叶酸受体介导的负载紫杉醇纳米药物输送系统的体外生物活性的研究  

In Vitro Biological Activities of Folate Receptor-mediated Delivery of Paclitaxel Nanoparticle System

作　　者：王莺[1] 

机构地区：[1]南方医科大学基础医学院肿瘤研究所,广州510515

出　　处：《数理医药学杂志》2013年第3期278-281,共4页Journal of Mathematical Medicine

基　　金：国家自然科学基金(21204036);广东省自然科学基金资助(S2011040003731)

摘　　要：目的:叶酸受体介导的负载紫杉醇纳米药物输送系统的的体外生物活性研究。方法:应用激光共聚焦观察肝素-叶酸-紫杉醇纳米粒进入叶酸受体阳性表达KB细胞和叶酸受体阴性表达A549细胞的情况,考察纳米粒对靶细胞摄取情况;以原药紫杉醇为对照组,应用MTT法检测纳米粒子对叶酸受体阳性表达KB细胞的抗癌抑制活性;应用流式细胞仪对纳米粒子抗癌机制进行分析。结果:细胞摄取实验表明,肝素-叶酸-紫杉醇纳米药物是通过叶酸受体介导的内吞作用实现对靶细胞的特异性;与紫杉醇对比,纳米粒子的针对叶酸受体阳性细胞的抑制效果更好,半数抑制浓度(IC50)为0.06g/mL,MTT实验结果与细胞摄取实验结果一致;流式细胞仪检测表明肝素-叶酸-紫杉醇纳米药物也表现出与紫杉醇相似的抑制作用,即G2/M期均有所增长。结论:体外生物活性检测表明叶酸受体介导的负载紫杉醇的纳米药物输送系统有较好的靶向性,其应用前景值得期待。Objective： The investigation about in vitro biological activites of folate receptor-mediated de- livery of paclitaxel nanoparticle system. Methods： To evaluate the targeted effect of heparin-folate-paclitaxel nanoparticles, KB cells and A549 cells were employed as folate receptor overexpressing cancer cells and folate receptor deficiency cancer cells treated with nanoparticles. The anticancer inhibition activity of heparimfolate- paclitaxel nanoparticles was measured by MTT assay and cell cycle profile of KB cell treated with heparin-fo- late-paclitaxel nanoparticles was assayed by flow cytometry. Results. The cellular uptake experiment sugges- ted folate receptor-mediated endocytosis was considered to affect the cellular uptake eficiency of heparin-folate-paclitaxel nanoparticles. The heparin-folate-paclitaxel nanoparticles exhibited increased cytotoxicity （IC50 0.06 g/mL） as compared to free drug. Flow cytornetry analysis showed that KB cells treated with hepa- rin-folate-paelitaxel nanoparticles were arrested in the G2/M phase of the cell cycle. The results of MTT assay was in accordance with that of cellular uptake experiment. Conclusions. Heparin-folate-paclitaxel nanop- articles displayed folate receptor-mediated endoeyctosis effect. The nanoparticle system could be used as a promising eancer cell specific delivery system for further investigation.

关 键 词：叶酸受体 紫杉醇 纳米药物输送系统 体外生物活性 

分 类 号：Q819[生物学—生物工程]