转铁蛋白修饰脂质体的制备及其肝癌靶向性研究

目的：肿瘤的靶向治疗是当前研究的热点，肝肿瘤细胞表面有大量的转铁蛋白受体表达，而正常组织较少，因此本研究制备转铁蛋白（TF）修饰的脂质体（TFLPs），并对其肝肿瘤靶向性进行研究。方法：采用薄膜分散法制备普通脂质体，考察其形态，粒径，电位。通过体外血清稳定性模拟脂质体进入体内后的稳定性。通过HepG2肿瘤细胞对TFLPs的摄取实验考查脂质体与肝癌细胞的亲和力。构建荷瘤裸鼠模型，考查TFLPs在荷瘤裸鼠体内的分布。结果：所制备的TFLPs平均粒径为108．8±9．5nm，Zeta电位为．1．80±0．73mV。学期稳定性试验结果显示，TFLPs在24h内具有良好的血清稳定性。体外细胞摄取实验表明，HepG2细胞对TFLPs的摄取效率是普通长循环脂质体（LPs）的3．4倍。荷瘤裸鼠肝组织和肿瘤组织切片结果显示，TFLPs比LPs具有更好的肿瘤靶向性。结论：该脂质体制备方法简单，与LPs相比，经转铁蛋白修饰可显著提高肿瘤细胞对脂质体的摄取，TFLPs是一种潜在高效的肝癌靶向给药系统。

The Preparation of Transferrin Modified Liposome for Hepatoma Targeting

Objective： Nowadays, tumor targeting therapy is widely studied, there are plenty of transferrin receptor over-expressed on the surface of liver cancer whereas there are less transferrin receptor in normal tissue, we prepared transferrin modified liposome for hepatoma targeting. Methods： Liposome was prepared by film-ultrasonic method. The size, zeta potential and stability of liposomes in serum was evaluated. And stability of liposomes in serum were used to imitate the stability of liposome in vivo. Cellular uptake by HepG2 cells was explored. The biodistribution of TFLPs was explored by nude mouse beard HepG2. Results The particle diameter of the co-modified liposome was 108.8＋ 9.5 nm with the Zeta potential of-1.80＋ 0.73 mV. The results demonstrated that TFLPs keep stable in serum after 24 h. The evaluation of cells uptake showed TFLPs is a good delivery system for hepatoma. The cell uptake efficiency of TFLPs was 3.4 times higher than LPs. The biodistribution demonstrated that TFLPs could accumulate in tumor more efficiently. Conclusion： The TF modified liposome is easy to prepare. TFLPs could improve the uptake efficiency by tumor cells compared to LPs. TFLPs, as a new nanometer drug, has a special application value for the therapy of hepatoma.