Charge effects of self-assembled chitosan-hyaluronic acid nanoparticles on inhibiting amyloid β-protein aggregation

Abstract

Amyloid β-protein (Aβ) aggregation is crucial for the pathogenesis of Alzheimer's disease, and surface charge of nanoparticles (NPs) has been recognized as an important factor influencing Aβ aggregation. Herein, we report a systematic study on the issue with a series of self-assembled chitosan-hyaluronic acid composite (CH) NPs of different surface charges (CH1 to CH7, zeta potentials from +38 to -35 mV). Both the positive and negative CH NPs inhibited Aβ aggregation and the inhibitory effect increased with increasing the surface charges density. Circular dichroism spectroscopy and atomic force microscopy revealed the difference in their working mechanisms. Studies at different pH values further confirmed the importance of electrostatic interactions in Aβ aggregation and presented that the effects of CH NPs changed due to the change of Aβ charge property with pH. This work has thus provided new insight into the surface charge effects on Aβ aggregation.

Keywords: Amyloid β-protein; Electrostatic interaction; Fibrillogenesis; Inhibition; Nanoparticle; Surface charge.