کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10162212 | 1114323 | 2015 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Reducible Poly(Oligo-d-Arginine) as an Efficient Carrier of the Thymidine Kinase Gene in the Intracranial Glioblastoma Animal Model
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
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 (25Â 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. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association. J Pharm Sci 104:3743-3751, 2015.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 104, Issue 11, November 2015, Pages 3743-3751
Journal: Journal of Pharmaceutical Sciences - Volume 104, Issue 11, November 2015, Pages 3743-3751
نویسندگان
Hyun Ah Kim, Hyun-Lin Lee, Eunji Choi, Yong-Hee Kim, Minhyung Lee,