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

Pengjun Yuan; Yujing Wang; Ao Wang; Jinhui Lin; Xingzhu Chen; Xiyu Liu; Yingrui Zhang; Wenjuan Gao; Peiyuan Wang; Guilong Zhang; Lu Liu

doi:10.1016/j.jcis.2025.138260

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

J Colloid Interface Sci. 2025 Jun 20;699(Pt 2):138260. doi: 10.1016/j.jcis.2025.138260. Online ahead of print.

Authors

Pengjun Yuan¹, Yujing Wang¹, Ao Wang², Jinhui Lin², Xingzhu Chen¹, Xiyu Liu¹, Yingrui Zhang¹, Wenjuan Gao¹, Peiyuan Wang³, Guilong Zhang⁴, Lu Liu⁵

Affiliations

¹ School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, PR China.
² Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences (CAS), Fuzhou, China.
³ Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences (CAS), Fuzhou, China. Electronic address: wangpeiyuan@fjirsm.ac.cn.
⁴ School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, PR China. Electronic address: glzhang@bzmc.edu.cn.
⁵ School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, PR China. Electronic address: luliu@bzmc.edu.cn.

PMID: 40578089
DOI: 10.1016/j.jcis.2025.138260

Abstract

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.

Keywords: Cancer treatment; Cuproptosis; Nanocatalyst; X-ray-induced photodynamic therapy (X-PDT).