Near-Infrared Photoactivatable Oxygenation Catalysts of Amyloid Peptide

Abstract

Summary Toxic aggregation of amyloid peptide and protein is intimately related to a number of human diseases, including Alzheimer's disease (AD). Here, we developed biocompatible photooxygenation catalyst 9 , which can selectively oxygenate and degrade the pathogenic aggregation of AD-related amyloid-β peptide (Aβ) under near-infrared (NIR) light irradiation. On the basis of the structure of a fluorescent Aβ probe, CRANAD-2, a bromine atom was introduced to increase the production of singlet oxygen for photooxygenation. The use of julolidine and perfluoroalkylborate moieties as electron-donor and -acceptor components, respectively, markedly enhanced the photocatalytic activity and reduced phototoxicity. Photooxygenation of aggregated Aβ by 9 under NIR irradiation in the presence of cells attenuated the cytotoxicity of Aβ. The tissue permeability of NIR enabled catalytic photooxygenation of aggregated Aβ under the mouse skin. Moreover, injection of the catalyst to the AD-model mouse brain along with NIR light irradiation led to a significant decrease in the intact Aβ level in the brain.