Functionalized Gold Nanoparticles As Novel Alzheimer's Therapeutics

Aggregation of amyloid-β protein (Aβ) into toxic structures in the brain has been indicated as a major etiological factor in Alzheimer’s disease. Much of contemporary Alzheimer’s research seeks to obtain a greater understanding of the Aβ aggregation process, and evaluate compounds that inhibit it. Previous research has explored the effects of inorganic nanoparticles with functional coatings on Aβ aggregation. One hypothesis suggests that such systems influence this process by acting as point sources of local solution destabilization. This project describes the modeling and synthesis of gold nanoparticles (AuNPs) functionalized with poly(acrylic acid) (PAA) chains as a novel aggregation inhibitor. PAA samples were synthesized and grafted onto AuNPs in a ligand exchange process. These PAA-AuNPs were characterized through various chemical analysis methods. The previous hypothesis was confirmed in part by study of such NP systems with a statistical thermodynamics model for molecular dynamics. Equilibrium calculations reveal that the polyelectrolyte brush “pulls” species in toward the surface to relieve negative charge density, affecting solution characteristics such as local pH. Therapeutic potential of these PAA-AuNPs was evaluated with direct introduction into an Aβ monomer solution; aggregation was subsequently measured with fluorescence spectroscopy. The combined theory and experiment will yield a better understanding of amyloid aggregation mechanics, and a process for optimizing the design of an aggregation inhibitor.