title: Gene carrier showing all-or-none response to cancer cell signaling.
abstract: In this work we designed a novel nano carrier, a linear polyethylenimine (LPEI)-peptide conjugate, for cancer-specific expression of transgenes. The conjugate was easily synthesized by using a click chemistry scheme orthogonal to the reactive side groups of the peptide, which is the substrate of protein kinase Cα (PKCα). Polyplexes of the conjugates with plasmid DNA (pDNA) were intact and stably dispersed even in the presence of cell lysate. Despite this stability, the polyplexes readily dissociated upon phosphorylation of the grafted peptides by PKCα. Because of its endosomal escape ability and adequate susceptibility to PKCα, the polyplexes showed an all-or-none type response to PKCα activity in transgene expression in vitro. The polyplexes achieved cancer tissue-specific transgene expression even for a tumor with a relatively low PKCα activity. Thus the LPEI-peptide conjugate has high potential as a nanocarrier for cancer-targeted gene therapy.
authors.affiliation: Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Fukuoka, 819-0395, Japan.
authors.forename: Riki
authors.initials: R
authors.lastname: Toita
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Kang
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Tomiyama
authors.forename: Chan Woo
authors.initials: CW
authors.lastname: Kim
authors.forename: Shujiro
authors.initials: S
authors.lastname: Shiosaki
authors.forename: Takuro
authors.initials: T
authors.lastname: Niidome
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mori
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Katayama
mesh_terms: D045744:Cell Line, Tumor; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D015398:Signal Transduction; D019076:Transgenes