Evaluation of HOCl-generating anticancer agents by an ultrasensitive dual-mode fluorescent probe

Donglei Shi, Shuqiang Chen, Biao Dong, Yanhui Zhang, Chunquan Sheng, Tony D. James, Yuan Guo

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 probes C1-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, probe C7 exhibited both a turn-on signal at biologically relevant concentrations (LOD 1 = 18 nM) and a ratiometric response at the high risk pathogenic concentrations (LOD 2 = 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.

Original languageEnglish
Pages (from-to)3715-3722
Number of pages8
JournalChemical Science
Volume10
Issue number13
Early online date4 Mar 2019
DOIs
Publication statusPublished - 7 Apr 2019

ASJC Scopus subject areas

  • Chemistry(all)

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