纳米氧化铁颗粒表征分析及其对体外标记肿瘤细胞磁信号变化的影响

背景：超顺磁性纳米氧化铁颗粒的粒径小，且具有良好的水溶性、组织相容性、超顺磁性及表面积效应，使其应用于磁共振成像和作为生物大分子等药物载体成为可能。 目的：构建葡聚糖包被的超顺磁性四氧化三铁纳米颗粒(dextran coated iron oxide nanoparticles, DCIONP)，分析其主要物理性质和磁学特性，并探讨其标记肿瘤细胞后对肿瘤细胞磁学特性的影响。方法：通过化学共沉淀法制备葡聚糖包被的DCIONP。透射电镜和X射线粉末衍射法分析DCIONP的粒径和晶体结构，磁共振仪测定其弛豫率等主要物理和磁学参数。体外DCIONP分别标记人骨肉瘤MG63细胞、人肝癌HGP2细胞和鼠骨髓间充质干细胞后，用普鲁士蓝铁显色法和透射电镜观察DCIONP粒子在细胞内的分布，1.5T磁共振仪测量DCIONP体外标记肿瘤细胞后对肿瘤细胞磁信号的影响。结果与结论：X射线衍射分析确定所制备的葡聚糖包被的磁性纳米粒子主要为Fe3O4晶体，氧化铁核心约为10 nm，具有超顺磁性，其弛豫率达3.936×106 mol/s。体外标记3种细胞后，见DCIONP主要分布在细胞核中，细胞浆中所占比率相对较小。体外磁标记后，肿瘤细胞的T2信号随着细胞数的增加而逐渐缩短，且2×109 L-1和2×1010 L-1磁标记细胞的磁信号呈明显的衰减状态。结果证实所制备的DCIONP粒子物理性能稳定，磁标记肿瘤细胞后在MR上能产生特征性的低信号。关键词：超顺磁性四氧化三铁纳米颗粒；肿瘤；细胞；磁共振成像；衰减；纳米生物材料doi:10.3969/j.issn.1673-8225.2010.08.017

Characterization and influence of superparamagnetic iron oxide nanoparticles on magnetic signal of magnetic labeled tumor cells in vitro

BACKGROUND: superparamagnetic ferric oxide nanoparticle exhibits small diameter, good water solubility, histocompatibility, superparamagnetism and surface area effect, allowing the application in nuclear magnetic resonance and biomacromolecule as carriers.OBJECTIVE: To construct superparamagnetic iron oxide nanoparticles coated by dextran (DCIONP), determine its physical and magnetic properties and evaluate the magnetic properties of tumor cells labeled by DCIONP in vitro. METHODS: The DCIONP was obtained by means of classical coprecipitation in dextran solution. Its size was determined by the transmission electron microscopy, and the crystal formation in DCIONP was measured by X-ray diffraction analysis. T2 values as well as relaxation rate were evaluated with a 1.5T MR system. After osteosarcoma cell line MG63, hepatocellular carcinoma cell line HGP2 and rat bone marrow-derived mesenchymal cells were labeled by DCIONP in vitro, the perls blue staining and the transmission electron microscopy were performed to observe intracellular iron. In addition, the change of magnetic signal intensity was measured by 1.5T MR. RESULTS AND CONCLUSION: The iron size was 10 nm and the formation of Fe3O4 crystal in DCIONP was confirmed by X-ray diffraction analysis. These nanoparticles possessed some characteristic of superparamagnetic and showed the spin-spin relaxation rate of 3.936×106 mol/s. After three kinds of cells were labeled by DCIONP, the nanoparticles were mainly located in nucleus, and partially in cytoplasm confirmed. The spin-spin relaxations were shortened gradually compared with increasing labeled cells. Obvious magnetic attenuation was measured at 2×109/L and 2×1010/L labeled cells. Results show that the prepared nanoparticle with stable physical and magnetic prosperities was developed, and it is able to product characteristic magnetic attenuation on the magnetic labeled tumor cells by 1.5T MR.