Activatable Small-Molecule Photoacoustic Probes that Cross the Blood-Brain Barrier for Visualization of Copper(II) in Mice with Alzheimer's Disease.
Shichao WangZonghai ShengZhenguo YangDehong HuXiaojing LongGang FengYubin LiuZhen YuanJingjing ZhangHairong ZhengXuanjun ZhangPublished in: Angewandte Chemie (International ed. in English) (2019)
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.
Keyphrases
- fluorescence imaging
- living cells
- fluorescent probe
- small molecule
- photodynamic therapy
- high resolution
- aqueous solution
- white matter
- single molecule
- cognitive decline
- metal organic framework
- high fat diet induced
- resting state
- quantum dots
- cerebral ischemia
- skeletal muscle
- insulin resistance
- mass spectrometry
- metabolic syndrome
- type diabetes
- label free
- adipose tissue