title: Effect of peptide content on the regulation of transgene expression by protein kinase Cα-responsive linear polyethylenimine-peptide conjugates.
abstract: We examined a series of linear polyethylenimine (LPEI)-based nanocarriers that activate transgene expression in response to cancer-specific protein kinase Cα (PKCα). Eight types of LPEI-peptide conjugate differing in peptide content and number were synthesized using click chemistry. The conjugates could form polyplexes with pDNA through electrostatic interaction, but the degree of pDNA condensation, sizes, and surface charges of the resulting polyplexes depended on the pendant-peptide content and number. None of the polyplexes showed significant cytotoxicity toward human hepatoma cells (HepG2). Furthermore, pendant peptide content and number markedly affected transgene activation in response to PKCα. To achieve an all-or-none response to PKCα, we determined the optimum peptide content and number in LPEI-peptide conjugates as ≈6 mol% and ≈40 peptides/conjugate.
authors.affiliation: Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
authors.forename: Riki
authors.initials: R
authors.lastname: Toita
authors.affiliation: Division of Biopharmaceutics and Pharmacokinetics, Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
authors.forename: Chan Woo
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
authors.forename: Shujiro
authors.initials: S
authors.lastname: Shiosaki
authors.affiliation: Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan; Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mori
authors.affiliation: Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Niidome
authors.affiliation: Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan; Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan; International Research Center for Molecular Systems, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan; Center for Advanced Medical Innovation, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan. Electronic address: ykatatcm@mail.cstm.kyushu-u.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Katayama
mesh_terms: D056945:Hep G2 Cells; D006801:Humans; D010455:Peptides / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics*
chemical_list: D010455:Peptides; D011094:Polyethyleneimine; D051571:Protein Kinase C-alpha
keywords: Gene delivery; Polyethylenimine; Polyplexes; Protein kinase; Signal-responsive polymers