title: Stabilization of cancer-specific gene carrier via hydrophobic interaction for a clear-cut response to cancer signaling.
abstract: Here, we developed a new gene carrier, comprising a linear polyethylenimine (LPEI) grafted with a hydrophobically modified cationic peptide containing a long alkyl chain, for use in cancer-specific gene delivery. The cationic peptide is a substrate of protein kinase Cα (PKCα), which is known to be activated specifically in cancer cells. The hydrophobically modified LPEI-peptide conjugate (LPEI-C10-peptide) could form a polyplex with DNA through electrostatic and hydrophobic interactions between the anionic DNA strands and the cationic peptide substrate. The hydrophobic modification of the peptide did not affect the reactivity of the peptide toward PKCα, while the polyplex showed improved intracellular uptake. Because of the efficient endosomal escape and enhanced stability, the polyplex significantly improved the transgene regulation responding to intracellular PKCα activity.
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.forename: Riki
authors.initials: R
authors.lastname: Toita
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Kang
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
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: Yuta
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mori
authors.forename: Takuro
authors.initials: T
authors.lastname: Niidome
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Katayama
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008156:Luciferases / Q000235:genetics; D009369:Neoplasms / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D051571:Protein Kinase C-alpha / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D010455:Peptides; D011094:Polyethyleneimine; D004247:DNA; D008156:Luciferases; D051571:Protein Kinase C-alpha
keywords: Cancer; Gene delivery; Hydrophobic interaction; Protein kinase; Transgene regulation