“Three‐in‐One” Nanozyme Composite for Augmented Cascade Catalytic Tumor Therapy

Cascade catalytic reaction exhibits simple procedure and high efficiency, such as that from the orderly assembly of different enzymes in biological systems. Mimicking of the natural cascade procedure becomes critical, but the orderly assembly of different enzymes is still challenging. Herein, single Au-Pt nanozyme is reported with "three-in-one" functions to initiate cascade conversions for O₂ supply as mimic catalase, H₂ O₂ production with its glucose oxidase-like property, and ^• OH generation as mimic peroxidase for chemodynamic therapy (CDT). Thus, the complex assembly and cross-talk among the different enzymes are avoided. To this end, metastable Cu₂ O NPs, as scaffolds, are used to anchor ultrasmall Au-Pt nanozyme, while metal-organic framework (MOF) is used to encapsulate the nanozyme for tumor microenvironment response and shielding protein adsorption. Pluronic F127 is then modified on the surface to improve hydrophilicity and biocompatibility of the composite. The endogenous acidity and glutathione in tumor degrade MOF to expose nanozyme for cascade catalytic CDT. The high photothermal conversion ability also enhances the CDT, while Cu²⁺ ions consume GSH to further improve CDT efficiency as augmented cascade catalytic tumor therapy. Thus, a new paradigm is provided with drug-free single nanozyme for improving tumor therapeutic efficacy and minimizing side effects.