Radioresistance resulted from the intrinsic features of tumors often gives rise to unsatisfied therapeutic outcome. In particular, the tumor microenvironment (TME) with abundant antioxidants, elevated hydrogen peroxide (H₂O₂) and hypoxia has been believed as a tremendous obstacle for radiotherapy. Therefore, developing an effective radiosensitizer in response to both X-ray and the TME is highly imperative but remains a challenge so far. Here, we for the first time explore bismuth heteropolytungstate (BiP₅W₃₀) nanoclusters as radiosensitizers for the TME-manipulated enhancement of radiotherapy. On the one hand, BiP₅W₃₀ nanoclusters can increase radiation dose deposition within tumors by high-Z elements like Bi and W. On the other hand, in virtue of the unique electron structure and multi-electron property, they have the capability of depleting glutathione (GSH) via redox reaction and catalyzing the decomposition of H₂O₂ to HO to enhance ROS generation upon X-ray radiation. Moreover, reduced graphene oxide (rGO) coupled with BiP₅W₃₀ can further improve radiocatalytic activity through promoting electron-hole separation. Simultaneously, due to the considerable near-infrared absorption of rGO, photothermal therapy can overcome the tumor hypoxia microenvironment and thus synergize with radiotherapy. In addition to providing a promising radiosensitizer, this finding is expected to extend the application of polyoxometalates used in the biomedical field.

由肿瘤的内在特征引起的抗辐射性常常引起不满意的治疗结果。特别地，具有丰富的抗氧化剂，升高的过氧化氢（H ₂ O ₂）和低氧的肿瘤微环境（TME）被认为是放疗的巨大障碍。因此，迫切需要开发一种对X射线和TME都有效的放射增敏剂，但迄今为止仍然是一个挑战。在这里，我们第一次探索铋异多钨酸铋（BiP ₅ W ₃₀）纳米簇作为放射增敏剂，以TME操纵增强放射治疗。一方面，BiP ₅ W ₃₀纳米团簇可以通过Bi和W等高Z元素来增加肿瘤内的辐射剂量沉积。另一方面，由于独特的电子结构和多电子性质，它们具有通过氧化还原反应消耗谷胱甘肽（GSH）的能力。催化H ₂ O ₂分解为HO，以增强X射线辐射时ROS的生成。此外，还原的氧化石墨烯（rGO）与BiP ₅ W ₃₀耦合可以通过促进电子-空穴分离来进一步提高放射催化活性。同时，由于rGO的近红外吸收，光热疗法可以克服肿瘤缺氧的微环境，从而与放射疗法协同作用。除了提供有希望的放射增敏剂外，预期该发现还将扩展生物医学领域中使用的多金属氧酸盐的应用。