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

Anal Chem. 2023 Nov 21;95(46):16868-16876. doi: 10.1021/acs.analchem.3c02634. Epub 2023 Nov 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / diagnostic imaging
  • Animals
  • Brain / metabolism
  • Butyrylcholinesterase / metabolism
  • Fluorescent Dyes / chemistry
  • Hypochlorous Acid
  • Mice

Substances

  • Butyrylcholinesterase
  • Hypochlorous Acid
  • Fluorescent Dyes