<br>纳米酶作为葡萄糖清除剂和氧发生器，用于增强肿瘤放疗,ACS Applied Materials & Interfaces

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纳米酶作为葡萄糖清除剂和氧发生器，用于增强肿瘤放疗
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2024-10-31 , DOI: 10.1021/acsami.4c18066
Yuxuan Zhang ₁ , Xingchen Li ₂ , Xiaojun Ren ₁ , Dongzhou Wang ₁ , Yuechen Zhao ₁ , Yuan Wang ₁ , Shunzi Jin ₃ , Quan Lin ₂ , Kun Zou ₄ , Tiejun Wang ₁

Affiliation

由于肿瘤缺氧导致活性氧（ROS）积累不足显着导致辐射抵抗力增加和放疗（RT）失败。因此，开发缓解缺氧和提高 ROS 水平的方法代表了增强放射敏感性的有前途的策略。本研究介绍了一种自级联催化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，不仅消耗葡萄糖以诱导饥饿治疗，还产生过氧化氢（H₂O₂）进行级联反应。此外，Pt@Au纳米酶表现出类似 CAT 的活性，催化 H₂O₂ 转化为 O₂。这种转化有效缓解缺氧，稳定 ROS，增加 DNA 损伤，显着增强 RT 疗效并维持饥饿疗法的效果。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 H₂O₂ 转化为高反应性羟基自由基（·OH），可增加 ROS 水平并增强 RT。Pt@Au纳米酶用作 X 射线计算机断层扫描（CT）显像剂，可以明确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来诱导饥饿治疗、增强级联反应和抑制肿瘤增殖，从而作为有效的放射增敏剂。通过它们的自级联反应，这些纳米酶显着增加肿瘤内的氧水平，减少缺氧，并提高 ROS 水平。这一进展解决了与缺氧肿瘤相关的放射耐药性，为 RT 的创新策略铺平了道路。

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Nanozymes as Glucose Scavengers and Oxygenerators for Enhancing Tumor Radiotherapy

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 (H₂O₂) for cascade reactions. Moreover, Pt@Au nanozymes demonstrate CAT-like activity, catalyzing the conversion of H₂O₂ to O₂. 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 H₂O₂ 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.

更新日期：2024-11-02

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