title: Design and evaluation of a stearylated multicomponent peptide-siRNA nanocomplex for efficient cellular siRNA delivery.
abstract: OBJECTIVE
  To develop a new synthetic peptide-based nanoparticulate siRNA delivery system.
  
  
  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.
  
  
  CONCLUSIONS
  Our stearylated multicomponent delivery system has great potential as an efficient siRNA delivery vector.
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wan
authors.affiliation: School of Pharmacy, The University of Queensland, Woolloongabba 4102, Queensland, Australia.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Moyle
authors.affiliation: School of Pharmacy, The University of Queensland, Woolloongabba 4102, Queensland, Australia.
authors.forename: Pei Z
authors.initials: PZ
authors.lastname: Gn
authors.affiliation: 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.|Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Queensland, Australia.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D013229:Stearic Acids / Q000737:chemistry*; D014162:Transfection
chemical_list: D057846:Cell-Penetrating Peptides; D010455:Peptides; D034741:RNA, Small Interfering; D013229:Stearic Acids; C485184:enhanced green fluorescent protein; C066951:GALA peptide; D049452:Green Fluorescent Proteins; C031183:stearic acid; D011094:Polyethyleneimine
keywords: cell-penetrating peptide; endosome-disrupting peptide; lipidic peptide; nonviral vectors; poly-L-lysine; siRNA delivery