依他硝唑纳米粒对乏氧肿瘤细胞辐射增敏作用的研究  

Effect of etanidazole-loaded nanoparticles on radiosensitization of hypoxic tumor cells

作　　者：金成[1] 白玲[2] 吴红[3] 腾增辉[4] 郭国祯[1] 

机构地区：[1]第四军医大学放射医学教研室,西安,710032 [2]西安高新医院检验科 [3]第四军医大学放射化学教研室,西安,710032 [4]第四军医大学放射药理学教研室,西安,710032

出　　处：《中华放射医学与防护杂志》2008年第2期-,共3页Chinese Journal of Radiological Medicine and Protection

摘　　要：目的 制备出具有生物活性并可控制释放的依他硝唑纳米粒,探讨其对乏氧人乳腺癌细胞(MCF-7)和人子宫颈癌细胞(HeLa)的辐射增敏作用.方法 采用复乳溶剂挥发法制备聚乳酸.聚羟基乙酸共聚物(PLGA)包裹的依他硝唑纳米粒,高效液相色谱分析纳米粒的载药率、包封率和模拟体外释药,透射电镜研究纳米粒的形态,激光衍射粒度分析仪检测纳米粒的粒径分布.经乏氧处理的MCF-7和HeLa细胞与依他硝唑纳米粒和药物单体共培养,采用平板克隆形成实验检验其辐射增敏作用.结果 成功制备依他硝唑纳米粒,呈光滑球形,粒径分布在90～190 nm之间,载药率为1.66%,包封率为18.02%,模拟体外释药曲线呈双相,即在爆发释放之后为缓慢释放.同依他硝唑纳米粒和药物单体共培养的乏氧MCF-7和HeLa细胞克隆形成能力照射后明显降低,依他硝唑纳米粒作用更为显著.结论 具有生物活性的依他硝唑从纳米粒中以可控的方式被释放,有效地增加了乏氧肿瘤细胞的辐射敏感性.为辐射增敏剂的临床应用提供了一种新的给药方式.Objective To prepare active and controlled etanidazole-loaded nanoparticles and to determine the ability to radiosensitize hypoxic human breast carcinoma cells(MCF-7)and human carcinoma cervices cells(HeLa).Methods The poly(D,L-lactide-CO-glycolide)(PLGA)nanoparticles containing etanidazole were prepared by w/o/w emulsification-solvent evaporation method.The drug loading efficiency,the encapsulation efficiency(EE)and the release profile in vitro were measured by high-performance liquid chromatography.The morphology of the etanidazole-loaded nanoparticles was investigated by transmission electron microscope.The size distribution of nanoparticles was determined by laser diffraction analyzer.Cell viability was measured by the ability of single cell to form colonies in vitro.Results The prepared nanoparticles were spherical in shape with sizes between 90 and 190 nm.The drug loading efficiency and EE was 1.66%and 18.02%.respectively.The drug release pattern was biphasic with a fast release rate followed by a slow one.Co cqlture of hypoxic MCF-7 and HeLa cells with etanidazole-loaded nanoparticles and free etanidazole demonstrated that released etanidazole effectively sensitized hypoxic tumor cells to irradiation.Compared with free etanidasole,radiosensitization of etanidazole-loaded nanoparticles was more significant.Conclusions It is demonstrated that etanidazole can be effectively released from a biodegradable PLGA nanopartiele delivery system while maintaining potent radiosensitizing ability for hypoxic tumor cells.

关 键 词：依他硝唑 纳米粒 辐射 乏氧肿瘤细胞 

分 类 号：R686[医药卫生—骨科学]