Curcumin-decorated nanoliposomes with very high affinity for amyloid-beta1-42 peptide.

摘要

Amyloid beta (Abeta) aggregates are considered as possible targets for therapy and/or diagnosis of Alzheimer disease (AD). It has been previously shown that curcumin targets Abeta plaques and interferes with their formation, suggesting a potential role for prevention or treatment of AD. Herein, a click chemistry method was used to generate nanoliposomes decorated with a curcumin derivative, designed to maintain the planar structure required for interaction with Abeta, as directly confirmed by Surface Plasmon Resonance experiments. Another type of liposomes was formed starting from curcumin-phospholipid conjugate, in which the planar structure of curcumin is disrupted. Both types of generated curcumin-decorated vesicles had mean diameters in the nano range (131-207 nm) and slightly negative zeta-potential values according to their lipid composition, and were stable for periods up to 20 days. They also demonstrated high integrity during incubation in presence of plasma proteins. Surface Plasmon Resonance experiments, measuring the binding of flowing liposomes to immobilized Abeta1-42, indicated that the liposomes exposing the curcumin derivative (maintaining the planarity) have extremely high affinity for Abeta1-42 fibrils (1-5 nM), likely because of the occurrence of multivalent interactions, whereas those exposing non-planar curcumin did not bind to Abeta1-42. In summary, we describe here the preparation and characterization of new nanoparticles with a very high affinity for Abeta1-42 fibrils, to be exploited as vectors for the targeted delivery of new diagnostic and therapeutic molecules for AD.