Activatable Small‐Molecule Photoacoustic Probes that Cross the Blood–Brain Barrier for Visualization of Copper(II) in Mice with Alzheimer's Disease

作者：Shichao Wang, Zonghai Sheng, Zhenguo Yang, Di Hu, Xiaojing Long, Gang Feng, Yubin Liu, Zhen Yuan, Jingjing Zhang, Hairong Zheng, Xuanjun Zhang · 发表于：Angewandte Chemie International Edition · 年份：2019 · DOI：10.1002/anie.201904047 · 被引用次数：119 · 研究领域：Photoacoustic and Ultrasonic Imaging、Nanoplatforms for cancer theranostics、Advanced Nanomaterials in Catalysis

Abstract 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.