摘要目的 制备可断裂PEG修饰的载紫杉醇脂质体(CLP-PTX),探讨其体外抗肿瘤能力.方法 采用薄膜分散法制备CLP-PTX.通过流式细胞实验考察肝癌HepG2细胞在PEG断裂前后对脂质体摄取率的变化,MTT实验研究脂质体对HepG2细胞的增殖抑制率.结果 CLP-PTX的粒径为(95±9.5) nm,Zeta电位为(-3±1.05)mV,紫杉醇的包封率为85.6％.加入还原剂半胱氨酸(Cys)后,HepG2细胞对PEG断裂后的脂质体摄取率显著高于断裂前,PEG断裂后的脂质体摄取量是断裂前的2.8倍,差异具有统计学意义(P＜0.01).采用荧光显微镜定性观察细胞摄取发现,PEG断裂后细胞的荧光强度显著强于断裂前.MTT实验结果表明,CLP-PTX对HepG2细胞的增殖抑制作用呈浓度依赖性,PEG断裂后对HepG2细胞的增殖抑制率是断裂前的1.6倍,与细胞摄取实验结果相一致,差异具有统计学意义(P＜0.01).结论 CLP-PTX在PEG断裂后能更有效地被肝癌HepG2细胞摄取,且对肿瘤细胞的增殖抑制作用更强.

abstractsObjective To prepared cleavable PEG modified paclitaxel loaded liposome (CLP-PTX) and to study its capability for tumor targeting.Methods Liposome was prepared by film-ultrasonic method.Cellular uptake by HepG2 cells was explored.The anti-proliferation efficiency of CLP-PTX was evaluated by MTF assay.HepG2 cells were xenografted in athymic nude mice to establish the animal models,which were used to evaluate the anti-cancer effect.Results The mean size of CLP-PTX was (95±9.5) nm with the Zeta potential of (-3±1.05) mV,and the entrapment efficiency of PTX was 85.6％.The cellular uptake of liposomes with addition of cysteine (Cys)was 2.8 times as high as that in the absence of Cys,and the difference was statistically significant (P＜0.01).Fluorescent microscopy qualitative observation demonstrated that the cells showed higher fluorescence intensity in the presence of Cys.The MTT assay showed the anti-proliferative activity against HepG2 cells of CLP-PTX depended on the paclitaxel concentration,and the inhibition ratio of CLP-PTX with addition of Cys was 1.6 times as high as that in the absence of Cys (P＜0.01),which was consistent with the cellular uptake results.Conclusions Comparing with paclitaxel,CLP-PTX inhibited the proliferation of HepG2 cells more persistently.Thus,CLP-PTX,as a new nanometer drug,has a special application value for tumor therapy.