Nanozymes as Glucose\nScavengers and Oxygenerators\nfor Enhancing Tumor Radiotherapy

Insufficient accumulation of reactive oxygen species\n(ROS) due\nto tumor hypoxia significantly contributes to increased radiation\nresistance and the failure of radiotherapy (RT). Therefore, developing\nmethods to alleviate hypoxia and boost ROS levels represents a promising\nstrategy for enhanced radiosensitivity. This study introduced a self-cascade\ncatalytic Pt@Au nanozymes as a radiosensitizer, using glucose oxidase\n(GOx)-, catalase (CAT)-, and peroxidase (POD)-like activities to improve\nhypoxia and increase ROS accumulation, thereby affecting glucose metabolism\nand enhancing the effects of RT. Pt@Au nanozymes exhibit GOx-like\nactivity, which not only depletes glucose to induce starvation therapy,\nbut also generates hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)\nfor cascade reactions. Moreover, Pt@Au nanozymes demonstrate CAT-like\nactivity, catalyzing the conversion of H<sub>2</sub>O<sub>2</sub> to\nO<sub>2</sub>. This conversion effectively alleviates hypoxia, stabilizes\nROS, increases DNA damage, significantly enhancing RT efficacy and\nsustaining the effects of starvation therapy. As high-Z materials,\nPt@Au nanozymes can deposit more X-ray energy. Furthermore, the POD-like\nactivity catalyzes the conversion of H<sub>2</sub>O<sub>2</sub> into\nhighly reactive hydroxyl radicals (·OH), which increases ROS\nlevels and enhances RT. Pt@Au nanozymes serve as X-ray computed tomography\n(CT) imaging agents, allowing for clear differentiation between tumor\nand normal tissue boundaries and enhancing the precision of RT. In\nsummary, Pt@Au nanozymes serve as effective radiosensitizers by depleting\nglucose to induce starvation therapy, enhancing cascade reactions,\nand inhibiting tumor proliferation. Through their self-cascade reactions,\nthese nanozymes dramatically increase oxygen levels within tumors,\nreduce hypoxia, and enhance ROS levels. This advancement addresses\nthe radioresistance associated with hypoxic tumors, paving the way\nfor innovative strategies in RT.