上睑下垂
癌症治疗
铜
癌症研究
癌症
医学
材料科学
化学
内科学
细胞凋亡
冶金
程序性细胞死亡
生物化学
作者
Jun Zhong,Xiao-Chang Lu,Xiang Zheng,Ranjith Kumar Kankala,Sheng Wang,Ai‐Zheng Chen
出处
期刊:ACS materials letters
[American Chemical Society]
日期:2024-08-20
卷期号:: 4282-4290
标识
DOI:10.1021/acsmaterialslett.4c01142
摘要
Copper overload shows promise as a therapeutic strategy by disrupting copper homeostasis and inducing cell death pathways. However, challenges include the expulsion of excess copper from cells. This study introduces ZCCP NPs, three-metal MOF nanoparticles that amplify reactive oxygen species (ROS) to enhance cellular copper uptake and reduce copper efflux. In the tumor microenvironment, ZCCP NPs decompose in response to H+ and glutathione (GSH), releasing Zn and Co ions that increase intracellular ROS. Additionally, the TMPyP ligand converts to Phlorin under near-infrared (NIR) excitation, raising tumor site temperature and increasing cancer cell susceptibility to cuproptosis. Elevated ROS and temperature activate the NLRP3 inflammasome and Caspase-1, leading to gasdermin D cleavage and pyroptosis. Enhanced ROS generation impairs mitochondrial function and reduces copper efflux protein ATP7A expression, promoting cuproptosis. This strategy combines pyroptosis and cuproptosis for effective tumor treatment.
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