Xin Le, Ning Shipeng, Wang Hongwei, Shi Runze
Department of General Surgery, Longgang Central Hospital of Shenzhen, Shenzhen, 518116, People's Republic of China.
Department of Breast Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530031, People's Republic of China.
Int J Nanomedicine. 2025 Mar 19;20:3643-3652. doi: 10.2147/IJN.S504148. eCollection 2025.
Cuproptosis, distinguished from apoptosis, necroptosis, pyroptosis, and ferroptosis, is a current form of programmed cell death that provides novel strategies for tumor therapy. Nanotechnology inducing cuproptosis showed potential in tumor ablation. However, these strategies might induce cellular damage due to a lack of tumor-targeting ability or insufficient tumor inhibition alone.
Here, biomimetic copper-doped polydopamine nanoparticles (PC NPs) were developed to specifically induce tumor cell cuproptosis to enhance radiotherapy (RT). PC NPs were characterized before application for tumor ablation.
These PC NPs improve tumor targeting and accumulation. After entering the tumor region, PC degrades in cells responsive to acidic tumor microenvironment (TME). Next, Cu is reduced to Cu after consuming overexpressed glutathione (GSH), which induces dihydrolipoamide S-acetyltransferase (DLAT) aggression and cuproptosis. Under RT, reactive oxygen species (ROS) are generated and consume GSH, leading to cuproptosis. The decreasing of GSH content in tumor tissues can improve the treatment effect of RT by inhibiting self-repair of tumor cells, hindering cell survival and proliferation. The combination of PC and RT alleviate tumor growth, reaching a tumor growth inhibition rate of 93.0%.
This tumor-specific targeting nano platform is a valuable radiosensitizer responsive to TME for improving therapeutic efficacy against tumors.
铜死亡不同于凋亡、坏死性凋亡、焦亡和铁死亡，是一种程序性细胞死亡的新形式，为肿瘤治疗提供了新策略。诱导铜死亡的纳米技术在肿瘤消融方面显示出潜力。然而，由于缺乏肿瘤靶向能力或单独的肿瘤抑制作用不足，这些策略可能会诱导细胞损伤。
在此，开发了仿生铜掺杂聚多巴胺纳米颗粒（PC NPs）以特异性诱导肿瘤细胞铜死亡，从而增强放射治疗（RT）。在应用于肿瘤消融之前对PC NPs进行了表征。
这些PC NPs改善了肿瘤靶向性和蓄积。进入肿瘤区域后，PC在对酸性肿瘤微环境（TME）有反应的细胞中降解。接下来，铜在消耗过表达的谷胱甘肽（GSH）后还原为亚铜，从而诱导二氢硫辛酰胺S - 乙酰转移酶（DLAT）损伤和铜死亡。在放疗过程中，会产生活性氧（ROS）并消耗GSH，导致铜死亡。肿瘤组织中GSH含量的降低可通过抑制肿瘤细胞的自我修复、阻碍细胞存活和增殖来提高放疗的治疗效果。PC与放疗的联合应用可减轻肿瘤生长，肿瘤生长抑制率达到93.0%。
这种肿瘤特异性靶向纳米平台是一种有价值的对TME有反应的放射增敏剂，可提高对肿瘤的治疗效果。
