Jacobin-Valat Marie-Josée, Laroche-Traineau Jeanny, Larivière Mélusine, Mornet Stéphane, Sanchez Stéphane, Biran Marc, Lebaron Caroline, Boudon Julien, Lacomme Sabrina, Cérutti Martine, Clofent-Sanchez Gisèle
CNRS, UMR5536, CRMSB, Centre de Résonance Magnétique des Systèmes Biologiques, Université Bordeaux, Bordeaux, France; Plateforme Technologique et d'Innovation Biomédicale, Pessac, France.
CNRS, UPR9048, Université de Bordeaux, Institut de Chimie de la Matière Condensée de Bordeaux, Pessac, France.
Nanomedicine. 2015 May;11(4):927-37. doi: 10.1016/j.nano.2014.12.006. Epub 2015 Feb 12.
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.
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.
动脉粥样硬化是一种与易破裂的动脉粥样斑块形成相关的炎症性疾病,血小板参与动脉粥样硬化形成和动脉粥样硬化血栓形成过程。斑块破裂与易损斑块的分子组成有关,可引发急性心血管事件。在本研究中,我们提出了一种用于动脉粥样硬化分子成像的新型靶向造影剂。多功能超顺磁性氧化铁(VUSPIO)纳米颗粒可增强磁共振成像对比度,用靶向人活化血小板的重组人IgG4抗体rIgG4 TEG4进行功能化修饰。通过流式细胞术、透射电子显微镜和光学显微镜在体外证实了靶向VUSPIO对血小板的免疫反应性得以维持。在动脉粥样硬化ApoE(-/-)小鼠模型中,高分辨率离体磁共振成像显示TEG4-VUSPIO在动脉粥样斑块上的选择性结合。值得注意的是,我们的靶向造影剂使用人抗αIIbβ3抗体作为靶向部分,突出了靶向动脉粥样硬化病变内血小板的基本原理。
目前对动脉粥样硬化斑块的临床评估并不理想。本文作者设计了用重组人抗体TEG4功能化的超顺磁性氧化铁纳米颗粒,以靶向活化血小板。通过磁共振成像,这些纳米颗粒可用于研究动脉粥样硬化发病机制。