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Molecular radio afterglow probes for cancer radiodynamic theranostics

Nature Materials volume 22, pages 1421–1429 (2023)Cite this article

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Abstract

X-ray-induced afterglow and radiodynamic therapy tackle the tissue penetration issue of optical imaging and phototherapy. However, inorganic nanophosphors used in this therapy have their radio afterglow dynamic function as always on, limiting the detection specificity and treatment efficacy. Here we report organic luminophores (IDPAs) with near-infrared afterglow and 1O2 production after X-ray irradiation for cancer theranostics. The in vivo radio afterglow of IDPAs is >25.0 times brighter than reported inorganic nanophosphors, whereas the radiodynamic production of 1O2 is >5.7 times higher than commercially available radio sensitizers. The modular structure of IDPAs permits the development of a smart molecular probe that only triggers its radio afterglow dynamic function in the presence of a cancer biomarker. Thus, the probe enables the ultrasensitive detection of a diminutive tumour (0.64 mm) with superb contrast (tumour-to-background ratio of 234) and tumour-specific radiotherapy for brain tumour with molecular precision at low dosage. Our work reveals the molecular guidelines towards organic radio afterglow agents and highlights new opportunities for cancer radio theranostics.

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Fig. 1: Synthesis and characterization of radio afterglow dynamic luminophores.
Fig. 2: Deep-tissue radio afterglow dynamic process.
Fig. 3: In vitro studies for radio afterglow dynamic cancer theranostics.
Fig. 4: MRAP-mediated RAI and RDT.
Fig. 5: MRAP-mediated ultrasmall-tumour detection and precision tumour ablation.

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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

K.P. thanks Singapore National Research Foundation (NRF) (NRF-NRFI07-2021-0005) and the Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19, RT05/20) and Academic Research Fund Tier 2 (MOE-T2EP30220-0010, MOE-T2EP30221-0004) for financial support. R.Z. thanks the National Natural Science Foundation of China (nos. 82120108016 and 82071987) for financial support. J.S. thanks the National Natural Science Foundation of China (No. U22A20348, U21A20377) and the Natural Science Foundation of Fujian Province (No. 2020J02012).

Author information

Authors and Affiliations

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

    Jingsheng Huang, Cheng Xu & Kanyi Pu

  2. College of Chemical Engineering and College of Chemistry, Fuzhou University, Fuzhou, People’s Republic of China

    Lichao Su, Xiaoguang Ge & Jibin Song

  3. Department of Radiology, Shanxi Provincial People’s Hospital, Taiyuan, People’s Republic of China

    Ruiping Zhang

  4. College of Chemistry, Beijing University of Chemical Technology, Beijing, People’s Republic of China

    Jibin Song

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

    Kanyi Pu

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Contributions

J.H., L.S. and C.X. contributed equally to this paper. K.P. conceived and designed the study. J.H. synthesized and characterized the molecules. L.S. performed the cell and animal studies. J.H., L.S., C.X., R.Z., J.S. and K.P. analysed the data and drew the figures. X.G. helped in the experiments. J.H., C.X. and K.P. drafted the manuscript. R.Z., J.S. and K.P. revised the manuscript. All authors contributed to the writing of this paper.

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Correspondence to Ruiping Zhang, Jibin Song or Kanyi Pu.

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Nature Materials thanks Cyrille Richard and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Radioafterglow mechanism and photophysical property study.

(a) Proposed radioafterglow mechanism of IDPASu and HRMS analysis of the new peaks at 6.0 (b) and 14.8 min (c) in Fig. 1g, confirming the generation of dioxetane intermediate and activated IDPASu. (d) Radioafterglow intensity of IDPASu as a function of its concentration in PBS (0.01 M, pH 7.4, 50% DMSO) after X-ray irradiation at 250 μGy•s−1 for 20 s. Data were presented as mean ± s.d (n = 3 independent experiments). (e) Temperature of PBS and IDPASu (100 mM) in PBS (0.01 M, pH 7.4, 50% DMSO) before and after X-ray irradiation at 250 μGy•s−1 for 20 s at room temperature. Data were presented as mean ± s.d (n = 3 independent experiments).

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Huang, J., Su, L., Xu, C. et al. Molecular radio afterglow probes for cancer radiodynamic theranostics. Nat. Mater. 22, 1421–1429 (2023). https://doi.org/10.1038/s41563-023-01659-1

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