Abstract
As key biomarkers,amyloid-β(Aβ)plaques are frequently used to diagnose Alzheimer's disease(AD).Although fluorescence imaging has proven to be effective in detecting these plaques,the gold standard probe thioflavin T(ThT),used for Aβ aggregates,cannot be applied in vivo owing to its invasive na-ture.Therefore,the development of novel fluorescent probes capable of identifying Aβ plaques in situ is necessary.Based on the ThT structure,two π-conjugated heterocyclic D-π-A probes were designed bearing the hydroxytricyanopyrrole acceptor and N,N-dimethylaminophenyl donor.These probes exhib-ited red to near-infrared fluorescence emission(λmax=732 nm),large Stokes shifts(＞100nm),excep-tional signal-to-noise ratio,rapid response(＜30s),and high binding affinity(NT-HTCP=33.32 nmol/L;NF-HTCP=53.35 nmol/L)for Aβ aggregates.As the best candidate,NT-HTCP was used for in situ imag-ing of Aβ plaques in AD mouse models.Furthermore,in vivo research demonstrated that NT-HTCP could cross the blood-brain barrier and continue imaging the Aβ plaques with a good signal-to-noise ratio.Additionally,the outcomes of the docking computations helped guide the development of the Aβ probes.This study expands the family of N,N-dimethylaminophenyl-based Aβ-sensitive fluorophores,with NT-HTCP emerging as a highly promising imaging agent.
维普
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