A cuproptosis nanocapsule for cancer radiotherapy

Menée à l'aide de lignées cellulaires, de modèles murins et d'échantillons tumoraux issus de patientes atteintes d'un cancer du col de l'utérus, cette étude met en évidence l'intérêt de nanocapsules de polyoxométalate capables, sous irradiation, de libérer du cuivre et de déclencher la cuproptose pour sensibiliser les cellules cancéreuses résiduelles aux rayonnements ionisants

Résumé en anglais

Residual tumours that persist after radiotherapy often develop acquired radiation resistance, increasing the risk of recurrence and metastasis while providing obstacles to re-irradiation. Using samples from patients and experimental mice, we discovered that FDX1 and LIAS, key regulators of cuproptosis, were up-regulated in residual tumours following radiotherapy, conferring the increased sensitivity to cuproptosis. Therefore, we proposed a novel radiosensitization strategy focused on cuproptosis, using a copper-containing nanocapsule-like polyoxometalate as a paradigm. In an initial demonstration, we showed that the nanocapsule released copper ions in a controlled manner upon exposure to ionizing radiation. Furthermore, radiation-triggered cuproptosis overcame acquired radiation resistance even at clinically relevant radiation doses and activated a robust abscopal effect, with a 40% cure rate in both radioresistant and re-irradiation tumour models. Collectively, targeting cuproptosis is a compelling strategy for addressing acquired radiation resistance, optimizing the local antitumour effects of radiotherapy while simultaneously activating systemic antitumour immunity.