title: Comparison of Various Types of Ligand Decorated Nanoliposomes for their Ability to Inhibit Amyloid Aggregation and to Reverse Amyloid Cytotoxicity.
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.
authors.forename: Eleni
authors.initials: E
authors.lastname: Markoutsa
authors.forename: Spyridon
authors.initials: S
authors.lastname: Mourtas
authors.forename: Erika
authors.initials: E
authors.lastname: Bereczki
authors.forename: Cristiano
authors.initials: C
authors.lastname: Zona
authors.forename: Barbara
authors.initials: B
authors.lastname: La Ferla
authors.forename: Fransesco
authors.initials: F
authors.lastname: Nicotra
authors.forename: Orfeu
authors.initials: O
authors.lastname: Flores
authors.forename: Jin-Jing
authors.initials: JJ
authors.lastname: Pei
authors.affiliation: University of Patras & FORTH/ICES-HT, Patras, Greece. santimis@upatras.gr.
authors.forename: Sophia G
authors.initials: SG
authors.lastname: Antimisiaris
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000682:Amyloid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000633:toxicity; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008024:Ligands; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D018675:Toxicity Tests / Q000379:methods
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D008024:Ligands; D008081:Liposomes; D003474:Curcumin