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Plasmid pORF-hTRAIL targeting to glioma using transferrin-modified polyamidoamine dendrimer

Authors Gao S, Li J, Jiang C, Hong B, Hao B

Received 6 September 2015

Accepted for publication 19 November 2015

Published 17 December 2015 Volume 2016:10 Pages 1—11

DOI https://doi.org/10.2147/DDDT.S95843

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Rekha Dhanwani

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Wei Duan


Song Gao,1,* Jianfeng Li,2 Chen Jiang,2 Bo Hong,3 Bing Hao4,*

1Department of Clinical Laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 2Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 3Department of Pathology, The Second Affiliated Hospital, 4Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China

*These authors contributed equally to this work

Abstract: A gene drug delivery system for glioma therapy based on transferrin (Tf)-modified polyamidoamine dendrimer (PAMAM) was prepared. Gene drug, tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL)-encoding plasmid open reading frame (pORF-hTRAIL, Trail), was condensed by Tf-modified PAMAM to form nanoparticles (NPs). PAMAM-PEG-Tf/DNA NPs showed higher cellular uptake, in vitro gene expression, and cytotoxicity than PAMAM-PEG/DNA NPs in C6 cells. The in vivo targeting efficacy of NPs was visualized by ex vivo fluorescence imaging. Tf-modified NPs showed obvious glioma-targeting trend. Plasmid encoding green fluorescence protein (GFP) was also condensed by modified or unmodified PAMAM to evaluate the in vivo gene expression level. The PAMAM-PEG-Tf/plasmid encoding enhanced green fluorescence protein (pEGFP) NPs exhibited higher GFP expression level than PAMAM-PEG/pEGFP NPs. TUNEL assay revealed that Tf-modified NPs could induce much more tumor apoptosis. The median survival time of PAMAM-PEG-Tf/Trail-treated rats (28.5 days) was longer than that of rats treated with PAMAM-PEG/Trail (25.5 days), temozolomide (24.5 days), PAMAM-PEG-Tf/pEGFP (19 days), or saline (17 days). The therapeutic effect was further confirmed by magnetic resonance imaging. This study demonstrated that targeting gene delivery system had potential application for the treatment of glioma.

Keywords: gene therapy, BBB, hTRAIL, PAMAM, C6 glioma
 

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