Polyoxometalate-Decorated Gold Nanoparticles Inhibit β-Amyloid Aggregation and Cross the Blood–Brain Barrier in a µphysiological Model

Alzheimer’s disease is characterized by a 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 time, there are no effective treatments available. Here, we develope...

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Bibliographic Details
Main Authors: Marta Perxés Perich, Sujey Palma-Florez, Clara Solé, Sara Goberna-Ferrón, Josep Samitier, Pedro Gómez-Romero, Mònica Mir, Anna Lagunas
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Nanomaterials
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Online Access:https://www.mdpi.com/2079-4991/13/19/2697
Description
Summary:Alzheimer’s disease is characterized by a 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 time, 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 the inhibition of the formation of amyloid fibrils, showing a 75% decrease in Aβ aggregation in vitro. As it is a potential candidate for the treatment of Alzheimer’s disease, we evaluated the cytotoxicity of AuNPs@POM@PEG and its ability 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 vitro microphysiological model of the BBB (BBB-on-a-chip), containing 3D human neurovascular cell co-cultures and microfluidics. The results show 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 the green light to further studies into this system as a nanotherapeutic.
ISSN:2079-4991