Abstract
We recently developed a novel tumor-targeted gene delivery system responding to hyperactivated intracellular signals. Polymeric carrier for gene delivery consists of hydrophilic neutral polymer as main chains and cationic peptide substrate for target enzyme as side chains, and was named polymer-peptide conjugate (PPC). Introduction of chondroitin sulfate (CS), which induces receptor-medicated endocytosis, into polymers mainly with a high cationic charge density such as polyethylenimine can increase tumor-targeted gene delivery. In the present study, we examined whether introduction of CS into PPC containing five cationic amino acids can increase gene expression in tumor cells. Size and zeta potential of plasmid DNA (pDNA)/PPC/CS complex were <200 nm and between -10 and -15 mV, respectively. In tumor cell experiments, pDNA/PPC/CS complex showed lower stability and gene regulation, compared with that of pDNA/PPC. Moreover, no difference in gene expression was identified between positive and negative polymer. These results were caused by fast disintegration of pDNA/PPC/CS complexes in the presence of serum. Thus, we suggest that introduction of negatively charged CS into polymers with a low charge density may lead to low stability and gene regulation of complexes.
| Original language | English |
|---|---|
| Article number | 532 |
| Pages (from-to) | 1-7 |
| Number of pages | 7 |
| Journal | Nanoscale Research Letters |
| Volume | 6 |
| DOIs | |
| Publication status | Published - Dec 1 2011 |
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All Science Journal Classification (ASJC) codes
- Materials Science(all)
- Condensed Matter Physics
Cite this
Effect of introduction of chondroitin sulfate into polymer-peptide conjugate responding to intracellular signals. / Tomiyama, Tetsuro; Toita, Riki; Kang, Jeong Hun; Koga, Haruka; Shiosaki, Shujiro; Mori, Takeshi; Niidome, Takuro; Katayama, Yoshiki.
In: Nanoscale Research Letters, Vol. 6, 532, 01.12.2011, p. 1-7.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of introduction of chondroitin sulfate into polymer-peptide conjugate responding to intracellular signals
AU - Tomiyama, Tetsuro
AU - Toita, Riki
AU - Kang, Jeong Hun
AU - Koga, Haruka
AU - Shiosaki, Shujiro
AU - Mori, Takeshi
AU - Niidome, Takuro
AU - Katayama, Yoshiki
PY - 2011/12/1
Y1 - 2011/12/1
N2 - We recently developed a novel tumor-targeted gene delivery system responding to hyperactivated intracellular signals. Polymeric carrier for gene delivery consists of hydrophilic neutral polymer as main chains and cationic peptide substrate for target enzyme as side chains, and was named polymer-peptide conjugate (PPC). Introduction of chondroitin sulfate (CS), which induces receptor-medicated endocytosis, into polymers mainly with a high cationic charge density such as polyethylenimine can increase tumor-targeted gene delivery. In the present study, we examined whether introduction of CS into PPC containing five cationic amino acids can increase gene expression in tumor cells. Size and zeta potential of plasmid DNA (pDNA)/PPC/CS complex were <200 nm and between -10 and -15 mV, respectively. In tumor cell experiments, pDNA/PPC/CS complex showed lower stability and gene regulation, compared with that of pDNA/PPC. Moreover, no difference in gene expression was identified between positive and negative polymer. These results were caused by fast disintegration of pDNA/PPC/CS complexes in the presence of serum. Thus, we suggest that introduction of negatively charged CS into polymers with a low charge density may lead to low stability and gene regulation of complexes.
AB - We recently developed a novel tumor-targeted gene delivery system responding to hyperactivated intracellular signals. Polymeric carrier for gene delivery consists of hydrophilic neutral polymer as main chains and cationic peptide substrate for target enzyme as side chains, and was named polymer-peptide conjugate (PPC). Introduction of chondroitin sulfate (CS), which induces receptor-medicated endocytosis, into polymers mainly with a high cationic charge density such as polyethylenimine can increase tumor-targeted gene delivery. In the present study, we examined whether introduction of CS into PPC containing five cationic amino acids can increase gene expression in tumor cells. Size and zeta potential of plasmid DNA (pDNA)/PPC/CS complex were <200 nm and between -10 and -15 mV, respectively. In tumor cell experiments, pDNA/PPC/CS complex showed lower stability and gene regulation, compared with that of pDNA/PPC. Moreover, no difference in gene expression was identified between positive and negative polymer. These results were caused by fast disintegration of pDNA/PPC/CS complexes in the presence of serum. Thus, we suggest that introduction of negatively charged CS into polymers with a low charge density may lead to low stability and gene regulation of complexes.
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UR - http://www.scopus.com/inward/citedby.url?scp=84856048030&partnerID=8YFLogxK
U2 - 10.1186/1556-276X-6-532
DO - 10.1186/1556-276X-6-532
M3 - Article
C2 - 21961843
AN - SCOPUS:84856048030
VL - 6
SP - 1
EP - 7
JO - Nanoscale Research Letters
JF - Nanoscale Research Letters
SN - 1931-7573
M1 - 532
ER -