Chemotherapy is a powerful tool in the armoury against cancer, but it is fraught with problems due to its global systemic toxicity. Here we report the proof of concept of a chemistry-based strategy, whereby gamma/X-ray irradiation mediates the activation of a cancer prodrug, thereby enabling simultaneous chemo-radiotherapy with radiotherapy locally activating a prodrug. In an initial demonstration, we show the activation of a fluorescent probe using this approach. Expanding on this, we show how sulfonyl azide- and phenyl azide-caged prodrugs of pazopanib and doxorubicin can be liberated using clinically relevant doses of ionizing radiation. This strategy is different to conventional chemo-radiotherapy radiation, where chemo-sensitization of the cancer takes place so that subsequent radiotherapy is more effective. This approach could enable site-directed chemotherapy, rather than systemic chemotherapy, with âreal timeâ drug decaging at the tumour site. As such, it opens up a new era in targeted and directed chemotherapy. Prodrugs offer one route to treat cancer, but they require activation once they have been delivered to the tumour. Now, a simultaneous chemo-radiotherapy strategy has been demonstrated in mice that uses gamma or X-ray irradiation to locally activate an anticancer prodrug.
化疗是抗击癌症的有力武器,但由于其全身性的毒性,存在诸多问题。在此,我们报告了一种基于
化学的策略的概念验证,该策略通过γ射线/X射线辐射介导激活一种癌症前药,从而实现化疗与局部激活前药的放射疗法的同步进行。在初步演示中,我们展示了利用这种方法激活荧光探针的过程。在此基础上,我们展示了如何利用临床相关剂量的电离辐射释放pazopanib和doxorubicin的磺酰
叠氮化物和苯基
叠氮化物笼蔽前药。这种策略与传统化疗-放射疗法中通过化疗增敏使后续放射疗法更有效的辐射不同。这种方法可能实现靶向局部化疗,而非全身性化疗,在肿瘤部位实现“实时”药物释放。因此,它开启了靶向和定向化疗的新纪元。
前药为治疗癌症提供了一条途径,但一旦送达肿瘤后需要激活。现在,在小鼠身上展示了一种同步化疗-放射疗法策略,使用γ或X射线辐射在局部激活抗癌前药。