Nanoparticles functionalised with an anti-platelet human antibody for in vivo detection of atherosclerotic plaque by magnetic resonance imaging

• Published in: Nanomedicine 2015-05, Vol.11 (4), p.927-937
• Main Authors: Jacobin-Valat, Marie-Josée, PhD, Laroche-Traineau, Jeanny, PhD, Larivière, Mélusine, Mornet, Stéphane, PhD, Sanchez, Stéphane, Biran, Marc, PhD, Lebaron, Caroline, Boudon, Julien, PhD, Lacomme, Sabrina, Cérutti, Martine, PhD, Clofent-Sanchez, Gisèle, PhD
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - pharmacology; Atherosclerosis; Blood Platelets; Chemical Sciences; Contrast Media - chemistry; Contrast Media - pharmacology; Disease Models, Animal; Human antibody; Humans; Internal Medicine; Material chemistry; Mice; Mice, Knockout; Molecular Imaging - methods; MRI contrast agents; Nanoparticles; Nanoparticles - chemistry; Plaque, Atherosclerotic - metabolism; Plaque, Atherosclerotic - pathology; Platelet Glycoprotein GPIIb-IIIa Complex; Platelets
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2014.12.006

Abstract Atherosclerosis is an inflammatory disease associated with the formation of atheroma plaques likely to rupture in which platelets are involved both in atherogenesis and atherothrombosis. The rupture is linked to the molecular composition of vulnerable plaques, causing acute cardiovascular events. In this study we propose an original targeted contrast agent for molecular imaging of atherosclerosis. Versatile USPIO (VUSPIO) nanoparticles, enhancing contrast in MR imaging, were functionalised with a recombinant human IgG4 antibody, rIgG4 TEG4, targeting human activated platelets. The maintenance of immunoreactivity of the targeted VUSPIO against platelets was confirmed in vitro by flow cytometry, transmission electronic and optical microscopy. In the atherosclerotic ApoE−/− mouse model, high-resolution ex vivo MRI demonstrated the selective binding of TEG4-VUSPIO on atheroma plaques. It is noteworthy that the rationale for targeting platelets within atherosclerotic lesions is highlighted by our targeted contrast agent using a human anti-αIIbβ3 antibody as a targeting moiety. From the Clinical Editor Current clinical assessment of atherosclerotic plagues is suboptimal. The authors in the article designed functionalized superparamagnetic iron oxide nanoparticles with TEG4, a recombinant human antibody, to target activated platelets. By using MRI, these nanoparticles can be utilized to study the process of atheroma pathogenesis.