Self‐Reinforced Bimetallic Mito‐Jammer for Ca2+ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization
Abstract Overproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria‐mediated cell death. However, the highly adaptive nature and damage‐repair capabilities of malignant tumors strongly limit the efficacy of treat...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-04-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202306031 |
| _version_ | 1831870879238193152 |
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| author | Chier Du Xun Guo Xiaoling Qiu Weixi Jiang Xiaoting Wang Hongjin An Jingxue Wang Yuanli Luo Qianying Du Ruoyao Wang Chen Cheng Yuan Guo Hua Teng Haitao Ran Zhigang Wang Pan Li Zhiyi Zhou Jianli Ren |
| author_facet | Chier Du Xun Guo Xiaoling Qiu Weixi Jiang Xiaoting Wang Hongjin An Jingxue Wang Yuanli Luo Qianying Du Ruoyao Wang Chen Cheng Yuan Guo Hua Teng Haitao Ran Zhigang Wang Pan Li Zhiyi Zhou Jianli Ren |
| author_sort | Chier Du |
| collection | DOAJ |
| description | Abstract Overproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria‐mediated cell death. However, the highly adaptive nature and damage‐repair capabilities of malignant tumors strongly limit the efficacy of treatments based on a single treatment mode. To address this challenge, a self‐reinforced bimetallic Mito‐Jammer is developed by incorporating doxorubicin (DOX) and calcium peroxide (CaO2) into hyaluronic acid (HA) ‐modified metal‐organic frameworks (MOF). After cellular, Mito‐Jammer dissociates into CaO2 and Cu2+ in the tumor microenvironment. The exposed CaO2 further yields hydrogen peroxide (H2O2) and Ca2+ in a weakly acidic environment to strengthen the Cu2+‐based Fenton‐like reaction. Furthermore, the combination of chemodynamic therapy and Ca2+ overload exacerbates ROS storms and mitochondrial damage, resulting in the downregulation of intracellular adenosine triphosphate (ATP) levels and blocking of Cu‐ATPase to sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic cell death and suppresses tumor metastasis simultaneously. This study presents a multivariate model for revolutionizing mitochondria damage, relying on the continuous retention of bimetallic ions to boost cuproptosis/immunotherapy in cancer. |
| first_indexed | 2024-04-24T08:04:41Z |
| format | Article |
| id | doaj.art-26627474b79a430f9d05ee77d51935bb |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2025-03-21T19:32:59Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-26627474b79a430f9d05ee77d51935bb2024-06-03T14:05:50ZengWileyAdvanced Science2198-38442024-04-011115n/an/a10.1002/advs.202306031Self‐Reinforced Bimetallic Mito‐Jammer for Ca2+ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis SensitizationChier Du0Xun Guo1Xiaoling Qiu2Weixi Jiang3Xiaoting Wang4Hongjin An5Jingxue Wang6Yuanli Luo7Qianying Du8Ruoyao Wang9Chen Cheng10Yuan Guo11Hua Teng12Haitao Ran13Zhigang Wang14Pan Li15Zhiyi Zhou16Jianli Ren17Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Intensive Care Unit the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Radiology Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Breast and Thyroid Surgery Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaDepartment of General Practice Chongqing General Hospital Chongqing 400010 P. R. ChinaDepartment of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaAbstract Overproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria‐mediated cell death. However, the highly adaptive nature and damage‐repair capabilities of malignant tumors strongly limit the efficacy of treatments based on a single treatment mode. To address this challenge, a self‐reinforced bimetallic Mito‐Jammer is developed by incorporating doxorubicin (DOX) and calcium peroxide (CaO2) into hyaluronic acid (HA) ‐modified metal‐organic frameworks (MOF). After cellular, Mito‐Jammer dissociates into CaO2 and Cu2+ in the tumor microenvironment. The exposed CaO2 further yields hydrogen peroxide (H2O2) and Ca2+ in a weakly acidic environment to strengthen the Cu2+‐based Fenton‐like reaction. Furthermore, the combination of chemodynamic therapy and Ca2+ overload exacerbates ROS storms and mitochondrial damage, resulting in the downregulation of intracellular adenosine triphosphate (ATP) levels and blocking of Cu‐ATPase to sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic cell death and suppresses tumor metastasis simultaneously. This study presents a multivariate model for revolutionizing mitochondria damage, relying on the continuous retention of bimetallic ions to boost cuproptosis/immunotherapy in cancer.https://doi.org/10.1002/advs.202306031Ca2+ overloadcascade mitochondria damagechemodynamic therapycuproptosisimmunotherapy |
| spellingShingle | Chier Du Xun Guo Xiaoling Qiu Weixi Jiang Xiaoting Wang Hongjin An Jingxue Wang Yuanli Luo Qianying Du Ruoyao Wang Chen Cheng Yuan Guo Hua Teng Haitao Ran Zhigang Wang Pan Li Zhiyi Zhou Jianli Ren Self‐Reinforced Bimetallic Mito‐Jammer for Ca2+ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization Advanced Science Ca2+ overload cascade mitochondria damage chemodynamic therapy cuproptosis immunotherapy |
| title | Self‐Reinforced Bimetallic Mito‐Jammer for Ca2+ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization |
| title_full | Self‐Reinforced Bimetallic Mito‐Jammer for Ca2+ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization |
| title_fullStr | Self‐Reinforced Bimetallic Mito‐Jammer for Ca2+ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization |
| title_full_unstemmed | Self‐Reinforced Bimetallic Mito‐Jammer for Ca2+ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization |
| title_short | Self‐Reinforced Bimetallic Mito‐Jammer for Ca2+ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization |
| title_sort | self reinforced bimetallic mito jammer for ca2 overload mediated cascade mitochondrial damage for cancer cuproptosis sensitization |
| topic | Ca2+ overload cascade mitochondria damage chemodynamic therapy cuproptosis immunotherapy |
| url | https://doi.org/10.1002/advs.202306031 |
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