油酸钠、壳聚糖和葡聚糖修饰的超顺磁性Fe_3O_4纳米粒作为MRI对比剂的实验研究

Research on the imaging effect of sodium oleate-,chitosan-and dextran-modified SPIONs applied as the contrast agent of MRI

目的：观察油酸钠、壳聚糖和葡聚糖分别修饰的超顺磁性Fe3O4纳米微粒（SPIONs）的物理和化学特性，评估其作为MRI对比剂的成像效果，为进一步优化MRI对比剂配方提供实验基础。方法：通过激光衍射分析仪、透射电镜及振动磁强计对油酸钠、壳聚糖和葡聚糖修饰的SPIONs的结构、粒径分布和磁性性能表征进行观察。选用32只SD大鼠随机分为4组，分别注射生理盐水（对照组）或油酸钠、壳聚糖或葡聚糖修饰的SPIONs，并于给药后10min、30min、60min、3h和6h分别进行肝脏MRI扫描，观察三种SPIONs对肝脏T2弛豫时间的作用。结果：①激光衍射粒度分析、透射电镜和振荡磁强计检测结果显示，三种SPIONs粒子均匀度好，呈粒径10～20nm的类球形结晶，均具有超顺磁性。②三种SPIONs注射后10min，T2WI显示大鼠肝脏的信号强度均明显降低，与对照组间的差异均有统计学意义（P〈O．05），以壳聚糖SPIONs的作用更明显，与另外2组间的差异有统计学意义（P〈O．05）。③三种SPIONs注射后肝脏的T。值均表现为先降低后升高，在各个时间点与对照组间的差异均有统计学意义（P〈0．05）。壳聚糖组肝脏T2值下降最快，约30min达最低峰值，达峰时间较另两组短（P〈O．05）。三组间肝脏T2峰值两两比较，差异无统计学意义（P〉0．05）。结论：油酸钠、壳聚糖和葡聚糖修饰的SPIONs均能缩短肝脏的T2弛豫时间，引起磁共振信号的变化；其中壳聚糖SPIONs对降低T2WI上肝脏信号的作用最明显，肝脏T2值达峰值时间最短，体内清除速率快，认为是较好的表面修饰材料。

Objective：To study the physical and chemical characteristics of sodium oleate,chitosan and dextran coated superparamagnetic iron oxide nanoparticles （SPIONs）, and to evaluate their imaging effects as MRI contrast agent, and to provide experimental basis for further improvement of MRI contrast agent compositions. Methods：With the aid of laser-dif- fraction analyzer, scanning electron microscopy （SEM） and vibration magnetometer, the morphology structure, particle size distribution and magnetic properties of three types of SPIONs （modified by sodium oleate, chitosan or dextran, respectively） were observed. Then,32 adult SD rats were selected and randomly divided into four groups,in each group saline （control group） or one of the three types of SPIONs was used as contrast medium. Liver MRI scans were performed at five time- points （10min, 30min, 60min, 3h and 6h） after injection of contrast medium,and the T2 relaxation time of liver in each group was measured and analyzed. Results： ①Laser-diffraction analyzer, SEM and vibration magnetometer indicated that the funda- mental physical properties of the three types of SPIOs were similar：Fe3O4 nanoparticles were almost evenly distributed and presented in the form of sphere like crystallizations,with diameters ranging from 10 to 20 nm;all of them had super para- magnetic property. ②10minutes after injection of SPIONs, signal intensity of liver on T2 WI decreased markedly with statis- tic significance （P〈0.05） compared with control group, especially in chitosan group, there was significant difference in liver SI between chitosan group and the other groups. ③After injection of the three types of SPIONs, the T2 value of liver de- creased at first and then increased,which was significant lower than that of control group at each time-point. Precisely,T2 value of liver in chitosan group decreased much faster than that of the other two groups,its peak-time was about 30min after injection, which was shorter than that of the other groups. Further, there was no statistic difference among the peak values of the three groups （P〉0.05）. Conclusion：All of the sodium oleate, chitosan and dextran modified SPIONs under investiga- tion can shorten the T2 relaxation time and cause variations of magnetic resonance signals. To be emphasized,the chitosan- modified SPIONs degrade the resonance signal in a more obvious manner, make T2 reaching its peak value at the earliest time,and can be removed rapidly from the body. Thus,it is considered to be a better choice for surface modification of SPI- ONs.