RGD修饰紫杉醇脂质体靶向抑制肝癌HepG2细胞

RGD modified paclitaxel liposome targeted inhibition for HepG2 cells

目的制备整合素受体RGD修饰的紫杉醇脂质体(PTX-RGDLPs),并对其肝癌HepG2细胞靶向性和抑制效果进行评价。方法采用薄膜分散法制备RGD修饰的脂质体,研究其形态、粒径、电位、体外血清稳定性。通过定性和定量的细胞摄取实验研究HepG2肝癌细胞与RGDLPs的亲和力。MTT实验研究紫杉醇脂质体对HepG2肝癌细胞的增殖抑制能力。结果所制备的TFLPs平均粒径为(118.5±11.2)nm,Zeta电位为(-2.55±0.43)mV。体外细胞摄取实验表明,HepG2细胞对RGDLPs的摄取率是普通长循环脂质体(LPs)的3.1倍,差异具有显著统计学意义(P<0.01)。与生理盐水组和普通脂质体组相比,RGD修饰的紫杉醇脂质体对肝癌HepG2细胞的毒性是普通紫杉醇脂质体的2.8倍,差异具有统计学意义(P<0.05)。结论该脂质体制备方法简单,与LPs相比,经RGD修饰可显著提高肿瘤细胞对脂质体的摄取,RGDLPs是一种潜在高效的肝癌靶向给药系统。

Objective To prepare RGD modified paclitaxel liposome and evaluate its inhibition effect on HepG2.Methods Liposome was prepared by film-ultrasonic method.Morphology,particle diameter,zeta potential and stability of liposomes in serum were evaluated.Cellular uptake by HepG2 cells was explored.The MTT assay was used to evaluate the anti-proliferation efficiency of PTX-RGDLPs.Results The particle diameter of the co-modified liposome was （118.5 ± 11.2） nm and the zeta potential was （2.55 ± 0.43） mV.The results demonstrated that RGDLPs kept stable in serum after 24 hours.The evaluation of cells uptake showed RGDLPs was 3.1 time higher than LPs （P ＜ 0.01）.Compared with saline group and PTX-LPs group,the toxicity of PTX-RGDLPs for HepG2 cells was 2.8 times than communis paclitaxel liposome （P ＜ 0.05）.Conclusion RGDLPs,as a new nanometer drug,which can help the tumor cell to absorb more leptosomes than LPs,is apotential targeting system for hepatoma.