金成,吴红,刘军叶,白玲,郭国祯.紫杉醇纳米粒对乏氧MCF-7细胞的辐射增敏作用[J].中华放射医学与防护杂志,2008,28(1):43-46
紫杉醇纳米粒对乏氧MCF-7细胞的辐射增敏作用
Radiosensitization of paclitaxel-loaded nanoparticles on hypoxic MCF-7 cells
投稿时间:2006-12-08  
DOI:
中文关键词:  紫杉醇  药物传输  纳米粒  辐射  人乳腺癌
英文关键词:Paclitaxel  Drug delivery  Nanoparticle  Radiation  Human breast carcinoma
基金项目:
作者单位E-mail
金成 710032 西安, 第四军医大学放射医学教研室  
吴红 化学教研室  
刘军叶 710032 西安, 第四军医大学放射医学教研室  
白玲 西安高新医院检验科  
郭国祯 710032 西安, 第四军医大学放射医学教研室 guozhengg@tom.com 
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中文摘要:
      目的 制备出具有生物活性并可控制释放的紫杉醇纳米粒,探讨其对乏氧人乳腺癌细胞(MCF-7)的辐射增敏作用。方法 采用单乳溶剂挥发法制备聚乳酸-聚羟基乙酸共聚物[Poly (D,L- lactide-co-glycolide),PLGA]包裹的紫杉醇纳米粒,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,扫描电镜研究纳米粒的形态。经乏氧处理的MCF-7细胞与紫杉醇纳米粒共培养,通过细胞形态和细胞周期变化来分析从纳米粒中释放出来的紫杉醇的生物活性,采用平板克隆形成实验检验其辐射增敏作用。结果 成功制备出的紫杉醇纳米粒呈光滑球形,粒径分布为200~800 nm,载药率为4.5%,包封率为85.5%,模拟体外释药曲线呈双相,即在暴发释放之后为缓慢释放。同紫杉醇纳米粒共培养的乏氧MCF-7细胞形态发生改变,极性增加,呈梭形,并且G2期细胞比例升高,克隆形成能力明显降低。结论 本研究证实具有生物活性的紫杉醇从纳米粒中以可控的方式被释放,有效地增加了乏氧MCF-7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。
英文摘要:
      Objective To prepare active and controlled paclitaxel-loaded nanoparticles and to determine the ability to radiosensitize hypoxic human breast carcinoma cells (MCF-7). Methods The poly D,L-lactide-co-glycolide (PLGA) nanoparticles containing paclitaxel were prepared with emulsification-solvent evaporation method. The drug loading efficiency, encapsulation efficiency (EE) and release profile in vitro were measured by high-performance liquid chromatography. The morphology of the paclitaxel-loaded nanoparticles was investigated by scanning electron microscopy. Cell cycle was evaluated by flow cytometry. Cell viability was measured by the ability of single cell to form colonies in vitro.Results The prepared nanoparticles were spherical shape with size between 200 and 800 nm. The drug loading efficiency and EE was 4.5% and 85.5%, respectively. The drug release pattern was biphasic with a fast release rate followed by a slow one. Co-culture of MCF-7 cells with paclitaxel-loaded nanoparticles demonstrated that released paclitaxel resulted in increase of asymmetry of cells and blocked cells in the G2 phase of the cell cycle. Paclitaxel-loaded nanoparticles effectively sensitized hypoxic MCF-7 cells to irradiation. Conclusions Paclitaxel could be effectively released from a biodegradable PLGA nanoparticle delivery system while maintaining potent radiosensitizing ability for hypoxic MCF-7 cells.
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