聚乙二醇化
基因沉默
脂质体
体内
阳离子脂质体
阳离子聚合
内体
化学
聚乙二醇
体外
小干扰RNA
细胞生物学
转染
基因传递
RNA干扰
生物物理学
生物化学
药理学
生物
细胞
基因
核糖核酸
生物技术
有机化学
作者
Yusuke Sato,Hiroto Hatakeyama,Yasuhisa Sakurai,Mamoru Hyodo,Hidetaka Akita,Hideyoshi Harashima
标识
DOI:10.1016/j.jconrel.2012.09.009
摘要
Modification of liposomal siRNA carriers with polyethylene glycol, i.e., PEGylation, is a generally accepted strategy for achieving in vivo stability and delivery to tumor tissue. However, PEGylation significantly inhibits both cellular uptake and the endosomal escape process of the carriers. In a previous study, we reported on the development of a multifunctional envelope-type nano device (MEND) for siRNA delivery and peptide-based functional devices for overcoming the limitations and succeeded in the efficient delivery of siRNA to tumors. In this study, we synthesized a pH-sensitive cationic lipid, YSK05, to overcome the limitations. The YSK05-MEND had a higher ability for endosomal escape than other MENDs containing conventional cationic lipids. The PEGylated YSK05-MEND induced efficient gene silencing and overcame the limitations followed by optimization of the lipid composition. Furthermore, the intratumoral administration of the YSK05-MEND resulted in a more efficient gene silencing compared with MENDs containing conventional cationic lipids. Collectively, these data confirm that YSK05 facilitates the endosomal escape of the MEND and thereby enhances the efficacy of siRNA delivery into cytosol and gene silencing.
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