Issue 7, 2016

A quadrupolar two-photon fluorescent probe for in vivo imaging of amyloid-β plaques


The formation of beta amyloid (Aβ) plaques in specific brain regions is one of the early pathological hallmarks of Alzheimer's disease (AD). To enable the early detection of AD and related applications, a method for real-time, clear 3D visualization of Aβ plaques in vivo is highly desirable. Two-photon microscopy (TPM) which utilizes two near-infrared photons is an attractive tool for such applications. However, this technique needs a sensitive and photostable two-photon (TP) probe possessing bright TP exited fluorescence to impart high signal-to-noise (S/N) visualization of Aβ plaques. Herein, we report a quadrupolar TP fluorescent probe (QAD1) having large TP action cross section (Φδmax = 420 GM) and its application for in vivo TPM imaging of Aβ plaques. This probe, designed with a centrosymmetric D–A–D motif with a cyclic conjugating bridge and solubilizing unit, displays bright TP excited fluorescence, appreciable water solubility, robust photostability, and high sensitivity and selectivity for Aβ plaques. Using the real-time TPM imaging of transgenic 5XFAD mice after intravenous injection of QAD1, we show that this probe readily enters the blood brain barrier and provides high S/N ratio images of individual Aβ plaques in vivo. We also used QAD1 in dual-color TPM imaging for 3D visualization of Aβ plaques along with blood vessels and cerebral amyloid angiopathy (CAA) inside living mouse brains. These findings demonstrate that this probe will be useful in biomedical applications including early diagnosis and treatments of AD.

Graphical abstract: A quadrupolar two-photon fluorescent probe for in vivo imaging of amyloid-β plaques

Supplementary files

Article information

Article type
Edge Article
25 Jan 2016
07 Apr 2016
First published
07 Apr 2016
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2016,7, 4600-4606

A quadrupolar two-photon fluorescent probe for in vivo imaging of amyloid-β plaques

C. H. Heo, A. R. Sarkar, S. H. Baik, T. S. Jung, J. J. Kim, H. Kang, I. Mook-Jung and H. M. Kim, Chem. Sci., 2016, 7, 4600 DOI: 10.1039/C6SC00355A

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