Title:Comparison of Various Types of Ligand Decorated Nanoliposomes for their Ability to Inhibit Amyloid Aggregation and to Reverse Amyloid Cytotoxicity
VOLUME: 15 ISSUE: 22
Author(s):Eleni Markoutsa, Spyridon Mourtas, Erika Bereczki, Cristiano Zona, Barbara La Ferla, Fransesco Nicotra, Orfeu Flores, Jin-Jing Pei and Sophia G. Antimisiaris
Affiliation:University of Patras & FORTH/ICES-HT, Patras, Greece.
Keywords:Alzheimer’s disease, Amyloid, Aggregation, Curcumin, Liposomes, Monoclonal Antibody, Nanoparticle, Targeting.
Abstract:Three different amyloid targeting ligands, previously shown to exhibit amyloid specific
properties, have been used to develop amyloid -targeted nanoliposomes (AT-NLs). For this a MAb against Aβ-peptides
(Aβ-MAb) (immobilized on NLs at 0.015 and 0.05 mol %), and two different curcumin-lipid derivatives were attached to
the surface of preformed NLs or incorporated in NL membranes during their formation. Following physicochemical characterization,
these AT-NLs were studied for their ability to inhibit or delay amyloid peptide aggregation –using the
thioflavin-T assay, and for their potential to reverse amyloid-induced (and Zn, or, amyloid + Zn) cytotoxicity, on wild
type (N2aWT) and transformed (N2aAPP) neuroblastoma cells, applying the MTT assay. Experimental results reveal that
all formulations were found to strongly delay amyloid peptide aggregation (with no significant differences between the
different AT-NL types). However, although Aβ-MAb-NLs significantly reversed amyloid-induced cytotoxicity in all
cases, both curcumin-NL types did not reverse Zn-induced, nor Zn+Aβ-induced cytotoxicity in N2aWT cells, suggesting
lower activity against synthetic-Aβ peptides (compared to endogenous Aβ peptides); perhaps due to different affinity towards
different (aggregation stages of) peptide species (monomers, oligomers, fibrils, etc). Taken into account that the
aggregation stage of amyloid species is an important determinant of their toxicity, the importance of the affinity of each
AT-NL type towards specific species, is highlighted.
