Attenuation of blood-brain barrier dysfunction by functionalized gold nanoparticles against amyloid-β peptide in an Alzheimer's disease-on-a-chip model
Gold nanoparticles (GNP) are highly valuable in nanotechnology due to their biocompatibility and unique physicochemical properties, which make them attractive as nanocarriers for targeted drug delivery. In the context of neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), GNP hold promise for reducing the toxicity of Amyloid-β peptide (Aβ) aggregates. However, a major challenge in developing new therapies for NDDs lies in the limited reliance on animal models and the difficulty of crossing the blood-brain barrier (BBB). This study investigates the effects of GNP on Aβ toxicity using a human-based BBB-organ-on-a-chip model (BBB-oC), mimicking the 3D cellular architecture of the BBB under both normal and pathological conditions. We rationally designed a novel nanosystem functionalized with the peptide D3, which functions both as a selective Aβ toxicity inhibitor and a BBB-targeting agent. The results show that GNP can cross the BBB, reduce the Aβ-induced cytotoxicity, and promote the maintenance of the BBB integrity. Moreover, controlling the shape of GNP further enhanced their protective effect. Overall, this work highlights the feasibility of rationally designed GNP as a promising therapeutic strategy for AD, evaluated through a more reliable and predictive human-relevant model.
Authors
- Rebeca Aldunate (ORCID: https://orcid.org/0000-0002-5540-3187)
- Anna Lagunas (ORCID: https://orcid.org/0000-0002-0936-3401)
- Freddy Célis (ORCID: https://orcid.org/0000-0003-3195-3018)
- Andreas Tapia-Arellano (ORCID: https://orcid.org/0000-0003-0660-8837)
- Marcelo J. Kogan (ORCID: https://orcid.org/0000-0003-0608-5087)
- Pablo Cabrera-Barona (ORCID: https://orcid.org/0000-0002-6225-5717)
- Amado Cruz Crespo
- Josep Samitier (ORCID: https://orcid.org/0000-0002-1140-3679)
- Karen Bolaños (ORCID: https://orcid.org/0000-0001-5469-2661)
- Eyleen Araya (ORCID: https://orcid.org/0000-0002-4486-384X)
- Sujey Palma-Florez (ORCID: https://orcid.org/0000-0002-6806-0056)
- Elizabeth Cortés-Adasme (ORCID: https://orcid.org/0000-0003-0401-1631)
- Michael Matus (ORCID: https://orcid.org/0000-0002-7891-1096)
- Natalia Hassan (ORCID: https://orcid.org/0000-0001-5001-5102)
- Mònica Mir (ORCID: https://orcid.org/0000-0002-1490-8373)
- Melina Pérez
- Aurora J. Araya-Vergara
Institutions
- Universidad Andrés Bello (CL)
- Millennium Science Initiative (CL)
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Pontificial Catholic University of Valparaiso (CL)
- Millennium Nucleus of Ion Channel Associated Diseases (CL)
- Universidad Santo Tomás (CL)
- Advanced Center for Chronic Diseases (CL)
- Metropolitan University of Technology (CL)
- Institute for Bioengineering of Catalonia (ES)
- University of Chile (CL)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Materials Today Bio
- Published
- 2025-10-25
- DOI
- https://doi.org/10.1016/j.mtbio.2025.102453
- Citations
- 1
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.16