转铁蛋白与R8共修饰脂质体的制备及其肝癌靶向性研究

摘要

目的：制备转铁蛋白（transferrin，TF）和八聚精氨酸（R8）共修饰脂质体（TF/R8-LP），对其理化性质进行表征，研究脂质体对肿瘤细胞的靶向性。方法采用薄膜分散法制备TF/R8-LP，研究脂质体的粒径，电位和血清稳定性。细胞摄取实验研究肝癌HepG2细胞对TF/R8-LP的摄取效率。构建裸鼠肝癌异位瘤模型，研究脂质体的体内靶向性。结果 TF/R8-LP的粒径在（108.5±12.6）nm，电位为（24.15±4.78）mV。TF/R8-LP在50％血清中具有良好的稳定性。细胞摄取实验结果显示：TF/R8-LP在4 h摄取效率是2 h的1.85倍，差异具有统计学意义（P＜0.05）；肝癌HepG2细胞在与脂质体共同孵育4 h后对TF/R8-LP的摄取效率分别是R8-LP、TF-LP和LP的2.4倍、2.8倍和3.9倍，差异均有统计学意义（P＜0.01）；近红外活体成像实验结果显示：TF/R8-LP组在肿瘤组织荧光明显强于其他组。结论转铁蛋白和八聚精氨酸共修饰脂质体具有良好的肝癌细胞亲和力，是一种潜在高效的肝癌靶向给药系统。%Objective To prepare transferring and R8 co-modified liposome (TF/R8-LP)for forhepatoma targeting.Methods The co-modified liposome were prepared by film-ultrasonic method.The appearance,particle size,Zeta potential were evaluated.The cellular uptake by HepG2 cell in vitro was used to evaluate the targeting efficiency and in vivo imaging were used to evaluate the targeting efficiency. Results The particle diameter of the co-modified liposome was(108.5 ±12.6)nm and the Zeta potential was(24.15 ±4.78)mV.The liposome kept stable in 50% FBS at 24 h.The result demonstrated that the co-modified liposome uptaken by HepG2 were 2.4,2.6 times higher than that of R8-LP and TF-LP,respectively(P<0.05).The evaluation of tumor spheroid penetration and in vivo imaging results showed the co-modified liposome had the strongest fluorescence intensity. Conclusion The co-modified liposome might serve as a promising hepatoma delivery system of antitumor drugs.