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

Ulanova, M; Gloag, L; Bongers, A; Kim, C-K; Duong, HTK; Kim, HN; Gooding, JJ; Tilley, RD; Biazik, J; Wen, W; Sachdev, PS; Braidy, N

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

Ulanova, M Gloag, L

Bongers, A Kim, C-K Duong, HTK Kim, HN Gooding, JJ Tilley, RD Biazik, J Wen, W Sachdev, PS Braidy, N

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Publisher:: MDPI
Publication Type:: Journal Article
Citation:: Cells, 2023, 12, (18), pp. 2279
Issue Date:: 2023-09-14

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Field	Value	Language
dc.contributor.author	Ulanova, M
dc.contributor.author	Gloag, L https://orcid.org/0000-0001-7548-1521
dc.contributor.author	Bongers, A
dc.contributor.author	Kim, C-K
dc.contributor.author	Duong, HTK
dc.contributor.author	Kim, HN
dc.contributor.author	Gooding, JJ
dc.contributor.author	Tilley, RD
dc.contributor.author	Biazik, J
dc.contributor.author	Wen, W
dc.contributor.author	Sachdev, PS
dc.contributor.author	Braidy, N
dc.date.accessioned	2024-03-15T02:50:56Z
dc.date.available	2023-09-06
dc.date.available	2024-03-15T02:50:56Z
dc.date.issued	2023-09-14
dc.identifier.citation	Cells, 2023, 12, (18), pp. 2279
dc.identifier.issn	2073-4409
dc.identifier.issn	2073-4409
dc.identifier.uri	http://hdl.handle.net/10453/176758
dc.description.abstract	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.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI
dc.relation.ispartof	Cells
dc.relation.isbasedon	10.3390/cells12182279
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	31 Biological sciences
dc.subject.classification	32 Biomedical and clinical sciences
dc.title	Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer's Disease.
dc.type	Journal Article
utslib.citation.volume	12
utslib.location.activity	Switzerland
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	open_access	*
dc.date.updated	2024-03-15T02:50:55Z
pubs.issue	18
pubs.publication-status	Published online
pubs.volume	12
utslib.citation.issue	18

Abstract:

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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http://hdl.handle.net/10453/176758