Up-regulation of FDX1 and LIAS in tumor cells after X-ray irradiation. Credit: Nature Nanotechnology (2024). DOI: 10.1038/s41565-024-01784-1

In a study published in Nature Nanotechnology, researchers discovered that cuproptosis may serve as a new target for radiosensitization in re-irradiation.

In cancer treatment, patients who undergo secondary radiotherapy often face the dual challenge of acquired radiation resistance in tumor cells and weakened physical condition, making re-irradiation a significant clinical challenge. This is especially true for advanced cancer patients and elderly individuals who have a pressing need for radiosensitizing drugs during clinical radiotherapy.
Using synchrotron radiation facilities, researchers for the first time found that cuproptosis-related proteins in tumor tissues were highly expressed under X-ray irradiation, and revealed a novel cell death mechanism induced by copper ions—cuproptosis which could serve as a new target for radiosensitization.
Based on this, researchers designed and synthesized a copper-containing polyoxometalate, named PWCu, as a targeted radiosensitizer for re-irradiation.
The PWCu nanocapsules can enter tumor cells, release copper ions during radiotherapy to trigger cuproptosis, overcoming acquired radiation resistance in tumors. In addition, they can activate an abscopal effect, inducing immunogenic cell death and stimulating an antitumor immune response.
These findings suggest that the PWCu nanocapsules offer a multifaceted strategy that not only enhances the local antitumor effects of radiotherapy but also activates systemic antitumor immunity. The potential of this strategy to improve patient outcomes, especially in the context of recurrent and metastatic diseases, is immense.

Additionally, researchers established advanced analytical methods using synchrotron radiation facilities to study the oxidation states, biological distribution, and metabolic transformation of copper ions within tumor tissues, providing direct methodological support for the research on structure-function relationships and metabolic processes of copper drug-based radiosensitizers, which is essential for preclinical safety and pharmacokinetic evaluation.
This study offers a new solution to the clinical challenge of re-irradiation in cancer patients, with significant academic significance and promising clinical applications.
The team includes Prof. Gu Zhanjun from the Institute of High Energy Physics of the Chinese Academy of Sciences, in collaboration with Dr. Yan Junfang and Dr. Zhang Fuquan from the Peking Union Medical College Hospital.

More information:
You Liao et al, A cuproptosis nanocapsule for cancer radiotherapy, Nature Nanotechnology (2024). DOI: 10.1038/s41565-024-01784-1

Provided by
Chinese Academy of Sciences

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Copper-based nanocapsules shown to enhance radiotherapy effectiveness (2024, September 20)
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