Cu0-based nanoparticles boost anti-tumor efficacy via synergy of cuproptosis and ferroptosis enhanced by cuproptosis-induced glutathione synthesis disorder

被引：3

作者：

Wan, Yichen ^{[1
]}

Chen, Junge ^{[2
]}

Li, Jiaxuan ^{[1
]}

Chen, Zelong ^{[1
]}

Wang, Yi ^{[1
]}

Li, Jiahui ^{[1
]}

Pei, Zhichao ^{[1
]}

Pei, Yuxin ^{[1
]}

机构：

[1] Northwest A&F Univ, Coll Chem & Pharm, Yangling 712100, Shaanxi, Peoples R China

[2] Beihang Univ, Beijing Adv Innovat Ctr Biomed Engn, Sch Engn Med, Key Lab Biomech & Mechanobiol,Minist Educ, Beijing 100083, Peoples R China

来源：

COLLOIDS AND SURFACES B-BIOINTERFACES | 2025年 / 245卷

基金：

中国国家自然科学基金;

关键词：

Cuproptosis; Ferroptosis; Glutathione synthesis; Zero-valent copper; Synergistic therapy;

D O I：

10.1016/j.colsurfb.2024.114196

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

Apoptotic resistance of tumor often leads to poor efficacy from mono-therapy based on apoptosis. Cuproptosis, a new type of non-apoptotic cell death related to mitochondrial dysfunction, can alter metabolism and enhance ferroptosis, providing a promising strategy for effective synergistic cancer treatment. In this work, Cu-0-based nanoparticles (denoted as HA-ZCu) were successfully developed to improve anti-tumor efficacy by combining cuproptosis with enhanced ferroptosis, which was achieved by cuproptosis-induced glutathione synthesis disorder. In vitro studies revealed that HA-ZCu effectively induced cuproptosis and ferroptosis in HepG2 cells. Moreover, HA-ZCu induced mitochondrial dysfunction and decreased intracellular adenosine triphosphate (ATP), glutamate, and glutathione, demonstrating the effective synergy. In vivo studies further approved the synergistic therapeutic efficacy of HA-ZCu, where the inhibition rate of tumor growth reached 83.2 %. This work represents the first example of enhanced anti-tumor efficacy via cuproptosis and ferroptosis synergy through cuproptosis-induced glutathione synthesis disorder.

引用

页数：9