Rational design synthesis and evaluation of a novel near-infrared fluorescent probe for selective imaging of amyloid-ß aggregates in Alzheimer's disease.
Anal Chim Acta
; 1281: 341900, 2023 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-38783740
ABSTRACT
Alzheimer's disease (AD) is a degenerative neurological disorder that remains incurable to date, seriously affecting the quality of life and health of those affected. One of the key neuropathological hallmarks of AD is the formation of amyloid-ß (Aß) plaques. Near-infrared (NIR) probes that possess a large Stokes shift show great potential for imaging of Aß plaques in vivo and in vitro. Herein, we proposed a rational strategy for design and synthesis of a series of NIR fluorescent probes that incorporate a tricarbonitrile group as a strong electron-withdrawing group (EWG) to enable NIR emission and large Stokes shift for optimal imaging of Aß plaques. The probe TCM-UM exhibited remarkable in vitro performance, including strong NIR emission (λem = 670 nm), large Stokes shift (120-245 nm), and its affinity for Aß42 aggregates (Kd = 43.78 ± 4.09 nM) was superior to the commercially available probe Thioflavin T (ThT, Kd = 896.04 ± 33.43 nM). Further, TCM-UM was selected for imaging Aß plaques in brain tissue slices and APP/PS1 transgenic (AD) mice, the results indicated that TCM-UM had an excellent ability to penetrate the blood-brain barrier (BBB) compared with ThT, and it could effectively distinguish wild-type (Wt) mice and APP/PS1 transgenic (AD) mice.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Camundongos Transgênicos
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Peptídeos beta-Amiloides
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Doença de Alzheimer
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Corantes Fluorescentes
Limite:
Animals
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Humans
Idioma:
En
Revista:
Anal Chim Acta
Ano de publicação:
2023
Tipo de documento:
Article