Butyrylcholinesterase-Activated Near-Infrared Fluorogenic Probe for In Vivo Theranostics of Alzheimer’s Disease

Butyrylcholinesterase
(BChE) is a promising biomarker
and effective
therapeutic target for Alzheimer’s disease (AD). Herein, we
designed a BChE-activated near-infrared (NIR) probe, DTNP, which could be activated by BChE and inhibit its enzymatic activity. DTNP is composed of a cyclopropane moiety as the recognition
unit, a NIR fluorophore hemicyanine as the NIR reporter, and a BChE
inhibitor as the therapeutic unit. DTNP specifically
binds BChE with high sensitivity and exhibits strong “turn-on”
NIR fluorescence as well as nerve cell protection. In vivo imaging
shows DTNP has favorable blood–brain barrier permeability
and long-term tracking ability with preliminary competence in AD diagnosis. DTNP can significantly inhibit BChE activity, promote the
release of ACh, and rescue learning deficits and cognitive impairment.
Therefore, DTNP, the first reported and partially validated
theranostic probe for the detection of BChE in AD, may provide a foundation
and inspiration for imaging and therapy in AD.