NDLI: A quadrupolar two-photon fluorescent probe for <i>in vivo</i> imaging of amyloid-β plaques

Content Provider	Royal Society of Chemistry (RSC)
Author	Mook-Jung, Inhee Kim, Hwan Myung Baik, Sung Hoon Kim, Jeong Jin Heo, Cheol Ho Kang, Hyuk Jung, Tae Sung Sarkar, Avik Ranjan
Copyright Year	2016
Abstract	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.
Starting Page	4600
Ending Page	4606
Page Count	7
File Format	HTM / HTML PDF
ISSN	20416520
Volume Number	7
Issue Number	7
Journal	Chemical Science
DOI	10.1039/c6sc00355a
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Subscribed
Subject Keyword	CAA Cerebral amyloid angiopathy Amyloid beta Microscopy GM Genetically modified mouse Fluorescence Signal-to-noise ratio Blood\u2013brain barrier Three-dimensional space
Content Type	Text
Resource Type	Article
Subject	Chemistry

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