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线粒体靶向近红外荧光探针用于肺损伤、肝损伤和肿瘤模型中过氧化氢的可视化。

Mitochondria-Targetable Near-Infrared Fluorescent Probe for Visualization of Hydrogen Peroxide in Lung Injury, Liver Injury, and Tumor Models.

机构信息

School of Chemistry and Chemical Engineering, Institute of Environmental Science, Shanxi University, Taiyuan, 030006, P. R. China.

Laboratory Animal Center, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, P. R. China.

出版信息

Anal Chem. 2024 Jul 2;96(26):10488-10495. doi: 10.1021/acs.analchem.3c05479. Epub 2024 Jun 20.

Abstract

Hydrogen peroxide (HO) overexpressed in mitochondria has been regarded as a key biomarker in the pathological processes of various diseases. However, there is currently a lack of suitable mitochondria-targetable near-infrared (NIR) probes for the visualization of HO in multiple diseases, such as PM exposure-induced lung injury, hepatic ischemia-reperfusion injury (HIRI), nonalcoholic fatty liver (NAFL), hepatic fibrosis (HF), and malignant tumor tissues containing clinical cancer patient samples. Herein, we conceived a novel NIR fluorescent probe () by introducing pentafluorobenzenesulfonyl as a HO sensing unit into the NIR hemicyanine platform. exhibits good sensitivity and selectivity toward HO, accompanied by a remarkable "turn-on" fluorescence signal at 720 nm. Meanwhile, has stable mitochondria-targetable ability and permits monitoring of the up-generated HO level during mitophagy. Furthermore, using , we have successfully observed an overproduced mitochondrial HO in ambient PM exposure-induced lung injury, HIRI, NAFL, and HF models through NIR fluorescence imaging. Significantly, the visualization of HO has been achieved in both tumor-bear mice as well as surgical specimens of cancer patients, making a promising tool for cancer diagnosis and imaging-guided surgery.

摘要

过表达的过氧化氢(HO)已被认为是各种疾病病理过程中的一个关键生物标志物。然而,目前缺乏适用于多种疾病的线粒体靶向近红外(NIR)探针来可视化 HO,如 PM 暴露诱导的肺损伤、肝缺血再灌注损伤(HIRI)、非酒精性脂肪肝(NAFL)、肝纤维化(HF)和包含临床癌症患者样本的恶性肿瘤组织。在这里,我们通过将五氟苯磺酰基引入 NIR 半花菁平台,设计了一种新型的 NIR 荧光探针()。 对 HO 表现出良好的灵敏度和选择性,伴随着在 720nm 处显著的“开启”荧光信号。同时, 具有稳定的线粒体靶向能力,并允许监测线粒体自噬过程中产生的 HO 水平。此外,我们使用 ,通过 NIR 荧光成像成功观察到环境 PM 暴露诱导的肺损伤、HIRI、NAFL 和 HF 模型中过表达的线粒体 HO。值得注意的是,HO 的可视化已经在荷瘤小鼠以及癌症患者的手术标本中实现,使 成为癌症诊断和成像引导手术的有前途的工具。

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