一种用于乳腺癌症细胞线粒体谷胱甘肽S-转移酶成像的Switch-On亲和铱(III)结合探针

IF 3.9 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS
Ling Wang, Jingqi Liu, Feng Chen, Guodong Li, Jing Wang, Daniel Shiu-Hin Chan, Chun-Yuen Wong, Wanhe Wang* and Chung-Hang Leung*, 
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引用次数: 0

摘要

谷胱甘肽S-转移酶在乳腺癌症细胞中异源性表达,因此正在成为研究乳腺癌异质性的潜在诊断生物标志物。然而,GSTs的可用荧光探针在很大程度上依赖于GSTs催化的谷胱甘肽(GSH)亲核取代反应,这使得它们容易受到细胞环境中高浓度亲核物质的干扰。此外,由于缺乏合适的发光探针,亚细胞GSTs的功能通常被忽视。在此,我们报道了一种基于亲和性的高选择性发光探针1,通过将GST抑制剂ethacrynic acid与铱(III)复合物连接,检测癌症细胞中的GST。与需要使用GSH的基于活性的探针相比,该探针可以通过与活细胞中的GST-pi(或潜在的GST-pi/GS)直接加合来在线粒体中成像GST-pi。探针1具有理想的光物理性质,包括911ns的寿命、343nm的斯托克斯位移和高光稳定性。探针的“开启”发光模式能够高选择性地检测GST,检测极限为1.01μM,而其长发射寿命能够通过时间分辨模式在有机染料掺入的自发荧光样品中进行灵敏检测。该探针通过与线粒体GST的特异性结合,进一步用于特异性和定量地观察MDA-MB-231细胞,并可根据其GST的表达水平分化乳腺细胞系。据我们所知,该探针是第一个用于亚细胞GST的基于亲和性的铱(III)成像探针。我们的工作为揭示亚细胞GST在生活系统中的不同作用以及研究乳腺癌的异质性提供了一个有价值的工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A Switch-On Affinity-Based Iridium(III) Conjugate Probe for Imaging Mitochondrial Glutathione S-Transferase in Breast Cancer Cells

A Switch-On Affinity-Based Iridium(III) Conjugate Probe for Imaging Mitochondrial Glutathione S-Transferase in Breast Cancer Cells

Glutathione S-transferase is heterogeneously expressed in breast cancer cells and is therefore emerging as a potential diagnostic biomarker for studying the heterogeneity of breast cancers. However, available fluorescent probes for GSTs depend heavily on GSTs-catalyzed glutathione (GSH) nucleophilic substitution reactions, making them susceptible to interference by the high concentration of nucleophilic species in the cellular environment. Moreover, the functions of subcellular GSTs are generally overlooked due to the lack of suitable luminescence probes. Herein, we report a highly selective affinity-based luminescence probe 1 for GST in breast cancer cells through tethering a GST inhibitor, ethacrynic acid, to an iridium(III) complex. Compared to activity-based probes which require the use of GSH, this probe could image GST-pi in the mitochondria by directly adducting to GST-pi (or potentially GST-pi/GS) in living cells. Probe 1 possesses desirable photophysical properties including a lifetime of 911 ns, a Stokes shift of 343 nm, and high photostability. The “turn on” luminescence mode of the probe enables highly selective detection of the GST with a limit of detection of 1.01 μM, while its long emission lifetime allows sensitive detection in organic dye-spiked autofluorescence samples by a time-resolved mode. The probe was further applied to specifically and quantitatively visualize MDA-MB-231 cells via specific binding to mitochondrial GST, and could differentiate breast cell lines based on their expression levels of GST. To the best of our knowledge, this probe is the first affinity-based iridium(III) imaging probe for the subcellular GST. Our work provides a valuable tool for unmasking the diverse roles of a subcellular GST in living systems, as well as for studying the heterogeneity of breast cancers.

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来源期刊
Bioconjugate Chemistry
Bioconjugate Chemistry 生物-化学综合
CiteScore
9.00
自引率
2.10%
发文量
236
审稿时长
1.4 months
期刊介绍: Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.
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