase (GOD) unlocked the oxidase and peroxidase activities of IrO_x by the production of gluconic acid from glucose by GOD catalysis in cancer cells, and the produced H₂ O₂ was converted into O₂ to compensate its consumption in GOD catalysis owing to the catalase-like function of the nanozyme, thus resulting in the continual consumption of glucose and the self-supply of substrates to generate superoxide anion and hydroxyl radical. Moreover, IrO_x can constantly consume glutathione (GSH) by self-cyclic valence alternation of Ir^IV and Ir^III . These cascade reactions lead to a "butterfly effect" of initial starvation therapy and the subsequent pressure of multiple reactive oxygen species (ROS) to completely break the self-adaption of cancer cells.