A cascade X-ray energy converting approach toward radio-afterglow cancer theranostics

• Main Authors: Xu, Cheng, Qin, Xue, Wei, Xin, Yu, Jie, Zhang, Youjia, Zhang, Yan, Ding, Dan, Song, Jibin, Pu, Kanyi
• Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
• Format: Article
• Language: English
• Published: 2025
• Subjects: Chemistry; Medicine, Health and Life Sciences; Biosensors; X-rays
• Online Access: https://hdl.handle.net/10356/181950
• Institution: Nanyang Technological University

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.