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用于监测热射病期间溶酶体 pH 值的光稳定 Si-罗丹明基近红外荧光探针。

A photostable Si-rhodamine-based near-infrared fluorescent probe for monitoring lysosomal pH during heat stroke.

机构信息

Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007, PR China.

Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007, PR China.

出版信息

Anal Chim Acta. 2019 Dec 27;1092:117-125. doi: 10.1016/j.aca.2019.09.053. Epub 2019 Sep 21.

Abstract

Heat stroke is a symptom of hyperthermia with a temperature of more than 40 °C, which usually leads to all kinds of physical discomfort and even death. It is necessary to study the mechanism of action of heat stroke on cells or organelles (such as cytotoxicity of heat) and the processes of cells or organelles during heat stroke. Recent studies have shown that there is a certain correlation between heat stroke and lysosome acidity. In order to clarify their relationship, Lyso-NIR-pH, a photostable Si-rhodamine-based near-infrared fluorescent probe, was developed for sensing pH changes in lysosomes during heat stroke in this paper. For Lyso-NIR-pH, a morpholine group is employed as the lysosome-targeting unit and a H-triggered openable deoxylactam is employed as the response unit to pH. Lyso-NIR-pH can detect pH with a high selectivity and a sensitivity, and its pK is 4.63. Lyso-NIR-pH also has outstanding imaging performances, such as excellent lysosome-targeting ability, low autofluorescence and photostable fluorescence signal, which are in favor of long-term imaging of pH with accurate fluorescence signals. Moreover, we successfully applied Lyso-NIR-pH to monitor lysosomal pH increases induced by chloroquine and apoptosis in live cells. Finally, we successfully applied Lyso-NIR-pH for monitoring changes of lysosomal pH during heat stroke. These results confirmed that Lyso-NIR-pH is a powerful tool to monitor pH change in lysosomes and study its possible effects.

摘要

中暑是体温超过 40°C 的过热症状,通常会导致各种身体不适,甚至死亡。有必要研究中暑对细胞或细胞器的作用机制(如热细胞毒性)以及中暑过程中细胞或细胞器的过程。最近的研究表明,中暑与溶酶体酸度之间存在一定的相关性。为了阐明它们之间的关系,本文开发了一种基于硅罗丹明的光稳定近红外荧光探针 Lyso-NIR-pH,用于感测中暑过程中溶酶体中 pH 值的变化。对于 Lyso-NIR-pH,采用吗啉基作为溶酶体靶向单元,采用 H 触发的可开环去氧内酰胺作为 pH 响应单元。Lyso-NIR-pH 对 pH 值具有高选择性和灵敏度,其 pK 为 4.63。Lyso-NIR-pH 还具有出色的成像性能,例如出色的溶酶体靶向能力、低自发荧光和光稳定的荧光信号,有利于准确荧光信号的长期 pH 值成像。此外,我们成功地应用 Lyso-NIR-pH 监测氯喹诱导的活细胞溶酶体 pH 值升高和细胞凋亡。最后,我们成功地应用 Lyso-NIR-pH 监测中暑过程中溶酶体 pH 值的变化。这些结果证实,Lyso-NIR-pH 是监测溶酶体中 pH 值变化并研究其可能影响的有力工具。

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