Design and evaluation of a stearylated multicomponent peptide-siRNA nanocomplex for efficient cellular siRNA delivery. (February 2017)

• Record Type: Journal Article
• Authors: Wan, Yu; Moyle, Peter M; Gn, Pei Z; Toth, Istvan
• Is Part Of: Nanomedicine. Volume 12:Number 4(2017)
• Page Start: 281
• Page End: 293
• Publication Date: 2017-02
• Subjects: cell-penetrating peptide -- endosome-disrupting peptide -- lipidic peptide -- nonviral vectors -- poly-L-lysine -- siRNA delivery; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm-2016-0354
• Languages: English
• ISSNs: 1743-5889

Abstract

Aim: 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.Results: 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.Conclusion: Our stearylated multicomponent delivery system has great potential as an efficient siRNA delivery vector.