Developing a Two-Photon "AND" Logic Probe and Its Application in Alzheimer's Disease Differentiation

In Alzheimer's disease, hypochlorous acid involved in the clearance of invading bacteria or pathogens and butyrylcholinesterase engaged in the hydrolysis of the neurotransmitter acetylcholine are relatively significantly altered. However, there are few dual detection probes for hypochlorous aci...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2023-11, Vol.95 (46), p.16868-16876
Main Authors: Guo, Jingxuan, Sun, Jia, Liu, Donghui, Liu, Ji, Gui, Lijuan, Luo, Man, Kong, Dexin, Wusiman, Sainaiwaiergul, Yang, Chang, Liu, Ting, Yuan, Zhenwei, Li, Ruixi
Format: Article
Language:English
Subjects:
Acids
Alzheimer Disease - diagnostic imaging
Alzheimer's disease
Animals
Blood-brain barrier
Brain - metabolism
Butyrylcholinesterase - metabolism
Fluorescent Dyes - chemistry
Fluorescent indicators
Hydrolysis
Hypochlorous Acid
Infrared instruments
Medical imaging
Mice
Molecular weight
Neurodegenerative diseases
Neuroimaging
Pheochromocytoma cells
Photons
Probes
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Summary:In Alzheimer's disease, hypochlorous acid involved in the clearance of invading bacteria or pathogens and butyrylcholinesterase engaged in the hydrolysis of the neurotransmitter acetylcholine are relatively significantly altered. However, there are few dual detection probes for hypochlorous acid and butyrylcholinesterase. In addition, single-response probes suffer from serious off-target effects and near-infrared probes do not easily penetrate the blood-brain barrier due to their excessive molecular weight. In this work, we constructed a two-photon fluorescent probe that recognizes hypochlorous acid and butyrylcholinesterase based on a dual-lock strategy. The thiocarbonyl group is oxidized in the presence of hypochlorous acid, and the hydrolysis occurs at the 7-position ester bond in the existence of butyrylcholinesterase, releasing a strongly fluorescent fluorophore, 4-methylumbelliferone. Excellent imaging was performed in PC12 cells using this probe, and deep two-photon imaging was observed in the brains of AD mice after tail vein injection with this probe. It indicates that the probe can provide a promising tool for the more precise diagnosis of Alzheimer's disease.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.3c02634