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

Laura Bana, Stefania Minniti, Elisa Salvati, Silvia Sesana, Vanessa Zambelli, Alfredo Cagnotto, Antonina Orlando, Emanuela Cazzaniga, Rob Zwart, Wiep Scheper, Massimo Masserini, Francesca Re

Research output: Contribution to journalArticlepeer-review

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=0.6μM), while Thioflavin-T and SDS-PAGE/WB assays show that liposomes inhibit peptide aggregation (70% inhibition after 72h) and trigger the disaggregation of preformed aggregates (60% decrease after 120h incubation). Moreover, experiments with dually radiolabelled LIP suggest that bi-functionalization enhances the passage of radioactivity across the BBB either in vitro (permeability=2.5×10-5cm/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.

Original languageEnglish
Pages (from-to)1583-1590
Number of pages8
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume10
Issue number7
DOIs
Publication statusPublished - Oct 1 2014

Keywords

  • Abeta peptide
  • Alzheimer disease
  • ApoE peptide
  • Blood-brain barrier
  • Liposomes

ASJC Scopus subject areas

  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering
  • Materials Science(all)
  • Medicine (miscellaneous)
  • Pharmaceutical Science
  • Medicine(all)

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