转铁蛋白与细胞穿膜肽共修饰脂质体的制备及其抗肿瘤效果  

Preparation of TF and TAT co-modified paclitaxel loaded liposome and its anti-cancer effect

作　　者：宿怀予 周劲[2] 

机构地区：[1]乐山市人民医院,四川乐山614000 [2]四川大学华西药学院

出　　处：《中国老年学杂志》2014年第12期3363-3365,共3页Chinese Journal of Gerontology

基　　金：国家自然科学基金资助项目(81072599)

摘　　要：目的制备转铁蛋白(TF)与细胞穿膜肽(TAT)共修饰载紫杉醇(PTX)脂质体(TF/TATLP-PTX),对其体外性质进行评价。方法采用薄膜分散法制备TF与TAT共修饰TF/TATLP-PTX,考察其粒径、电位、包封率等理化特征。通过MTT实验考察脂质体对肝癌HepG2细胞的毒性,流式细胞仪检测肿瘤细胞对脂质体的摄取能力。构建HepG2肝癌异位瘤模型,考察不同脂质体对肿瘤的生长抑制能力。结果制备的TF/TATLP-PTX粒径为(137.8±13.5)nm,Zeta电位(17.55±3.85)mV,紫杉醇的包封率为85.3%。MTT实验结果显示,给药72 h后,以生理盐水组为对照,未修饰紫杉醇脂质体(LP-PTX)、转铁蛋白修饰紫杉醇脂质体(TFLP-PTX)、TAT修饰紫杉醇脂质体(TATLP-PTX)和TF/TATLP-PTX肝癌HepG2细胞存活率分别为62.4%、45.5%、39.2%和17.7%,组间比较差异显著(P<0.01);体外细胞摄取实验表明,肝癌HepG2细胞对TF/TATLP的摄取效率分别是TFLP、TATLP和LP的2.7倍、2.2倍和3.9倍,组间比较差异显著(P<0.01);荷瘤裸鼠治疗实验以生理盐水组为对照,给药20 d后,生理盐水组体积变为给药前的2.55倍,LP-PTX、TFLP-PTX、TATLP-PTX和TF/TATLP-PTX组肿瘤体积分别增长到原体积的2.22、1.73、1.89、1.29倍,与其他组间差异显著(P<0.01)。结论 TF/TATLP-PTX制备工艺简单,与肝癌HepG2细胞具有良好的亲和性,是一种潜在高效的肿瘤靶向给药系统。Objective To prepare transferrin ( TF) and TAT co-modified paclitaxel loaded liposome ( TF/TATLP-PTX) for cancer tar-geting and therapy.Methods The co-modified liposome was prepared by film-ultrasonic method .The particle size ,Zeta potential were evalu-ated.The cellular uptake by HepG 2 cells in vitro was used to evaluate the targeting efficiency .The anti-proliferation efficiency of TF/TATLP-PTX was evaluated by MTT assay .HepG2 cells were xenografted in mice to establish the animal model , which were used to evaluate the effect of anti-tumor.Results The particle diameter of the co-modified liposome was (137.8 ±13.5) nm with the Zeta potential of (17.55 ± 3.85)mV.The entrapment efficiency of paclitaxel was 85.3%.The result demonstrated that the co-modified liposome uptaken by HepG2 were 2.7 and 2.2 times higher than those of TFLP and TATLP , respectively(P<0.01).The MTT assay and the inhibitory of tumor in vivo demonstrate that TF/TATLP-PTX inhibited the tumor and tumor cells efficiently .Conclusions Conclusions: The co-modified liposome might serve as a promising cancer delivery system of antitumor drugs .

关 键 词：转铁蛋白 细胞穿膜肽 紫杉醇 肿瘤靶向 脂质体 

分 类 号：R73[医药卫生—肿瘤]