Targeting of ICAM-1 on vascular endothelium under static and shear stress conditions using a liposomal Gd-based MRI contrast agent

Paulis, Jacobs Igor, Van, Geelen Tessa, Molin, Starmans, Nicolay Klaas, Strijkers

Description

The upregulation of intercellular adhesion molecule-1 (ICAM-1) on the endothelium of blood vessels in response to pro-inflammatory stimuli is of major importance for the regulation of local inflammation in cardiovascular diseases such as atherosclerosis, myocardial infarction and stroke. In vivo molecular imaging of ICAM-1 will improve diagnosis and follow-up of patients by non-invasive monitoring of the progression of inflammation. Results A paramagnetic liposomal contrast agent functionalized with anti-ICAM-1 antibodies for multimodal magnetic resonance imaging (MRI) and fluorescence imaging of endothelial ICAM-1 expression is presented. The ICAM-1-targeted liposomes were extensively characterized in terms of size, morphology, relaxivity and the ability for binding to ICAM-1-expressing endothelial cells in vitro . ICAM-1-targeted liposomes exhibited strong binding to endothelial cells that depended on both the ICAM-1 expression level and the concentration of liposomes. The liposomes had a high longitudinal and transversal relaxivity, which enabled differentiation between basal and upregulated levels of ICAM-1 expression by MRI. The liposome affinity for ICAM-1 was preserved in the competing presence of leukocytes and under physiological flow conditions. Conclusion This liposomal contrast agent displays great potential for in vivo MRI of inflammation-related ICAM-1 expression.

Sujets

• Liposome
• ICAM-1
• Endothélium
• White blood cell
• Shear stress

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 24
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Pauliset al. Journal of Nanobiotechnology2012,10:25 http://www.jnanobiotechnology.com/content/10/1/25

R E S E A R C HOpen Access Targeting of ICAM1 on vascular endothelium under static and shear stress conditions using a liposomal Gdbased MRI contrast agent 1 12 13 1 Leonie EM Paulis , Igor Jacobs , Nynke M van den Akker , Tessa Geelen , Daniel G Molin , Lucas WE Starmans , 1 1* Klaas Nicolayand Gustav J Strijkers

Abstract Background:The upregulation of intercellular adhesion molecule1 (ICAM1) on the endothelium of blood vessels in response to proinflammatory stimuli is of major importance for the regulation of local inflammation in cardiovascular diseases such as atherosclerosis, myocardial infarction and stroke.In vivomolecular imaging of ICAM1 will improve diagnosis and followup of patients by noninvasive monitoring of the progression of inflammation. Results:A paramagnetic liposomal contrast agent functionalized with antiICAM1 antibodies for multimodal magnetic resonance imaging (MRI) and fluorescence imaging of endothelial ICAM1 expression is presented. The ICAM1targeted liposomes were extensively characterized in terms of size, morphology, relaxivity and the ability for binding to ICAM1expressing endothelial cellsin vitro. ICAM1targeted liposomes exhibited strong binding to endothelial cells that depended on both the ICAM1 expression level and the concentration of liposomes. The liposomes had a high longitudinal and transversal relaxivity, which enabled differentiation between basal and upregulated levels of ICAM1 expression by MRI. The liposome affinity for ICAM1 was preserved in the competing presence of leukocytes and under physiological flow conditions. Conclusion:This liposomal contrast agent displays great potential forin vivoMRI of inflammationrelated ICAM1 expression. Keywords:Molecular MRI, Liposome, ICAM1, Endothelium, Leukocyte, Shear stress

Background The vascular endothelium plays an essential role in the regulation of the inflammatory phases of atherosclerosis and related cardiovascular complications such as myocar dial infarction and stroke [13]. In response to local pro inflammatory stimuli, the endothelial expression of cell adhesion molecules is upregulated to mediate interactions with leukocytes circulating in the blood [4,5]. This allows for leukocyte adhesion to the endothelium, followed by extravasation of leukocytes through the endothelial cell layer to the site of inflammation.

* Correspondence: [e-mail] 1 Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB, Eindhoven, the Netherlands Full list of author information is available at the end of the article

Intercellular adhesion molecule1 (ICAM1), a trans membrane immunoglobulin protein that is predominantly expressed on endothelial cells, is of major importance in leukocyte recruitment [6]. Upregulation of ICAM1 contri butes to stable binding of leukocytes and facilitates their transmigration by rearranging the endothelial cytoskeleton and lowering the strength of endothelial cell junctions [7]. Noninvasivein vivomolecular imaging of endothelial ICAM1 expression could therefore provide valuable insights in the progression of cardiovascular diseaserelated inflammation to improve diagnosis and treatment [8]. Molecular imaging employs sophisticated contrast agents that combine high affinity targeting ligands with imaging labels forin vivovisualization of biological pro cesses at the cellular and molecular level. In this study, we introduce a novel liposomal contrast agent functionalized

© 2012 Paulis et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.