El-Dakdouki Mohammad H, El-Boubbou Kheireddine, Kamat Medha, Huang Ruiping, Abela George S, Kiupel Matti, Zhu David C, Huang Xuefei
Department of Chemistry, Michigan State University, Chemistry Building, Room 426, 578 S. Shaw Lane, East Lansing, Michigan, 48824, USA.
Pharm Res. 2014 Jun;31(6):1426-37. doi: 10.1007/s11095-013-1021-8. Epub 2013 Apr 9.
The cell surface adhesion molecule CD44 plays important roles in the initiation and development of atherosclerotic plaques. We aim to develop nanoparticles that can selectively target CD44 for the non-invasive detection of atherosclerotic plaques by magnetic resonance imaging.
Magnetic glyconanoparticles with hyaluronan immobilized on the surface have been prepared. The binding of these nanoparticles with CD44 was evaluated in vitro by enzyme linked immunosorbent assay, flow cytometry and confocal microscopy. In vivo magnetic resonance imaging of plaques was performed on an atherosclerotic rabbit model.
The magnetic glyconanoparticles can selectively bind CD44. In T2* weighted magnetic resonance images acquired in vivo, significant contrast changes in aorta walls were observed with a very low dose of the magnetic nanoparticles, allowing the detection of atherosclerotic plaques. Furthermore, imaging could be performed without significant delay after probe administration. The selectivity of hyaluronan nanoparticles in plaque imaging was established by several control experiments.
Magnetic nanoparticles bearing surface hyaluronan enabled the imaging of atherosclerotic plaques in vivo by magnetic resonance imaging. The low dose of nanoparticles required, the possibility to image without much delay and the high biocompatibility are the advantages of these nanoparticles as contrast agents for plaque imaging.
细胞表面黏附分子CD44在动脉粥样硬化斑块的起始和发展过程中发挥重要作用。我们旨在开发能够选择性靶向CD44的纳米颗粒，用于通过磁共振成像对动脉粥样硬化斑块进行无创检测。
制备了表面固定有透明质酸的磁性糖纳米颗粒。通过酶联免疫吸附测定、流式细胞术和共聚焦显微镜在体外评估了这些纳米颗粒与CD44的结合情况。在动脉粥样硬化兔模型上进行了斑块的体内磁共振成像。
磁性糖纳米颗粒能够选择性结合CD44。在体内采集的T2*加权磁共振图像中，使用极低剂量的磁性纳米颗粒即可观察到主动脉壁的显著对比度变化，从而实现对动脉粥样硬化斑块的检测。此外，在注射探针后无需显著延迟即可进行成像。通过多项对照实验确定了透明质酸纳米颗粒在斑块成像中的选择性。
表面带有透明质酸的磁性纳米颗粒能够通过磁共振成像在体内对动脉粥样硬化斑块进行成像。所需纳米颗粒剂量低、能够在无太多延迟的情况下成像以及具有高生物相容性是这些纳米颗粒作为斑块成像造影剂的优势。
