Activatable Small-Molecule Photoacoustic Probes that Cross the Blood–Brain Barrier for Visualization of Copper(II) in Mice with Alzheimer's Disease
Dr. Shichao Wang
Cancer Centre and Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, P. R. China
Search for more papers by this authorCorresponding Author
Prof. Zonghai Sheng
Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 P. R. China
Search for more papers by this authorZhenguo Yang
Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001 P. R. China
Search for more papers by this authorDr. Dehong Hu
Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 P. R. China
Search for more papers by this authorXiaojing Long
Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 P. R. China
Search for more papers by this authorGang Feng
Cancer Centre and Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, P. R. China
Search for more papers by this authorDr. Yubin Liu
Cancer Centre and Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, P. R. China
Search for more papers by this authorProf. Zhen Yuan
Cancer Centre and Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, P. R. China
Search for more papers by this authorProf. Jingjing Zhang
Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001 P. R. China
Search for more papers by this authorProf. Hairong Zheng
Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Xuanjun Zhang
Cancer Centre and Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, P. R. China
Search for more papers by this authorDr. Shichao Wang
Cancer Centre and Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, P. R. China
Search for more papers by this authorCorresponding Author
Prof. Zonghai Sheng
Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 P. R. China
Search for more papers by this authorZhenguo Yang
Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001 P. R. China
Search for more papers by this authorDr. Dehong Hu
Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 P. R. China
Search for more papers by this authorXiaojing Long
Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 P. R. China
Search for more papers by this authorGang Feng
Cancer Centre and Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, P. R. China
Search for more papers by this authorDr. Yubin Liu
Cancer Centre and Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, P. R. China
Search for more papers by this authorProf. Zhen Yuan
Cancer Centre and Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, P. R. China
Search for more papers by this authorProf. Jingjing Zhang
Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001 P. R. China
Search for more papers by this authorProf. Hairong Zheng
Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Xuanjun Zhang
Cancer Centre and Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, P. R. China
Search for more papers by this authorGraphical Abstract
Photoacoustic imaging of copper(II) in the brain: Small-molecule probe RPS1 can selectively bind to Cu2+ to form a radical with a turn-on photoacoustic response in the near-infrared region. RPS1 can effectively cross the blood–brain barrier and image copper(II) in the brain of a mouse suffering form Alzheimer's disease.
Abstract
Copper enrichment in the brain is highly related to Alzheimer's disease (AD) pathogenesis, but in vivo tracing of Cu2+ 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 Cu2+ 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 Cu2+ with high selectivity and a low PA detection limit of 90.9 nm. 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 Cu2+ in vivo via PA imaging in the brains of AD mice.
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