RRC ID 37650
Author Toita R, Kang JH, Kim JH, Tomiyama T, Mori T, Niidome T, Jun B, Katayama Y.
Title Protein kinase C alpha-specific peptide substrate graft-type copolymer for cancer cell-specific gene regulation systems.
Journal J Control Release
Abstract We recently proposed a novel gene regulation system responding to specifically and abnormally activated intracellular enzymes in diseased cells. In the present study, we focused on protein kinase C (PKC)alpha, which is hyper-activated in most tumor cells, as a trigger for transgene regulation. We prepared cationic copolymers comprising hydrophilic and neutral polymers in main chains and cationic peptide substrates with different contents in side chains. Our copolymer with high peptide content (>3 mol%) condensed with pDNA more weakly than with poly(L-lysine) (pLL) having a similar molecular weight, but gene suppression was nearly identical to that of pLL, probably due to the steric hindrance of the main chains in our copolymer. Steric hindrance of the main chains barely affected the phosphorylation reaction of the pendant peptide. In cell and mouse experiments, higher gene expression was observed in complexes of pDNA with copolymers pended PKC alpha-specific substrate peptide than that in complexes with negative copolymers pended peptide substituted phosphorylation site of serine residues with alanine. These results indicate that our system can recognize intracellular PKC alpha as a trigger to regulate transgene expression, and may be useful for tumor gene therapy.
Volume 139(2)
Pages 133-9
Published 2009-10-15
DOI 10.1016/j.jconrel.2009.06.011
PII S0168-3659(09)00421-0
PMID 19545594
MeSH Amino Acid Sequence Animals Cell Line, Tumor DNA / administration & dosage* Gene Expression Regulation, Neoplastic* Genetic Therapy Male Melanoma / genetics Melanoma / therapy Mice Mice, Inbred BALB C Peptides / chemistry* Plasmids / administration & dosage Polylysine / chemistry* Protein Kinase C-alpha / genetics* Protein Kinase C-alpha / metabolism Transfection*
IF 7.727
Times Cited 17
Human and Animal Cells