Electrostatic assembly of gold nanoparticle and metal-organic framework nanoparticles attenuates amyloid β aggregate-mediated neurotoxicity.

Abstract

The deposition of amyloid β (Aβ) is a conventional pathological hallmark of Alzheimer's disease (AD). Consequently, the inhibition of Aβ aggregation combined with the disaggregation of Aβ fibrils is an important therapeutic method for AD treatment. In this study, a gold nanoparticle-decorated porous metal organic framework MIL-101(Fe) (AuNPs@PEG@MIL-101) was created as an Aβ inhibitor. The high positively charged MIL-101 induced a high number of Aβ40 to be absorbed or aggregated on the surface of nanoparticles. In addition, AuNPs improved the surface property of MIL-101, causing it to uniformly bind Aβ monomers and Aβ fibrils. Thus, this framework can efficiently suppress extracellular Aβ monomer fibrillation and disrupt the preformed Aβ fibers. AuNPs@PEG@MIL-101 also decreases intracellular Aβ40 aggregation and the amount of Aβ40 immobilized on the cell membrane, thus protecting PC12 cells from Aβ40-induced microtubular defects and cell membrane damage. In summary, AuNPs@PEG@MIL-101 shows great potential for application in AD therapy.