摘要
目的在小鼠模型上对比分析抗Fab′片段脂质体与完整抗体脂质体的药代动力学特点,探讨Fab′片段脂质体在肿瘤靶向治疗方面的应用前景。方法制备非靶向脂质体、完整抗体脂质体及Fab′片段脂质体。于体外分别计算各脂质体与靶细胞的结合能力。MTT法评价载药完整抗体免疫脂质体与Fab′免疫脂质体的细胞毒性。^(125)I标记检测分析三种脂质体经注射后在小鼠体内的药代动力学与生物分布。利用人B细胞淋巴瘤小鼠模型评价用不同载药脂质体治疗后各组小鼠的生存期。结果 Fab′靶向脂质体完全保留了完整抗体靶向脂质体的细胞结合特性,且两者载药后细胞毒性相似;Fab′靶向脂质体在小鼠血液中的半衰期较完整抗体脂质体有所延长;经Fab′片段载药脂质体治疗的荷淋巴瘤小鼠生存期最长。结论 Fab′片段脂质体与完整抗体免疫脂质体相比,具有更理想的药代动力学特点及治疗效果。
Objective To compare and analyze the pharmacodynamic features of Fab＇ liposome and whole antibody liposome and explore the application prospects of Fab＇liposome in terms of tumor - targeted therapy. Methods The in vitro binding capacity of liposome to targeting cell was calculated. The modified MTT method was employed to evaluate the cytotoxicity of whole antibody immunoliposome and Fab＇immunoliposome. ^125I tagging assay was used to analyze the in vivo pharmacodynamics and biodistribution of liposomes in mice. The survival periods of mice treated with non - targeted liposome, whole antibody li- posome and Fab＇ liposome were evaluated using exnograft model. Results The Fab＇targeting liposome preserved the cell - binding capacity of whole antibody targeting liposome and the two had similar cytotoxcities to targeted cancer cells ; Fab＇targering liposome had a somewhat prolonged half-life in circulation as compared with the whole antibody liposome; The mice with tumor had a long survival time after treatment with Fab＇liposome. Conclusions As compared with the whole antibody immunoliposome, the Fab＇liposome has a more ideal pharmacodynamic feature and therapeutic efficacy. The results derived from this study will create new directions for tumor - targeting drug delivery.
出处
《癌症进展》
2010年第3期299-303,310,共6页
Oncology Progress
