Arginine modified PAMAM dendrimer for interferon beta gene delivery to malignant glioma

A xenograft brain tumor model was established by the subcutaneous injection of U87MG cells into nude mice to investigate the efficacy of a non-viral vector, arginine-modified polyamidoamine dendrimer (PAMAM-R), in delivering a therapeutic gene, human interferon beta (IFN-β). We used 4′,6-diamidino-2...

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Bibliographic Details
Published in:International journal of pharmaceutics 2013-03, Vol.445 (1-2), p.79-87
Main Authors: Bai, Cheng Zhe, Choi, Sunghyun, Nam, Kihoon, An, Songhie, Park, Jong-Sang
Format: Article
Language:English
Subjects:
Animals
Apoptosis
arginine
Arginine - chemistry
brain
Brain Neoplasms - pathology
Brain Neoplasms - therapy
Caspase 3 - metabolism
caspase-3
Cell Line
Cell Line, Tumor
Dendrimers - administration & dosage
Dendrimers - chemistry
Gene delivery
Gene Transfer Techniques
genes
Genetic Therapy
Glioma - pathology
Glioma - therapy
Humans
immunohistochemistry
Interferon beta
Interferon-beta - genetics
Malignant glioma
Mice
Mice, Nude
neoplasms
PAMAM-R
reverse transcriptase polymerase chain reaction
subcutaneous injection
transfection
Tumor Burden - drug effects
vascular endothelial growth factor receptors
Xenograft Model Antitumor Assays
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Summary:A xenograft brain tumor model was established by the subcutaneous injection of U87MG cells into nude mice to investigate the efficacy of a non-viral vector, arginine-modified polyamidoamine dendrimer (PAMAM-R), in delivering a therapeutic gene, human interferon beta (IFN-β). We used 4′,6-diamidino-2-phenylindole staining, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and the caspase-3 activity assay to determine the induction of apoptosis upon transfection with the PAMAM-R/IFN-β gene polyplex in vitro. The polyplex was injected into xenograft brain tumors. Mice treated with PAMAM-R/pORF-IFN-β exhibited a significantly smaller tumor size than control mice and PAMAM-R/pORF treated mice. Hematoxylin/eosin staining and immunohistochemistry with the endothelial growth factor receptor antibody also revealed inhibition of tumor growth. Furthermore, reverse transcription polymerase chain reaction and the TUNEL assay also verified the expression of IFN-β and induction of apoptosis in vivo. These results indicate that the PAMAM-R/pORF-IFN-β polyplex is an effective therapeutic candidate for glioblastoma multiforme due to its selective induction of apoptosis in tumor cells.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2013.01.057