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Polymers 2017, 9(6), 197; doi:10.3390/polym9060197

Apoptin Gene Delivery by the Functionalized Polyamidoamine (PAMAM) Dendrimer Modified with Ornithine Induces Cell Death of HepG2 Cells

1
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 plus Project Team, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea
2
Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305-764, Korea
3
Department of Biomedical Laboratory Science, College of Health Science, Eulji University, Seongnam, Gyeonggi-Do 461-713, Korea
4
BK21Plus Program, Department of Senior Healthcare, Graduate School, Eulji University, Daejeon 305-764, Korea
5
Department of Internal Medicine, Sanggye Paik Hospital, Cardiovascular and Metabolic Disease Center, Inje University, Seoul 139-707, Korea
*
Authors to whom correspondence should be addressed.
Academic Editor: Ravin Narain
Received: 10 March 2017 / Revised: 23 May 2017 / Accepted: 24 May 2017 / Published: 29 May 2017
(This article belongs to the Special Issue Polymers and Nanogels for Gene Therapy)
View Full-Text   |   Download PDF [5585 KB, uploaded 31 May 2017]   |  

Abstract

The use of tumor-specific therapeutic agents is a promising option for efficient and safe nonviral gene transfer in gene therapy. In this study, we describe the efficacy of polyamidoamine (PAMAM)-based nonviral gene delivery carriers, namely, an ornithine conjugated PAMAM (PAMAM-O) dendrimer in delivering apoptin, a tumor-specific killer gene, into human hepatocellular carcinoma (HepG2 cells) and dermal fibroblasts. We analyzed the transfection efficiency by the luciferase assay and assessed cell viability in both cell types. The transfection efficiency of the PAMAM-O dendrimer was found to be higher than that of the PAMAM dendrimer. Moreover, the cytotoxicity of the PAMAM-O dendrimer was very low. We treated both cell types with a polyplex of PAMAM-O dendrimer with apoptin, and analyzed its cellular uptake and localization by confocal microscopy. Cell cycle distribution, tetramethylrhodamine, ethyl ester (TMRE) analysis, and transmission electron microscopy imaging showed that apoptin induced cell death in HepG2 cells. We therefore demonstrated that a PAMAM-O/apoptin polyplex can be used as an effective therapeutic strategy in cancer owing to its effectiveness as a suitable nonviral gene vector for gene therapy. View Full-Text
Keywords: apoptin; nonviral gene delivery; apoptosis; polyamidoamine dendrimer; gene therapy apoptin; nonviral gene delivery; apoptosis; polyamidoamine dendrimer; gene therapy
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Bae, Y.; Song, S.J.; Mun, J.Y.; Ko, K.S.; Han, J.; Choi, J.S. Apoptin Gene Delivery by the Functionalized Polyamidoamine (PAMAM) Dendrimer Modified with Ornithine Induces Cell Death of HepG2 Cells. Polymers 2017, 9, 197.

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