(391c) Influence of Gold Nanoparticle Surface Chemistry and Diameter upon Alzheimer’s Disease Amyloid-β Protein Aggregation

Authors: 
Moss, M. A., University of South Carolina
Pate, K., University of South Carolina
Soto-Ortega, D., University of South Carolina
Lohse, S., University of Illinois at Urbana-Champaign
van der Munnik, N., University of South Carolina
Lim, M., University of South Carolina
Moore, K. A., University of South Carolina
Jackson, K., SC State University
Uline, M. J., University of South Carolina
Mahtab, R., SC State University
Murphy, C., University of Illinois at Urbana-Champaign
Lyles, V., South Carolina State University
Jones, L., South Carolina State University
Deposits of aggregated amyloid-β protein (Aβ) are a pathological hallmark of Alzheimerâ??s disease (AD). Thus, one therapeutic strategy is to eliminate these deposits by halting Aβ aggregation. While a variety of possible aggregation inhibitors have been explored, only nanoparticles (NPs) exhibit promise at low substoichiometric ratios. With tunable size, shape, and surface properties, NPs present an ideal platform for rationally designed Aβ aggregation inhibitors. In this study, we characterized the inhibitory capabilities of gold nanospheres exhibiting different surface coatings and diameters. Both diameter and surface chemistry were found to modulate the extent of aggregation, while NP electric charge influenced aggregate morphology. Notably, 8 nm and 18 nm poly(acrylic acid) NPs abrogated Aβ aggregation at a substoichiometric ratio of 1:2,000,000. Theoretical calculations suggest that this stoichiometry could arise from altered solution conditions near the NP surface. Insights provided by this study will inform future rational design of effective NP-based therapeutics for AD.