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

被引:14
作者
Bae, