Near-Infrared Fluorescence Probe for Monoamine Oxidase A with a Large Stokes Shift for Intraoperative Navigation

Area of Science:

• Biochemistry
• Molecular Imaging
• Chemical Biology

Background:

• Monoamine oxidase A (MAO-A) is a mitochondrial flavoprotein crucial in neurotransmitter metabolism.
• Existing near-infrared fluorescent probes (NIR-FPs) lack the specificity and sensitivity required for accurate MAO-A detection and imaging.
• Challenges in visualizing MAO-A hinder in vitro and in vivo cellular studies.

Purpose of the Study:

• To design and synthesize a novel NIR-FP, DDM-NH, for specific and sensitive detection of MAO-A.
• To evaluate the performance of DDM-NH in detecting MAO-A in live biological systems.
• To demonstrate the potential of DDM-NH for in vivo imaging applications.

Main Methods:

• Synthesis of the NIR-FP DDM-NH, incorporating a dicyanoisophosphone NIR dye precursor and an alanine recognition moiety.
• Characterization of DDM-NH's photophysical properties, including emission peak, Stokes shift, and response factor.
• Assessment of DDM-NH's sensitivity, selectivity (vs. MAO-B), and detection limit.
• Application of DDM-NH for imaging MAO-A activity in HeLa cells, zebrafish, and tumor-bearing mice.

Main Results:

• DDM-NH demonstrated specific MAO-A detection with an NIR emission peak at 770 nm and a large Stokes shift (180 nm).
• The probe exhibited an 11-fold response factor, a low detection limit of 99.7 nM, and high affinity for MAO-A over MAO-B.
• DDM-NH successfully visualized MAO-A activity in HeLa cells, zebrafish, and tumor-bearing mice.

Conclusions:

• DDM-NH is a sensitive and specific NIR-FP for MAO-A detection.
• The probe facilitates accurate imaging of MAO-A in live biological systems, including cellular and in vivo models.
• DDM-NH shows significant potential for MAO-A related research and diagnostic applications.