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载葛根素的心脏靶向和 ROS 响应脂质体减轻心肌缺血再灌注损伤。

Cardiac-targeted and ROS-responsive liposomes containing puerarin for attenuating myocardial ischemia-reperfusion injury.

机构信息

Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.

Institution of Clinical Pharmacy, Central South University, Changsha, 410011, China.

出版信息

Nanomedicine (Lond). 2024;19(28):2335-2355. doi: 10.1080/17435889.2024.2402678. Epub 2024 Sep 24.

Abstract

This study aimed to construct an ischemic cardiomyocyte-targeted and ROS-responsive drug release system to reduce myocardial ischemia-reperfusion injury (MI/RI). We constructed thioketal (TK) and cardiac homing peptide (CHP) dual-modified liposomes loaded with puerarin (PUE@TK/CHP-L), which were expected to deliver drugs precisely into ischemic cardiomyocytes and release drugs in response to the presence of high intracellular ROS levels. The advantages of PUE@TK/CHP-L were assessed by cellular pharmacodynamics, fluorescence imaging and animal pharmacodynamics. PUE@TK/CHP-L significantly inhibited apoptosis and ferroptosis in H/R-injured cardiomyocytes and also actively targeted ischemic myocardium. Based on these advantages, PUE@TK/CHP-L could significantly enhance the drug's ability to attenuate MI/RI. PUE@TK/CHP-L had potential clinical value in the precise treatment of MI/RI.

摘要

本研究旨在构建一种针对缺血性心肌细胞和 ROS 响应的药物释放系统,以减轻心肌缺血再灌注损伤(MI/RI)。我们构建了硫代缩酮(TK)和心脏归巢肽(CHP)双重修饰的载葛根素(PUE@TK/CHP-L)脂质体,以期将药物精确递送到缺血性心肌细胞,并响应细胞内高 ROS 水平释放药物。通过细胞药效学、荧光成像和动物药效学评估了 PUE@TK/CHP-L 的优势。PUE@TK/CHP-L 显著抑制了 H/R 损伤的心肌细胞中的细胞凋亡和铁死亡,并且还能主动靶向缺血性心肌。基于这些优势,PUE@TK/CHP-L 可以显著增强药物减轻 MI/RI 的能力。PUE@TK/CHP-L 在 MI/RI 的精确治疗方面具有潜在的临床价值。

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