Feng Huan, Zhang Zhiqiang, Meng Qingtao, Jia Hongmin, Wang Yue, Zhang Run
School of Chemical Engineering University of Science and Technology Liaoning Anshan Liaoning 114051 P. R. China.
Australian Institute for Bioengineering and Nanotechnology The University of Queensland Brisbane 4072 Australia.
Adv Sci (Weinh). 2018 Jun 7;5(8):1800397. doi: 10.1002/advs.201800397. eCollection 2018 Aug.
Diagnosis and early assessment of the treatment response of rheumatoid arthritis (RA) necessitates a reliable bioanalytical method for rapid, sensitive, and specific detection of the hypochlorous acid (HOCl) biomarker in inflammatory diseases. Herein, two fluorescence probes, Probe- and Probe- are developed for quantitative monitoring and visualization of inflammatory response-related HOCl levels in vitro and in vivo. In the presence of HOCl, fluorescence "OFF-ON" response is obtained for both the probes as a result of specific HOCl-triggered C=N bond cleavage reaction. Probe- and Probe- feature rapid response (<4 s), a high degree of sensitivity and selectivity toward HOCl, which allow them to be used for quantification of HOCl in a simulated physiological condition. Using Probe- as the probe, fluorescence imaging and flow cytometry analysis of HOCl levels in lysosome of inflammatory mimic cells, visualization of HOCl generation in endotoxin-induced inflammation of adult zebrafish and RA of mice are possible. Probe- exhibits high effectiveness for early assessment of the treatment response of HOCl-mediated RA in mice with an antiarthritic drug, methotrexate (MTX). The results demonstrate that Probe- is a powerful tool for future studies on diagnosis and monitoring treatment efficiency in a broad range of inflammatory diseases, including RA.
类风湿性关节炎（RA）治疗反应的诊断和早期评估需要一种可靠的生物分析方法，用于快速、灵敏且特异地检测炎症性疾病中的次氯酸（HOCl）生物标志物。在此，开发了两种荧光探针Probe-和Probe-，用于在体外和体内定量监测和可视化炎症反应相关的HOCl水平。在HOCl存在的情况下，由于特定的HOCl触发的C=N键裂解反应，两种探针均获得荧光“关-开”响应。Probe-和Probe-具有快速响应（<4 s）、对HOCl具有高度的灵敏度和选择性，这使得它们可用于在模拟生理条件下定量HOCl。以Probe-作为探针，可以对炎症模拟细胞溶酶体中的HOCl水平进行荧光成像和流式细胞术分析，对内毒素诱导的成年斑马鱼炎症和小鼠RA中HOCl的产生进行可视化。Probe-在使用抗关节炎药物甲氨蝶呤（MTX）的小鼠中对HOCl介导的RA治疗反应的早期评估显示出高效性。结果表明，Probe-是未来在包括RA在内的广泛炎症性疾病中进行诊断和监测治疗效果研究的有力工具。
