An Activity‐Based Fluorescent Probe for Imaging Fluctuations of Peroxynitrite (ONOO ⁻ ) in the Alzheimer's Disease Brain

Peroxynitrite (ONOO - ) plays a critical role in Alzheimer's disease (AD), and the association between ONOO - and AD is inexplicit. To reveal the ONOO - influxes in AD brains, an activatable activity-based fluorescence probe Rd-DPA3 was rationally designed by a structure-modulated strategy. Taking advantage of ONOO - -sparked two-step cascade reactions of a novel chemical trigger, Rd-DPA3 specifically responds to ONOO - among 0.3 mM other ROS and varied proteins, accompanied by an intensive fluorescence enhancement ( F/F 0 = 50). Moreover, with the mitochondria-targeting ability, Rd-DPA3 can efficiently monitor the alternations of intracellular ONOO - levels in the cerebral cells during oxidative stress. Significantly, due to NIR emission and superb blood-brain barrier (BBB) crossing ability, Rd-DPA3 is capable of in vivo imaging cerebral ONOO - influxes and illustrating an age-dependent accumulation of native ONOO - in AD mice brains. This work discloses that Rd-DPA3 would be beneficial for AD diagnosis, treatment evaluation, and potential pathogenesis study.