【作者】 赵明；

【导师】 李安民；

【作者基本信息】 中国人民解放军军医进修学院 ， 外科学， 2010， 博士

【摘要】 目的研究超顺磁性紫杉醇纳米微粒对恶性脑胶质细胞瘤细胞的抑制作用。方法利用纳米技术制作出超顺磁性紫杉醇纳米微粒,并观察其粒径、磁响应性和缓控释药速度。将其与人恶性脑胶质瘤细胞系U251共同孵育后观察纳米微粒在细胞内的分布,并用CCK-8法和流式细胞法检测不同浓度紫杉醇纳米微粒对U251细胞的细胞毒性作用和诱导凋亡作用。立体定向向SD大鼠脑内基底节区种植C6恶性胶质瘤细胞,建立荷胶质瘤大鼠模型,对比静脉注射超顺磁性紫杉醇纳米微粒和单纯紫杉醇后大鼠的生存时间。结果超顺磁性紫杉醇纳米微粒粒径约20nm,具备超顺磁性,体外可持续释药15天以上。其能有效进入肿瘤细胞内部并释放药物,诱导肿瘤细胞发生凋亡,其细胞毒性作用与紫杉醇相近。荷瘤大鼠注射超顺磁性紫杉醇纳米微粒并用0.5T磁场进行磁靶向治疗后生存期较紫杉醇治疗组延长1倍。结论超顺磁性紫杉醇纳米微粒改变了紫杉醇的弱水溶性,并且安全稳定,能持续缓慢释放药物。因其粒径小,能顺利进入肿瘤细胞内部发挥显著抗肿瘤作用。同时,在外磁场引导下能聚集于磁靶向区域,提高肿瘤局部药物浓度,达到杀灭肿瘤、延长生存期的作用。更多还原

【Abstract】 Objective:The inhibitive effects of superparamagnetic paclitaxel nanoparticles to the malignant glioma growth were studied both in vivo and in vitro.Methods:Superparamagnetic paclitaxel nanoparticles were fabricated by nanotechnology before their diameters, magnetism as well as drug release rate were tested. After incubation with human malignant glioma cell line U251, the intracellular distribution of nanoparticles was observed. Afterwards the cytotoxicity and apoptosis-inducing capacity of superparamagnetic paclitaxel nanoparticles at different concentrations to U251 were tested by CCK-8 kit and flow cytometry. Rat malignant glioma cell line C6 was implanted into SD rats’ head stereotactically to obtain the glioma-bearing rats. After intravenous administration of superparamagnetic paclitaxel nanoparticles and magnetic targeting, the rats’survival was recorded and compared with that after pure paclitaxel injection.Results:Superparamagnetic paclitaxel nanoparticles had a mean diameter of 20 nm with a narrow distribution. They were superparamagnetic and released drugs for more than 15 days constantly. Besides they could enter the glioma cells effectively and inducing apoptosis with a similar cytotoxicity with paclitaxel. After intravenous injection of superparamagnetic paclitaxel nanoparticles and magnetic targeting with a 0.5T magnet, the survival of glioma-bearing rats were prolonged for 1 fold compared to rats treated with paclitaxel.Conclusion:Superparamagnetic paclitaxel nanoparticles converted the poor solubility of paclitaxel. They are safe and stable with a long release of loaded drugs. The superparamagnetic paclitaxel nanoparticles can enter the glioma cells to inhibit their growth because of their ultrasmall size. Besides, they can accumulate in magnetic targeted area and result in a high local drug concentration to inhibit the tumor growth and prolong the glioma-bearing rats’survival.更多还原