TY - JOUR
T1 - Antibody-functionalized polymer nanoparticle leading to memory recovery in Alzheimer's disease-like transgenic mouse model
AU - Carradori, Dario
AU - Balducci, Claudia
AU - Re, Francesca
AU - Brambilla, Davide
AU - Le Droumaguet, Benjamin
AU - Flores, Orfeu
AU - Gaudin, Alice
AU - Mura, Simona
AU - Forloni, Gianluigi
AU - Ordoñez-Gutierrez, Lara
AU - Wandosell, Francisco
AU - Masserini, Massimo
AU - Couvreur, Patrick
AU - Nicolas, Julien
AU - Andrieux, Karine
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Antibody
KW - Blood-brain barrier
KW - Polymer nanoparticles
KW - β-Amyloid peptide
UR - http://www.scopus.com/inward/record.url?scp=85041402235&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041402235&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2017.12.006
DO - 10.1016/j.nano.2017.12.006
M3 - Article
C2 - 29248676
AN - SCOPUS:85041402235
SN - 1549-9634
VL - 14
SP - 609
EP - 618
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 2
ER -