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

• Published in: Journal of nanobiotechnology 2012-06, Vol.10 (1), p.25-25, Article 25
• Main Authors: Paulis, Leonie E M, Jacobs, Igor, van den Akker, Nynke M, Geelen, Tessa, Molin, Daniel G, Starmans, Lucas W E, Nicolay, Klaas, Strijkers, Gustav J
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Atherosclerosis; Cardiovascular diseases; Cell adhesion & migration; Cell Line; Contrast agents; Contrast media; Contrast Media - chemistry; Drug Delivery Systems; Endothelial Cells - metabolism; Endothelium; Fluorescence; Gadolinium - chemistry; Heart attack; Heart attacks; ICAM-1; Immunoglobulin G - chemistry; Immunoglobulin G - metabolism; Inflammation; Intercellular Adhesion Molecule-1 - chemistry; Intercellular Adhesion Molecule-1 - metabolism; Lasers; Leukocyte; Leukocytes - metabolism; Ligands; Liposome; Liposomes - chemistry; Liposomes - metabolism; LSD; Lysergic acid diethylamide; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Mass spectrometry; Mice; Molecular Imaging; Molecular MRI; Nanoparticles; NMR; Nuclear magnetic resonance; Physiological aspects; Shear Strength; Shear stress; Stress, Mechanical; Transmission electron microscopy; Tumor Necrosis Factor-alpha - metabolism; Viral antibodies
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/1477-3155-10-25

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