Reducible Poly(Oligo-d-Arginine) as an Efficient Carrier of the Thymidine Kinase Gene in the Intracranial Glioblastoma Animal Model
- Authors
- Kim, Hyun Ah; Lee, Hyun-Lin; Choi, Eunji; Kim, Yong-Hee; Lee, Minhyung
- Issue Date
- Nov-2015
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- cancer; gene delivery; gene therapy; polymeric drug carrier; polymeric drug delivery systems
- Citation
- JOURNAL OF PHARMACEUTICAL SCIENCES, v.104, no.11, pp.3743 - 3751
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF PHARMACEUTICAL SCIENCES
- Volume
- 104
- Number
- 11
- Start Page
- 3743
- End Page
- 3751
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/155973
- DOI
- 10.1002/jps.24576
- ISSN
- 0022-3549
- 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 invivo 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.
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