Highly Sensitive Near-Infrared Fluorophores for in Vivo Detection of Amyloid‑β Plaques in Alzheimer’s Disease

Alzheimer’s
disease (AD) is pathologically characterized
by the accumulation of β-amyloid (Aβ) deposits in the
parenchymal and cortical brain. In this work, we designed, synthesized,
and evaluated a series of near-infrared (NIR) probes with electron
donor–acceptor end groups interacting through a π-conjugated
system for the detection of Aβ deposits in the brain. Among
these probes, 3b and 3c had excellent fluorescent
properties (emission maxima > 650 nm and high quantum yields) and
displayed high sensitivity and high affinities to Aβ aggregates
(3b, Kd = 8.8 nM; 3c, Kd = 1.9 nM). Both 3b and 3c could readily penetrate the blood–brain barrier
with high initial brain uptake and fast to moderate washout from the
brain. In vivo NIR imaging revealed that 3b and 3c could efficiently differentiate transgenic and wild-type
mice. In summary, our research provides new hints for developing smarter
and more activatable NIR probes targeting Aβ.