Work

Smart Chemiluminescence Probes and Dual-Amplification of Signal for Detection of Amyloid Beta Species in Alzheimer’s Disease Model

Year: 2020

Type: preprint

Abstract: Fluorescence and chemiluminescence imaging are the most widely applied optical emissive imaging methods in biomedical research. “Smart” (turn-on) fluorescence imaging has been routinely used for in vitro, cellular, and in vivo imaging; however, smart chemiluminescence imaging has been rarely explored. In this report, we designed chemiluminescence probe ADLumin-1 and validated that ADLumin-1 was a smart chemiluminescence probe for amyloid beta (Ab) species, evidenced by a 216-fold amplification of chemiluminescence intensity upon mixing with Abs in vitro. In vivo two photon imaging indicated that ADLumin-1 could efficiently cross blood-brain- barrier (BBB) and provided excellent contrast both for Ab plaques and cerebral amyloid angiopathy (CAA). In vivo whole brain imaging showed that the chemiluminescence signal of ADLumin-1 from 5-month-old transgenic AD (5xFAD) mice was 1.80-fold higher than that from the age-matched wild-type mice. Moreover, we demonstrated that it was feasible to further dually-amplify signal via chemiluminescence resonance energy transfer (DAS-CRET) using two non-conjugated smart probes (ADLumin-1 and CRANAD-3) in solutions, brain homogenates, and in vivo whole brain imaging. Our results showed that DAS-CRET could provide a 2.25-fold margin between 5- month-old 5xFAD mice and wild type mice. To our knowledge, this is the first report that a chemiluminescence probe could be used for detecting Ab species both in vitro and in vivo. Although ADLumin-1 was designed for Abs, we believe that our strategy could be potentially extended to a wide range of targets, including other aggregating-prone proteins. Notably, our results suggested that the strategies for turning-on fluorescence could be used for amplifying chemiluminescence, and we believe that our studies could inspire considerably more research on chemiluminescence imaging

Source: ChemRxiv

DOI: 10.26434/chemrxiv.12142578