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Functionalization with ApoE-derived peptides enhances the interaction with brain capillary endothelial cells of nanoliposomes binding amyloid-beta peptide.

Abstract：

:Nanoliposomes containing phosphatidic acid or cardiolipin are able to target in vitro with very high affinity amyloid-β (Aβ), a peptide whose overproduction and progressive aggregation in the brain play a central role in the pathogenesis of Alzheimer's disease. However, the presence of the blood-brain barrier (BBB) severely limits the penetration of either drugs or drug vehicles (nanoparticles) to the brain. Therefore, there is a need to develop and design approaches specifically driving nanoparticles to brain in a better and effective way. The aim of the present investigation is the search of a strategy promoting the interaction of liposomes containing acidic phospholipids with brain capillary endothelial cells, as a first step toward their passage across the BBB. We describe the preparation and physical characterization of nano-sized liposomes decorated with peptides derived from apolipoprotein E and characterize their interaction with human immortalized brain capillary cells cultured in vitro (hCMEC/D3). For this purpose, we synthesized two ApoE-derived peptides (the fragment 141-150 or its tandem dimer) containing a cysteine residue at the C-terminus and decorated NL by exploiting the cysteine reaction with a maleimide-group on the nanoparticle surface. NL without ApoE functionalization did not show either relevant membrane accumulation or cellular uptake, as monitored by confocal microscopy using fluorescently labeled nanoliposomes or quantifying the cell-associated radioactivity of isotopically labeled nanoliposomes. The uptake of nanoliposomes by cell monolayers was enhanced by ApoE-peptide-functionalization, and was higher with the fragment 141-150 than with its tandem dimer. The best performance was displayed by nanoliposomes containing phosphatidic acid and decorated with the ApoE fragment 141-150. Moreover, we show that the functionalization of liposomes containing acidic phospholipids with the ApoE fragment 141-150 scarcely affects their reported ability to bind Aβ peptide in vitro. These are important and promising features for the possibility to use these nanoliposomes for the targeting of Aβ in the brain districts.

journal_name

J Biotechnol

journal_title

Journal of biotechnology

authors

Re F,Cambianica I,Sesana S,Salvati E,Cagnotto A,Salmona M,Couraud PO,Moghimi SM,Masserini M,Sancini G

doi

10.1016/j.jbiotec.2011.06.037

subject

Has Abstract

pub_date

2011-12-20 00:00:00

pages

341-6

issue

eissn

0168-1656

issn

1873-4863

pii

S0168-1656(11)00336-1

journal_volume

156

pub_type

杂志文章

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Functionalization with ApoE-derived peptides enhances the interaction with brain capillary endothelial cells of nanoliposomes binding amyloid-beta peptide.