Abstract
Persistent luminescence is a promising approach for photodynamic therapy (PDT) in deep-seated tumors, as it provides sustained light within tissues, eliminating the need for continuous external illumination. However, the uncontrollability of light within the body complicates precise spatiotemporal regulation. In this study, we report X-ray preactivated elimusertib-loaded tumor-targeted photodynamic nanoparticles (ETPNs), featuring reversible “on-off” afterglow properties. The excellent afterglow properties of X-ray-activated porous NaYF4:Er@NaGdF4 persistent luminescence nanoparticles enable the continuous activation of chlorin e6 (Ce6) to generate reactive oxygen species (ROS), leading to DNA damage. The integration of elimusertib potentiates ROS-induced DNA damage and activates the cGAS-STING pathway, thereby enhancing immuno-photodynamic therapeutic efficacy. All in vivo experiments were conducted using female mice. Our findings highlight the potential of ETPNs to advance the therapeutic landscape for deep-seated tumors, offering a robust and controllable platform for combined immuno-photodynamic therapy.
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All data underlying this study are available from the corresponding author upon request (and its Supplementary Information files). Source data are provided with this paper.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (Nos. 82473007, 82202873, 52173290, T2122003, and W2433188); Zhejiang Provincial Natural Science Foundation of China (No. LR25H160001); The Fundamental Research Funds for the Central Universities (No. 226-2025-00172); and State Key Laboratory of Advanced Drug Delivery and Release Systems (No. DSQZ-QN-202303). The authors would like to thank Huiwen Wang and Chaogang Xing from the Analysis Center of Agrobiology and Environmental Sciences, Zhejiang University; Yayu Qiu from the Department of Chemistry, Zhejiang University; Yu Liu and Xinhang Jiang from the College of Life Sciences, Zhejiang University; Lucheng Cai from the School of Materials Science and Engineering, Zhejiang University, and Guoqing Zhu from the Center for Electron Microscopy of Zhejiang University for their technical assistance in nanoparticle characterization; Yuchen Zhang from the Center of Cryo-Electron Microscopy (CCEM), Zhejiang University for technical assistance on Cryo-TEM; as well as Qike Jiang from the Instrumentation and Service Center for Physical Sciences, Westlake University for technical assistance on HAADF-STEM. The figures in this article were created using Adobe Illustrator, Adobe Photoshop, BioRender, Blender v4.0, and Microsoft PowerPoint.
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W. Topatana, Y. Sun, T. Xie, Y. Zhu, S. Juengpanich, and M. Chen designed the experiments, analyzed the data, and wrote the manuscript. X. Cai, R. Deng, S. Juengpanich, and M. Chen supervised the project and revised the manuscript. W. Topatana, T. Xie, Y. Zhu, T. Yang, P. Ran, C. Li, J. Chen, and Z. Lu synthesized and characterized the nanoparticles. W. Topatana, Y. Sun, R. Shen, X. Shen, Y. Han, Y. Shan, S. Li, and T. Chen performed in vitro and in vivo experiments. All authors discussed the results throughout the project and approved the final version of the manuscript.
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Topatana, W., Sun, Y., Xie, T. et al. X-ray preactivated reversible persistent luminescence enables photodynamic immunotherapy of deep tumors. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71028-4
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DOI: https://doi.org/10.1038/s41467-026-71028-4
