Reducible Poly(Oligo-d-Arginine) as an Efficient Carrier of the Thymidine Kinase Gene in the Intracranial Glioblastoma Animal Model

Title
Reducible Poly(Oligo-d-Arginine) as an Efficient Carrier of the Thymidine Kinase Gene in the Intracranial Glioblastoma Animal Model
Author
김용희
Keywords
cancer; gene delivery; gene therapy; polymeric drug carrier; polymeric drug delivery systems
Issue Date
2015-01
Publisher
WILEY-BLACKWELL
Citation
JOURNAL OF PHARMACEUTICAL SCIENCES, v. 104, NO 11, Page. 3743-3751
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. (c) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3743-3751, 2015
URI
http://onlinelibrary.wiley.com/doi/10.1002/jps.24576/fullhttp://hdl.handle.net/20.500.11754/22101
ISSN
0022-3549; 1520-6017
DOI
10.1002/jps.24576
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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