Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation.
Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation.
复制标题
透明质酸试剂功能性壳聚糖-PEI缀合物与AQP2-siRNA抑制子宫内膜异位病变形成
DOI：
10.2147/ijn.s99692
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发表时间：
2016
影响因子：
8
通讯作者：
Huang HF
中科院分区：
文献类型：
--
作者：
Zhao MD;Cheng JL;Yan JJ;Chen FY;Sheng JZ;Sun DL;Chen J;Miao J;Zhang RJ;Zheng CH;Huang HF
为寻找一种副作用小的治疗子宫内膜异位症的新药候选药物，设计了一种由聚乙烯亚胺接枝壳寡糖（CSO-PEI）、透明质酸（HA）和小干扰RNA（siRNA）组成的新型聚合物纳米粒基因递送系统。在（CSO-PEI/siRNA）HA和CSO-PEI/siRNA之间没有观察到明显的尺寸差异，但是由于HA与CD 44的特异性结合，与CSO-PEI/siRNA相比，（CSO-PEI/siRNA）HA在肿瘤病变中的荧光积累更显著。此外，（CSO-PEI/siRNA）HA纳米颗粒基因治疗显著降低了异位病灶的大小，并伴有异位子宫内膜的萎缩和变性。用（CSO-PEI/siRNA）HA治疗后，来自子宫内膜异位症大鼠模型的异位子宫内膜上皮细胞显示出显著低于对照组的CD 44表达。此外，在电子显微镜下观察显示对生殖器官没有明显的毒性作用。因此，（CSO-PEI/siRNA）HA基因递送系统可作为治疗子宫内膜异位症的有效方法。
To identify a new drug candidate for treating endometriosis which has fewer side effects, a new polymeric nanoparticle gene delivery system consisting of polyethylenimine-grafted chitosan oligosaccharide (CSO-PEI) with hyaluronic acid (HA) and small interfering RNA (siRNA) was designed. There was no obvious difference in sizes observed between (CSO-PEI/siRNA)HA and CSO-PEI/siRNA, but the fluorescence accumulation in the endometriotic lesion was more significant for (CSO-PEI/siRNA)HA compared with CSO-PEI/siRNA due to the specific binding of HA to CD44. In addition, the (CSO-PEI/siRNA)HA nanoparticle gene therapy significantly decreased the endometriotic lesion sizes with atrophy and degeneration of the ectopic endometrium. The epithelial cells of ectopic endometrium from rat models of endometriosis showed a significantly lower CD44 expression than control after treatment with (CSO-PEI/siRNA)HA. Furthermore, observation under an electron microscope showed no obvious toxic effect on the reproductive organs. Therefore, (CSO-PEI/siRNA)HA gene delivery system can be used as an effective method for the treatment of endometriosis.