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.
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, People's Republic of China.
Hualong
H
Fu
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, People's Republic of China.
Mengchao
M
Cui
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, People's Republic of China.
Liu
L
Zhao
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, People's Republic of China.
Peiyu
P
Tu
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, People's Republic of China.
Kaixiang
K
Zhou
Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities , Wuhan 430074, People's Republic of China.
Jiapei
J
Dai
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, People's Republic of China.
Boli
B
Liu
D015081:2-Naphthylamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D008875:Middle Aged; D062105:Molecular Docking Simulation; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D011485:Protein Binding; D019265:Spectroscopy, Near-Infrared; D013237:Stereoisomerism
C000603351:2-(3-(6-(dimethylamino)naphthalen-2-yl)allylidene)malononitrile; D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D009570:Nitriles; D015081:2-Naphthylamine