A Cardiac‐Targeting and Anchoring Bimetallic Cluster Nanozyme Alleviates Chemotherapy‐Induced Cardiac Ferroptosis and PANoptosis
Abstract Doxorubicin (DOX), a potent antineoplastic agent, is commonly associated with cardiotoxicity, necessitating the development of strategies to reduce its adverse effects on cardiac function. Previous research has demonstrated a strong correlation between DOX‐induced cardiotoxicity and the act...
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2025-01-01
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| Online Access: | https://doi.org/10.1002/advs.202405597 |
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| author | Junyue Xing Xiaohan Ma Yanan Yu Yangfan Xiao Lu Chen Weining Yuan Yingying Wang Keyu Liu Zhiping Guo Hao Tang Kelong Fan Wei Jiang |
| author_facet | Junyue Xing Xiaohan Ma Yanan Yu Yangfan Xiao Lu Chen Weining Yuan Yingying Wang Keyu Liu Zhiping Guo Hao Tang Kelong Fan Wei Jiang |
| author_sort | Junyue Xing |
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| description | Abstract Doxorubicin (DOX), a potent antineoplastic agent, is commonly associated with cardiotoxicity, necessitating the development of strategies to reduce its adverse effects on cardiac function. Previous research has demonstrated a strong correlation between DOX‐induced cardiotoxicity and the activation of oxidative stress pathways. This work introduces a novel antioxidant therapeutic approach, utilizing libraries of tannic acid and N‐acetyl‐L‐cysteine‐protected bimetallic cluster nanozymes. Through extensive screening for antioxidative enzyme‐like activity, an optimal bimetallic nanozyme (AuRu) is identified that possess remarkable antioxidant characteristics, mimicking catalase‐like enzymes. Theoretical calculations reveal the surface interactions of the prepared nanozymes that simulate the hydrogen peroxide decomposition process, showing that these bimetallic nanozymes readily undergo OH⁻ adsorption and O₂ desorption. To enhance cardiac targeting, the atrial natriuretic peptide is conjugated to the AuRu nanozyme. These cardiac‐targeted bimetallic cluster nanozymes, with their anchoring capability, effectively reduce DOX‐induced cardiomyocyte ferroptosis and PANoptosis without compromising tumor treatment efficacy. Thus, the therapeutic approach demonstrates significant reductions in chemotherapy‐induced cardiac cell death and improvements in cardiac function, accompanied by exceptional in vivo biocompatibility and stability. This study presents a promising avenue for preventing chemotherapy‐induced cardiotoxicity, offering potential clinical benefits for cancer patients. |
| format | Article |
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| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-bb26306acd6d4c568d9315c8c87c31742025-01-09T11:44:45ZengWileyAdvanced Science2198-38442025-01-01121n/an/a10.1002/advs.202405597A Cardiac‐Targeting and Anchoring Bimetallic Cluster Nanozyme Alleviates Chemotherapy‐Induced Cardiac Ferroptosis and PANoptosisJunyue Xing0Xiaohan Ma1Yanan Yu2Yangfan Xiao3Lu Chen4Weining Yuan5Yingying Wang6Keyu Liu7Zhiping Guo8Hao Tang9Kelong Fan10Wei Jiang11National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Central China Subcenter of National Center for Cardiovascular Diseases Henan Cardiovascular Disease Center Fuwai Central‐China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University Zhengzhou 450046 ChinaNational Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Central China Subcenter of National Center for Cardiovascular Diseases Henan Cardiovascular Disease Center Fuwai Central‐China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University Zhengzhou 450046 ChinaNational Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Central China Subcenter of National Center for Cardiovascular Diseases Henan Cardiovascular Disease Center Fuwai Central‐China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University Zhengzhou 450046 ChinaNational Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Central China Subcenter of National Center for Cardiovascular Diseases Henan Cardiovascular Disease Center Fuwai Central‐China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University Zhengzhou 450046 ChinaDepartment of Cardiovascular Diseases the First Clinical Medical College Shanxi Medical University Taiyuan Shanxi 030001 ChinaNational Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Central China Subcenter of National Center for Cardiovascular Diseases Henan Cardiovascular Disease Center Fuwai Central‐China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University