TY - JOUR
T1 - Curcumin-decorated nanoliposomes with very high affinity for amyloid-β1-42 peptide
AU - Mourtas, Spyridon
AU - Canovi, Mara
AU - Zona, Cristiano
AU - Aurilia, Dario
AU - Niarakis, Anna
AU - La Ferla, Barbara
AU - Salmona, Mario
AU - Nicotra, Francesco
AU - Gobbi, Marco
AU - Antimisiaris, Sophia G.
PY - 2011/2
Y1 - 2011/2
N2 - Amyloid β (Aβ) aggregates are considered as possible targets for therapy and/or diagnosis of Alzheimer disease (AD). It has been previously shown that curcumin targets Aβ 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 Aβ, 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 ζ-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 Aβ1-42, indicated that the liposomes exposing the curcumin derivative (maintaining the planarity) have extremely high affinity for Aβ1-42 fibrils (1-5 nM), likely because of the occurrence of multivalent interactions, whereas those exposing non-planar curcumin did not bind to Aβ1-42. In summary, we describe here the preparation and characterization of new nanoparticles with a very high affinity for Aβ1-42 fibrils, to be exploited as vectors for the targeted delivery of new diagnostic and therapeutic molecules for AD.
AB - Amyloid β (Aβ) aggregates are considered as possible targets for therapy and/or diagnosis of Alzheimer disease (AD). It has been previously shown that curcumin targets Aβ 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 Aβ, 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 ζ-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 Aβ1-42, indicated that the liposomes exposing the curcumin derivative (maintaining the planarity) have extremely high affinity for Aβ1-42 fibrils (1-5 nM), likely because of the occurrence of multivalent interactions, whereas those exposing non-planar curcumin did not bind to Aβ1-42. In summary, we describe here the preparation and characterization of new nanoparticles with a very high affinity for Aβ1-42 fibrils, to be exploited as vectors for the targeted delivery of new diagnostic and therapeutic molecules for AD.
KW - Alzheimer disease (AD)
KW - Amyloid beta (Aβ)
KW - Click chemistry
KW - Curcumin
KW - Liposomes
KW - Structure
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U2 - 10.1016/j.biomaterials.2010.10.027
DO - 10.1016/j.biomaterials.2010.10.027
M3 - Article
C2 - 21131044
AN - SCOPUS:78650300340
VL - 32
SP - 1635
EP - 1645
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
IS - 6
ER -