474337 Influence of Gold Nanoparticle Surface Chemistry and Diameter upon Alzheimer’s Disease Amyloid-β Protein Aggregation

Tuesday, November 15, 2016: 4:05 PM
Union Square 23 & 24 (Hilton San Francisco Union Square)
Kelly A. Moore1, Kayla Pate2, Deborah Soto-Ortega2, Sam Lohse3, Nicholas van der Munnik2, Mihyun Lim4, Kaliah Jackson5, Venetia Lyles5, Lemeisha Jones5, Nisha Glassgow5, Vanessa Napumecheno6, Shanee Mobley5, Mark J. Uline2, Rahina Mahtab5, Catherine Murphy3 and Melissa A. Moss2, (1)Biomedical Engineering Program, University of South Carolina, Columbia, SC, (2)Department of Chemical Engineering, University of South Carolina, Columbia, SC, (3)Department of Chemistry, University of Illinois at Urbana-Champaign, Champaign, IL, (4)Department of Biological Sciences, University of South Carolina, Columbia, SC, (5)Biological and Physical Sciences, South Carolina State University, Orangeburg, SC, (6)South Carolina State University, Orangeburg, SC

Deposits of aggregated amyloid-β protein (Aβ) are a pathological hallmark of Alzheimer’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.

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