基于HMSN载药系统的NVP联合DOX靶向治疗卵巢癌

发布时间：2018-06-27 17:27

  本文选题：卵巢癌 + 中空介孔二氧化硅纳米　； 参考：《南京医科大学学报(自然科学版)》2017年09期

【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p H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(P0.05)。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: to construct a hollow mesoporous silica nano (hollow mesoporous silica nanoparticles, HMSN) compound drug delivery system to target ovarian cancer cells, evaluate the role of the compound drug delivery system and explore the specific inhibitor of the insulin like growth factor 1 receptor (insulin-like growth factor receptor, IGF-1R) NVP through HMSN The therapeutic effect of system combined with doxorubicin (DOX) on ovarian cancer. Methods: modify the carboxyl group on the surface of HMSN, construct HMSN compound drug loading system by mechanical agitation and electrostatic attraction, encapsulate DOX and fluorescent NVP, and use transmission electron microscope, infrared spectrometer, Zeta potential and other methods to characterize the drug carrying system, and detect DOX and fluorescein in HMSN carrier system. The release rate of light NVP in different pH environment; the aggregation of the drug delivery system at different time points was observed by fluorescence confocal microscope; the experiment was divided into HMSN-DOX-NVP group, HMSN-DOX group and free control group, which acted on the SKOV-3 cell line of ovarian cancer, and the inhibition rate of 3 groups of cells was detected by MTT method, and the flow cytometry was used. The apoptosis rate of 3 groups of cells was detected. Results: the charge of HMSN before the modified carboxyl group was -22.3 mV, and the negative charge of HMSN increased to -44.9 mV after the surface modification of the carboxyl group. The morphology and particle size of the HMSN loaded drugs were not changed; when the P H value of the HMSN compound carrier system was gradually reduced, the release rate of DOX and fluorescent NVP was gradual. HMSN-DOX-NVP and HMSN-DOX could accumulate in the cells, and the apoptosis rate and inhibition rate of.HMSN-DOX-NVP group were higher than that of group HMSN-DOX and free control group (P0.05). Conclusion: the HMSN compound drug carrying system can gather in the cell well through the non specific endocytic pathway. Drug release and drug activity can be ensured. NVP combined with DOX can increase the killing rate of DOX to ovarian cancer cells and achieve targeted inhibition of IGF-1R.
【作者单位】： 东南大学医学院临床医学系;东南大学附属中大医院妇产科;
【基金】：江苏省妇幼保健科研项目(F201351)
【分类号】：R737.31
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本文编号：2074671