细胞内
癌症研究
免疫系统
癌细胞
新陈代谢
细胞毒性
转移
活性氧
免疫原性细胞死亡
化学
氧化还原
细胞生物学
程序性细胞死亡
生物物理学
生物
生物化学
癌症
细胞凋亡
免疫学
体外
遗传学
有机化学
作者
He Zu,Yanxian Wu,Hongyu Meng,Xiaju Cheng,Yangyun Wang,Leshuai W. Zhang,Yong Wang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-08-22
标识
DOI:10.1021/acsnano.3c10588
摘要
Cuproptosis is an emerging form of cell death that relies on the targeted delivery of copper ions to lipoylated tricarboxylic acid cycle proteins. However, a major challenge associated with cuproptosis is its potential to kill both normal and tumor cells without discrimination. Therefore, it is crucial to develop strategies for precise intracellular delivery and redox control of copper to create effective cuproptosis-based tumor therapies. We have introduced a class of nanoagents called metabolism aiming Cu2–xS (MACuS) through a glucose-mediated biomineralization approach. MACuS nanoagents can be specifically targeted to tumors via the glucose transport receptor 1, and we found that NIR-II irradiation can not only result in direct hyperthermia ablation of tumor cells but also facilitate efficient cuproptosis and enhance reactive oxygen species-induced cytotoxicity in tumor cells. As a result, the triple effect of MACuS treatment induced immunogenic cell death, which triggered systemic antitumor immune responses and demonstrated potent efficacy in inhibiting growth, metastasis, and recurrence in mouse and rabbit breast cancer models. The precise intracellular delivery and redox control of copper provided by MACuS hold great potential for the development of highly efficient cuproptosis-based tumor therapies with minimal off-target effects.
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