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

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. Ministry of Education (MOE) National Research Foundation (NRF) The authors thank the financial support from National Natural Science Foundation of China (22106115, 81901803, and 22274107), Jiangsu Specially Appointed Professorship, Natural Science Foundation of Jiangsu Province (BK20190830and BK20190811), Leading Talents of Innovation and Entrepreneurship of Gusu (ZXL2021457),and Soochow Technological Project(SYS2020082).K.P. thanks Singapore National Research Foundation(NRF)(NRF-NRFI07-2021-0005), and Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19, RT05/20), Academic Research Fund Tier 2 (MOE-T2EP30220-0010; MOE-T2EP30221-0004), for the financial support.