Radiation therapy remains one of the main treatments for cancer. However, conventional radiotherapy not only manifests a low radiation accumulation in the tumor site, but also displays numerous negative effects. The most serious clinical problem is the radiotherapy resistance leading to cancer deterioration. As an important gaseous signal molecule, nitric oxide (NO) has been widely studied for its role in regulating angiogenesis, improving hypoxia, and inhibiting tumor growth. However, due to the unstable characteristic, the application of NO in cancer therapy is still limited. Here, we designed a micellar system formed by a NO donor, D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-NO, for enabling sustained NO release to efficiently deliver NO into the tumor area. TPGS-NO could accumulate in the tumor site for extended circulation, thereby releasing NO to exert antitumor effects and enhance radiotherapy effects under low-oxygen conditions. It demonstrated the increased sensitivity of radiotherapy through enhancing tumor angiogenesis appropriately reducing tumor area hypoxia, which significantly induced tumor cell apoptosis and inhibited its repair during radiation. This work may show great potential in synergistic radiotherapy against cancer by facile NO donor administration.

放射疗法仍然是癌症的主要疗法之一。然而，常规放射疗法不仅表现出在肿瘤部位的低辐射蓄积，而且表现出许多负面影响。最严重的临床问题是导致癌症恶化的放射疗法抵抗力。作为重要的气体信号分子，一氧化氮（NO）在调节血管生成，改善缺氧和抑制肿瘤生长方面的作用已得到广泛研究。然而，由于不稳定的特性，NO在癌症治疗中的应用仍然受到限制。在这里，我们设计了由NO供体D-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）-NO形成的胶束系统，以实现持续的NO释放，从而将NO有效地传递到肿瘤区域。TPGS-NO可能积聚在肿瘤部位以延长循环，从而释放出NO，在低氧条件下发挥抗肿瘤作用并增强放射治疗作用。它表明通过增强肿瘤血管生成，适当减少肿瘤区域的缺氧，可以显着诱导肿瘤细胞凋亡并抑制其在放射过程中的修复，从而提高放疗的敏感性。这项工作可能显示通过便利的NO供体给药在针对癌症的协同放疗中的巨大潜力。