High Efficiency Intracellular Transport of Cationic Peptide Stearate for Gene Delivery in Tumor Cells and Multipotent Stem Cells

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 mu g/mL, and condense plasmid DNA effectively above weight ratio of 1: 1 to form nano-size 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 (TM) 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 (TM) 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.