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 language | English |
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Pages (from-to) | 3715-3722 |
Number of pages | 8 |
Journal | Chemical Science |
Volume | 10 |
Issue number | 13 |
Early online date | 4 Mar 2019 |
DOIs | |
Publication status | Published - 7 Apr 2019 |
Funding
This work was supported by the National Natural Science Foundation of China (No. 21472148, 21072158 and 81602659), Open Funding Project of the State Key Laboratory of Bioreactor Engineering (2018OPEN12), Overseas Students Science and Technology Activities Project Merit Funding of Shaanxi Province (No. 20151190) and Academic Backbone of Northwest University Outstanding Youth Support Program. We thank Prof. Zhixiang Yu at Peking University and Prof. Sanping Chen at Northwest University for insightful discussions on this work. T. D. J. wishes to thank the Royal Society for a Wolfson Research Merit Award.
ASJC Scopus subject areas
- General Chemistry