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使用线粒体靶向近红外比率荧光探针原位评估急性肝损伤小鼠模型中次氯酸的波动情况。

In-situ evaluation the fluctuation of hypochlorous acid in acute liver injury mice models with a mitochondria-targeted NIR ratiometric fluorescent probe.

作者信息

Liang Yueyin, Zhang Chunjie, Meng Zhiyuan, Gong Shuai, Tian Jixiang, Li Ruoming, Wang Zhonglong, Wang Shifa

机构信息

Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, International Innovation Center for Forest Chemicals and Materials, College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China.

School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China.

出版信息

Talanta. 2024 Sep 1;277:126355. doi: 10.1016/j.talanta.2024.126355. Epub 2024 Jun 3.

DOI:10.1016/j.talanta.2024.126355
PMID:38838563
Abstract

Acute liver injury (ALI) is a frequent and devastating liver disease that has been made more prevalent by the excessive use of chemicals, drugs, and alcohol in modern life. Hypochlorous acid (HClO), an important biomarker of oxidative stress originating mainly from the mitochondria, has been shown to be intimately connected to the development and course of ALI. Herein, a novel BODIPY-based NIR ratiometric fluorescent probe Mito-BS was constructed for the specific recognition of mitochondrial HClO. The probe Mito-BS can rapidly respond to HClO within 20 s with a ratiometric fluorescence response (from 680 nm to 645 nm), 24-fold fluorescence intensity ratio enhancement (I/I), a wide pH adaptation range (5-9) and the low detection limit (31 nM). The probe Mito-BS has been effectively applied to visualize endogenous and exogenous HClO fluctuations in living zebrafish and cells based on its low cytotoxicity and prominent mitochondria-targeting ability. Furthermore, the fluorescent probe Mito-BS makes it possible to achieve the non-invasive in-situ diagnosis of ALI through in mice, and provides a feasible strategy for early diagnosis and drug therapy of ALI and its complications.

摘要

急性肝损伤(ALI)是一种常见且严重的肝脏疾病,在现代生活中,由于化学物质、药物和酒精的过度使用,其发病率有所上升。次氯酸(HClO)是主要源于线粒体的氧化应激的重要生物标志物,已被证明与ALI的发生发展过程密切相关。在此,构建了一种基于硼二吡咯(BODIPY)的新型近红外比率荧光探针Mito-BS,用于特异性识别线粒体中的HClO。探针Mito-BS能够在20秒内对HClO迅速做出响应,呈现比率荧光响应(从680纳米到645纳米),荧光强度比率增强24倍(I/I),具有较宽的pH适应范围(5-9)和较低的检测限(31纳摩尔)。基于其低细胞毒性和出色的线粒体靶向能力,探针Mito-BS已有效地应用于可视化活斑马鱼和细胞内源性和外源性HClO的波动情况。此外,荧光探针Mito-BS使得通过小鼠实现ALI的非侵入性原位诊断成为可能,并为ALI及其并发症的早期诊断和药物治疗提供了一种可行的策略。

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引用本文的文献

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A mitochondrial-targeted fluorescent probe for imaging HOCl in ferroptosis and multiple liver injury models.一种用于铁死亡和多种肝损伤模型中成像次氯酸的线粒体靶向荧光探针。
Anal Bioanal Chem. 2025 Aug 5. doi: 10.1007/s00216-025-06028-2.