MR imaging and targeting of a specific alveolar macrophage subpopulation in LPS-induced COPD animal model using antibody-conjugated magnetic nanoparticles

Achraf Al Faraj,1 Asma Sultana Shaik,1 Sibtain Afzal,2 Baraa Al Sayed,1 Rabih Halwani21King Saud University, College of Applied Medical Sciences, Department of Radiological Sciences, Molecular and Cellular Imaging Lab, Riyadh, Saudi Arabia; 2King Saud University, Prince Naif Center for Immunology R...

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Autores principales: Al Faraj A, Shaik AS, Afzal S, Al Sayed B, Halwani R
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Publicado: Dove Medical Press 2014
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spelling oai:doaj.org-article:f61eeacc71c44bdf876baf98930af0082021-12-02T02:42:17ZMR imaging and targeting of a specific alveolar macrophage subpopulation in LPS-induced COPD animal model using antibody-conjugated magnetic nanoparticles1178-2013https://doaj.org/article/f61eeacc71c44bdf876baf98930af0082014-03-01T00:00:00Zhttp://www.dovepress.com/mr-imaging-and-targeting-of-a-specific-alveolar-macrophage-subpopulati-a16207https://doaj.org/toc/1178-2013 Achraf Al Faraj,1 Asma Sultana Shaik,1 Sibtain Afzal,2 Baraa Al Sayed,1 Rabih Halwani21King Saud University, College of Applied Medical Sciences, Department of Radiological Sciences, Molecular and Cellular Imaging Lab, Riyadh, Saudi Arabia; 2King Saud University, Prince Naif Center for Immunology Research, Asthma Research Chair, College of Medicine, Riyadh, Saudi ArabiaPurpose: Targeting and noninvasive imaging of a specific alveolar macrophage subpopulation in the lung has revealed the importance for early and better diagnosis and therapy of chronic obstructive pulmonary disease (COPD). In this study, the in vivo effect of pulmonary administration of iron oxide nanoparticles on the polarization profile of macrophages was assessed, and a noninvasive free-breathing magnetic resonance imaging (MRI) protocol coupled with the use of biocompatible antibody-conjugated superparamagnetic iron oxide (SPIO) nanoparticles was developed to enable specific targeting and imaging of a particular macrophage subpopulation in lipopolysaccharide-induced COPD mice model.Materials and methods: Enzyme-linked immunosorbent assay, Real-time polymerase chain reaction, and flow cytometry analysis were performed to assess the biocompatibility of PEGylated dextran-coated SPIO nanoparticles. Specific biomarkers for M1 and M2 macrophages subsets were selected for conjugation with magnetic nanoparticles. MRI protocol using ultra-short echo time sequence was optimized to enable simultaneous detection of inflammation progress in the lung and detection of macrophages subsets. Flow cytometry and immunohistochemistry analysis were finally performed to confirm MRI readouts and to characterize the polarization profile of targeted macrophages.Results: The tested SPIO nanoparticles, under the current experimental conditions, were found to be biocompatible for lung administration in preclinical settings. Cluster of differentiation (CD)86- and CD206-conjugated magnetic nanoparticles enabled successful noninvasive detection of M1 and M2 macrophage subpopulations, respectively, and were found to co-localize with inflammatory regions induced by lipopolysaccharide challenge. No variation in the polarization profile of targeted macrophages was observed, even though a continuum switch in their polarization might occur. However, further confirmatory studies are required to conclusively establish this observation.Conclusion: Coupling of magnetic iron oxide nanoparticles with a specific antibody targeted to a particular macrophage subpopulation could offer a promising strategy for an early and better diagnosis of pulmonary inflammatory diseases using noninvasive MRI.Keywords: magnetic resonance imaging, MRI, lung imaging, lung inflammation, iron oxide nanoparticles, macrophage tracking, lipopolysaccharideAl Faraj AShaik ASAfzal SAl Sayed BHalwani RDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 1491-1503 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Al Faraj A
Shaik AS
Afzal S
Al Sayed B
Halwani R
MR imaging and targeting of a specific alveolar macrophage subpopulation in LPS-induced COPD animal model using antibody-conjugated magnetic nanoparticles
