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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2013
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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. |
format | Online Article Text |
id | pubmed-3814992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
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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