title: Nanoliposomes presenting on surface a cis-glycofused benzopyran compound display binding affinity and aggregation inhibition ability towards Amyloid β1-42 peptide.
abstract: Nanoliposomes decorated on their surface with ligands for Aβ-peptides, the key morphological features of Alzheimer's disease (AD), have been synthesized and characterized for their ability to target Aβ-peptide aggregates. A tricyclic benzopyrane-glycofused structure has been exploited as Aβ-peptide ligand, which was linked to liposomes via a copper-free, chemoselective, biocompatible click chemistry reaction. The tricyclic-decorated liposomes presented a mean diameter in the nanomolar range (150-200 nm), a negative z-potential and a good stability, at least up to one month. Integrity studies performed in the presence of serum proteins indicated that these decorated nanoliposomes fulfill the requirements for in vivo applications. NMR experiments carried out with Aβ1-42 oligomers using both surface functionalized and plain (control) liposomes, revealed that the binding ability of the nanoliposomes was mediated by the presence of the tricyclic ligand on their surface. Finally ThT assay carried out with tricyclic-decorated liposomes showed significant decrease in thioflavine T fluorescence after 24 h, suggesting a significant inhibition/delay of Aβ1-42 aggregation.
authors: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors: Cristina
authors: C
authors: Airoldi
authors: Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Patras, Greece.
authors: Spyridon
authors: S
authors: Mourtas
authors: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy; Department of Chemistry, University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro, Portugal.
authors: Francisco
authors: F
authors: Cardona
authors: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors: Cristiano
authors: C
authors: Zona
authors: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors: Erika
authors: E
authors: Sironi
authors: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors: Giuseppe
authors: G
authors: D'Orazio
authors: Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Patras, Greece.
authors: Eleni
authors: E
authors: Markoutsa
authors: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors: Francesco
authors: F
authors: Nicotra
authors: Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Patras, Greece; Institute of Chemical Engineering and Sciences, FORTH/ICES, Rio 26504, Patras, Greece.
authors: Sophia G
authors: SG
authors: Antimisiaris
authors: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy. Electronic address: barbara.laferla@unimib.it.
authors: Barbara
authors: B
authors: La Ferla
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D001578:Benzopyrans / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D057930:Click Chemistry; D006031:Glycosylation; D008024:Ligands; D008081:Liposomes; D053758:Nanoparticles; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary; D013237:Stereoisomerism; D013499:Surface Properties
chemical_list: D016229:Amyloid beta-Peptides; D001578:Benzopyrans; D008024:Ligands; D008081:Liposomes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer disease (AD); Amyloid β (Aβ); Copper-free click chemistry; Glycoderivatives; Liposomes; NMR interaction studies