基于HMSN载药系统的NVP联合DOX靶向治疗卵巢癌
作者:
作者单位:

作者简介:

通讯作者:

中图分类号:

基金项目:

江苏省妇幼保健科研项目(F201351)


NVP combined with DOX targeted therapy for ovarian cancer based on HMSN drug deli-very system
Author:
Affiliation:

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    目的:构建中空介孔二氧化硅纳米(hollow mesoporous silica nanoparticles,HMSN)复合载药系统靶向作用于卵巢癌细胞,评估此复合药物运载系统的作用,探究胰岛素样生长因子1受体(insulin-like growth factor receptor , IGF-1R)特异性抑制剂NVP通过HMSN运载系统联合阿霉素(doxorubicin,DOX)对卵巢癌的治疗效果。方法:在HMSN表面修饰羧基,通过机械搅拌和静电吸引作用包载DOX和荧光NVP构建HMSN复合载药系统;采用透射电镜、红外光谱仪、Zeta电位等方法表征此载药系统;检测HMSN载药系统中DOX和荧光NVP在不同pH值环境中的释放率;通过荧光共聚焦显微镜观察药物运载系统不同时间点在细胞中的聚集情况;将实验分为 HMSN-DOX-NVP组、HMSN-DOX组和游离对照组,分别作用于卵巢癌SKOV-3细胞株,MTT法检测3组细胞的抑制率,并通过流式细胞仪检测3组细胞的凋亡率。结果:HMSN在修饰羧基之前所带电荷为-22.3 mV,在其表面修饰羧基后,HMSN所带负电荷增多至-44.9 mV;HMSN负载药物后,其形态和粒径均未发生改变;HMSN复合载药系统所处环境的pH值逐渐降低时,DOX和荧光NVP的释放率逐渐升高;HMSN-DOX-NVP及HMSN-DOX可在细胞中聚集,并可随着作用时间的延长逐渐渗透进入胞核释放药物。HMSN-DOX-NVP组的细胞凋亡率和抑制率均高于HMSN-DOX组和游离对照组(P<0.05)。结论:HMSN复合载药系统通过非特异性的内吞途径可以良好聚集在胞中释放药物并可保证药物活性,NVP联合DOX可提高DOX对卵巢癌细胞的杀伤率并实现针对IGF-1R的靶向抑制。

    Abstract:

    Objective:We sought to construct hollow mesoporous silica nanoparticles(HMSN) compound drug delivery system, which can target ovarian cancer cells, and to assess the effect of this drug delivery system as well as explore the treatment effect of insulin-like growth factor receptor(IGF-1R) specific inhibitor NVP combined with doxorubicin(DOX) by HMSN delivery system. Methods: We modified carboxyl on the surface of HMSN, then loaded DOX and fluorescent NVP through mechanical mixing and the electrostatic attraction. The compound drug system was characterized by TEM, infrared spectrometer and Zeta potential. The drug release rates of DOX and fluorescence NVP were detected in different pH environment. Drug delivery system gathered in cells was observed by immunofluorescence laser scanning confocal microscope at different times. We divided this experiment into HMSN-DOX-NVP group, HMSN-DOX group and the control group, and acted on SKOV-3 cells respectively. Cell apoptosis rates and cell inhibition rates in there three groups were detected by flow cytometry. Results: Zeta potentially showed that the charge of HMSN was about -22.3 mV before modified carboxyl, and the charge of HMSN raised to -44.9 mV after modified carboxyl. The size and shape of HMSN were not changed after loaded drugs observed by TEM. The drug release rates of DOX and fluorescence NVP were gradually increased with the environmental pH value gradually reduced. HMSN-DOX-NVP and HMSN-DOX gathered in cells and gradually infiltrated into the nucleus with the prolongation of time. The cell apoptosis rate and MTT inhibition rate of the HMSN-DOX-NVP group were higher than those of the HMSN-DOX group and the free control group(P<0.05). Conclusion: HMSN compound drug delivery system can be well gathered in cytoplasm mainly through nonspecific endocytosis and ensure pharmacological activity of the released drugs simultaneously. NVP combine with DOX can improve the killing rate of DOX for cancer cells and achieve targeted inhibition of IGF-R.

    参考文献
    相似文献
    引证文献
引用本文

郭 欣,蔡云朗,任慕兰.基于HMSN载药系统的NVP联合DOX靶向治疗卵巢癌[J].南京医科大学学报(自然科学版),2017,(9):1093-1098

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2016-08-17
  • 最后修改日期:
  • 录用日期:
  • 在线发布日期: 2017-09-25
  • 出版日期:
通知关闭
郑重声明