心脏毒性
双金属片
药理学
化学
阿霉素
氧化应激
抗氧化剂
癌症研究
医学
化疗
生物化学
内科学
催化作用
作者
Junyue Xing,Xiaohan Ma,Yanan Yu,Yangfan Xiao,Lu Chen,Wenhua Yuan,Yingying Wang,Keyu Liu,Guo Zhiping,Hao Tang,Kelong Fan,Wei Jiang
标识
DOI:10.1002/advs.202405597
摘要
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.
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