Polyoxometalate decorated gold nanoparticles inhibit β -amyloid aggregation and cross the blood brain barrier in a µphysiological model

Abstract

Abstract Alzheimer’s disease is characterized by the combination of several neuropathological hallmarks such as extracellular aggregates of beta amyloid (Aβ). Numerous alternatives have been studied for inhibiting Aβ aggregation but at this moment there are no effective treatments available. Here, we developed the tri-component nanohybrid system AuNPs@POM@PEG, based on gold nanoparticles (AuNPs) covered with polyoxometalates (POMs) and polyethylene glycol (PEG). In this work, AuNPs@POM@PEG demonstrated to inhibit the formation of amyloid fibrils showing a 75% decrease in Aβ aggregation in vitro. As a potential candidate for the treatment of Alzheimer’s disease, we evaluated the cytotoxicity and ability of the AuNPs@POM@PEG to cross the blood-brain barrier (BBB). We achieved a stable nanosystem that is non-cytotoxic below 2.5 nM to human neurovascular cells. The brain permeability of AuNPs@POM@PEG was analyzed in an in vitromicrophysiological model of the BBB (BBB-on-a-chip), containing 3D human neurovascular cell co-culture and microfluidics. Results showed that AuNPs@POM@PEG was able to cross the brain endothelial barrier in the chip and demonstrated that POM does not affect the barrier integrity, giving green light to further studies as nanotherapeutic system.