Yuan Pengjun, Wang Yujing, Wang Ao, Lin Jinhui, Chen Xingzhu, Liu Xiyu, Zhang Yingrui, Gao Wenjuan, Wang Peiyuan, Zhang Guilong, Liu Lu
School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, PR China.
Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences (CAS), Fuzhou, China.
J Colloid Interface Sci. 2025 Dec;699(Pt 2):138260. doi: 10.1016/j.jcis.2025.138260. Epub 2025 Jun 20.
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.
X射线诱导的光动力疗法（X-PDT）在临床环境中治疗深部癌症方面带来了巨大希望。然而，X-PDT的临床应用仍然有限，主要是由于与癌细胞内在抗氧化机制相关的问题以及放射治疗的低疗效。为了解决这些问题，本研究提出了一种基于纳米催化剂的放射增敏剂PCuLu，它经过精心设计和构建，以增强X-PDT联合铜诱导的细胞死亡（铜死亡）治疗肿瘤的效果。利用稀土元素镥的独特性质，PCuLu有效地吸收X射线并沉积辐射能量，对癌细胞的脱氧核糖核酸（DNA）造成不可逆的损伤。PCuLu纳米催化剂还促进增强的铜死亡，进一步放大X-PDT的治疗效果。我们的研究结果揭示了增强铜毒性在放射治疗（RT）中的有益作用，为铜死亡与放射治疗的协同整合提供了一种新策略。这项工作拓宽了铜介导的癌症治疗范围。它提供了一种有前途的方法来克服当前X-PDT的局限性，有可能在肿瘤治疗中带来更有效的临床结果。
