Novel HypochlorousAcid-Activated Near-Infrared ProbeMonitors the Dynamic Changes of Myeloperoxidase Activity in IschemicBrain

Myeloperoxidase (MPO) contributes to the progression of ischemic damage. To fully understand MPO biology, highly sensitive and specific probes that can trace the activity of endogenous MPO fluxes are indispensable. Here, we developed two hypochlorous acid (HClO)-activated near-infrared probes to image MPO activity in a noninvasive manner. The probe <b>MPO-NIR-II</b> could track MPO-induced HClO in real time and in situ upon various stimuli with high sensitivity and specificity. Furthermore, <b>MPO-NIR-II</b> could monitor the MPO activity by in vivo fluorescence imaging and confocal laser scanning microscopy in mice with ischemic stroke. Moreover, a high-content screening system for MPO inhibitors was established by combining <b>MPO-NIR-II</b> with MPO-overexpressed cells and mouse brain slices with ischemic stroke, and the candidate compound AZD5904 was found to effectively attenuate ischemic brain injury. Overall, this work provides a versatile fluorescence tool that holds great promise for visualizing endogenous MPO fluxes of brain ischemia.