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
An emerging challenge for nanoscale measurements is to capture and quantify the magnitude of structural changes in response to environmental changes. Certain environmental parameters can affect the nanoscale morphology of samples, such as changing the pH, solvent polarity, ionic strength, and temperature. We prepared test platforms of n-octadecyltrichlorosilane ring nanostructures to study surface morphology changes at the nanoscale in selected liquid media compared to dry conditions in air. Particle lithography combined with organosilane vapor deposition was used to fabricate nanostructures of regular dimensions. Multilayer nanostructures of OTS were used as a test platform for scanning probe studies of solvent-responsive properties where the sides of designed ring structures expose a 3D interface for studying the interaction of solvents with molecular side groups. In dry, ambient conditions, nanostructures of OTS were first imaged using contact mode atomic force microscopy (AFM). Next, ethanol or buffer was introduced to the sample cell, and images were acquired using the same probe. We observed substantial changes in the lateral and vertical dimensions of the ring nanostructures in AFM topography frames; the sizes of the rings were observed to swell by tens of nanometers. Even after heat treatment of samples to promote cross-linking, the samples still evidenced swelling in liquid media. This research will have consequences for studies of the properties of nanomaterials, such as solvent-responsive organic films and polymers.
