中文摘要：

背景：利用转铁蛋白受体表达的特异性和转铁蛋白-转铁蛋白受体结合的亲和性,转铁蛋白修饰药物载体可以明显提高药物的特异结合能力和疗效。转铁蛋白也可修饰影像对比剂,针对肿瘤组织的转铁蛋白受体,实现肿瘤的特异性靶向成像。目的：评价转铁蛋白-磁性纳米粒的理化特性,并对其细胞结合特性进行体外实验研究。方法：采用旋转蒸发法制备磁性脂质体,共价结合法制备转铁蛋白-磁性纳米粒。对转铁蛋白-磁性纳米粒的粒径、电位、形态、转铁蛋白结合效率、r2弛豫率、细胞结合特性及细胞毒性等指标进行分析评价。转铁蛋白-磁性纳米粒与转铁蛋白受体高表达Hep G2肝癌细胞特异性结合后进行体外MR成像。结果与结论：1转铁蛋白-磁性纳米粒平均粒径为95.1 nm,多分散系数为0.21,Zeta电位为-1.25 m V,r2弛豫率为94.62 mmol-1·s-1,每个磁性脂质体约结合27个转铁蛋白分子;2荧光共聚焦电镜显示转铁蛋白-磁性纳米粒与转铁蛋白受体高表达Hep G2肝癌细胞发生特异结合,荧光胞浆出现罗丹明红染;普鲁士蓝铁染色显示Hep G2细胞内和细胞表面有铁染色颗粒;3体外细胞MR T2WI成像显示,转铁蛋白-磁性纳米粒与Hep G2细胞标记后,离心管信号强度下降;而空白磁性纳米粒与细胞不发生结合,故无明显信号强度下降;4细胞毒性实验显示细胞生长曲线良好;5以上结果表明,转铁蛋白-磁性纳米粒满足MR分子探针的所需要求,可用于MR分子成像。

英文摘要：

BACKGROUND： Transferrin（Tf） is one suitable ligand to be conjugated to drug delivery systems to achieve site-specific targeting and desired therapeutic effect, due to its specific binding to transferrin receptors（Tf R）, and high expression on the surface of tumor cells. Contrast agents are also modified with Tf to achieve specific tumor imaging. OBJECTIVE： To prepare Tf-labeled magnetoliposomes（MLs）, and characterize their utility as Tf R targeted MR specific contrast agent in vitro. METHODS： MLs and Tf-MLs were prepared by lipid film hydration method and covalent coupling method, respectively. Tf-MLs were characterized by their mean size, zeta potential, polyindex, r2 relaxivity, Tf-binding efficacy and cytotoxicity. In vitro MRI contrasting properties of the suspended nanoparticles incubated with HepG2 cells were determined. RESULTS AND CONCLUSION： The mean diameter, polydisperisity index, zeta potential and r2 relexivity of Tf-ML were 95.1 nm, 0.21,-1.25 mv and 94.62 mmol-1/s, respectively. The coupling efficiency was calculated and the values obtained were 59.4 μg Tf/μmol phospholipid corresponding to about 27 molecules of Tf-MLs. After a 2-hour incubation with rhodamine-labeled Tf-MLs, rhodamine fluorescence was detected intensively in the plasma membrane and the cytoplasm of the Tf R-overexpressing HepG2 cells. In contrast, Tf-ML showed little binding in MCF-7 cells that had low Tf R level. HepG2 cells incubated with Tf-ML showed much higher intracellualar iron density than incubated with non-targeted MLs. In vitro MR T2 WI of cells demonstrated the centrifuge tube containing HepG2 cells incubated with Tf-MLs produced a lower visible signal intensity than that treated with non-targeted MLs. Tf-MLs showed their potentials such as high r2 relaxivity, specific binding ability characteristics. These results suggest the availability of Tf-MLs to serve as a targeted contrast agent.