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理性构建荧光传感器,用于活细胞、组织和炎症大鼠模型中次氯酸和过氧亚硝酸盐的同时检测和成像。

Rational construction of a fluorescent sensor for simultaneous detection and imaging of hypochlorous acid and peroxynitrite in living cells, tissues and inflammatory rat models.

机构信息

Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, School of Public Health, Guilin Medical University, Guilin, Guangxi 541001, China.

College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan 410004, China.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2022 Dec 5;282:121691. doi: 10.1016/j.saa.2022.121691. Epub 2022 Jul 28.

DOI:10.1016/j.saa.2022.121691
PMID:35917618
Abstract

Modern medical research indicates that hypochlorous acid (HClO) and peroxynitrite (ONOO) are important biomarkers of oxidative stress. However, the up- or down-regulation of HClO or ONOO has been closely associated with the occurrence and development of various diseases. In order to investigate the intrinsic entanglement relationship between HClO and ONOO and their relationship with the occurrence and development of inflammation, it is very valuable to develop fluorescent sensors that are capable of displaying different signals towards HClO, ONOO and HClO/ONOO. In this work, we rationally design and construct a novel robust small organic molecule fluorescent sensor (RhNp-ClO-ONOO) towards ONOO, HClO and HClO/ONOO with green, red, and green-red three different fluorescent signal outputs, respectively. RhNp-ClO-ONOO has fast responsive time for HClO (∼60 s) and ONOO (∼20 s). Also it has markedly low detection limits for HClO (∼25.3 nM) and ONOO (12.4 nM) respectively. In addition, RhNp-ClO-ONOO could be further shown to detect endogenous HClO/ONOO in living cells, inflammatory tissues and rat model successfully. Therefore, this novel fluorescent sensor with double responsive moiety can offer a powerful tool for studying the role of HClO and ONOO and the occurrence and development of inflammatory diseases.

摘要

现代医学研究表明,次氯酸(HClO)和过氧亚硝酸盐(ONOO)是氧化应激的重要生物标志物。然而,HClO 或 ONOO 的上调或下调与各种疾病的发生和发展密切相关。为了研究 HClO 和 ONOO 之间的内在纠缠关系及其与炎症发生和发展的关系,开发能够显示 HClO、ONOO 和 HClO/ONOO 不同信号的荧光传感器具有很高的价值。在这项工作中,我们合理设计并构建了一种新型的稳健小分子有机荧光传感器(RhNp-ClO-ONOO),可分别对 ONOO、HClO 和 HClO/ONOO 产生绿色、红色和绿-红三种不同的荧光信号输出。RhNp-ClO-ONOO 对 HClO(∼60 s)和 ONOO(∼20 s)具有快速的响应时间。此外,它对 HClO(∼25.3 nM)和 ONOO(12.4 nM)的检测限分别明显较低。此外,RhNp-ClO-ONOO 还可以进一步成功地在活细胞、炎症组织和大鼠模型中检测内源性 HClO/ONOO。因此,这种具有双重响应基团的新型荧光传感器可为研究 HClO 和 ONOO 的作用以及炎症性疾病的发生和发展提供有力工具。

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