用于高分辨血管成像和斑块标记的双功能超顺磁造影剂的研制

项目名称： 用于高分辨血管成像和斑块标记的双功能超顺磁造影剂的研制

项目编号： No.30870706

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 林江

作者单位： 复旦大学

项目金额： 30万元

中文摘要： 本研究先通过微波法快速合成水溶性、尺寸精确调控、聚丙烯酸包覆的纳米磁颗粒，然后通过在该颗粒表面构建两性离子结构得到了一种新的长循环周期的血池造影剂。两性离子结构是通过EDC/NHS催化方法在包覆聚丙烯酸（PAA）的纳米磁颗粒表面上部分接上3-二乙氨基丙胺得到的。经两性离子结构修饰后的纳米颗粒2小时巨噬细胞的吞噬量只有修饰前的五分之一，并具很低的细胞毒性。动物体内试验显示修饰后粒子与修饰前相比，循环时间显著延长，也比国外同类产品SHU555C更长，故可称为一种较为理想的血池造影剂。另外该粒子最终被网状内皮细胞吞噬的结果，也提示它同时可以用于标记动脉壁上不稳定或炎性斑块，故具备双功能造影剂的应用潜能。该合成工艺合成的造影剂粒子分布均匀、生物相容性好、稳定性高、制作工艺简单，影像学评价效果可靠，具有推广使用的价值。

中文关键词： 血管成像；磁共振；造影剂；斑块

英文摘要： Long circulation time is critical for blood pool contrast agents used in high resolution magnetic resonance angiography. For iron oxide particle contrast agents, size and surface properties significantly influence their in vivo performance. We developed a novel long circulating blood pool contrast agent by introducing zwitterionic structure onto the particle surface. Zwitterionic structure was fabricated by 3-(diethylamino) propylamine (DEAPA) grafted onto the surface of poly acrylic acid coated magnetite nanoparticles by means of EDC/NHS chemistry. The process produced particles with precisely controlled size and high water solubility. Zwitterionic particles demonstrated five times lower macrophage cell uptake at 2-hour incubation than that of original particles and low cell toxicity. In vivo animal magnetic resonance angiography indicated that zwitterionic nanoparticles had much longer in vivo circulation time than the original particles and were an ideal candidate for blood pool contrast agent. Furthermore, its final uptake by macrophages at 24-hour or longer incubation time indicated that it be a potential marker of vulnerable plaque. This nano-particle may be useful as a dual-functional contrast media for both high-resolution vessel luminal imaging and vessel wall plaque labelling.

英文关键词： vascular imaging;MRI;contrast agent;plaque