Design and evaluation of a stearylated multicomponent peptide-siRNA nanocomplex for efficient cellular siRNA delivery

作者：Wan Yu; Moyle Peter M; Gn Pei Z; Toth Istvan

来源：Nanomedicine, 2017, 12(4): 281-293.

DOI：10.2217/nnm-2016-0354

• cell-penetrating peptide
• endosome-disrupting peptide
• lipidic peptide
• nonviral vectors
• poly-L-lysine
• siRNA delivery

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.

• 出版日期2017-2