Macrophage uptake switches on OCT contrast of superparamagnetic nanoparticles for imaging of atherosclerotic plaques

Angela Ariza de Schellenberger,1,* Wolfram C Poller,2,* Verena Stangl,2 Ulf Landmesser,3 Eyk Schellenberger1 1Department of Radiology, Charité-Universitätsmedizin Berlin, Germany; 2Department of Interventional Cardiology, Charité-Universitätsmedizin Berlin, G...

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Autores principales:	Ariza de Schellenberger A, Poller WC, Stangl V, Landmesser U, Schellenberger E
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Atherosclerotic plaques macrophages ferumoxytol superparamagnetic iron oxide particles Optical coherence tomography Magnetic resonance imaging Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c6f56a4806d04ecc820ff73899ab5962
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spelling	oai:doaj.org-article:c6f56a4806d04ecc820ff73899ab59622021-12-02T03:23:47ZMacrophage uptake switches on OCT contrast of superparamagnetic nanoparticles for imaging of atherosclerotic plaques1178-2013https://doaj.org/article/c6f56a4806d04ecc820ff73899ab59622018-11-01T00:00:00Zhttps://www.dovepress.com/macrophage-uptake-switches-on-oct-contrast-of-superparamagnetic-nanopa-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Angela Ariza de Schellenberger,1,* Wolfram C Poller,2,* Verena Stangl,2 Ulf Landmesser,3 Eyk Schellenberger1 1Department of Radiology, Charité-Universitätsmedizin Berlin, Germany; 2Department of Interventional Cardiology, Charité-Universitätsmedizin Berlin, Germany; 3Department of Cardiology, Charité- Universitätsmedizin Berlin, Berlin Institute of Health (BIH) and Deutsches Zentrum für Herz-Kreislaufforschung (DZHK), Berlin, Germany *These authors contributed equally to this work Background: Optical coherence tomography (OCT) is an intravascular, high-resolution imaging technique that is used to characterize atherosclerotic plaques. However, the identification of macrophages as important markers of inflammation and plaque vulnerability remains difficult. Here, we investigate whether the uptake of very small iron oxide particles (VSOP) in macrophages, that cluster in phagolysosomes and allow high-quality magnetic resonance imaging (MRI) of atherosclerotic plaques, and uptake of ferumoxytol nanoparticles enhance detection of macrophages by OCT.Materials and methods: RAW 264.7 macrophage cells were incubated with VSOP (1 and 2 mM Fe) that have been clinically tested and ferumoxytol (8.9 mM Fe) that is approved for iron deficiency treatment and currently investigated as an MRI contrast agent. The light scattering of control macrophages, nanoparticle-labeled macrophages (2,000,000 in 500 µL) and nanoparticle suspensions was measured in synchronous wavelength scan mode using a fluorescence spectrophotometer. For OCT analyses, pellets of 8,000,000 non-labeled, VSOP-labeled and ferumoxytol-labeled RAW 264.7 macrophages were imaged and analyzed on an OPTIS™ OCT imaging system.Results: Incubation with 1 and 2 mM VSOP resulted in uptake of 7.1±1.5 and 12±1.5 pg Fe per cell, which increased the backscattering of the macrophages in spectrophotometry 2.5- and 3.6-fold, whereas incubation with 8.9 mM Fe ferumoxytol resulted in uptake of 6.6±2 pg Fe per cell, which increased the backscattering 1.5-fold at 700 nm. In contrast, backscattering of non-clustered nanoparticles in suspension was negligible. Accordingly, OCT imaging could visualize significantly increased backscattering and signal attenuation of nanoparticle-labeled macrophages in comparison with controls.Conclusion: We conclude that VSOP and, to a lesser extent, ferumoxytol increase light scattering and attenuation when taken up by macrophages and can serve as a multimodal imaging probe for MRI and OCT to improve macrophage detection in atherosclerotic plaques by OCT in the future. Keywords: intravascular, inflammation, vulnerability, multimodal imaging, optical coherence tomography, magnetic resonance imagingAriza de Schellenberger APoller WCStangl VLandmesser USchellenberger EDove Medical PressarticleAtherosclerotic plaquesmacrophagesferumoxytolsuperparamagnetic iron oxide particlesOptical coherence tomographyMagnetic resonance imagingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 7905-7913 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Atherosclerotic plaques macrophages ferumoxytol superparamagnetic iron oxide particles Optical coherence tomography Magnetic resonance imaging Medicine (General) R5-920
spellingShingle	Atherosclerotic plaques macrophages ferumoxytol superparamagnetic iron oxide particles Optical coherence tomography Magnetic resonance imaging Medicine (General) R5-920 Ariza de Schellenberger A Poller WC Stangl V Landmesser U Schellenberger E Macrophage uptake switches on OCT contrast of superparamagnetic nanoparticles for imaging of atherosclerotic plaques
