Nanozyme\nas Tumor Energy Homeostasis Disruptor to\nAugment Cascade Catalytic Therapy

Breaking\nthe balance of the tumor microenvironment and reshaping\nit sustainably remain major challenges in lung cancer treatment. Here,\na “tumor energy homeostasis disruptor”, the Cu<sub>2</sub>O@Au nanozyme was developed, which exhibits excellent glucose oxidase-like\nactivity, enabling it to be used for starvation therapy and as a mimic\nperoxidase for chemodynamic therapy (CDT), producing <sup>•</sup>OH. Cu<sub>2</sub>O@Au nanozymes consume glucose at the tumor site\nto block the tumor’s energy supply, produce H<sub>2</sub>O<sub>2</sub> continuously, and lower the pH to enhance the efficiency\nof CDT, initiating a cascade reaction that leads to a storm of reactive\noxygen species (ROS). Furthermore, Cu<sub>2</sub>O@Au nanozyme consumes\nglutathione and reduces the expression of the SLC7A11 (<i>x</i>CT) protein to decrease cancer cell uptake of cysteine, further enhancing\nthe burst of ROS, resulting in lipid peroxidation in tumor cells and\nultimately leading to ferroptosis. The excellent photothermal performance\nof Cu<sub>2</sub>O@Au can further enhance CDT. Additionally, Cu<sub>2</sub>O@Au nanozyme also has computed tomography (CT) and photothermal\nimaging capabilities. In conclusion, Cu<sub>2</sub>O@Au nanozymes,\nacting as tumor energy homeostasis disruptor, can effectively inhibit\ntumor growth and successfully achieve the synergistic effects of starvation\ntherapy/CDT/photothermal therapy (PTT). This multifunctional nanozyme\nholds promise for providing valuable insights and therapeutic strategies\nfor cancer treatment.