Format

Send to

Choose Destination
Nanomedicine. 2018 Feb;14(2):609-618. doi: 10.1016/j.nano.2017.12.006. Epub 2017 Dec 15.

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

Author information

1
Institut Galien Paris Sud, CNRS UMR 8612, Univ Paris-Sud, Univ. Paris Saclay, Châtenay-Malabry, France.
2
Istituto Mario Negri, Milano, Italy.
3
School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. Electronic address: francesca.re1@unimib.it.
4
Université Paris-Est, Institut de Chimie et des Matériaux Paris-Est (ICMPE), UMR 7182 CNRS-UPEC, 2 rue Henri Dunant, 94320, Thiais, France.
5
Stab Vida, Madan Parque, Rua dos Inventores, Caparica, Portugal.
6
Centro de Biología Molecular Severo Ochoa CSIC-UAM & CIBERNED, Madrid, Spain.
7
School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
8
Institut Galien Paris Sud, CNRS UMR 8612, Univ Paris-Sud, Univ. Paris Saclay, Châtenay-Malabry, France. Electronic address: julien.nicolas@u-psud.fr.
9
Faculté de Pharmacie de Paris, UTCBS, CNRS UMR 8258, Inserm U1022, Univ. Paris Descartes, Univ. Sorbonne Paris Cité, Paris, France.

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.

KEYWORDS:

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

PMID:
29248676
DOI:
10.1016/j.nano.2017.12.006
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center