Antibody-functionalized polymer nanoparticle leading to memory recovery in Alzheimer's disease-like transgenic mouse model

Dario Carradori, Claudia Balducci, Francesca Re, Davide Brambilla, Benjamin Le Droumaguet, Orfeu Flores, Alice Gaudin, Simona Mura, Gianluigi Forloni, Lara Ordoñez-Gutierrez, Francisco Wandosell, Massimo Masserini, Patrick Couvreur, Julien Nicolas, Karine Andrieux

Research output: Contribution to journalArticle

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder related, in part, to the accumulation of amyloid-β peptide (Aβ) and especially the Aβ peptide 1-42 (Aβ1-42). The aim of this study was to design nanocarriers able to: (i) interact with the Aβ1-42 in the blood and promote its elimination through the “sink effect” and (ii) correct the memory defect observed in AD-like transgenic mice. To do so, biodegradable, PEGylated nanoparticles were surface-functionalized with an antibody directed against Aβ1-42. Treatment of AD-like transgenic mice with anti-Aβ1-42-functionalized nanoparticles led to: (i) complete correction of the memory defect; (ii) significant reduction of the Aβ soluble peptide and its oligomer level in the brain and (iii) significant increase of the Aβ levels in plasma. This study represents the first example of Aβ1-42 monoclonal antibody-decorated nanoparticle-based therapy against AD leading to complete correction of the memory defect in an experimental model of AD.

Original languageEnglish
Pages (from-to)609-618
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

Keywords

  • Alzheimer's disease
  • Antibody
  • Blood-brain barrier
  • Polymer nanoparticles
  • β-Amyloid peptide

ASJC Scopus subject areas

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

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  • Cite this

    Carradori, D., Balducci, C., Re, F., Brambilla, D., Le Droumaguet, B., Flores, O., Gaudin, A., Mura, S., Forloni, G., Ordoñez-Gutierrez, L., Wandosell, F., Masserini, M., Couvreur, P., Nicolas, J., & Andrieux, K. (2018). Antibody-functionalized polymer nanoparticle leading to memory recovery in Alzheimer's disease-like transgenic mouse model. Nanomedicine: Nanotechnology, Biology, and Medicine, 14(2), 609-618. https://doi.org/10.1016/j.nano.2017.12.006