Heterostructure engineering of Au@UiO-67-bpy(Cu)/MoS2 cascade nanozymes for self-fueled and NIR-enhanced chemodynamic/photothermal cancer therapy.

The development of multifunctional nanozymes capable of integrating catalytic cascade reactions with externally controllable therapeutic activation remains an important challenge in cancer nanomedicine. Herein, we report a heterostructure-engineered cascade nanozyme, Au@UiO-67-bpy(Cu)/MoS2, constructed by integrating a catalytically active Au@UiO-67-bpy(Cu) nanozyme with NIR-responsive MoS2 nanosheets. Unlike conventional UiO-67-based nanotherapeutics that commonly rely on post-synthetic incorporation of photoactive complexes or drug/photosensitizer payloads, this strategy introduces NIR functionality through composite engineering with a 2D photothermal motif while preserving the coordination-defined catalytic roles of the MOF nanozyme. Ultrasmall Au nanoparticles serve as glucose oxidase (GOx)-like catalytic centers to continuously generate H2O2 from glucose, thereby providing a self-supplied peroxide source for downstream chemodynamic therapy (CDT). Meanwhile, the coordinated Cu centers in UiO-67-bpy(Cu) deplete intracellular glutathione (GSH) and catalyze the conversion of self-generated H2O2 into highly reactive •OH through Fenton-like reactions. MoS2 nanosheets endow the system with strong 808 nm absorption and efficient photothermal therapy (PTT), which accelerates the integrated GOx-like and Fenton-like catalytic processes under NIR irradiation. Systematic spectroscopic and in vitro cellular investigations confirmed efficient H2O2 generation, GSH depletion, •OH production, cascade ROS amplification, and NIR-enhanced therapeutic efficacy against A549 cancer cells. This work highlights a modular heterostructure-engineering strategy for constructing drug-free, self-fueled UiO-67-based cascade nanozymes and provides new insight into coupling coordination-defined catalytic sites with photothermal acceleration for synergistic CDT/PTT cancer therapy.