Nanomedicine Against Aβ Aggregation by β–Sheet Breaker Peptide Delivery: In Vitro Evidence
Francesca Pederzoli,
Barbara Ruozi,
Jason Duskey,
Simone Hagmeyer,
Ann Katrin Sauer,
Stefanie Grabrucker,
Romina Coelho,
Natalia Oddone,
Ilaria Ottonelli,
Eleonora Daini,
Michele Zoli,
Maria Angela Vandelli,
Giovanni Tosi,
Andreas M. Grabrucker
Affiliations
Francesca Pederzoli
Department of Life Sciences Te.Far.T.I. Research Center, University of Modena and Reggio Emilia, 41124 Modena, Italy
Barbara Ruozi
Department of Life Sciences Te.Far.T.I. Research Center, University of Modena and Reggio Emilia, 41124 Modena, Italy
Jason Duskey
Department of Life Sciences Te.Far.T.I. Research Center, University of Modena and Reggio Emilia, 41124 Modena, Italy
Simone Hagmeyer
Cellular Neurobiology and Neuro-Nanotechnology lab, Department of Biological Sciences, University of Limerick, Limerick, V94PH61, Ireland
Ann Katrin Sauer
Cellular Neurobiology and Neuro-Nanotechnology lab, Department of Biological Sciences, University of Limerick, Limerick, V94PH61, Ireland
Stefanie Grabrucker
Cellular Neurobiology and Neuro-Nanotechnology lab, Department of Biological Sciences, University of Limerick, Limerick, V94PH61, Ireland
Romina Coelho
Biosystems and Integrative Sciences Institute, Faculdade de Ciências, Departamento de Química e Bioquímica, Universidade de Lisboa, 1749-016 Lisbon, Portugal
Natalia Oddone
Department of Life Sciences Te.Far.T.I. Research Center, University of Modena and Reggio Emilia, 41124 Modena, Italy
Ilaria Ottonelli
Department of Life Sciences Te.Far.T.I. Research Center, University of Modena and Reggio Emilia, 41124 Modena, Italy
Eleonora Daini
Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, 41124 Modena, Italy
Michele Zoli
Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, 41124 Modena, Italy
Maria Angela Vandelli
Department of Life Sciences Te.Far.T.I. Research Center, University of Modena and Reggio Emilia, 41124 Modena, Italy
Giovanni Tosi
Department of Life Sciences Te.Far.T.I. Research Center, University of Modena and Reggio Emilia, 41124 Modena, Italy
Andreas M. Grabrucker
Cellular Neurobiology and Neuro-Nanotechnology lab, Department of Biological Sciences, University of Limerick, Limerick, V94PH61, Ireland
The accumulation of amyloid β (Aβ) triggers a cascade of toxic events in Alzheimer’s disease (AD). The KLVFF peptide can interfere with Aβ aggregation. However, the peptide suffers from poor bioavailability and the inability to cross the blood−brain barrier. In this work, we study the possibility of adopting nanomedicine to overcome KLVFF limits in biodistribution. We produced new engineered polymeric nanoparticles (NPs), and we evaluated the cellular toxicity of these NPs and validated that KVLFF peptides released by NPs show the same promising effects on AD pathology. Our results revealed the successful generation of KVLFF loaded NPs that, without significant effects on cell heath, are even more potent in reversing Aβ-induced pathologies compared to the free peptide. Therefore, NPs will significantly advance KVLFF treatment as a therapeutic option for AD.
