Responsive ROS‐Augmented Prodrug Hybridization Nanoassemblies for Multidimensionally Synergitic Treatment of Hepatocellular Carcinoma in Cascade Assaults
Abstract 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...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202501420 |
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| author | Yingjie Zeng Yuening Cao Senmiao Ren Chaozheng Zhang Jianan Liu Ke Liu Yan Wang Hongyu Chen Fengjiao Zhou Xiuli Yang Xian Ge Tingting Zhang Tianbao Wang Yao He Defang Li Chuantao Zhang Jun Lu |
| author_facet | Yingjie Zeng Yuening Cao Senmiao Ren Chaozheng Zhang Jianan Liu Ke Liu Yan Wang Hongyu Chen Fengjiao Zhou Xiuli Yang Xian Ge Tingting Zhang Tianbao Wang Yao He Defang Li Chuantao Zhang Jun Lu |
| author_sort | Yingjie Zeng |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-1dad7de46b2c42bb91333cb0dbd77cdb |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-1dad7de46b2c42bb91333cb0dbd77cdb2025-08-20T04:01:15ZengWileyAdvanced Science2198-38442025-08-011229n/an/a10.1002/advs.202501420Responsive ROS‐Augmented Prodrug Hybridization Nanoassemblies for Multidimensionally Synergitic Treatment of Hepatocellular Carcinoma in Cascade AssaultsYingjie Zeng0Yuening Cao1Senmiao Ren2Chaozheng Zhang3Jianan Liu4Ke Liu5Yan Wang6Hongyu Chen7Fengjiao Zhou8Xiuli Yang9Xian Ge10Tingting Zhang11Tianbao Wang12Yao He13Defang Li14Chuantao Zhang15Jun Lu16State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu 611137 ChinaState Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu 611137 ChinaState Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu 611137 ChinaState Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu 611137 ChinaState Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu 611137 ChinaDepartment of Respiratory Medicine Hospital of Chengdu University of Traditional Chinese Medicine Chengdu 610075 ChinaState Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu 611137 ChinaState Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu 611137 ChinaDepartment of Respiratory Medicine Hospital of Chengdu University of Traditional Chinese Medicine Chengdu 610075 ChinaDepartment of Respiratory Medicine Hospital of Chengdu University of Traditional Chinese Medicine Chengdu 610075 ChinaState Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu 611137 ChinaState Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu 611137 ChinaSichuan Clinical Research Center for Cancer Sichuan Cancer Hospital & Institute Sichuan Cancer Center Affiliated Cancer Hospital of University of Electronic Science and Technology of China Chengdu 610041 ChinaState Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu 611137 ChinaCollege of Pharmacy Hebei University of Chinese Medicine Shijiazhuang 050200 ChinaDepartment of Respiratory Medicine Hospital of Chengdu University of Traditional Chinese Medicine Chengdu 610075 ChinaState Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu 611137 ChinaAbstract 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.https://doi.org/10.1002/advs.202501420cascade assaultscuproptosishepatocellular carcinomaoxidative stressprodrug hybridization nanoassembly |
| spellingShingle | Yingjie Zeng Yuening Cao Senmiao Ren Chaozheng Zhang Jianan Liu Ke Liu Yan Wang Hongyu Chen Fengjiao Zhou Xiuli Yang Xian Ge Tingting Zhang Tianbao Wang Yao He Defang Li Chuantao Zhang Jun Lu Responsive ROS‐Augmented Prodrug Hybridization Nanoassemblies for Multidimensionally Synergitic Treatment of Hepatocellular Carcinoma in Cascade Assaults Advanced Science cascade assaults cuproptosis hepatocellular carcinoma oxidative stress prodrug hybridization nanoassembly |
| title | Responsive ROS‐Augmented Prodrug Hybridization Nanoassemblies for Multidimensionally Synergitic Treatment of Hepatocellular Carcinoma in Cascade Assaults |
| title_full | Responsive ROS‐Augmented Prodrug Hybridization Nanoassemblies for Multidimensionally Synergitic Treatment of Hepatocellular Carcinoma in Cascade Assaults |
| title_fullStr | Responsive ROS‐Augmented Prodrug Hybridization Nanoassemblies for Multidimensionally Synergitic Treatment of Hepatocellular Carcinoma in Cascade Assaults |
| title_full_unstemmed | Responsive ROS‐Augmented Prodrug Hybridization Nanoassemblies for Multidimensionally Synergitic Treatment of Hepatocellular Carcinoma in Cascade Assaults |
| title_short | Responsive ROS‐Augmented Prodrug Hybridization Nanoassemblies for Multidimensionally Synergitic Treatment of Hepatocellular Carcinoma in Cascade Assaults |
| title_sort | responsive ros augmented prodrug hybridization nanoassemblies for multidimensionally synergitic treatment of hepatocellular carcinoma in cascade assaults |
| topic | cascade assaults cuproptosis hepatocellular carcinoma oxidative stress prodrug hybridization nanoassembly |
| url | https://doi.org/10.1002/advs.202501420 |
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