动脉粥样硬化造影剂PGMA-EDA-g-PEG-g-DS@IO的合成及性能

Synthetic of PGMA-EDA-g-PEG-g-DS@IO as a Magnetic Resonance Contrast Agent for Atherosclerosis

利用乙二胺(EDA)对聚甲基丙烯酸缩水甘油酯(PGMA)进行开环反应,制备了侧链多氨基聚合物PGMA-EDA;再利用聚乙二醇(PEG-COOH)和硫酸葡聚糖钠盐(DS)分别对PGMA-EDA上氨基进行酰胺化反应和还原胺化反应,制备含动脉粥样硬化斑块靶向分子DS的双亲性接枝共聚物PGMA-EDA-g-PEG-g-DS.通过核磁共振(1H NMR)谱和红外光谱(FTIR)表征了聚合物的结构.利用凝胶渗透色谱(GPC)表征了聚合物的数均分子量Mn=16255,多分散性指数PDI=1.54.采用配体交换法,利用该聚合物对油胺配体超顺磁性氧化铁纳米粒子进行修饰,制备了水溶性氧化铁纳米粒子PGMA-EDA-g-PEG-g-DS@IO.通过透射电镜(TEM)和动态光散射(DLS)表征了纳米粒子的形貌和粒度,采用热重分析(TGA)和振动样品磁强(VSM)仪表征了纳米粒子的包覆率和磁强度.采用细胞计数试剂盒(CCK)测定了纳米粒子的细胞毒性,结果表明,水溶性纳米粒子的生物相容性较好,可作为动脉粥样硬化斑块的特异性磁共振检测用造影剂.

To design a new magnetic resonance（ MR） imaging contrast agent of atherosclerosis,poly（ glycidyl methacrylate）-graft-ethane diamine（ PGMA-g-EDA） was prepared by the ring-opening reaction of PGMA which was synthesized by atom transfer radical polymerization（ ATRP）. Poly-ethylene glycol（ PEG） and dextran sulfate（ DS） were graft modified to PGMA-g-EDA continuously via amidation reaction and reductive amination to synthesis PGMA-EDA-g-PEG-g-DS. The structure and properties of PGMA-EDA-g-PEG-g-DS were characterized through nuclear magnetic resonance（1H NMR）. Fourier transform infrared spectroscopy（ FTIR） and gel permeation chromatography（ GPC）. The superparamagnetic iron oxide nanoparticles（ IONPs）were coated with PGMA-EDA-g-PEG-g-DS by ligand exchange to prepare water-soluble IO. The transmission electron microscopy（ TEM） analysis indicated that micelles were well dispersed in water and had uniform sizes.The result of thermogravimetric analysis（ TGA） indicated that about 70%（ mass fraction） polymers coated on the surface of IO. The cell counting kit（ CCK） assay showed no significant toxicity to RAW264. 7. The above results confirm that PGMA-EDA-g-PEG-g-DS@ IO can be used as a potential contrast agent for atherosclerosis MR imaging.