Stimuli-responsive copper-iodide nanoparticles for low-dose X-ray-induced photodynamic therapy and enhanced cuproptosis

  • Acta Biomater. 2026 Jun:216:379-388. doi: 10.1016/j.actbio.2026.04.017.
Chao Xu  1 ,  Muzhen He  1 ,  Nuo Lin  2 ,  Xiaoqian Ma  2 ,  Lixuan Ren  2 ,  Shileng Chen  2 ,  Lu Liu  2 ,  Haizhen Ding  2 ,  Peifei Liu  2 ,  Qunying Shi  2 ,  Ke Hu  2 ,  Zhujun Pan  2 ,  Yimin Li  3 ,  Hongmin Chen  4 ,  Fangqin Xue  5
Affiliations
  • 1. Department of Gastrointestinal Surgery and Department of Radiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, China.
  • 2. State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Intergration in Vaccine Research, School of Public Health, Xiamen University, Xiamen 361102, China.
  • 3. Department of Radiation Oncology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China. Electronic address: [email protected].
  • 4. Department of Gastrointestinal Surgery and Department of Radiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, China; State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Intergration in Vaccine Research, School of Public Health, Xiamen University, Xiamen 361102, China; Department of Radiation Oncology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China. Electronic address: [email protected].
  • 5. Department of Gastrointestinal Surgery and Department of Radiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, China. Electronic address: [email protected].
PMID: 41990934 DOI: 10.1016/j.actbio.2026.04.017
Abstract

High-dose radiotherapy is known to enhance Cuproptosis, and when combined with copper-coordinated delivery to tumors, it shows promise as a synergistic treatment mechanism. In this study, we present a simple method for synthesizing stimuli-responsive copper-iodide nanoparticles using a commercial, insoluble copper-iodide powder that emitted a strong radioluminescence matching the absorbance of the clinical dye indocyanine green. The copper-iodide nanoparticles efficiently absorbed and transferred radiation energy to ICG activating an X-ray-induced photodynamic therapy (X-PDT) mechanism. After accumulating in tumors, the low-dose X-PDT process first generated Reactive Oxygen Species to induce cell death. The tumor microenvironment then caused the copper-iodide nanoparticles to decompose and release copper and iodide ions, which promoted Cuproptosis. X-PDT followed by ion-induced cell death achieved 87.7% tumor regression in CT26 tumor-bearing mice without systemic toxicity. This work establishes a therapeutic paradigm that exploits metal metabolism dysregulation to potentiate radiation-based therapies. STATEMENT OF SIGNIFICANCE: Stimuli-responsive copper-iodide nanoparticles were synthesized and induced by X-ray-induced photodynamic therapy to decompose, releasing copper and iodide ions that caused tumor cell death. (1) Commercial copper-iodide powder exhibited strong radioluminescent properties and formed stable nanoparticles with the clinical dye indocyanine green, which realized X-ray-induced photodynamic therapy under X-ray irradiation. (2) After accumulating in tumors and following X-ray-induced photodynamic therapy, the decomposition of copper-iodide nanoparticles in the tumor tissue induced cell death.

Keywords
Copper-iodide nanoparticles; Cuproptosis; Stimuli-responsive property; X-ray-induced photodynamic therapy.
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