RESUMO
BACKGROUND: Deposits of aggregated amyloid-ß protein (Aß) are a pathological hallmark of Alzheimer's disease (AD). Thus, one therapeutic strategy is to eliminate these deposits by halting Aß 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 Aß aggregation inhibitors. In this study, we characterized the inhibitory capabilities of gold nanospheres exhibiting different surface coatings and diameters. RESULTS: Both NP 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)-coated NPs abrogated Aß aggregation at a substoichiometric ratio of 1:2,000,000. Theoretical calculations suggest that this low stoichiometry could arise from altered solution conditions near the NP surface. Specifically, local solution pH and charge density are congruent with conditions that influence aggregation. CONCLUSIONS: These findings demonstrate the potential of surface-coated gold nanospheres to serve as tunable therapeutic agents for the inhibition of Aß aggregation. Insights gained into the physiochemical properties of effective NP inhibitors will inform future rational design of effective NP-based therapeutics for AD.
RESUMO
Gold nanorods show great promise as light-controlled molecular release systems. Dye molecules were loaded within a variable number of polyelectrolyte multilayers wrapped around gold nanorods. The dye photoinduced release rate depended on the quantity and type of polyelectrolyte trapping layers and could be tuned by a factor of 100. Only two molecular capping layers were sufficient to turn off release. Comparison of the phototriggered molecular release rate to a pure thermal experiment provides an estimate of the effective temperature of the nanorod solution upon irradiation.