Cuproptosis-based nanoparticles for cascade reaction to boost radioimmunotherapy
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Updated: Oct 28, 2026
Synthesis of Immunotargeted Magneto-plasmonic Nanoclusters
Published on: August 22, 2014
Yang Zhong1, Yang Zhang2, Wei Peng3
1School of Nuclear Science and Technology, University of Science and Technology of China, Hefei 230026, China; Anhui Province Key Laboratory of Occupational Health, Anhui No. 2 Provincial People's Hospital, Hefei 230031, China.
Background:
Radiation resistance significantly limits the effectiveness of radiotherapy, presenting substantial challenges in breast cancer treatment.
Methods:
This work developed a novel cuproptosis-based nanoparticle system, ZnO2@Cu, composed of a ZnO2 core and a Cu-doped polydopamine shell. The nanoparticles were characterized using transmission electron microscopy (TEM) for morphology, X-ray photoelectron spectroscopy (XPS) for elemental analysis, and dynamic light scattering (DLS) for stability assessment. In the mild acidic tumor microenvironment, ZnO2@Cu decomposed, releasing copper ions and ZnO2, which generated significant amounts of H2O2. The released copper ions triggered cuproptosis and depleted glutathione (GSH), while also converting H2O2 into toxic reactive oxygen species (ROS) through Fenton-like activity. Upon X-ray irradiation, the radiotherapy-induced tumor cell death synergized with copper ion-induced cuproptosis and the Fenton-like activity promoted by ZnO2@Cu.
Conclusion:
In vivo experiments demonstrated that ZnO2@Cu mediated a cascade reaction that generated abundant ROS, induced cuproptosis by disrupting copper metabolism, and effectively killed tumor cells under X-ray irradiation. This process promoted immunogenic cell death (ICD), activated systemic immune responses, and alleviated radioresistance through ROS generation and cuproptosis, leading to enhanced tumor suppression.
