Novel Hypochlorous Acid-Activated Near-Infrared Probe Monitors the Dynamic Changes of Myeloperoxidase Activity in Ischemic Brain

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 MPO-NIR-II could track MPO-induced HClO in real time and in
situ upon various stimuli with high sensitivity and specificity. Furthermore, MPO-NIR-II 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 MPO-NIR-II 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.