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

Nature Nanotechnology volume 20, pages 286–295 (2025)Cite this article

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Abstract

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.

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Fig. 1: Screening of radio-afterglow composition.
Fig. 2: Radioluminescence energy transfer.
Fig. 3: Radio-afterglow mechanism.
Fig. 4: In vitro studies of radio-afterglow imaging depth and radiodynamic cytotoxicity.
Fig. 5: Tumour-specific in vivo radio-afterglow imaging.
Fig. 6: In vivo radiodynamic cancer therapy.

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Data availability

All relevant data supporting the findings of this study are available within the Article and its Supplementary Information, or from the corresponding authors on reasonable request. Source data are provided with this paper.

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Acknowledgements

Y.Z. thanks the National Natural Science Foundation of China (22322406) for financial support. D.D. thanks the National Natural Science Foundation of China (52225310) for financial support. J.S. thanks the National Natural Science Foundation of China (21874024, U21A20377, U22A20348), the Fundamental Research Funds for the Central Universities (buctrc202235) and the National Key Research and Development Plan (2023YFB3810002). K.P. thanks the Singapore National Research Foundation (NRF) (NRF-NRFI07-2021-0005) and the Singapore Ministry of Education Academic Research Fund Tier2 (MOE-T2EP30220-0010 and MOE-T2EP30221-0004) for financial support. We thank D. Shiye, L. Qingqing and L. Xing for assistance in operating the equipment.

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Authors and Affiliations

  1. School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore

    Cheng Xu, Xin Wei & Kanyi Pu

  2. State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, PR China

    Xue Qin & Jibin Song

  3. National Engineering Research Centre for Nanomedicine, College of Life Science and Technology, Hubei Key Laboratory of Bio-inorganic Chemistry and Materia Medical, Huazhong University of Science and Technology, Wuhan, PR China

    Jie Yu & Yan Zhang

  4. Department of Nuclear Medicine, China–Japan Union Hospital of Jilin University, Changchun, Jilin, PR China

    Youjia Zhang

  5. Frontiers Science Center for New Organic Matter, Engineering & Smart Sensing Interdisciplinary Science Center, MOE Key Laboratory of Bioactive Materials, and College of Life Sciences, Nankai University, Tianjin, PR China

    Dan Ding

  6. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

    Kanyi Pu

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Contributions

K.P. conceived the study. K.P., Y.Z. and C.X. designed the experiments. C.X. and X.Q. prepared the nanomaterials and conducted the in vitro characterization. X.W. conducted the chemical syntheses. C.X., J.Y. and Y.Z. conducted the cell experiments. C.X. performed the in vivo experiments. K.P., J.S., Y.Z., D.D. and C.X. analysed the data and drafted the manuscript.

Corresponding authors

Correspondence to Yan Zhang, Dan Ding, Jibin Song or Kanyi Pu.

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Nature Nanotechnology thanks Marc Vendrell and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Xu, C., Qin, X., Wei, X. et al. A cascade X-ray energy converting approach toward radio-afterglow cancer theranostics. Nat. Nanotechnol. 20, 286–295 (2025). https://doi.org/10.1038/s41565-024-01809-9

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