A H(2)O(2)-Responsive Theranostic Probe for Endothelial Injury Imaging and Protection

Overproduction of H(2)O(2) causes oxidative stress and is the hallmark of vascular diseases. Tracking native H(2)O(2) in the endothelium is therefore indispensable to gain fundamental insights into this pathogenesis. Previous fluorescent probes for H(2)O(2) imaging were generally arylboronates which were decomposed to emissive arylphenols in response to H(2)O(2). 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 H(2)O(2)-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 H(2)O(2) 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.