Theranostics 2017; 7(15):3803-3813. doi:10.7150/thno.21068

Research Paper

A H2O2-Responsive Theranostic Probe for Endothelial Injury Imaging and Protection

Cheng-Kun Wang1*, Juan Cheng1*, Xing-Guang Liang1, Chao Tan1, Quan Jiang1, Yong-Zhou Hu1, Ying-Mei Lu2, Kohji Fukunaga3, Feng Han1✉, Xin Li1✉

1. College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Rd., Hangzhou 310058, China;
2. School of Medicine, Zhejiang University City College, 51 Huzhou Rd., Hangzhou 310015, China;
3. Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-Ku, Sendai 980-8578, Japan.
* These authors contributed equally to this work.

Abstract

Overproduction of H2O2 causes oxidative stress and is the hallmark of vascular diseases. Tracking native H2O2 in the endothelium is therefore indispensable to gain fundamental insights into this pathogenesis. Previous fluorescent probes for H2O2 imaging were generally arylboronates which were decomposed to emissive arylphenols in response to H2O2. Except the issue of specificity challenged by peroxynitrite, boric acid by-produced in this process is actually a waste with unknown biological effects. Therefore, improvements could be envisioned if a therapeutic agent is by-produced instead. Herein, we came up with a “click-to-release-two” strategy and demonstrate that dual functional probes could be devised by linking a fluorophore with a therapeutic agent via a H2O2-responsive bond. As a proof of concept, probe AP consisting of a 2-(2'-hydroxyphenyl) benzothiazole fluorophore and an aspirin moiety has been prepared and confirmed for its theranostic effects. This probe features high specificity towards H2O2 than other reactive species including peroxynitrite. Its capability to image and ameliorate endothelial injury has been verified both in vitro and in vivo. Noteworthy, as a result of its endothelial-protective effect, AP also works well to reduce thrombosis formation in zebrafish model.

Keywords: theranostic probe, fluorescent imaging, hydrogen peroxide, endothelial injury, oxidative stress.

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How to cite this article:
Wang CK, Cheng J, Liang XG, Tan C, Jiang Q, Hu YZ, Lu YM, Fukunaga K, Han F, Li X. A H2O2-Responsive Theranostic Probe for Endothelial Injury Imaging and Protection. Theranostics 2017; 7(15):3803-3813. doi:10.7150/thno.21068. Available from http://www.thno.org/v07p3803.htm