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Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer’s Disease

Nanoparticle-based magnetic contrast agents have opened the potential for magnetic resonance imaging (MRI) to be used for early non-invasive diagnosis of Alzheimer’s disease (AD). Accumulation of amyloid pathology in the brain has shown association with cognitive decline and tauopathy; hence, it is...

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Autores principales: Ulanova, Marina, Gloag, Lucy, Bongers, Andre, Kim, Chul-Kyu, Duong, Hong Thien Kim, Kim, Ha Na, Gooding, John Justin, Tilley, Richard D., Biazik, Joanna, Wen, Wei, Sachdev, Perminder S., Braidy, Nady
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527350/
https://www.ncbi.nlm.nih.gov/pubmed/37759500
http://dx.doi.org/10.3390/cells12182279
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author Ulanova, Marina
Gloag, Lucy
Bongers, Andre
Kim, Chul-Kyu
Duong, Hong Thien Kim
Kim, Ha Na
Gooding, John Justin
Tilley, Richard D.
Biazik, Joanna
Wen, Wei
Sachdev, Perminder S.
Braidy, Nady
author_facet Ulanova, Marina
Gloag, Lucy
Bongers, Andre
Kim, Chul-Kyu
Duong, Hong Thien Kim
Kim, Ha Na
Gooding, John Justin
Tilley, Richard D.
Biazik, Joanna
Wen, Wei
Sachdev, Perminder S.
Braidy, Nady
author_sort Ulanova, Marina
collection PubMed
description Nanoparticle-based magnetic contrast agents have opened the potential for magnetic resonance imaging (MRI) to be used for early non-invasive diagnosis of Alzheimer’s disease (AD). Accumulation of amyloid pathology in the brain has shown association with cognitive decline and tauopathy; hence, it is an effective biomarker for the early detection of AD. The aim of this study was to develop a biocompatible magnetic nanoparticle targeted to amyloid beta (Aβ) plaques to increase the sensitivity of T2-weighted MRI for imaging of amyloid pathology in AD. We presented novel iron core-iron oxide nanoparticles stabilized with a dimercaptosuccinic acid coating and functionalized with an anti-Aβ antibody. Nanoparticle biocompatibility and cellular internalization were evaluated in vitro in U-251 glioblastoma cells using cellular assays, proteomics, and transmission electron microscopy. Iron nanoparticles demonstrated no significant in vitro cytotoxicity, and electron microscopy results showed their movement through the endocytic cycle within the cell over a 24 h period. In addition, immunostaining and bio-layer interferometry confirmed the targeted nanoparticle’s binding affinity to amyloid species. The iron nanoparticles demonstrated favourable MRI contrast enhancement; however, the addition of the antibody resulted in a reduction in the relaxivity of the particles. The present work shows promising preliminary results in the development of a targeted non-invasive method of early AD diagnosis using contrast-enhanced MRI.
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spelling pubmed-105273502023-09-28 Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer’s Disease Ulanova, Marina Gloag, Lucy Bongers, Andre Kim, Chul-Kyu Duong, Hong Thien Kim Kim, Ha Na Gooding, John Justin Tilley, Richard D. Biazik, Joanna Wen, Wei Sachdev, Perminder S. Braidy, Nady Cells Article Nanoparticle-based magnetic contrast agents have opened the potential for magnetic resonance imaging (MRI) to be used for early non-invasive diagnosis of Alzheimer’s disease (AD). Accumulation of amyloid pathology in the brain has shown association with cognitive decline and tauopathy; hence, it is an effective biomarker for the early detection of AD. The aim of this study was to develop a biocompatible magnetic nanoparticle targeted to amyloid beta (Aβ) plaques to increase the sensitivity of T2-weighted MRI for imaging of amyloid pathology in AD. We presented novel iron core-iron oxide nanoparticles stabilized with a dimercaptosuccinic acid coating and functionalized with an anti-Aβ antibody. Nanoparticle biocompatibility and cellular internalization were evaluated in vitro in U-251 glioblastoma cells using cellular assays, proteomics, and transmission electron microscopy. Iron nanoparticles demonstrated no significant in vitro cytotoxicity, and electron microscopy results showed their movement through the endocytic cycle within the cell over a 24 h period. In addition, immunostaining and bio-layer interferometry confirmed the targeted nanoparticle’s binding affinity to amyloid species. The iron nanoparticles demonstrated favourable MRI contrast enhancement; however, the addition of the antibody resulted in a reduction in the relaxivity of the particles. The present work shows promising preliminary results in the development of a targeted non-invasive method of early AD diagnosis using contrast-enhanced MRI. MDPI 2023-09-14 /pmc/articles/PMC10527350/ /pubmed/37759500 http://dx.doi.org/10.3390/cells12182279 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ulanova, Marina
Gloag, Lucy
Bongers, Andre
Kim, Chul-Kyu
Duong, Hong Thien Kim
Kim, Ha Na
Gooding, John Justin
Tilley, Richard D.
Biazik, Joanna
Wen, Wei
Sachdev, Perminder S.
Braidy, Nady
Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer’s Disease
title Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer’s Disease
title_full Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer’s Disease
title_fullStr Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer’s Disease
title_full_unstemmed Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer’s Disease
title_short Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer’s Disease
title_sort evaluation of dimercaptosuccinic acid-coated iron nanoparticles immunotargeted to amyloid beta as mri contrast agents for the diagnosis of alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527350/
https://www.ncbi.nlm.nih.gov/pubmed/37759500
http://dx.doi.org/10.3390/cells12182279
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