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一种基于独特铱(III)配合物的化学传感器,用于肝损伤中次氯酸的多信号检测和多通道成像。

A unique iridium(III) complex-based chemosensor for multi-signal detection and multi-channel imaging of hypochlorous acid in liver injury.

机构信息

State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116024, PR China.

Therapeutics Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.

出版信息

Biosens Bioelectron. 2017 Jan 15;87:1005-1011. doi: 10.1016/j.bios.2016.09.067. Epub 2016 Sep 20.

Abstract

Although hypochlorous acid (HOCl) has long been associated with a number of inflammatory diseases in mammalian bodies, the functions of HOCl in specific organs at abnormal conditions, such as liver injury, remain unclear due to its high reactivity and the lack of effective methods for its detection. Herein, a unique Ir(III) complex-based chemosensor, Ir-Fc, was developed for highly sensitive and selective detection of HOCl. Ir-Fc was designed by incorporating a ferrocene (Fc) quencher to a Ir(III) complex through a HOCl-responsive linker. In the presence of HOCl, the fast cleavage of Fc moiety in less than 1s led to the enhancement of photoluminescence (PL) and electrochemical luminescence (ECL), by which the concentration of HOCl was determined by both PL and ECL analysis. Taking advantages of excellent properties of Ir(III) complexes, optical and electrochemical analyses of the response of Ir-Fc towards HOCl were fully investigated. Followed by the measurements of low cytotoxicity of Ir-Fc by MTT analysis, one-photon (OP), two-photon (TP) and lifetime imaging experiments were conducted to visualise the generation of HOCl in live microphage and HepG2 cells, and in zebrafish and mouse, respectively. Furthermore, the generation and distribution of HOCl in liver cells and liver injury of zebrafish and mouse were investigated. The results demonstrated the applicability of Ir-Fc as an effective chemosensor for imaging of HOCl generation in mitochondria of cells and liver injury in vivo, implying the potential of Ir-Fc for biomedical diagnosis and monitoring applications.

摘要

尽管次氯酸(HOCl)长期以来与哺乳动物体内的许多炎症性疾病有关,但由于其高反应性和缺乏有效的检测方法,HOCl 在异常条件下(如肝损伤)在特定器官中的功能仍不清楚。在此,开发了一种基于独特的 Ir(III) 配合物的化学传感器 Ir-Fc,用于高灵敏度和选择性检测 HOCl。Ir-Fc 通过将一个二茂铁(Fc)猝灭剂通过 HOCl 响应性连接体整合到 Ir(III) 配合物中而设计。在存在 HOCl 的情况下,Fc 部分在不到 1 秒内快速断裂导致光致发光(PL)和电化学发光(ECL)增强,通过 PL 和 ECL 分析确定 HOCl 的浓度。利用 Ir(III) 配合物的优异性质,充分研究了 Ir-Fc 对 HOCl 的响应的光学和电化学分析。继通过 MTT 分析测量 Ir-Fc 的低细胞毒性之后,进行了单光子(OP)、双光子(TP)和寿命成像实验,以分别可视化活微噬细胞和 HepG2 细胞、斑马鱼和小鼠中 HOCl 的产生。此外,研究了 HOCl 在肝细胞中的产生和分布以及斑马鱼和小鼠的肝损伤。结果表明,Ir-Fc 可作为用于细胞线粒体中 HOCl 生成和体内肝损伤成像的有效化学传感器,这意味着 Ir-Fc 具有用于生物医学诊断和监测应用的潜力。

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