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Open Access Nano Express

Effect of introduction of chondroitin sulfate into polymer-peptide conjugate responding to intracellular signals

Tetsuro Tomiyama1, Riki Toita1, Jeong-Hun Kang2, Haruka Koga1, Shujiro Shiosaki1, Takeshi Mori134, Takuro Niidome134 and Yoshiki Katayama134*

Author Affiliations

1 Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 819-0395, Japan

2 Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan

3 Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka 819-0395, Japan

4 Center for Future Chemistry, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka 819-0395, Japan

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Nanoscale Research Letters 2011, 6:532  doi:10.1186/1556-276X-6-532

Published: 30 September 2011

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.