Leveraging X-rays to initiate prolonged luminescence (radio-afterglow) and stimulate radiodynamic ¹O₂ production from optical agents provides opportunities for diagnosis and therapy at tissue depths inaccessible to light. However, X-ray-responsive organic luminescent materials are rare due to their intrinsic low X-ray conversion efficiency. Here we report a cascade X-ray energy converting approach to develop organic radio-afterglow nanoprobes (RANPs) for cancer theranostics. RANPs comprise a radiowave absorber that down-converts X-ray energy to emit radioluminescence, which is transferred to a radiosensitizer to produce singlet oxygen (¹O₂). ¹O₂ then reacts with a radio-afterglow substrate to generate an active intermediate that simultaneously decomposes to emit radio-afterglow. Through finetuning such a cascade, intraparticle radioluminescence energy transfer and the ¹O₂ transfer process, RANPs possess tunable wavelengths and long half-lives, and generate radio-afterglow and ¹O₂ at tissue depths of up to 15 cm. Moreover, we developed a biomarker-activatable nanoprobe (tRANP) that produces a tumour-specific radio-afterglow signal, leading to ultrasensitive detection and the possibility of surgical removal of diminutive tumours (1 mm³) under an X-ray dosage 20 times lower than inorganic materials. The efficient radiodynamic ¹O₂ generation of tRANP permits complete tumour eradication at an X-ray dosage lower than clinical radiotherapy and a drug dosage one to two orders of magnitude lower than most existing inorganic agents, leading to prolonged survival rates with minimized radiation-related adverse effects. Thus, our work reveals a generic approach to address the lack of organic radiotheranostic materials and provides molecular design towards precision cancer radiotherapy.

利用 X 射线引发长时间发光（放射性余辉）并刺激光学试剂产生放射动力学 ¹O₂，为在光线无法触及的组织深度进行诊断和治疗提供了机会。然而，由于 X 射线响应有机发光材料固有的 X 射线转换效率低，因此很少见。在这里，我们报告了一种级联 X 射线能量转换方法，用于开发用于癌症治疗诊断学的有机放射性余辉纳米探针 （RAP）。RANP 包括一个无线电波吸收器，该吸收器将 X 射线能量下转换以发射辐射发光，然后转移到辐射增敏器以产生单线态氧 （¹O₂）。¹然后，O₂ 与放射性余辉底物反应生成活性中间体，该中间体同时分解以发射放射性余辉。通过微调这种级联、粒子内辐射发光能量转移和 ¹O₂ 转移过程，RANP 具有可调波长和长半衰期，并在高达 15 cm 的组织深度产生放射性余辉和 ¹O₂。此外，我们开发了一种生物标志物可激活的纳米探针 （tRANP），它产生肿瘤特异性放射余辉信号，从而在比无机材料低 20 倍的 X 射线剂量下实现超灵敏检测和手术切除微小肿瘤 （1 mm³） 的可能性。高效的放射动力学 ¹O₂ 产生 tRANP 允许在低于临床放疗的 X 射线剂量和比大多数现有无机剂低 1 到 2 个数量级的药物剂量下完全根除肿瘤，从而延长存活率并最大限度地减少与辐射相关的不利影响。 因此，我们的工作揭示了一种解决有机放射热质材料缺乏的通用方法，并为精准癌症放射治疗提供了分子设计。