Photothermal ablation of amyloid aggregates by gold nanoparticles

Amyloid peptide (Abeta) is found in the brain and blood of both healthy and diseased individuals alike. However, upon secondary structure transformation to a beta-sheet dominated conformation, the protein aggregates. These aggregates accumulate to form neuritic plaques that are implicated in the pathogenesis of Alzheimer's disease. Gold nanoparticles are excellent photon-thermal energy converters. The extinction coefficient of the surface plasmon band of gold nanoparticles is very large when compared to typical organic dyes. In this study, gold nanoparticle-Abeta conjugates were prepared and the photothermal ablation of amyloid peptide aggregates by laser irradiation was studied. Monofunctional gold nanoparticles were prepared using a recently reported solid phase modification method and then coupled to fragments of Abeta peptide, namely Abeta(31-35) and Abeta(25-35). The conjugates were then mixed with Abeta fragments in solution. The aggregated peptide formation was studied by a series of spectroscopic and microscopic techniques. The peptide aggregates were then irradiated by a continuous laser. With gold nanoparticle-Abeta conjugates present the aggregates were destroyed by photothermal ablation. Gold nanoparticles without Abeta conjugation were not incorporated into the aggregates and when irradiated did not result in photothermal ablation. With gold nanoparticle-Abeta conjugates the ablation was selective to the site of irradiation and minimal damage was observed as a result of thermal diffusion. In addition to the application of photoablation to a protein-based sample the nanoparticles and the chemistry involved provide an easily monofunctionalized photothermal material for the biological conjugation.