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)α, 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 PKCα-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 PKCα as a trigger to regulate transgene expression, and may be useful for tumor gene therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 133-139 |
| Number of pages | 7 |
| Journal | Journal of Controlled Release |
| Volume | 139 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Oct 15 2009 |
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All Science Journal Classification (ASJC) codes
- Pharmaceutical Science
Cite this
Protein kinase Cα-specific peptide substrate graft-type copolymer for cancer cell-specific gene regulation systems. / Toita, Riki; Kang, Jeong Hun; Kim, Jong Hwan; Tomiyama, Tetsuro; Mori, Takeshi; Niidome, Takuro; Jun, Byungdug; Katayama, Yoshiki.
In: Journal of Controlled Release, Vol. 139, No. 2, 15.10.2009, p. 133-139.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Protein kinase Cα-specific peptide substrate graft-type copolymer for cancer cell-specific gene regulation systems
AU - Toita, Riki
AU - Kang, Jeong Hun
AU - Kim, Jong Hwan
AU - Tomiyama, Tetsuro
AU - Mori, Takeshi
AU - Niidome, Takuro
AU - Jun, Byungdug
AU - Katayama, Yoshiki
PY - 2009/10/15
Y1 - 2009/10/15
N2 - 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)α, 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 PKCα-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 PKCα as a trigger to regulate transgene expression, and may be useful for tumor gene therapy.
AB - 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)α, 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 PKCα-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 PKCα as a trigger to regulate transgene expression, and may be useful for tumor gene therapy.
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UR - http://www.scopus.com/inward/citedby.url?scp=69949137270&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2009.06.011
DO - 10.1016/j.jconrel.2009.06.011
M3 - Article
C2 - 19545594
AN - SCOPUS:69949137270
VL - 139
SP - 133
EP - 139
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 2
ER -