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基于巨噬细胞膜工程化纳米探针可视化动脉粥样硬化斑块中的铁死亡。

Visualization of the Ferroptosis in Atherosclerotic Plaques with Nanoprobe Engineered by Macrophage Cell Membranes.

机构信息

Department of Nuclear Medicine & Laboratory of Clinical Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610044, China.

Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China.

出版信息

Anal Chem. 2024 Jan 9;96(1):281-291. doi: 10.1021/acs.analchem.3c03999. Epub 2023 Dec 28.

Abstract

Atherosclerosis (AS) is the root cause of cardiovascular diseases. Ferroptosis is characterized by highly iron-dependent lipid peroxidation and has been reported to play an important role in the pathogenesis of AS. Visualization of the ferroptosis process in atherosclerotic plaques is of great importance for diagnosing and treating AS. In this work, the rationally designed fluorescent probe exhibited excellent advantages including large Stokes shift, sensitivity to environmental viscosity, good photostability, and improved water solubility. It also could co-locate with commercial lipid droplets (LDs) probes (BODIPY 493/503) well in RAW264.7 cells treated by the ferroptosis inducer. After self-assembly into nanoparticles and then encapsulation with macrophage membranes, the engineered @MM NPs could successfully target the atherosclerotic plaques in Western diet-induced apolipoprotein E knockout () mice and reveal the association of ferroptosis with AS through fluorescence imaging . This study may provide additional insights into the roles of ferroptosis in the diagnosis and treatment of AS.

摘要

动脉粥样硬化(AS)是心血管疾病的根源。铁死亡的特征是高度依赖铁的脂质过氧化,据报道其在 AS 的发病机制中发挥着重要作用。可视化动脉粥样硬化斑块中的铁死亡过程对于 AS 的诊断和治疗具有重要意义。在这项工作中,设计合理的荧光探针 表现出优异的优点,包括大斯托克斯位移、对环境粘度的敏感性、良好的光稳定性和提高的水溶性。它还可以与商业脂滴(LDs)探针(BODIPY 493/503)在铁死亡诱导剂处理的 RAW264.7 细胞中共定位。在自组装成纳米颗粒后,用巨噬细胞膜进行封装,工程化的 @MM NPs 可以成功靶向西方饮食诱导的载脂蛋白 E 基因敲除()小鼠中的动脉粥样硬化斑块,并通过荧光成像揭示铁死亡与 AS 的关联。这项研究可能为铁死亡在 AS 的诊断和治疗中的作用提供更多的见解。

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