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一种可靶向溶酶体的多功能荧光探针,用于在活细胞中以不同荧光信号成像粘度和过氧亚硝酸盐。

A lysosome targetable versatile fluorescent probe for imaging viscosity and peroxynitrite with different fluorescence signals in living cells.

作者信息

Guo Bingpeng, Jing Jing, Nie Longxue, Xin Fangyun, Gao Congcong, Yang Wen, Zhang Xiaoling

机构信息

Key Laboratory of Cluster Science of Ministry of Education, Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials, Analytical and Testing Center, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, P. R. China.

出版信息

J Mater Chem B. 2018 Jan 28;6(4):580-585. doi: 10.1039/c7tb02615c. Epub 2018 Jan 8.

Abstract

The lysosome, which acts as the cellular recycling centre, is filled with numerous hydrolases that can degrade most cellular macromolecules. The abnormalities of the lysosome are closely associated with diseases, such as Heřmanský-Pudlák syndrome, Griscelli syndrome and Chédiak-Higashi syndrome. Studies have shown that abnormal viscosity and the accumulation of reactive oxygen species (ROS) in the lysosome will disorder the normal function of the lysosome. In this research, a versatile fluorescent probe Lyso-NA has been developed for the multi-channel imaging of lysosomal viscosity and peroxynitrite (ONOO). When excited at 550 nm, the Lyso-NA exhibited about a 50-fold increase in fluorescence at 610 nm and also with the increasing viscosity from 1.0 cP to 1410 cP, and about a 3.5-fold increase in fluorescence at 510 nm (excitation at 440 nm) together with the increasing ONOO. These satisfactory response properties make it possible to use Lyso-NA to monitor changes in both viscosity and ONOO inside the lysosome. To achieve its practical application, it was further demonstrated that Lyso-NA exhibits low cytotoxicity, and good cell permeability, and could be used to monitor lysosomal viscosity and ONOO in living cells.

摘要

溶酶体作为细胞的回收中心,充满了许多能够降解大多数细胞大分子的水解酶。溶酶体的异常与多种疾病密切相关,如赫尔曼斯基-普德拉克综合征、格里塞利综合征和切迪雅克-希加什综合征。研究表明,溶酶体内异常的粘度和活性氧(ROS)的积累会扰乱溶酶体的正常功能。在本研究中,开发了一种多功能荧光探针Lyso-NA,用于溶酶体粘度和过氧亚硝酸盐(ONOO)的多通道成像。当在550 nm处激发时,Lyso-NA在610 nm处的荧光增加约50倍,并且随着粘度从1.0 cP增加到1410 cP,以及随着ONOO的增加,在510 nm处(440 nm激发)的荧光增加约3.5倍。这些令人满意的响应特性使得使用Lyso-NA监测溶酶体内粘度和ONOO的变化成为可能。为了实现其实际应用,进一步证明Lyso-NA具有低细胞毒性和良好的细胞渗透性,可用于监测活细胞中的溶酶体粘度和ONOO。

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