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). 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.