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

Yuanyuan Ma, Zhongju Ye, Chen Zhang, Xueli Wang, Hung Wing Li, Ricky M S WONG, Hai Bin Luo, Lehui Xiao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)11341-11351
Number of pages11
JournalACS Nano
Volume14
Issue number9
DOIs
Publication statusPublished - 22 Sep 2020

Scopus Subject Areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

User-Defined Keywords

  • amyloid fibrils
  • blinking
  • cyanine fluorophore
  • inhibition
  • nanoscopic imaging

Fingerprint

Dive into the research topics of 'Deep Red Blinking Fluorophore for Nanoscopic Imaging and Inhibition of β-Amyloid Peptide Fibrillation'. Together they form a unique fingerprint.

Cite this