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Báo cáo hóa học: " Effect of introduction of chondroitin sulfate into polymer-peptide conjugate responding to intracellular signals"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí hóa hoc quốc tế đề tài : Effect of introduction of chondroitin sulfate into polymer-peptide conjugate responding to intracellular signals | Tomiyama et al. Nanoscale Research Letters 2011 6 532 http www.nanoscalereslett.eom content 6 1 532 o Nanoscale Research Letters a SpringerOpen Journal NANO EXPRESS Open Access Effect of introduction of chondroitin sulfate into polymer-peptide conjugate responding to intracellular signals 1t 1t 2 1 1 13.4 Tetsuro Tomiyama Riki Toita Jeong-Hun Kang Haruka Koga Shujiro Shiosaki Takeshi Mori Takuro Niidome1 3 4 and Yoshiki Katayama1 3 4 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. Introduction Tumor-targeted gene delivery is beneficial for increasing therapeutic effects and reducing the desired side effect. These gene delivery systems are mainly based on passive targeting and active targeting methods. Nanoparticles pass through leaky tortuous and heterogeneous