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

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.