Wan Yu, Moyle Peter M, Gn Pei Z, Toth Istvan
School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia 4072, Queensland, Australia.
School of Pharmacy, The University of Queensland, Woolloongabba 4102, Queensland, Australia.
Nanomedicine (Lond). 2017 Feb;12(4):281-293. doi: 10.2217/nnm-2016-0354. Epub 2017 Jan 17.
To develop a new synthetic peptide-based nanoparticulate siRNA delivery system.
MATERIALS & METHODS: DEN-K(GALA)-TAT-K(STR) was generated by incorporating stearic acid into a multicomponent peptide (DEN-K(GALA)-TAT), containing a cationic poly-L-lysine dendron, an endosome-disrupting peptide GALA and a cell-penetrating peptide TAT(48-60). Its physicochemical characteristics, size, toxicity, cellular uptake and gene knockdown activity of the peptide/siRNA complexes were studied.
DEN-K(GALA)-TAT-K(STR) exhibited a pH-responsive behavior, which assists with endosomal escape. When siRNA was delivered by DEN-K(GALA)-TAT-K(STR), it showed a significantly enhanced cellular uptake, compared with the nonlipidic peptide. This system also displayed enhanced knockdown efficiency and reduced cytotoxicity over the widely used delivery system branched 25-kDa polyethyleneimine.
Our stearylated multicomponent delivery system has great potential as an efficient siRNA delivery vector.
开发一种基于合成肽的新型纳米颗粒siRNA递送系统。
通过将硬脂酸掺入多组分肽（DEN-K(GALA)-TAT）中生成DEN-K(GALA)-TAT-K(STR)，该多组分肽包含阳离子聚-L-赖氨酸树枝状大分子、内体破坏肽GALA和细胞穿透肽TAT(48 - 60)。研究了肽/siRNA复合物的物理化学特性、大小、毒性、细胞摄取和基因敲低活性。
DEN-K(GALA)-TAT-K(STR)表现出pH响应行为，有助于内体逃逸。当通过DEN-K(GALA)-TAT-K(STR)递送siRNA时，与非脂质肽相比，其细胞摄取显著增强。该系统与广泛使用的递送系统支链25 kDa聚乙烯亚胺相比，还显示出增强的敲低效率和降低的细胞毒性。
我们的硬脂酸化多组分递送系统作为一种高效的siRNA递送载体具有巨大潜力。
