title: Liposomes bi-functionalized with phosphatidic acid and an ApoE-derived peptide affect Aβ aggregation features and cross the blood-brain-barrier: implications for therapy of Alzheimer disease.
abstract: Targeting amyloid-β peptide (Aβ) within the brain is a strategy actively sought for therapy of Alzheimer's disease (AD). We investigated the ability of liposomes bi-functionalized with phosphatidic acid and with a modified ApoE-derived peptide (mApoE-PA-LIP) to affect Aβ aggregation/disaggregation features and to cross in vitro and in vivo the blood-brain barrier (BBB). Surface plasmon resonance showed that bi-functionalized liposomes strongly bind Aβ (kD=0.6 μM), while Thioflavin-T and SDS-PAGE/WB assays show that liposomes inhibit peptide aggregation (70% inhibition after 72 h) and trigger the disaggregation of preformed aggregates (60% decrease after 120 h incubation). Moreover, experiments with dually radiolabelled LIP suggest that bi-functionalization enhances the passage of radioactivity across the BBB either in vitro (permeability=2.5×10(-5) cm/min, 5-fold higher with respect to mono-functionalized liposomes) or in vivo in healthy mice. Taken together, our results suggest that mApoE-PA-LIP are valuable nanodevices with a potential applicability in vivo for the treatment of AD. From the clinical editor: Bi-functionalized liposomes with phosphatidic acid and a modified ApoE-derived peptide were demonstrated to influence Aβ aggregation/disaggregation as a potential treatment in an Alzheimer's model. The liposomes were able to cross the blood-brain barrier in vitro and in vivo. Similar liposomes may become clinically valuable nanodevices with a potential applicability for the treatment of Alzheimer's disease.
authors: Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors: Laura
authors: L
authors: Bana
authors: Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors: Stefania
authors: S
authors: Minniti
authors: Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors: Elisa
authors: E
authors: Salvati
authors: Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors: Silvia
authors: S
authors: Sesana
authors: Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors: Vanessa
authors: V
authors: Zambelli
authors: Department of Biochemistry and Molecular Pharmacology, Mario Negri Institute for Pharmacological Research IRCCS, Milano, Italy.
authors: Alfredo
authors: A
authors: Cagnotto
authors: Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors: Antonina
authors: A
authors: Orlando
authors: Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors: Emanuela
authors: E
authors: Cazzaniga
authors: Department of Genome Analysis, Academic Medical Center, Amsterdam, AZ, The Netherlands.
authors: Rob
authors: R
authors: Zwart
authors: Department of Genome Analysis, Academic Medical Center, Amsterdam, AZ, The Netherlands; Department of Neurology, Academic Medical Center, Amsterdam, AZ, The Netherlands.
authors: Wiep
authors: W
authors: Scheper
authors: Department of Health Sciences, University of Milano-Bicocca, Monza, Italy. Electronic address: massimo.masserini@unimib.it.
authors: Massimo
authors: M
authors: Masserini
authors: Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors: Francesca
authors: F
authors: Re
mesh_terms: D000544:Alzheimer Disease / Q000628:therapy*; D001057:Apolipoproteins E / Q000008:administration & dosage / Q000737:chemistry*; D001812:Blood-Brain Barrier; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008081:Liposomes; D010455:Peptides / Q000737:chemistry*; D010712:Phosphatidic Acids / Q000008:administration & dosage / Q000737:chemistry*; D020349:Surface Plasmon Resonance
chemical_list: D001057:Apolipoproteins E; D008081:Liposomes; D010455:Peptides; D010712:Phosphatidic Acids
keywords: Abeta peptide; Alzheimer disease; ApoE peptide; Blood–brain barrier; Liposomes