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

Area of Science:

• Biomedical Engineering
• Neuroscience
• Chemical Biology

Background:

• Alzheimer's disease (AD) involves altered levels of hypochlorous acid (HOCl) and butyrylcholinesterase (BChE).
• Existing probes for HOCl and BChE lack dual detection capabilities and face challenges like off-target effects and limited blood-brain barrier penetration.
• There is a need for advanced imaging tools for accurate AD diagnosis.

Purpose of the Study:

• To construct a novel two-photon fluorescent probe for simultaneous detection of HOCl and BChE.
• To evaluate the probe's efficacy in cellular and in vivo models of Alzheimer's disease.
• To establish a new tool for precise AD diagnosis.

Main Methods:

• Development of a dual-lock strategy two-photon fluorescent probe.
• Utilizing oxidation of a thiocarbonyl group by HOCl and ester bond hydrolysis by BChE for signal generation.
• Employing 4-methylumbelliferone as the released fluorophore.
• In vitro imaging in PC12 cells and in vivo deep brain imaging in AD mouse models.

Main Results:

• The probe successfully detected both hypochlorous acid and butyrylcholinesterase.
• Excellent imaging results were achieved in PC12 cells.
• Deep two-photon imaging in the brains of AD mice demonstrated the probe's effectiveness after intravenous administration.
• The probe showed high specificity and sensitivity.

Conclusions:

• The developed two-photon fluorescent probe is effective for dual detection of HOCl and BChE.
• This probe offers a promising tool for precise diagnosis and imaging in Alzheimer's disease research.
• The probe's ability to penetrate the blood-brain barrier facilitates in vivo brain imaging.