An Activatable NIR-II Fluorescent Reporter for In Vivo Imaging of Amyloid-β Plaques

Angew Chem Int Ed Engl. 2023 Feb 6;62(7):e202216351. doi: 10.1002/anie.202216351. Epub 2023 Jan 12.

Abstract

Fluorescence imaging in the second near-infrared (NIR-II) window holds great promise for in vivo visualization of amyloid-β (Aβ) pathology, which can facilitate characterization and deep understanding of Alzheimer's disease (AD); however, it has been rarely exploited. Herein, we report the development of NIR-II fluorescent reporters with a donor-π-acceptor (D-π-A) architecture for specific detection of Aβ plaques in AD-model mice. Among all the designed probes, DMP2 exhibits the highest affinity to Aβ fibrils and can specifically activate its NIR-II fluorescence after binding to Aβ fibrils via suppressed twisted intramolecular charge transfer (TICT) effect. With suitable lipophilicity for ideal blood-brain barrier (BBB) penetrability and deep-tissue penetration of NIR-II fluorescence, DMP2 possesses specific detection of Aβ plaques in in vivo AD-model mice. Thus, this study presents a potential agent for non-invasive imaging of Aβ plaques and deep deciphering of AD progression.

Keywords: Activatable Probes; Alzheimer's Disease; Amyloid-Beta Plaques; Detection; Second Near-Infrared Fluorescence Imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism
  • Fluorescent Dyes* / chemistry
  • Mice
  • Mice, Transgenic
  • Optical Imaging
  • Plaque, Amyloid / metabolism

Substances

  • Fluorescent Dyes
  • Amyloid beta-Peptides