title: High efficiency intracellular transport of cationic peptide stearate for gene delivery in tumor cells and multipotent stem cells.
abstract: Identifying an optimal gene vector is critical for improving transfection efficiency in gene therapy. In this study, a novel, non-viral gene vector composed of a stearate cationic peptide, Cys-Arg-His-Lys-Arg-His-Lys-Arg-His-Lys-Arg-His (CRHKRHKRHKRH), was engineered. The stearate cationic peptide (STR-Pep) could form micelles via its amphipathic properties at a concentration of 182 μg/mL, and condense plasmid DNA effectively above weight ratio of 1:1 to form nanosize complex nanoparticles. Cellular uptake experiments confirmed that STR-Pep micelles and STR-Pep/plasmid DNA complex nanoparticles could pass through cell membranes rapidly, promote endosomal escape and release plasmid DNA from the complex nanoparticles successfully. Compared to Lipofectamine 2000, a commercial gene transfection vector, the engineered vector displayed higher transfection efficiency in certain cell types. Moreover, the STR-Pep gene delivery system was less cytotoxic than Lipofectamine 2000. In vivo anti-tumor activity was achieved by STR-Pep-mediated gene therapy using the plasmid DNA of pigment epithelium derived factor (pPEDF). STR-Pep also regulated gene expression in bone-marrow-derived mesenchymal stem cells (MSCs), effectively inducing osteogenesis and neurogenesis. These results demonstrate that STR-Pep is a potential non-viral vector for in vitro and in vivo gene delivery.
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Shan
authors.forename: Bing
authors.initials: B
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: You
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Gao
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Hu
authors.forename: Yong-Zhong
authors.initials: YZ
authors.lastname: Du
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002460:Cell Line; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology*; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics*; D013228:Stearates / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D023181:Antimicrobial Cationic Peptides; D053769:Nanocapsules; D013228:Stearates