细胞穿透肽
小干扰RNA
体内
基因沉默
体外
聚乙二醇化
脂质体
肽
材料科学
RNA干扰
鱼精蛋白
内吞作用
免疫原性
生物物理学
细胞
转染
生物化学
化学
纳米技术
生物
核糖核酸
免疫系统
免疫学
基因
生物技术
肝素
作者
Yuhuan Li,Robert J. Lee,Kongtong Yu,Ye Bi,Yuhang Qi,Yating Sun,Yujing Li,Jing Xie,Lesheng Teng
标识
DOI:10.1021/acsami.6b09991
摘要
Clinical development of siRNA has been hindered by the lack of an effective delivery system. Here, we report the construction of a novel siRNA delivery system, sTOLP, which is based on cell penetrating peptide oleoyl-octaarginine (OA-R8) modified multifunctional lipid nanoparticles. sTOLP nanoparticles are composed of a protamine complexed siRNA core, OA-R8, cationic and PEGylated lipids, and transferrin as a targeting ligand. sTOLP formulation was optimized and characterized in vitro and showed excellent gene silencing activity. In vivo, siRNA encapsulated in sTOLP exhibited potent tumor inhibition (61.7%) and was preferentially taken up by hepatocytes and tumor cells in HepG2-bearing nude mice without inducing immunogenicity or hepatic or renal toxicity. Furthermore, sTOLP-loaded siRNA had stability in circulation greater than that of free siRNA. These data demonstrated potential utility of sTOLP-mediated siRNA delivery in cancer therapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI