期刊
ACS NANO
卷 14, 期 9, 页码 11341-11351出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.0c03400
关键词
amyloid fibrils; inhibition; cyanine fluorophore; nanoscopic imaging; blinking
类别
资金
- National Natural Science Foundation of China (NSFC) [21974073]
Deposition and aggregation of beta-amyloid (A beta) peptides are demonstrated to be closely related to the pathogenesis of Alzheimer's disease (AD). Development of functional molecules capable of visualizing A beta(1-40) aggregates with nanoscale resolution and even modulating A beta assembly has attracted great attention recently. In this work, we use monocyanine fluorophore as the lead structure to develop a set of deep red carbazole-based cyanine molecules, which can specifically bind with A beta(1-40) fibril via electrostatic and van der Waals interactions. Spectroscopic and microscopic characterizations demonstrate that one of these fluorophores, (E)-1-(2-(2-methoxyethoxy)ethyl)-4-(2-(9-methyl-9H-carbazol-3-yl)-vinyl) quinolinium iodide (me-slg) can bind to A beta(1-)(40)( )aggregates with strong fluorescence enhancement. The photophysical properties of me-slg at the single-molecule level, including low on/off' duty cycle, high photon output, and sufficient switching cycles, enable real-time nanoscopic imaging of A beta(1-)(40) aggregates. Morphology-dependent toxic effect of A beta(1-)(40) aggregates toward PC12 cells is unveiled from in situ nanoscopic fluorescence imaging. In addition, me-slg displays a strong inhibitory effect on A beta(1-)(40) fibrillation in a low inhibitor-protein ratio (e.g., = 0.2). A noticeably reduced cytotoxic effect of A beta(1-)(40) after the addition of me-slg is also confirmed. These results afford promising applications in the design of a nanoscopic imaging probe for amyloid fibril as well as the development of inhibitors to modulate the fibrillation process.
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