Nanoliposomes presenting on surface a cis-glycofused benzopyran compound display binding affinity and aggregation inhibition ability towards Amyloid β1-42 peptide

• We synthesized surface decorated liposomes with a synthetic tricyclic Aβ-ligand.
• We performed a structural characterization and stability studies.
• NMR spectrometry demonstrated the binding to Aβ aggregates.
• Thioflavine T assay showed Aβ aggregation delay inhibition properties.

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.

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