转铁蛋白修饰共载紫杉醇和金雀异黄素脂质体抑制卵巢癌株和荷瘤裸鼠肿瘤的生长

Transferrin modified paclitaxel and genistein co-loaded liposome for the inhibition of ovarian carcinoma cells and ovarian carcinoma bearing nude mice

摘要:

目的：制备转铁蛋白修饰共载紫杉醇（paclitaxel，PTX）和金雀异黄素（genistein，Gen）脂质体（liposome，LP），并对其A2780细胞及对荷瘤裸鼠的治疗效果进行初步评价。方法：采用薄膜分散法制备普通载药LP，后采用插入法制备转铁蛋白修饰载药LP。考察LP的粒径，电位以及包封率；通过细胞摄取实验考察卵巢癌细胞对普通LP和转铁蛋白修饰脂质体（transferrin conjugated liposome，TFLP）的摄取效率。MTT实验考察不同LP对耐药卵巢癌细胞的细胞毒性；构建卵巢癌细胞肿瘤球模型，考察不同LP对肿瘤球的穿透能力以及不同载药LP对肿瘤球的生长抑制能力。构建卵巢癌裸鼠异位模型，考察不同载药LP对肿瘤生长抑制效果。结果：TFLP-PTX/Gen的粒径在（115.0±9.5） nm，电位为（-4.00±2.15） mV，PTX与Gen的包封率分别为83.4%和79.6%。细胞摄取实验结果显示，A2780细胞对TFLP的摄取效率是LP的2.8倍；MTT实验表明TFLP-PTX/Gen对耐药卵巢癌细胞的毒性显著强于TFLP-PTX、TFLP-Gen和LP-PTX/Gen；肿瘤球抑制实验和荷瘤裸鼠肿瘤生长抑制实验结果都表明TFLP-PTX/Gen具有良好的抗肿瘤效果。结论：转铁蛋白修饰共载PTX和Gen LP具有良好的卵巢癌细胞靶向性和抗卵巢癌作用，是一种潜在的卵巢癌靶向给药系统。

Abstract:

Objective：To prepare transferrin conjugated paclitaxel（PTX） and genistein（Gen） loaded liposome and to evaluate their properties and effect on the treatment of ovarian carcinoma in vitro and in vivo. Methods：Liposomes were prepared by thin film hydra－tion method. The particle size，Zeta potential and entrapment efficiency were evaluated. Efficiency of cellular uptake and tumor sphe-roids penetration on MDR A2780 cells in vitro was evaluated. Anti-proliferation efficiency of TFLP-PTX/Gen was evaluated by MTT assay. Tumor spheroids were used to evaluate anti-tumor ability of TFLP-PTX/Gen. A2780 cells was xenografted in athymic mice to establish the animal model，which were used to evaluate the effect of anti-cancer. Results：Particle diameter of the TFLP-PTX/Gen was （115.0±9.5） nm with the Zeta potential of （-4.00±2.15） mV（Entrapment efficiency of PTX and Gen were 83.4% and 79.6% respectively）. Transferrin conjugated liposome（TFLP） uptaken by A2780 were 2.8 times higher than that of liposome（LP）. The MTT assay，the inhabitation of tumor spheroid and the inhabitation of tumor in vivo confirmed strong inhibitory effect of TFLP-PTX/Gen. Conclusions：TFLP-PTX/Gen is easy to prepare and it is a potential delivery system for the treatment of ovarian carcinoma．