PDF(Pubmed)
Abstract：
The E6 and E7 oncoproteins of high-risk types of human papillomavirus (HR-HPV) are crucial for the development of cervical cancer (CC). Small interfering RNAs (siRNAs) are explored as novel therapies that silence these oncogenes, but their clinical use is hampered by inefficient delivery systems. Modification (pegylation) with polyethylene glycol (PEG) of liposomal siRNA complexes (siRNA lipoplexes) may improve systemic stability. We studied the effect of siRNA targeting HPV16 E6, delivered via cationic liposomes (lipoplexes), on cellular processes in a cervical carcinoma cell line (CaSki) and its potential therapeutic use. Lipoplexes-PEG-HPV16 E6, composed of DOTAP, Chol, DOPE, and DSPE-PEG2000 were prepared. The results showed that pegylation (5% DSPE-PEG2000) provided stable siRNA protection, with a particle size of 86.42 ± 3.19 nm and a complexation efficiency of over 80%; the siRNA remained stable for 30 days. These lipoplexes significantly reduced HPV16 E6 protein levels and restored p53 protein expression, inhibiting carcinogenic processes such as proliferation by 25.74%, migration (95.7%), and cell invasion (97.8%) at concentrations of 20 nM, 200 nM, and 80 nM, respectively. In conclusion, cationic lipoplexes-PEG-HPV16 E6 show promise as siRNA carriers for silencing HPV16 E6 in CC.
摘要：
高危类型的人乳头瘤病毒（HR-HPV）的E6和E7癌蛋白对于宫颈癌（CC）的发展至关重要。小干扰RNA（siRNA）被探索作为沉默这些癌基因的新疗法，但是它们的临床使用受到低效的输送系统的阻碍。用聚乙二醇(PEG)修饰(聚乙二醇化)脂质体siRNA复合物(siRNA脂质体复合物)可改善系统稳定性。我们研究了通过阳离子脂质体（脂质体）递送的靶向HPV16E6的siRNA的作用，宫颈癌细胞系（CaSki）的细胞过程及其潜在的治疗用途。脂质体-PEG-HPV16E6，由DOTAP组成，Chol,DOPE,并制备了DSPE-PEG2000。结果表明聚乙二醇化(5%DSPE-PEG2000)提供稳定的siRNA保护,粒径为86.42±3.19nm，复合效率超过80％；siRNA保持稳定30天。这些脂质复合物显着降低HPV16E6蛋白水平并恢复p53蛋白表达，抑制致癌过程如增殖25.74%，迁移（95.7%），和20nM浓度的细胞侵袭（97.8%），200nM,80nM,分别。总之,阳离子脂质体-PEG-HPV16E6有望作为siRNA载体在CC中沉默HPV16E6。