description Achraf Al Faraj,1 Asma Sultana Shaik,1 Sibtain Afzal,2 Baraa Al Sayed,1 Rabih Halwani21King Saud University, College of Applied Medical Sciences, Department of Radiological Sciences, Molecular and Cellular Imaging Lab, Riyadh, Saudi Arabia; 2King Saud University, Prince Naif Center for Immunology Research, Asthma Research Chair, College of Medicine, Riyadh, Saudi ArabiaPurpose: Targeting and noninvasive imaging of a specific alveolar macrophage subpopulation in the lung has revealed the importance for early and better diagnosis and therapy of chronic obstructive pulmonary disease (COPD). In this study, the in vivo effect of pulmonary administration of iron oxide nanoparticles on the polarization profile of macrophages was assessed, and a noninvasive free-breathing magnetic resonance imaging (MRI) protocol coupled with the use of biocompatible antibody-conjugated superparamagnetic iron oxide (SPIO) nanoparticles was developed to enable specific targeting and imaging of a particular macrophage subpopulation in lipopolysaccharide-induced COPD mice model.Materials and methods: Enzyme-linked immunosorbent assay, Real-time polymerase chain reaction, and flow cytometry analysis were performed to assess the biocompatibility of PEGylated dextran-coated SPIO nanoparticles. Specific biomarkers for M1 and M2 macrophages subsets were selected for conjugation with magnetic nanoparticles. MRI protocol using ultra-short echo time sequence was optimized to enable simultaneous detection of inflammation progress in the lung and detection of macrophages subsets. Flow cytometry and immunohistochemistry analysis were finally performed to confirm MRI readouts and to characterize the polarization profile of targeted macrophages.Results: The tested SPIO nanoparticles, under the current experimental conditions, were found to be biocompatible for lung administration in preclinical settings. Cluster of differentiation (CD)86- and CD206-conjugated magnetic nanoparticles enabled successful noninvasive detection of M1 and M2 macrophage subpopulations, respectively, and were found to co-localize with inflammatory regions induced by lipopolysaccharide challenge. No variation in the polarization profile of targeted macrophages was observed, even though a continuum switch in their polarization might occur. However, further confirmatory studies are required to conclusively establish this observation.Conclusion: Coupling of magnetic iron oxide nanoparticles with a specific antibody targeted to a particular macrophage subpopulation could offer a promising strategy for an early and better diagnosis of pulmonary inflammatory diseases using noninvasive MRI.Keywords: magnetic resonance imaging, MRI, lung imaging, lung inflammation, iron oxide nanoparticles, macrophage tracking, lipopolysaccharide
format article
author Al Faraj A
Shaik AS
Afzal S
Al Sayed B
Halwani R
author_facet Al Faraj A
Shaik AS
Afzal S
Al Sayed B
Halwani R
author_sort Al Faraj A
title MR imaging and targeting of a specific alveolar macrophage subpopulation in LPS-induced COPD animal model using antibody-conjugated magnetic nanoparticles
title_short MR imaging and targeting of a specific alveolar macrophage subpopulation in LPS-induced COPD animal model using antibody-conjugated magnetic nanoparticles
title_full MR imaging and targeting of a specific alveolar macrophage subpopulation in LPS-induced COPD animal model using antibody-conjugated magnetic nanoparticles
title_fullStr MR imaging and targeting of a specific alveolar macrophage subpopulation in LPS-induced COPD animal model using antibody-conjugated magnetic nanoparticles
title_full_unstemmed MR imaging and targeting of a specific alveolar macrophage subpopulation in LPS-induced COPD animal model using antibody-conjugated magnetic nanoparticles
title_sort mr imaging and targeting of a specific alveolar macrophage subpopulation in lps-induced copd animal model using antibody-conjugated magnetic nanoparticles
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/f61eeacc71c44bdf876baf98930af008
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AT shaikas mrimagingandtargetingofaspecificalveolarmacrophagesubpopulationinlpsinducedcopdanimalmodelusingantibodyconjugatedmagneticnanoparticles
AT afzals mrimagingandtargetingofaspecificalveolarmacrophagesubpopulationinlpsinducedcopdanimalmodelusingantibodyconjugatedmagneticnanoparticles
AT alsayedb mrimagingandtargetingofaspecificalveolarmacrophagesubpopulationinlpsinducedcopdanimalmodelusingantibodyconjugatedmagneticnanoparticles
AT halwanir mrimagingandtargetingofaspecificalveolarmacrophagesubpopulationinlpsinducedcopdanimalmodelusingantibodyconjugatedmagneticnanoparticles
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