nn0c03400_si_001.pdf (2.53 MB)
0/0

Deep Red Blinking Fluorophore for Nanoscopic Imaging and Inhibition of β‑Amyloid Peptide Fibrillation

Download (2.53 MB)
journal contribution
posted on 02.09.2020 by Yuanyuan Ma, Zhongju Ye, Chen Zhang, Xueli Wang, Hung-Wing Li, Man Shing Wong, Hai-Bin Luo, Lehui Xiao
Deposition and aggregation of β-amyloid (Aβ) peptides are demonstrated to be closely related to the pathogenesis of Alzheimer’s disease (AD). Development of functional molecules capable of visualizing Aβ1–40 aggregates with nanoscale resolution and even modulating Aβ 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 Aβ1–40 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 Aβ1–40 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 Aβ1–40 aggregates. Morphology-dependent toxic effect of Aβ1–40 aggregates toward PC12 cells is unveiled from in situ nanoscopic fluorescence imaging. In addition, me-slg displays a strong inhibitory effect on Aβ1–40 fibrillation in a low inhibitor-protein ratio (e.g., I:P = 0.2). A noticeably reduced cytotoxic effect of Aβ1–40 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.

History

Exports