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

Abstract

Peroxynitrite (ONOO À ) plays a critical role in Alzheimer's disease (AD). To reveal the ONOO À influx in AD brains, an activatable activity-based fluorescence probe Rd-DPA3 was designed by a structure-modulated strategy. Taking advantage of ONOO À -initiated twostep cascade reactions of a novel chemical trigger, Rd-DPA3 specifically responds to ONOO À in 0.3 mM of other reactive oxygen species (ROS) and varied proteins, and gives an intensive fluorescence enhancement (F/F 0 = 50). Moreover, with its mitochondria-targeting ability, Rd-DPA3 can be used to efficiently monitor the alternations of intracellular ONOO À 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 À influx and illustrating an age-dependent accumulation of ONOO À in AD mice brains.

Recent Progress of Spectroscopic Probes for Peroxynitrite and Their Potential Medical Diagnostic Applications

“…The triggers of ONOO − -responsive probes with xanthene as a fluorophore core were generally built on (1) oxidation of the hydrazide (Xan1-Xan15) [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32], (2) oxidative cleavage of the substituents at the hydroxyl or amino group (Xan 16-Xan 28) [33][34][35][36][37][38][39][40][41][42][43][44][45], (3) oxidation of pyrylium (Xan 29-Xan 33) [46][47][48][49][50], and (4) oxidation of the hydrogenated xanthene (Xan 34-Xan 37) [51][52][53][54] and others (Xan 38-Xan 41) [55][56][57][58]. The key elements of the ONOO − response of probes are summarized in Table 1.…”

Reactive Species-Activatable AIEgens for Biomedical Applications

“…The excessive expression of ONOO − is an important feature of many major diseases such as cancer, diabetes, cardiopathy, Alzheimer’s disease, and acute and chronic inflammation [ 143 , 144 , 145 ]. Consequently, the specific detection of ONOO − is momentous for diagnosing these diseases and monitoring the therapeutic process.…”

Recent Developments in PET and SPECT Radiotracers as Radiopharmaceuticals for Hypoxia Tumors

“…Molecular imaging is defined as the visualization, characterization, and quantification of biological processes in intact living subjects using specific imaging probes [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. Nowadays, molecular imaging technologies provide insights into biological events, pathology, and the mechanisms of diseases; thus, they play an important role in various fields of neuroscience, cardiology, gene therapy, oncology, and so on [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ]. To visualize biological events in a non-invasive way, a variety of molecular imaging methods have been developed.…”