description	Angela Ariza de Schellenberger,1,* Wolfram C Poller,2,* Verena Stangl,2 Ulf Landmesser,3 Eyk Schellenberger1 1Department of Radiology, Charité-Universitätsmedizin Berlin, Germany; 2Department of Interventional Cardiology, Charité-Universitätsmedizin Berlin, Germany; 3Department of Cardiology, Charité- Universitätsmedizin Berlin, Berlin Institute of Health (BIH) and Deutsches Zentrum für Herz-Kreislaufforschung (DZHK), Berlin, Germany *These authors contributed equally to this work Background: Optical coherence tomography (OCT) is an intravascular, high-resolution imaging technique that is used to characterize atherosclerotic plaques. However, the identification of macrophages as important markers of inflammation and plaque vulnerability remains difficult. Here, we investigate whether the uptake of very small iron oxide particles (VSOP) in macrophages, that cluster in phagolysosomes and allow high-quality magnetic resonance imaging (MRI) of atherosclerotic plaques, and uptake of ferumoxytol nanoparticles enhance detection of macrophages by OCT.Materials and methods: RAW 264.7 macrophage cells were incubated with VSOP (1 and 2 mM Fe) that have been clinically tested and ferumoxytol (8.9 mM Fe) that is approved for iron deficiency treatment and currently investigated as an MRI contrast agent. The light scattering of control macrophages, nanoparticle-labeled macrophages (2,000,000 in 500 µL) and nanoparticle suspensions was measured in synchronous wavelength scan mode using a fluorescence spectrophotometer. For OCT analyses, pellets of 8,000,000 non-labeled, VSOP-labeled and ferumoxytol-labeled RAW 264.7 macrophages were imaged and analyzed on an OPTIS™ OCT imaging system.Results: Incubation with 1 and 2 mM VSOP resulted in uptake of 7.1±1.5 and 12±1.5 pg Fe per cell, which increased the backscattering of the macrophages in spectrophotometry 2.5- and 3.6-fold, whereas incubation with 8.9 mM Fe ferumoxytol resulted in uptake of 6.6±2 pg Fe per cell, which increased the backscattering 1.5-fold at 700 nm. In contrast, backscattering of non-clustered nanoparticles in suspension was negligible. Accordingly, OCT imaging could visualize significantly increased backscattering and signal attenuation of nanoparticle-labeled macrophages in comparison with controls.Conclusion: We conclude that VSOP and, to a lesser extent, ferumoxytol increase light scattering and attenuation when taken up by macrophages and can serve as a multimodal imaging probe for MRI and OCT to improve macrophage detection in atherosclerotic plaques by OCT in the future. Keywords: intravascular, inflammation, vulnerability, multimodal imaging, optical coherence tomography, magnetic resonance imaging
format	article
author	Ariza de Schellenberger A Poller WC Stangl V Landmesser U Schellenberger E
author_facet	Ariza de Schellenberger A Poller WC Stangl V Landmesser U Schellenberger E
author_sort	Ariza de Schellenberger A
title	Macrophage uptake switches on OCT contrast of superparamagnetic nanoparticles for imaging of atherosclerotic plaques
title_short	Macrophage uptake switches on OCT contrast of superparamagnetic nanoparticles for imaging of atherosclerotic plaques
title_full	Macrophage uptake switches on OCT contrast of superparamagnetic nanoparticles for imaging of atherosclerotic plaques
title_fullStr	Macrophage uptake switches on OCT contrast of superparamagnetic nanoparticles for imaging of atherosclerotic plaques
title_full_unstemmed	Macrophage uptake switches on OCT contrast of superparamagnetic nanoparticles for imaging of atherosclerotic plaques
title_sort	macrophage uptake switches on oct contrast of superparamagnetic nanoparticles for imaging of atherosclerotic plaques
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/c6f56a4806d04ecc820ff73899ab5962
work_keys_str_mv	AT arizadeschellenbergera macrophageuptakeswitchesonoctcontrastofsuperparamagneticnanoparticlesforimagingofatheroscleroticplaques AT pollerwc macrophageuptakeswitchesonoctcontrastofsuperparamagneticnanoparticlesforimagingofatheroscleroticplaques AT stanglv macrophageuptakeswitchesonoctcontrastofsuperparamagneticnanoparticlesforimagingofatheroscleroticplaques AT landmesseru macrophageuptakeswitchesonoctcontrastofsuperparamagneticnanoparticlesforimagingofatheroscleroticplaques AT schellenbergere macrophageuptakeswitchesonoctcontrastofsuperparamagneticnanoparticlesforimagingofatheroscleroticplaques
_version_	1718401819586068480

Macrophage uptake switches on OCT contrast of superparamagnetic nanoparticles for imaging of atherosclerotic plaques

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