Zhu Lichao, Guo Zhisheng, Luo Yu, Huang Haiyan, Zhang Kexin, Duan Bingbing, Peng Renmiao, Yao Haochen, Liang Chao, Wang Kaiyang
Shanghai Engineering Research Center of Pharmaceutical Intelligent Equipment, Shanghai Frontiers Science Research Center for Druggability of Cardiovascular Non-coding RNA, Institute for Frontier Medical Technology, School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, 201620, P. R. China.
Department of Urology, The First Affiliated Hospital of Nanjing Medical University and Jiangsu Province Hospital, Nanjing, 210029, P. R. China.
Adv Sci (Weinh). 2025 Aug;12(29):e00576. doi: 10.1002/advs.202500576. Epub 2025 May 21.
The spatiotemporal sequential treatment strategy of promoting rapid separation of charge carriers, amplifying oxidative stress, increasing the low content of intracellular Cu, enhancing cuproptosis, and cascading activation of immunotherapy is considered one of the most effective techniques for improving the comprehensive therapy of tumors. Herein, copper tungstate (CuWO₄, CWO) nanoparticles with ultrasmall bandgap (1.71 eV) is developed as both piezoelectric-catalysis agents and copper nanocarriers for synergistic sono-enhanced cuproptosis. Owing to the unique bandgap microstructure, exposure to ultrasound (US) significantly increase the generation of reactive oxygen species (ROS) and the release of Cu from CWO. Additionally, ≈60% of glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) are consumed in situ, leading to oxidative stress, ferroptosis, and cuproptosis in cancer cells. This cascading approach induces substantial mitochondrial dysfunction and the release of damage-associated molecular patterns (DAMPs), which promotes immunogenic cell death (ICD) and augments antitumor immunity. Both in vitro and in vivo studies have shown that this sono-enhanced cuproptosis-based therapy could effectively suppress tumor growth. Overall, this study investigates a novel Structure-Function therapeutic approach that combines piezoelectric catalysis, ferroptosis, cuproptosis, and cascade activation of immune regulation, opening up new possibilities for addressing the challenges associated with conventional cuproptosis therapy.
促进电荷载流子快速分离、放大氧化应激、增加细胞内低含量铜、增强铜死亡以及级联激活免疫治疗的时空序贯治疗策略被认为是改善肿瘤综合治疗的最有效技术之一。在此，开发了具有超小带隙（1.71 eV）的钨酸铜（CuWO₄，CWO）纳米颗粒作为压电催化剂和铜纳米载体，用于协同声增强铜死亡。由于独特的带隙微观结构，暴露于超声（US）会显著增加活性氧（ROS）的产生以及CWO中铜的释放。此外，约60%的谷胱甘肽（GSH）和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）在原位被消耗，导致癌细胞发生氧化应激、铁死亡和铜死亡。这种级联方法会诱导大量线粒体功能障碍以及损伤相关分子模式（DAMPs）的释放，从而促进免疫原性细胞死亡（ICD）并增强抗肿瘤免疫力。体外和体内研究均表明，这种基于声增强铜死亡的治疗方法能够有效抑制肿瘤生长。总体而言，本研究探索了一种将压电催化、铁死亡、铜死亡和免疫调节级联激活相结合的新型结构 - 功能治疗方法，为应对传统铜死亡治疗相关挑战开辟了新的可能性。
