Synergistic cancer treatment with PCuLu nanocatalysts by inducing cuproptosis and enhancing radiotherapy

The X-ray-induced photodynamic therapy (X-PDT) has brought significant promise for treating deeply seated cancers in clinical settings. However, the clinical application of X-PDT remains limited, primarily due to the issues related to cancer cells' intrinsic antioxidant mechanisms and radiotherapy's low efficacy. To address these issues, this study presents a nanocatalyst-based radiosensitizer PCuLu, which is meticulously designed and constructed to enhance the effectiveness of X-PDT combined with copper-induced cell death (Cuproptosis) for tumor treatment. Leveraging the unique properties of the rare-earth element lutetium, PCuLu effectively absorbs X-rays and deposits the radiation energy, causing irreversible damage to the deoxyribonucleic acid (DNA) of cancer cells. The PCuLu nanocatalyst also promotes enhanced cuproptosis, further amplifying the therapeutic effects of X-PDT. Our findings reveal the beneficial role of enhancing copper toxicity in radiotherapy (RT), offering a new strategy for the synergistic integration of cuproptosis with radiation therapy. This work broadens the scope of copper-mediated cancer treatment. It provides a promising approach to overcoming the current limitations in X-PDT, potentially leading to more effective clinical outcomes in tumor treatment.