Department of Radiation Oncology, The Second Affiliated Hospital of Jilin University, Changchun 130041, P. R. China.
State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, P. R. China.
ACS Appl Mater Interfaces. 2024 Nov 13;16(45):61805-61819. doi: 10.1021/acsami.4c18066. Epub 2024 Oct 31.
Insufficient accumulation of reactive oxygen species (ROS) due to tumor hypoxia significantly contributes to increased radiation resistance and the failure of radiotherapy (RT). Therefore, developing methods to alleviate hypoxia and boost ROS levels represents a promising strategy for enhanced radiosensitivity. This study introduced a self-cascade catalytic Pt@Au nanozymes as a radiosensitizer, using glucose oxidase (GOx)-, catalase (CAT)-, and peroxidase (POD)-like activities to improve hypoxia and increase ROS accumulation, thereby affecting glucose metabolism and enhancing the effects of RT. Pt@Au nanozymes exhibit GOx-like activity, which not only depletes glucose to induce starvation therapy, but also generates hydrogen peroxide (HO) for cascade reactions. Moreover, Pt@Au nanozymes demonstrate CAT-like activity, catalyzing the conversion of HO to O. This conversion effectively alleviates hypoxia, stabilizes ROS, increases DNA damage, significantly enhancing RT efficacy and sustaining the effects of starvation therapy. As high-Z materials, Pt@Au nanozymes can deposit more X-ray energy. Furthermore, the POD-like activity catalyzes the conversion of HO into highly reactive hydroxyl radicals (·OH), which increases ROS levels and enhances RT. Pt@Au nanozymes serve as X-ray computed tomography (CT) imaging agents, allowing for clear differentiation between tumor and normal tissue boundaries and enhancing the precision of RT. In summary, Pt@Au nanozymes serve as effective radiosensitizers by depleting glucose to induce starvation therapy, enhancing cascade reactions, and inhibiting tumor proliferation. Through their self-cascade reactions, these nanozymes dramatically increase oxygen levels within tumors, reduce hypoxia, and enhance ROS levels. This advancement addresses the radioresistance associated with hypoxic tumors, paving the way for innovative strategies in RT.
由于肿瘤缺氧导致活性氧（ROS）积累不足，这显著增加了放射抵抗性并导致放疗（RT）失败。因此，开发缓解缺氧并提高 ROS 水平的方法代表了增强放射敏感性的一种有前途的策略。本研究引入了一种自级联催化的 Pt@Au 纳米酶作为放射增敏剂，利用葡萄糖氧化酶（GOx）、过氧化氢酶（CAT）和过氧化物酶（POD）样活性来改善缺氧并增加 ROS 积累，从而影响葡萄糖代谢并增强 RT 的效果。Pt@Au 纳米酶表现出 GOx 样活性，不仅消耗葡萄糖诱导饥饿治疗，还产生过氧化氢（HO）用于级联反应。此外，Pt@Au 纳米酶表现出 CAT 样活性，催化 HO 转化为 O。这种转化有效地缓解了缺氧，稳定了 ROS，增加了 DNA 损伤，显著增强了 RT 效果并维持了饥饿治疗的效果。作为高 Z 材料，Pt@Au 纳米酶可以沉积更多的 X 射线能量。此外，POD 样活性催化 HO 转化为高反应性的羟基自由基（·OH），增加了 ROS 水平并增强了 RT。Pt@Au 纳米酶可用作 X 射线计算机断层扫描（CT）成像剂，能够清晰地区分肿瘤和正常组织边界，并提高 RT 的精度。总之，Pt@Au 纳米酶通过消耗葡萄糖诱导饥饿治疗、增强级联反应和抑制肿瘤增殖来作为有效的放射增敏剂。通过它们的自级联反应，这些纳米酶显著增加了肿瘤内的氧气水平，减少了缺氧并提高了 ROS 水平。这一进展解决了与缺氧肿瘤相关的放射抵抗性问题，为 RT 的创新策略铺平了道路。
