Protein Kinase C α-Responsive Gene Carrier for Cancer-Specific Transgene Expression and Cancer Therapy

Chan Woo Kim, Riki Toita, Jeong Hun Kang, Takeshi Mori, Akihiro Kishimura, Yoshiki Katayama

Research output: Contribution to journalArticlepeer-review

Abstract

The presence of intracellular signal transduction and its abnormal activities in many cancers has potential for medical and pharmaceutical applications. We recently developed a protein kinase C α (PKCα)-responsive gene carrier for cancer-specific gene delivery. Here, we demonstrate an in-depth analysis of cellular signal-responsive gene carrier and the impact of its selective transgene expression in response to malfunctioning intracellular signaling in cancer cells. We prepared a novel gene carrier consisting of a linear polyethylenimine (LPEI) main chain grafted to a cationic PKCα-specific substrate (FKKQGSFAKKK-NH2). The LPEI-peptide conjugate formed a nanosized polyplex with pDNA and mediated efficient cellular uptake and endosomal escape. This polyplex also led to successful transgene expression which responded to the target PKCα in various cancer cells and exhibited a 10-100-fold higher efficiency compared to the control group. In xenograft tumor models, the LPEI-peptide conjugate promoted transgene expression showing a clear-cut response to PKCα. Furthermore, when a plasmid containing a therapeutic gene, human caspase-8 (pcDNA-hcasp8), was used, the LPEI-peptide conjugate had significant cancer-suppressive effects and extended animal survival. Collectively, these results reveal that our method has great potential for cancer-specific gene delivery and therapy.

Original languageEnglish
Pages (from-to)2530-2537
Number of pages8
JournalACS Biomaterials Science and Engineering
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 14 2021

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering

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