Boosting cuproptosis by activating JAK-STAT signaling pathway and synergrtic with interface-enhanced sonodynamic immunotherapy against cancer

IF 13.2 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today Pub Date : 2025-03-15 DOI:10.1016/j.nantod.2025.102701

Changhong Zhao , Xinshu Zhu , Huili Yang , Fei Kong , Yuxin Yang , Ruohan Gong , Yuqiong Yang , Qinglu Luo , Ruike Zhang , Jieni Fu , Zhenhong Su , Yuan Li , Hongbo Wu

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Abstract

The poor immunogenicity of most tumors caused low eﬃcacy of immunotherapy underlines the importance of activating immune system and provoking immunogenic apoptosis to enhance the treatment efficiency of immunotherapy. Here, the heterojunction was designed against breast cancer through eliciting localized sonodynamic therapy and activating cuproptosis-mediated immunotherapy. The enhanced piezocatalysis effect of Cu₂O/vanadium carbide/curcumin (Cu₂O/V₂C/Cur) mainly originated from the formation of dual interfacial electric field in the heterojunction of Cu₂O/V₂C under ultrasound irradiation, which can efficiently improve the separation efficiency of electron-hole pairs, inhibit their compounding efficiency, thus enhance the sonodynamic activity. During the process, the apoptosis caused by cuproptosis was also enhanced by down-regulating the expression of downstream cuproptosis-related genes and enhancing the over-accumulation of Cu^2 + in mitochondrial respiration-dependent cells through activating JAK-STAT signaling pathway in 4T1 cells. Meanwhile, Cu₂O/V₂C/Cur also activated immune response by modulating the proportion of CD8⁺ T cells, which synergizes with sonodynamic-enhanced cuproptosis to efficiently treat breast cancer. Thus, this investigation put up with a feasible method for enhancing the treatment efficiency of immunotherapy by designing a sonodynamic-enhanced cuproptosis strategy.

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通过激活JAK-STAT信号通路促进铜细胞增生，并与界面增强声动力免疫治疗协同对抗癌症

大多数肿瘤的免疫原性较差，导致免疫治疗效果不佳，因此激活免疫系统和激发免疫原性细胞凋亡对提高免疫治疗效果非常重要。在这里，异质结通过激发局部声动力疗法和激活铜胞嘧啶介导的免疫疗法来对抗乳腺癌。Cu2O/碳化钒/姜黄素（Cu2O/V2C/Cur）增强的压电催化效果主要源于超声照射下Cu2O/V2C异质结形成双界面电场，有效提高电子-空穴对的分离效率，抑制其复合效率，从而增强声动力活性。在此过程中，4T1细胞通过激活JAK-STAT信号通路，下调下游cuprotoosis相关基因的表达，增强线粒体呼吸依赖细胞中Cu2 +的过度积累，从而增强cuprotosis引起的凋亡。同时，Cu2O/V2C/Cur还通过调节CD8+ T细胞的比例激活免疫应答，与声动力增强cuprotosis协同作用，有效治疗乳腺癌。因此，本研究提出了一种可行的方法来提高免疫治疗的治疗效率，设计一种声动力增强的铜凸策略。

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来源期刊

Nano Today 工程技术-材料科学：综合

CiteScore

21.50

自引率

3.40%

发文量

305

审稿时长

40 days

期刊介绍： Nano Today is a journal dedicated to publishing influential and innovative work in the field of nanoscience and technology. It covers a wide range of subject areas including biomaterials, materials chemistry, materials science, chemistry, bioengineering, biochemistry, genetics and molecular biology, engineering, and nanotechnology. The journal considers articles that inform readers about the latest research, breakthroughs, and topical issues in these fields. It provides comprehensive coverage through a mixture of peer-reviewed articles, research news, and information on key developments. Nano Today is abstracted and indexed in Science Citation Index, Ei Compendex, Embase, Scopus, and INSPEC.