Polyoxometalate-Decorated Gold Nanoparticles Inhibit β-Amyloid Aggregation and Cross the Blood–Brain Barrier in a µphysiological Model
Marta Perxés Perich,
Sujey Palma-Florez,
Clara Solé,
Sara Goberna-Ferrón,
Josep Samitier,
Pedro Gómez-Romero,
Mònica Mir,
Anna Lagunas
Affiliations
Marta Perxés Perich
Catalan Institute of Nanoscience and Nanotechnology(ICN2) CSIC and BIST, Campus UAB, Bellaterra, 08193 Barcelona, Spain
Sujey Palma-Florez
Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain
Clara Solé
Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain
Sara Goberna-Ferrón
Catalan Institute of Nanoscience and Nanotechnology(ICN2) CSIC and BIST, Campus UAB, Bellaterra, 08193 Barcelona, Spain
Josep Samitier
Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain
Pedro Gómez-Romero
Catalan Institute of Nanoscience and Nanotechnology(ICN2) CSIC and BIST, Campus UAB, Bellaterra, 08193 Barcelona, Spain
Mònica Mir
Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain
Anna Lagunas
Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain
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.
