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

Abstract

AbstractPeroxynitrite (ONOO−) plays a critical role in Alzheimer's disease (AD). To reveal the ONOO− influx in AD brains, an activatable activity‐based fluorescence probe Rd‐DPA3 was designed by a structure‐modulated strategy. Taking advantage of ONOO−‐initiated two‐step cascade reactions of a novel chemical trigger, Rd‐DPA3 specifically responds to ONOO− in 0.3 mM of other reactive oxygen species (ROS) and varied proteins, and gives an intensive fluorescence enhancement (F/F0=50). Moreover, with its mitochondria‐targeting ability, Rd‐DPA3 can be used to efficiently monitor the alternations of intracellular ONOO− levels in cerebral cells during oxidative stress. Significantly, due to NIR emission and good blood–brain barrier (BBB) crossing ability, Rd‐DPA3 is suitable for in vivo imaging of cerebral ONOO− influx and illustrating an age‐dependent accumulation of ONOO− in AD mice brains.