基因沉默
小发夹RNA
体内
转染
RNA干扰
遗传增强
体外
化学
细胞毒性
血管瘤
癌症研究
小干扰RNA
分子生物学
基因
核糖核酸
生物
医学
生物化学
病理
生物技术
作者
Xiaoshuang Guo,Zihan Yuan,Yu Xu,Minyan Wei,Zhiwei Fang,Weien Yuan
出处
期刊:Biomaterials Science
[The Royal Society of Chemistry]
日期:2020-01-01
卷期号:8 (8): 2129-2142
被引量:10
摘要
Hemangioma, one of the most common angiogenic diseases in infants and children, is characterized by the abnormal and aggressive proliferation of vascular endothelial cells. Advanced therapeutic strategies like RNA interference can inhibit the expression of target proteins at the translational level, but they are rarely used in hemangioma treatment owing to the lack of safe carriers. In this study, we showed for the first time that RNAi technology targeting HIF-1α (hypoxia-inducible factor-1 alpha) could benefit hemangioma therapy effectively. Heptafluorobutyric anhydride (HFAA) was used to modify low-molecular-weight PEI (PEI1.8k), and a novel fluorinated polycation carrier named fluorinated PEI (FPEI) was synthesized. Furthermore, HIF-1α-shRNA-pDNA was condensed by FPEI to fabricate FPEI polyplexes. Compared with PEI25k polyplexes, which are usually the gold standard used in gene delivery, FPEI polyplexes showed lower cytotoxicity and higher serum stability, transfection efficiency and gene silencing efficiency both in vitro and in vivo. In addition, we confirmed that FPEI polyplexes could efficiently inhibit the formation of new capillaries and tumor growth in vivo, which may provide a practicable strategy for clinical hemangioma treatment in the future.
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