Amyloid-β Deposits Target Efficient Near-Infrared Fluorescent Probes: Synthesis, in Vitro Evaluation, and in Vivo Imaging
- 12 January 2016
- journal article
- research article
- Published by American Chemical Society (ACS) in Analytical Chemistry
- Vol. 88 (3), 1944-1950
- https://doi.org/10.1021/acs.analchem.5b04441
Abstract
The formation of extracellular amyloid-β (Aβ) plaques is a common molecular change that underlies several debilitating human conditions, including Alzheimer's disease (AD); however, the existing near-infrared (NIR) fluorescent probes for the in vivo detection of Aβ plaques are limited by undesirable fluorescent properties and poor brain kinetics. In this work, we designed, synthesized, and evaluated a new family of efficient NIR probes that target Aβ plaques by incorporating hydroxyethyl groups into the ligand structure. Among these probes, DANIR 8c showed excellent fluorescent properties with an emission maximum above 670 nm upon binding to Aβ aggregates and also displayed a high sensitivity (a 629-fold increase in fluorescence intensity) and affinity (Kd = 14.5 nM). Because of the improved hydrophilicity that was induced by hydroxyls, 8c displayed increased initial brain uptake and a fast washout from the brain, as well as an acceptable biostability in the brain. In vivo NIR fluorescent imaging revealed that 8c could efficiently distinguish between AD transgenic model mice and normal controls. Overall, 8c is an efficient and veritable NIR fluorescent probe for the in vivo detection of Aβ plaques in the brain.Keywords
Funding Information
- Ministry of Science and Technology of the People's Republic of China (2014ZX09507007-002)
- National Natural Science Foundation of China (21201019, 21571022)
This publication has 27 references indexed in Scilit:
- Combinatorial Strategies in Fluorescent Probe DevelopmentChemical Reviews, 2012
- Fluorescence Molecular Tomography: Principles and Potential for Pharmaceutical ResearchPharmaceutics, 2011
- Multiphoton in vivo imaging of amyloid in animal models of Alzheimer’s diseaseNeuropharmacology, 2010
- New Strategies for Fluorescent Probe Design in Medical Diagnostic ImagingChemical Reviews, 2009
- Design, Synthesis, and Testing of Difluoroboron-Derivatized Curcumins as Near-Infrared Probes for in Vivo Detection of Amyloid-β DepositsJournal of the American Chemical Society, 2009
- Preclinical characterization of amyloid imaging probes with multiphoton microscopyJournal of Alzheimer's Disease, 2006
- Probing Protein Folding and Conformational Transitions with FluorescenceChemical Reviews, 2006
- In vivo detection of amyloid-β deposits by near-infrared imaging using an oxazine-derivative probeNature Biotechnology, 2005
- The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to TherapeuticsScience, 2002
- Alzheimer's Disease: The Amyloid Cascade HypothesisScience, 1992