期刊
TALANTA
卷 224, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.talanta.2020.121830
关键词
Amyloid-beta oligomer selectivity; NIR imaging; Aggregation inhibitor; ROS generation Inhibitor; Alzheimer's disease
资金
- General Research Fund of Research Grant Council of Hong Kong [HKBU12301317]
- National Natural Science Foundation of China [21675135, 81703487, 81773926]
- Research Committee of Hong Kong Baptist University [IRCMS/19-20/H02]
- Shenzhen Science and Technology Innovation Commission (SZSTI) [201803023000787]
- Hong Kong General Research Fund [GRF/HKBU12101417, GRF/HKBU12100618]
- Hong Kong Health and Medical Research Fund [HMRF14150811, HMRF15163481]
- Hong Kong Baptist University [HKBU/RC-IRCs/17-18/03, HKBU/RC-IRMS/15-16/04, FRGI/17-18/041, FRGII/17-18/021]
- Interdisciplinary Research Clusters Matching Scheme
Novel near infrared emissive fluorophores exhibit strong selectivity towards Aβ oligomers and monomers, good biocompatibility and stability, and significant inhibitory effects on Aβ aggregation.
To enable the early detection and intervention of Alzheimer's disease (AD), it is highly desirable to develop novel theranostic agents for simultaneous detection of toxic and pathogenic amyloid-beta (A beta) oligomers in vivo and attenuation of A beta-induced toxicity. Herein, we report a new series of oligomeric A beta targeted near infrared (NIR) emissive dibutylnaphthylamine-based cyanine probes for in vivo and ex vivo imaging of A beta in AD mouse model. These new fluorophores exhibited strong solvatochromism and a large bathochromic shift of the emission spectrum upon binding with A beta species, giving rise to advantageous NIR emission. Besides, they showed an intriguingly stronger fluorescence enhancement upon interacting with A beta oligomers and monomers, and binding affinity toward A beta oligomers and monomers than A beta fibrils, suggesting they were selective to A beta oligomers and monomers. In addition to low toxicity, one of the fluorophores, DBAN-SLM, showed remarkably effective inhibitory effect on A beta aggregation, significant neuroprotection effect against the A beta-induced toxicities, and suppression on A beta-induced reactive oxygen species (ROS) generation. Because of excellent blood-brain barrier (BBB) permeability, good biocompatibility and stability, high specificity towards A beta oligomers as well as strong turn-on fluorescence upon A beta binding, DBAN-SLM was successfully applied for in vivo and ex vivo imaging of A beta in AD mouse model, signifying its great promise as a useful theranostic agent for the early diagnosis and therapy of AD. Our results also demonstrated for the first time that the dibutyl-2-naphthylamine moiety is a useful and effective structural building block to promote the targeting capability of oligomeric A beta.
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