Gene carrier showing all-or-none response to cancer cell signaling

Riki Toita, Jeong Hun Kang, Tetsuro Tomiyama, Chan Woo Kim, Shujiro Shiosaki, Takuro Niidome, Takeshi Mori, Yoshiki Katayama

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)15410-15417
Number of pages8
JournalJournal of the American Chemical Society
Volume134
Issue number37
DOIs
Publication statusPublished - Sep 19 2012

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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