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Responsive ROS-Augmented Prodrug Hybridization Nanoassemblies for Multidimensionally Synergitic Treatment of Hepatocellular Carcinoma in Cascade Assaults

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机构: [1]Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China [2]Hosp Chengdu Univ Tradit Chinese Med, Dept Resp Med, Chengdu 610075, Peoples R China [3]Hebei Univ Chinese Med, Coll Pharm, Shijiazhuang 050200, Peoples R China [4]Univ Elect Sci & Technol China, Sichuan Canc Hosp & Inst, Sichuan Clin Res Ctr Canc, Sichuan Canc Ctr,Affiliated Canc Hosp, Chengdu 610041, Peoples R China
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关键词: cascade assaults cuproptosis hepatocellular carcinoma oxidative stress prodrug hybridization nanoassembly

摘要:
The rapid deterioration and progression of hepatocellular carcinoma (HCC) is intimately associated with copper ion overload, and integrating the cuproptosis mechanism for the treatment of HCC presents a promising prospect. Nevertheless, cell death complexity renders efficient removal of all HCC cells insufficient solely relying on the cuproptosis pathway. Herein, the GSH-responsive prodrug hybridization nanoassembly CA-4S2@ES-Cu is exploited, which targets the delivery of copper ions to mitochondria via Elesclomol, contributing to mitochondrial dysfunction and evoking cuproptosis. Simultaneously, CA-4S2 depletes GSH to release CA-4, disrupting microtubule function and suppressing HCC cell proliferation and angiogenesis, to realize a dual attack against copper ion-mediated deterioration and metastasis of HCC. Furthermore, both in the HCC mouse model synergistically elicit oxidative stress to amplify the cuproptosis effect and release activated immunogenetic cell death to initiate a vigorous antitumor immune response in cascade assault modality. Conclusively, the multilevel synergistic assault penetrates the limitations of single therapy and implements a multidimensional targeted treatment for HCC.

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出版当年[2025]版:
大类 | 1 区 综合性期刊
小类 | 1 区 化学:综合 1 区 材料科学:综合 1 区 纳米科技
最新[2025]版:
大类 | 1 区 综合性期刊
小类 | 1 区 化学:综合 1 区 材料科学:综合 1 区 纳米科技
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出版当年[2024]版:
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY
最新[2024]版:
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY

影响因子: 最新[2024版] 最新五年平均 出版当年[2024版] 出版当年五年平均 出版前一年[2024版]

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第一作者机构: [1]Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China
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