Light-triggered dissociation of self-assembled beta-amyloid aggregates into small, nontoxic fragments by ruthenium (II) complex

Abstract

The self-assembly of beta-amyloid (A beta) peptides into highly stable plaques is a major hallmark of Alzheimer's disease. Here, we report visible light-driven dissociation of beta-sheet-rich A beta aggregates into small, nontoxic fragments using ruthenium (II) complex ([Ru(bpy)(3)](2+)) that functions as a highly sensitive, biocompatible, photoresponsive anti-A beta agent. According to our multiple analyses using thioflavin T, bicinchoninic acid, dynamic light scattering, atomic force microscopy, circular dichroism, and Fourier transform infrared spectroscopy, [Ru(bpy)(3)](2+) successfully disassembled A beta aggregates by destabilizing the beta-sheet secondary structure under illumination of white light-emitting diode light. We validated that photoexcited [Ru(bpy)(3)](2+) causes oxidative damages of A beta peptides, resulting in the dissociation of A beta aggregates. The efficacy of [Ru(bpy)(3)](2+) is attributed to reactive oxygen species, such as singlet oxygen, generated from [Ru(bpy)(3)](2+) that absorbed photon energy in the visible range. Furthermore, photoexcited [Ru(bpy)(3)](2+) strongly inhibited the self-assembly of A beta monomers even at concentrations as low as 1 nM and reduced the cytotoxicity of A beta aggregates. Statement of Significance Alzheimer's disease is the most common progressive neurodegenerative disease, affecting more than 13% of the population over age 65. Over the last decades, researchers have focused on understanding the mechanism of amyloid formation, the hallmark of various amyloid diseases including Alzheimer's and Parkinson's. In this paper, we successfully demonstrate the dissociation of beta-Amyloid (A beta) aggregates into small, less-amyloidic fragments by photoexcited [Ru(bpy)(3)](2+) through destabilization of beta-sheet secondary structure. We validated the light-triggered dissociation of amyloid structure using multiple analytical tools. Furthermore, we confirmed that photoexcited [Ru(bpy)(3)](2+) reduces cytotoxicity of A beta aggregates. Our work should open a new horizon in the study of Alzheimer's amyloid aggregation by showing the potential of photoexcited dye molecules as an alternative therapeutic strategy for treating Alzheimer's disease in future. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.