Ti3C2 MXene Nanosheet-Based Dual-Enzyme Cascade Reaction to Facilitate Dual-Stimulation-Mediated Breast Cancer Therapy

Starvation therapy mediated by glucose oxidase is a widely used therapeutic approach for tumor treatment, but it is limited by the simultaneous drawbacks of weak therapeutic efficacy, nonspecificity, and systemic toxicity. Thus, combination therapy was used to complement the widely used therapeutic strategy for anticancer therapy. On the basis of starvation therapy, we designed a catalytic model of nanosheets with biological cascade enzymes synergizing with anticancer drugs. In short, two cascade enzymes (glucose oxidase and horseradish peroxidase) are covalently immobilized on Ti3C2 MXene nanosheet and a cascade enzyme nanoreactor is formed by electrostatically adsorbing positive charged DOX. Finally, the outer layer is coated with hyaluronic acid. By combining glucose oxidase-mediated starvation therapy, photothermal therapy, and chemotherapy, we have achieved the therapeutic effect of "killing three birds with one stone" by combining the dual stimulation response of endogenous and exogenous sources to the tumor site. This method not only achieves the targeting of cancer cells but also improves the systemic toxicity and reduced efficacy of biological enzymes and realizes synergistic cancer therapy with enhanced cascade reactions. It opens up a new path for the research of nanomedicine.