Gene therapy of endometriosis introduced by polymeric micelles with glycolipid-like structure.

Gene therapy of endometriosis introduced by polymeric micelles with glycolipid-like structure.
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具有糖脂样结构的聚合物胶束引入子宫内膜异位症的基因治疗。

DOI:
10.1016/j.biomaterials.2011.09.077
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发表时间:
2012
期刊:
影响因子:
14
通讯作者:
Fu-Qiang Hu
Fu-Qiang Hu
中科院分区:
工程技术1区
文献类型:
--
作者:
Hong Yuan;Cai-Hong Zheng;Xin-Mei Zhang;Fu-Qiang Hu

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为了减少子宫内膜异位症化疗的副作用并改善临床治疗对策的不足,设计了一种由脂质接枝壳聚糖胶束(CSO-SA)和色素上皮衍生因子(PEDF)组成的聚合胶束基因递送系统。由于阳离子特性,类糖脂胶束可以压缩 PEDF 形成复合纳米颗粒。 N/P 为 9.6 的复合纳米粒子的体积平均流体动力学直径为 135.6 nm,尺寸分布窄,表面电位为 6.4 ± 0.1 mV。在CSO-SA介导的腹膜子宫内膜异位症大鼠模型中,PEDF可以通过静脉注射分布到子宫内膜异位病灶。结果表明,CSO-SA/PEDF纳米颗粒基因治疗使子宫内膜异位病灶尺寸明显减小,异位子宫内膜明显萎缩、变性。电镜观察对生殖器官无毒性。此外,观察到血管性血友病因子标记的微血管密度减少,α-平滑肌肌动蛋白阳性成熟血管没有减少。 CSO-SA/PEDF组子宫内膜异位病灶细胞凋亡指数明显升高。因此,类糖脂结构胶束介导的PEDF基因传递系统可作为子宫内膜异位症的有效治疗方法。
To reduce the side effects and improve the lack of clinical treatment countermeasures in endometriosis chemotherapy, a polymeric micelle gene delivery system composed of lipid grafted chitosan micelles (CSO-SA) and the pigment epithelium derived factor (PEDF) was designed. Due to the cationic property, the glycolipid-like micelles could compact the PEDF to form complexes nanoparticles. The complexes nanoparticles with an N/P at 9.6 had 135.6 nm volume average hydrodynamic diameters with a narrow size distribution, and 6.4 ± 0.1 mV surface potential. PEDF can be distributed to endometriotic lesions in a rat model of peritoneal endometriosis mediated by CSO-SA via the intravenous injection. It showed that the CSO-SA/PEDF nanoparticles gene therapy caused decrease in the sizes of the endometriotic lesions and atrophy and degeneration of ectopic endometrium significantly. And it showed no toxicity to the reproductive organs under electron microscope observation. In addition, a reduction in microvessel density labeled by Von Willebrand factor was observed and no decrease in α-Smooth Muscle Actine-positive mature vessels. And the index of apoptotic was increased significantly in endometriotic lesions of CSO-SA/PEDF group. So, glycolipid-like structure micelles mediated PEDF gene delivery system could be used as an effective treatment approach for endometriosis disease.
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期刊: ANGIOGENESIS
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