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

Chan Woo Kim1, Riki Toita2,3, Jeong-Hun Kang4

  • 1Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.

ACS Biomaterials Science & Engineering
|April 23, 2021
PubMed

Insights

Researchers developed a novel gene carrier that targets cancer cells by responding to protein kinase C alpha (PKCα) signaling. This targeted delivery enhances gene expression and demonstrates significant cancer suppression in preclinical models.

Area of Science:

  • Biotechnology
  • Molecular Biology
  • Cancer Research

Background:

  • Intracellular signal transduction pathways, particularly abnormal signaling in cancer, offer therapeutic targets.
  • Protein kinase C alpha (PKCα) is implicated in various cancers, making it a potential target for selective therapies.

Purpose of the Study:

  • To analyze a novel cellular signal-responsive gene carrier for cancer-specific gene delivery.
  • To evaluate the impact of selective transgene expression in response to malfunctioning intracellular signaling in cancer cells.

Main Methods:

  • Preparation of a linear polyethylenimine (LPEI) main chain conjugated to a cationic PKCα-specific peptide substrate.
  • Formation of nanosized polyplexes with plasmid DNA (pDNA) for efficient cellular uptake and endosomal escape.
  • In vitro and in vivo testing in cancer cell lines and xenograft tumor models to assess gene delivery and therapeutic efficacy.

Main Results:

  • The LPEI-peptide conjugate effectively delivered genes into cancer cells, with transgene expression showing a 10-100 fold increase compared to controls.
  • The gene carrier demonstrated a clear response to PKCα in xenograft tumor models.
  • Delivery of a therapeutic gene (human caspase-8) resulted in significant cancer suppression and extended animal survival.

Conclusions:

  • The developed LPEI-peptide conjugate functions as an efficient and selective gene carrier for cancer therapy.
  • This approach holds significant potential for targeted cancer gene delivery and treatment by exploiting aberrant intracellular signaling pathways.
Keywords:
gene deliverypeptidepolymerprotein kinase

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