靶向癌胚抗原载药纳米超声造影剂体外抑制卵巢癌细胞生长

发布时间：2018-01-09 22:21

本文关键词：靶向癌胚抗原载药纳米超声造影剂体外抑制卵巢癌细胞生长　出处：《中国医学影像技术》2017年06期 　论文类型：期刊论文

【摘要】：目的制备靶向癌胚抗原(CEA)载药相变型PLGA纳米粒(Ab-PTX-NPs),探讨该纳米粒的体外寻靶及抑制肿瘤细胞生长的效能。方法乳化溶剂挥发法联合碳二亚胺法制备靶向CEA载紫杉醇纳米粒(Ab-PTX-NPs),采用马尔文粒径分析仪检测其粒径大小。采用高效液相色谱法检测紫杉醇包封率及载药量,恒温摇床透析法检测该纳米粒体外释药特征。激光共聚焦显微镜及流式细胞术观察该纳米粒体外寻靶情况,CCK-8试剂检测卵巢癌细胞存活率。结果制备的Ab-PTX-NPs粒径为(397.70±99.95)nm,紫杉醇包封率及载药量分别为(67.26±4.15)%和(6.31±0.39)%。抗CEA单克隆抗体与纳米粒连接率为(92.74±5.75)%。共聚焦显微镜下观察到靶向组卵巢癌SKOV3细胞周围见较多造影剂黏附,流式细胞术测得靶向组细胞平均荧光强度明显高于其余各组(P0.05),CCK-8试剂法测得靶向组在24h时,细胞存活率高于纯药组(P0.05),而低于无靶组(P0.05),当48h时,靶向组与纯药组细胞存活率差异无统计学意义(P0.05)。结论成功制备靶向CEA载药相变型PLGA纳米粒,该纳米粒经低功率聚焦超声治疗仪(LIFU)致相变后可明显增强超声显影,且载药量高,释药快,靶向能力强。
[Abstract]:Objective to prepare phase change PLGA nanoparticles (Ab-PTX-NPs) targeting carcinoembryonic antigen (CEA). Objective: to investigate the efficiency of targeting and inhibiting tumor cell growth of the nanoparticles in vitro. Methods CEA loaded paclitaxel nanoparticles Ab-PTX-NPs were prepared by emulsifying solvent volatilization combined with carbodiimide method. Ma Erwen particle size analyzer was used to detect the particle size and the encapsulation efficiency and drug loading capacity of paclitaxel were detected by high performance liquid chromatography (HPLC). The in vitro drug release characteristics of the nanoparticles were detected by constant temperature shaking bed dialysis. The target finding of the nanoparticles in vitro was observed by laser confocal microscopy and flow cytometry. The survival rate of ovarian cancer cells was determined by CCK-8 reagent. Results the diameter of Ab-PTX-NPs prepared was 397.70 卤99.95 nm. The entrapment efficiency and drug loading of paclitaxel were 67.26 卤4.15% and 6.31 卤0.39%, respectively. The binding rate of monoclonal antibody against CEA to nanoparticles was 92.74 卤5.75. Under confocal microscope, more contrast media adhesions were observed around the SKOV3 cells in the targeted group. The average fluorescence intensity of the target group was significantly higher than that of the other groups at 24 hours by flow cytometry. The cell survival rate was higher than that in the pure drug group (P 0.05), but lower than that in the target free group (P 0.05). There was no significant difference in cell survival rate between the target group and the pure drug group. Conclusion the phase change PLGA nanoparticles with targeted CEA were successfully prepared. After phase transition induced by low power focused ultrasound (LIFU), the nanoparticles can obviously enhance ultrasound development, and the drug loading is high, the drug release is fast, and the targeting ability is strong.
【作者单位】：重庆医科大学附属第一医院超声科;重庆医科大学超声影像学研究所;
【基金】：国家临床重点专科建设项目(国卫医办函[2013]544号)
【分类号】：R445.1;R737.31
【正文快照】： 卵巢癌是女性最常见的生殖系统肿瘤之一,其发病率仅次于宫颈癌和子宫内膜癌而居第3位,但病死率却高居第1位[1]。因此,早期准确地诊断与治疗,对其预后至关重要。随着超声分子影像学的发展,聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]纳米粒以其良好的生物组织

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