title: Reducible Poly(Oligo-D-Arginine) as an Efficient Carrier of the Thymidine Kinase Gene in the Intracranial Glioblastoma Animal Model.
abstract: Gene therapy has been considered as an alternative treatment for glioblastoma therapy. In this study, a glioblastoma-specific suicide gene, pEpo-NI2-SV-TK, was delivered into the intracranial glioblastoma model using reducible poly(oligo-d-arginines) (rPOA). pEpo-NI2-SV-TK has the erythropoietin (Epo) enhancer and the nestin intron 2 (NI2) for glioblastoma specific gene expression. The in vitro studies showed that the rPOA formed stable complexes with pEpo-NI2-SV-TK. In the MTT and TUNEL assays, rPOA showed lower cytotoxicity than polyethylenimine (25 kDa, PEI25k). In addition, the rPOA/pEpo-NI2-SV-TK complex induced higher glioblastoma cell death under hypoxic condition than normoxic condition, suggesting that pEpo-NI2-SV-TK induced gene expression in the hypoxic tumor tissue. For in vivo therapeutic efficacy evaluation, the rPOA/pEpo-NI2-SV-TK complex was injected into the brains of an intracranial glioblastoma rat model. The rPOA/pEpo-NI2-SV-TK injected group had a significantly reduced tumor size, compared with the control and the PEI25k/pEpo-NI2-SV-TK injected group. The TUNEL assay showed that the rPOA-pEpo-NI2-SV-TK complex had more apoptotic cells than the control and PEI25k/pEpo-NI2-SV-TK injected groups. These results suggest that the rPOA is an efficient carrier for pEpo-NI2-SV-TK and increased the therapeutic efficacy in the intracranial glioblastoma models. Therefore, the rPOA/pEpo-NI2-SV-TK complex may be useful for glioblastoma specific gene therapy.
authors.affiliation: BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Department of Bioengineering, College of Engineering, Seoul, 133-791, Republic of Korea; Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 133-791, Republic of Korea.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Kim
authors.affiliation: BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Department of Bioengineering, College of Engineering, Seoul, 133-791, Republic of Korea.
authors.forename: Hyun-Lin
authors.initials: HL
authors.lastname: Lee
authors.affiliation: BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Department of Bioengineering, College of Engineering, Seoul, 133-791, Republic of Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Choi
authors.affiliation: BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Department of Bioengineering, College of Engineering, Seoul, 133-791, Republic of Korea; Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 133-791, Republic of Korea. Electronic address: yongheekim@hanyang.ac.kr.
authors.forename: Yong-Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Department of Bioengineering, College of Engineering, Seoul, 133-791, Republic of Korea; Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 133-791, Republic of Korea. Electronic address: minhyung@hanyang.ac.kr.
authors.forename: Minhyung
authors.initials: M
authors.lastname: Lee
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives*; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D010084:Oxidation-Reduction; D051381:Rats; D013937:Thymidine Kinase / Q000235:genetics*
chemical_list: D001120:Arginine; D013937:Thymidine Kinase
keywords: cancer; gene delivery; gene therapy; polymeric drug carrier; polymeric drug delivery systems