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author:

Zhang, D. (Zhang, D..) [1] | Chen, Q. (Chen, Q..) [2] | Zhang, J. (Zhang, J..) [3] | Xing, X. (Xing, X..) [4] | Zhou, Y. (Zhou, Y..) [5] | Ou, X. (Ou, X..) [6] | Dai, S. (Dai, S..) [7] | Liu, X. (Liu, X..) [9] | Chen, X. (Chen, X..) [10] | Zeng, Y. (Zeng, Y..) [11]

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Scopus

Abstract:

X-ray-induced photodynamic therapy offers substantial promise for treating deep-seated tumors, but it is still limited by highly inefficient energy transfer processes and the stringent requirements for scintillators with high luminescence quantum yield and significant singlet-triplet intersystem crossing ratios. Herein, we describe X-ray-induced electron-dynamic therapy (X-eDT), which obviates the need for intersystem crossing by exposing nonluminescent hafnium-silica nanoparticles to X-rays, to generate high-energy electrons that can sensitize lower-lying triplet states of various photosensitizers. Our approach strongly induced the production of singlet oxygen (6.18-fold) in vitro even at lower X-ray doses, and in mice it strongly inhibited the growth of xenografts derived from liver, breast, or colon cancer cell lines (CDX), and growth of patient-derived xenografts (PDX) of hepatocellular carcinoma. In these CDX preclinical systems, X-eDT was not only effective against the irradiated xenograft but also against untreated xenografts in the same animal, and these abscopal effects involved enhanced tumor infiltration by CD4+T cells, CD8+T cells, and IFN-γ-polarized M1 macrophages within the tumor microenvironment. X-eDT even stimulated the production of memory T cells that inhibited rechallenges after treatment. These findings suggest that X-eDT can be effective against primary and metastatic tumors as well as tumor recurrence, which makes it much more powerful than conventional X-PDT. © 2025 American Chemical Society.

Keyword:

abscopal effect immunity metastatic cancer radiosensitizer radiotherapy X-ray-induced electron-dynamic therapy

Community:

  • [ 1 ] [Zhang D.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 2 ] [Zhang D.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 3 ] [Chen Q.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 4 ] [Chen Q.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 5 ] [Zhang J.]Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China
  • [ 6 ] [Xing X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 7 ] [Xing X.]MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fuzhou University, Fuzhou, 350108, China
  • [ 8 ] [Zhou Y.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 9 ] [Zhou Y.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 10 ] [Ou X.]Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, SE-58183, Sweden
  • [ 11 ] [Dai S.]MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fuzhou University, Fuzhou, 350108, China
  • [ 12 ] [Chen Q.]MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fuzhou University, Fuzhou, 350108, China
  • [ 13 ] [Liu X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 14 ] [Liu X.]CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, China
  • [ 15 ] [Liu X.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
  • [ 16 ] [Chen X.]Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine, Faculty of Engineering, National University of Singapore, Singapore, 119074, Singapore
  • [ 17 ] [Chen X.]Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 138667, Singapore
  • [ 18 ] [Chen X.]Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 138667, Singapore
  • [ 19 ] [Zeng Y.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
  • [ 20 ] [Zeng Y.]Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China

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Source :

ACS Nano

ISSN: 1936-0851

Year: 2025

Issue: 17

Volume: 19

Page: 16775-16793

1 5 . 8 0 0

JCR@2023

Cited Count:

WoS CC Cited Count:

SCOPUS Cited Count:

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 4

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