Development of Gene Therapy with Nanotechnology derived Intelligent Drug Deliver Systems

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We develop polyion complex with DNA and polycation for gene delivery systems. Polyethyleneimine was selected for polycation that have protonsponde effect on transfection to cancer cells. Polyethylene-glycol binding carboxyl chain was also used for coating the cationic charged DNA/polycation complex. To increase the transfection efficacy, we also examined pH sensitive peptide, JTS-1 that constructed with analysis of Influenza virus. Polyethyleneimine and DNA complex showed 1 × 10^9 IU/mg luciferase activity. In case of coating the DNA/polyion complex with PEG-C, the luciferase activity was increase to 3 × 10^9 IU/mg, because of the compaction and incresent of stability with addition of PEG-C to complex, so the transfection efficacy was increased. When addition of JTS-1 to the DNA/polyethyleneimine/lactose-binding PEG-C complex, it is easily to escape the lysis of lysosome and transfect the DNA to cytoplasm, and 6 × 10^9 IU/mg luciferase activity was obtained. Increasing of transfection efficacy of β-gal gene by intratumor injection of β-gal DNA plasmid/Polyethyleneimine/lactose-binding PEG-C/JTS-1 complex on gastric cancer tumor bearing mice model.According to the analysis of DNA microarray with ancer cell lines that were sensitive or resistant to Oxaliplatin or Cisplatin, Tubrin specific Chaperon E gene and CBP/P300-interacting transactivator (CITED2) gene were increased on Oxaliplatin or Cisplatin resistant cancer cells.