A Cascade Enzyme System Based on the Catalase-like Activity of Co-MQDs for Enhanced Visualized Tumor Combination Therapy

Catalytic therapy based on natural enzymes and nanozymes is a highly promising cancer treatment strategy. Glucose oxidase (GOx) is a natural enzyme that can decompose glucose in tumor cells to produce gluconic acid and hydrogen peroxide (H2O2) in the presence of oxygen, thereby inducing tumor starvation therapy. However, the hypoxic tumor microenvironment severely limits its therapeutic efficacy. To address the oxygen supply issue and enhance treatment outcomes, herein, by in situ introducing cobalt atoms at one end of the MXene quantum dots (MQDs), we obtained the quantum dot CM, which retains the outstanding properties of MQDs while exhibiting significantly enhanced CAT-like activity and photothermal performance. CM and GOx were loaded onto persistent luminescence nanoparticles (ZGGC PLNPs) and modified with human serum albumin (HSA) to construct an enzyme cascade system, Z-CM/GOx-HSA, for visualized tumor therapy. Afterglow imaging confirmed the system's enrichment at the tumor site, guiding the initiation of photothermal therapy (PTT) and achieving a temperature increase of about 20 °C. At the tumor site, CM decomposes the overexpressed H2O2 into oxygen, alleviating tumor hypoxia, while accelerating GOx-mediated glucose breakdown to starve the tumor and generate additional H2O2. The newly formed H2O2 is then continuously split by CM, creating a positive-feedback loop that markedly amplifies the synergistic photothermal/catalytic therapeutic effect. Z-CM/GOx-HSA exhibited remarkable tumor-killing efficacy with a tumor inhibition rate of 93.7%, far superior to single-treatment strategies. Moreover, its nonautofluorescent visualization capability allows for real-time monitoring of the therapeutic process. Overall, this visualized enzyme cascade system effectively enhances tumor therapeutic efficacy and demonstrates excellent biosafety, providing strong support for the visualized tumor catalytic combination therapy.