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

Journal of Nanobiotechnology

Research

Leonie EM Paulis¹  Lucas WE Starmans¹  Tessa Geelen¹  Klaas Nicolay¹  Igor Jacobs¹  Gustav J Strijkers²  Nynke M van den Akker³  Daniel G Molin⁴ 

[1] Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600, Eindhoven, MB, Netherlands;Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600, Eindhoven, MB, Netherlands;Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600, Eindhoven, MB, Netherlands;Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200, Maastricht, MD, Netherlands;Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200, Maastricht, MD, Netherlands;

关键词: Molecular MRI;    Liposome;    ICAM-1;    Endothelium;    Leukocyte;    Shear stress;   

DOI  :  10.1186/1477-3155-10-25

 received in 2012-03-19, accepted in 2012-06-04,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsA 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.ConclusionThis liposomal contrast agent displays great potential for in vivo MRI of inflammation-related ICAM-1 expression.

【 授权许可】

Unknown   
© Paulis et al.; licensee BioMed Central Ltd. 2012. This article is published under license to 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.