title: Tumor accumulation of protein kinase-responsive gene carrier/DNA polyplex stabilized by alkanethiol for intravenous injection.
abstract: We synthesized polymeric gene carriers consisting of poly-L-lysine (PLL) main chain modified both with substrate peptide for protein kinase Cα (PKCα) and alkanethiol (pentadecanethiol). Due to the grafted substrate peptide, the polyplex prepared from these carriers is expected to show gene expression triggered by the phosphorylation of the peptide by intracellular PKCα. The modified alkanethiol on the main chain stabilized the polyplex both via disulfide crosslinking and hydrophobic interaction. The polyplex found to show gene expression in vitro when the alkanethiol content in the main chain was enough low (4-mol%-modification of PLL's ε-amine group) to minimize cytotoxic effect. Even though the content of alkanethiol is low, the polyplex had significant stability in a model serum solution and showed longer blood circulation in vivo. The polyplex clearly accumulated in tumor after intravenous injection.
authors.affiliation: a Graduate School of Systems Life Sciences , Kyushu University , 744 Motooka, Nishi-ku, Fukuoka , 819-0395 , Japan.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Hikari
authors.initials: H
authors.lastname: Sato
authors.forename: Chan Woo
authors.initials: CW
authors.lastname: Kim
authors.forename: Yuta
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Guo Xi
authors.initials: GX
authors.lastname: Zhao
authors.forename: Daiki
authors.initials: D
authors.lastname: Funamoto
authors.forename: Takanobu
authors.initials: T
authors.lastname: Nobori
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kishimura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mori
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Katayama
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D004220:Disulfides / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007275:Injections, Intravenous; D042541:Intracellular Space / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D051571:Protein Kinase C-alpha / Q000235:genetics*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D014018:Tissue Distribution; D014162:Transfection; D019076:Transgenes / Q000235:genetics
chemical_list: D004220:Disulfides; D004337:Drug Carriers; D009842:Oligopeptides; D013438:Sulfhydryl Compounds; D011107:Polylysine; D004247:DNA; D051571:Protein Kinase C-alpha
keywords: cancer; disulfide bond; gene delivery; hydrophobic interaction; protein kinase