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. An artificial chemical catalysis that can selectively transform toxic aggregates of peptides and proteins to non-toxic species under physiologic conditions would find therapeutic applications to treat currently- incurable amyloid diseases. Because peptide and protein aggregation generally depends on intermolecular hydrophobic interactions, covalent installation of hydrophilic oxygen atoms from aerobic oxygen to a peptide or protein (i.e., oxygenation) would decrease the aggregative property. Here, we report a biocompatible photooxygenation catalyst that can selectively oxygenate and degrade the pathogenic aggregation of the peptide responsible for Alzheimer's disease (AD) under near-infrared light irradiation. The detoxicating chemical catalysis targeting aggregated amyloid-β peptide proceeded in the AD-model mouse brain. The results obtained in this study are an important step toward using artificial catalysis as a potential therapeutic strategy against amyloid diseases. A biocompatible photooxygenation catalyst that can selectively oxygenate and degrade the pathogenic aggregation of Alzheimer's disease (AD)-related amyloid-β peptide (Aβ) under near-infrared light irradiation has been developed. The catalyst oxygenates Aβ embedded under the skin of a living mouse and diminishes the intact Aβ level in an AD-model mouse brain. The new catalyst is potentially applicable for the treatment of peripheral amyloid diseases and AD.
All Science Journal Classification (ASJC) codes
- Environmental Chemistry
- Chemical Engineering(all)
- Biochemistry, medical
- Materials Chemistry