Zhengzhou 450046 ChinaNational Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Central China Subcenter of National Center for Cardiovascular Diseases Henan Cardiovascular Disease Center Fuwai Central‐China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University Zhengzhou 450046 ChinaSchool of Clinical Medicine Shandong Second Medical University Weifang Shandong 261053 ChinaNational Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Central China Subcenter of National Center for Cardiovascular Diseases Henan Cardiovascular Disease Center Fuwai Central‐China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University Zhengzhou 450046 ChinaNational Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Central China Subcenter of National Center for Cardiovascular Diseases Henan Cardiovascular Disease Center Fuwai Central‐China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University Zhengzhou 450046 ChinaCAS Engineering Laboratory for Nanozyme Key Laboratory of Biomacromolecules (CAS) CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 ChinaNational Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Central China Subcenter of National Center for Cardiovascular Diseases Henan Cardiovascular Disease Center Fuwai Central‐China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University Zhengzhou 450046 ChinaAbstract Doxorubicin (DOX), a potent antineoplastic agent, is commonly associated with cardiotoxicity, necessitating the development of strategies to reduce its adverse effects on cardiac function. Previous research has demonstrated a strong correlation between DOX‐induced cardiotoxicity and the activation of oxidative stress pathways. This work introduces a novel antioxidant therapeutic approach, utilizing libraries of tannic acid and N‐acetyl‐L‐cysteine‐protected bimetallic cluster nanozymes. Through extensive screening for antioxidative enzyme‐like activity, an optimal bimetallic nanozyme (AuRu) is identified that possess remarkable antioxidant characteristics, mimicking catalase‐like enzymes. Theoretical calculations reveal the surface interactions of the prepared nanozymes that simulate the hydrogen peroxide decomposition process, showing that these bimetallic nanozymes readily undergo OH⁻ adsorption and O₂ desorption. To enhance cardiac targeting, the atrial natriuretic peptide is conjugated to the AuRu nanozyme. These cardiac‐targeted bimetallic cluster nanozymes, with their anchoring capability, effectively reduce DOX‐induced cardiomyocyte ferroptosis and PANoptosis without compromising tumor treatment efficacy. Thus, the therapeutic approach demonstrates significant reductions in chemotherapy‐induced cardiac cell death and improvements in cardiac function, accompanied by exceptional in vivo biocompatibility and stability. This study presents a promising avenue for preventing chemotherapy‐induced cardiotoxicity, offering potential clinical benefits for cancer patients.https://doi.org/10.1002/advs.202405597antioxidant activitybimetallic cluster nanozymeDOX‐induced cardiotoxicityferroptosisPANoptosis |
| spellingShingle | Junyue Xing Xiaohan Ma Yanan Yu Yangfan Xiao Lu Chen Weining Yuan Yingying Wang Keyu Liu Zhiping Guo Hao Tang Kelong Fan Wei Jiang A Cardiac‐Targeting and Anchoring Bimetallic Cluster Nanozyme Alleviates Chemotherapy‐Induced Cardiac Ferroptosis and PANoptosis Advanced Science antioxidant activity bimetallic cluster nanozyme DOX‐induced cardiotoxicity ferroptosis PANoptosis |
| title | A Cardiac‐Targeting and Anchoring Bimetallic Cluster Nanozyme Alleviates Chemotherapy‐Induced Cardiac Ferroptosis and PANoptosis |
| title_full | A Cardiac‐Targeting and Anchoring Bimetallic Cluster Nanozyme Alleviates Chemotherapy‐Induced Cardiac Ferroptosis and PANoptosis |
| title_fullStr | A Cardiac‐Targeting and Anchoring Bimetallic Cluster Nanozyme Alleviates Chemotherapy‐Induced Cardiac Ferroptosis and PANoptosis |
| title_full_unstemmed | A Cardiac‐Targeting and Anchoring Bimetallic Cluster Nanozyme Alleviates Chemotherapy‐Induced Cardiac Ferroptosis and PANoptosis |
| title_short | A Cardiac‐Targeting and Anchoring Bimetallic Cluster Nanozyme Alleviates Chemotherapy‐Induced Cardiac Ferroptosis and PANoptosis |
| title_sort | cardiac targeting and anchoring bimetallic cluster nanozyme alleviates chemotherapy induced cardiac ferroptosis and panoptosis |
| topic | antioxidant activity bimetallic cluster nanozyme DOX‐induced cardiotoxicity ferroptosis PANoptosis |
| url | https://doi.org/10.1002/advs.202405597 |
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