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Antibody-conjugated, dual-modal, near-infrared fluorescent iron oxide nanoparticles for antiamyloidgenic activity and specific detection of amyloid-β fibrils

Amyloid-β (Aβ) peptide is the main fibrillar component of plaque deposits found in brains affected by Alzheimer’s disease (AD) and is related to the pathogenesis of AD. Passive anti-Aβ immunotherapy has emerged as a promising approach for the therapy of AD, based on the administration of specific an...

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Autores principales: Skaat, Hadas, Corem-Slakmon, Enav, Grinberg, Igor, Last, David, Goez, David, Mardor, Yael, Margel, Shlomo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814992/
https://www.ncbi.nlm.nih.gov/pubmed/24194640
http://dx.doi.org/10.2147/IJN.S52833
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author Skaat, Hadas
Corem-Slakmon, Enav
Grinberg, Igor
Last, David
Goez, David
Mardor, Yael
Margel, Shlomo
author_facet Skaat, Hadas
Corem-Slakmon, Enav
Grinberg, Igor
Last, David
Goez, David
Mardor, Yael
Margel, Shlomo
author_sort Skaat, Hadas
collection PubMed
description Amyloid-β (Aβ) peptide is the main fibrillar component of plaque deposits found in brains affected by Alzheimer’s disease (AD) and is related to the pathogenesis of AD. Passive anti-Aβ immunotherapy has emerged as a promising approach for the therapy of AD, based on the administration of specific anti-Aβ monoclonal antibodies (aAβmAbs) to delay Aβ aggregation in the brain. However, the main disadvantage of this approach is the required readministration of the aAβmAbs at frequent intervals. There are only a few reports describing in vitro study for the immobilization of aAβmAbs to nanoparticles as potential targeting agents of Aβ aggregates. In this article, we report the immobilization of the aAβmAb clone BAM10 to near-infrared fluorescent maghemite nanoparticles for the inhibition of Aβ(40) fibrillation kinetics and the specific detection of Aβ(40) fibrils. The BAM10-conjugated iron oxide nanoparticles were well-characterized, including their immunogold labeling and cytotoxic effect on PC-12 (pheochromocytoma cell line). Indeed, these antibody-conjugated nanoparticles significantly inhibit the Aβ(40) fibrillation kinetics compared with the same concentration, or even five times higher, of the free BAM10. This inhibitory effect was confirmed by different assays such as the photo-induced crosslinking of unmodified proteins combined with sodium dodecyl sulfate– polyacrylamide gel electrophoresis. A cell viability assay also confirmed that these antibody-conjugated nanoparticles significantly reduced the Aβ(40)-induced cytotoxicity to PC-12 cells. Furthermore, the selective labeling of the Aβ(40) fibrils with the BAM10-conjugated near-infrared fluorescent iron oxide nanoparticles enabled specific detection of Aβ(40) fibrils ex vivo by both magnetic resonance imaging and fluorescence imaging. This study highlights the immobilization of the aAβmAb to dual-modal nanoparticles as a potential approach for aAβmAb delivery, eliminating the issue of readministration, and contributes to the development of multifunctional agents for diagnosis and therapy of AD.
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spelling pubmed-38149922013-11-05 Antibody-conjugated, dual-modal, near-infrared fluorescent iron oxide nanoparticles for antiamyloidgenic activity and specific detection of amyloid-β fibrils Skaat, Hadas Corem-Slakmon, Enav Grinberg, Igor Last, David Goez, David Mardor, Yael Margel, Shlomo Int J Nanomedicine Original Research Amyloid-β (Aβ) peptide is the main fibrillar component of plaque deposits found in brains affected by Alzheimer’s disease (AD) and is related to the pathogenesis of AD. Passive anti-Aβ immunotherapy has emerged as a promising approach for the therapy of AD, based on the administration of specific anti-Aβ monoclonal antibodies (aAβmAbs) to delay Aβ aggregation in the brain. However, the main disadvantage of this approach is the required readministration of the aAβmAbs at frequent intervals. There are only a few reports describing in vitro study for the immobilization of aAβmAbs to nanoparticles as potential targeting agents of Aβ aggregates. In this article, we report the immobilization of the aAβmAb clone BAM10 to near-infrared fluorescent maghemite nanoparticles for the inhibition of Aβ(40) fibrillation kinetics and the specific detection of Aβ(40) fibrils. The BAM10-conjugated iron oxide nanoparticles were well-characterized, including their immunogold labeling and cytotoxic effect on PC-12 (pheochromocytoma cell line). Indeed, these antibody-conjugated nanoparticles significantly inhibit the Aβ(40) fibrillation kinetics compared with the same concentration, or even five times higher, of the free BAM10. This inhibitory effect was confirmed by different assays such as the photo-induced crosslinking of unmodified proteins combined with sodium dodecyl sulfate– polyacrylamide gel electrophoresis. A cell viability assay also confirmed that these antibody-conjugated nanoparticles significantly reduced the Aβ(40)-induced cytotoxicity to PC-12 cells. Furthermore, the selective labeling of the Aβ(40) fibrils with the BAM10-conjugated near-infrared fluorescent iron oxide nanoparticles enabled specific detection of Aβ(40) fibrils ex vivo by both magnetic resonance imaging and fluorescence imaging. This study highlights the immobilization of the aAβmAb to dual-modal nanoparticles as a potential approach for aAβmAb delivery, eliminating the issue of readministration, and contributes to the development of multifunctional agents for diagnosis and therapy of AD. Dove Medical Press 2013 2013-10-29 /pmc/articles/PMC3814992/ /pubmed/24194640 http://dx.doi.org/10.2147/IJN.S52833 Text en © 2013 Skaat et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Skaat, Hadas
Corem-Slakmon, Enav
Grinberg, Igor
Last, David
Goez, David
Mardor, Yael
Margel, Shlomo
Antibody-conjugated, dual-modal, near-infrared fluorescent iron oxide nanoparticles for antiamyloidgenic activity and specific detection of amyloid-β fibrils
title Antibody-conjugated, dual-modal, near-infrared fluorescent iron oxide nanoparticles for antiamyloidgenic activity and specific detection of amyloid-β fibrils
title_full Antibody-conjugated, dual-modal, near-infrared fluorescent iron oxide nanoparticles for antiamyloidgenic activity and specific detection of amyloid-β fibrils
title_fullStr Antibody-conjugated, dual-modal, near-infrared fluorescent iron oxide nanoparticles for antiamyloidgenic activity and specific detection of amyloid-β fibrils
title_full_unstemmed Antibody-conjugated, dual-modal, near-infrared fluorescent iron oxide nanoparticles for antiamyloidgenic activity and specific detection of amyloid-β fibrils
title_short Antibody-conjugated, dual-modal, near-infrared fluorescent iron oxide nanoparticles for antiamyloidgenic activity and specific detection of amyloid-β fibrils
title_sort antibody-conjugated, dual-modal, near-infrared fluorescent iron oxide nanoparticles for antiamyloidgenic activity and specific detection of amyloid-β fibrils
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814992/
https://www.ncbi.nlm.nih.gov/pubmed/24194640
http://dx.doi.org/10.2147/IJN.S52833
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