Evaluation of HOCl-generating anticancer agents by an ultrasensitive dual-mode fluorescent probe. Issue 13 (8th March 2019)

• Record Type: Journal Article
• Authors: Shi, Donglei; Chen, Shuqiang; Dong, Biao; Zhang, Yanhui; Sheng, Chunquan; James, Tony D.; Guo, Yuan
• Is Part Of: Chemical science. Volume 10:Issue 13(2019)
• Page Start: 3715
• Page End: 3722
• Publication Date: 2019-03-08
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c9sc00180h
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : ProbeC7 for the first time presents different modes of fluorescence signals to both nanomolar and micromolar concentrations of HOCl. Abstract : Hypochlorous acid (HOCl), a reactive oxygen species (ROS), plays a crucial role in the process of pathogenic oxidative stress. Some powerful anticancer agents, such as elesclomol, specifically induce cancer cell apoptosis by increasing HOCl levels. However, sensitive tools to monitor subtle changes of biological HOCl in vivo are limited. To achieve this, we herein present rationally designed probesC1–C7 through introducing a bioorthogonal dimethylthiocarbamate receptor. All the probes were shown to sensitively and rapidly detect HOCl in the nanomolar/biologically relevant concentration range with fluorescence turn-on observed in their respective optical regions, resulting in a blue-to-red "fluorescence rainbow" and providing a broad selection of colors for imaging HOCl in vivo . Remarkably, probeC7 exhibited both a turn-on signal at biologically relevant concentrations (LOD1 = 18 nM) and a ratiometric response at the high risk pathogenic concentrations (LOD2 = 0.47 μM), which gives a higher reliability compared to a single signal and avoids cross-talk caused by the combined use of several probes.C7 was used to monitor the oxidative stress process induced by elesclomol in live cancer cells, and using this probe it was further discovered that an evodiamine derivative was capable of generating cancer-cell HOCl.