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Activatable Small‐Molecule Photoacoustic Probes that Cross the Blood–Brain Barrier for Visualization of Copper(II) in Mice with Alzheimer's Disease
Author(s) -
Wang Shichao,
Sheng Zonghai,
Yang Zhenguo,
Hu Dehong,
Long Xiaojing,
Feng Gang,
Liu Yubin,
Yuan Zhen,
Zhang Jingjing,
Zheng Hairong,
Zhang Xuanjun
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201904047
Subject(s) - chemistry , in vivo , copper , biophysics , organic chemistry , microbiology and biotechnology , biology
Copper enrichment in the brain is highly related to Alzheimer's disease (AD) pathogenesis, but in vivo tracing of Cu 2+ in the brain by imaging techniques is still a great challenge. In this work, we developed a series of activatable photoacoustic (PA) probes with low molecular weights (less than 438 Da), RPS1 – RPS4 , which can specifically chelate with Cu 2+ to form radicals with turn‐on PA signals in the near‐infrared (NIR) region. Introducing the electron‐donating group N , N ‐dimethylaniline into the probe was found to significantly enhance the radical stability and PA intensity. The best probe in the series, RPS1 , showed a fast response (within seconds) to Cu 2+ with high selectivity and a low PA detection limit of 90.9 n m . Owing to the low molecular weight and amphiphilic structure, RPS1 could effectively cross the blood–brain barrier (BBB) and thus allowed us, for the first time, to visualize Cu 2+ in vivo via PA imaging in the brains of AD mice.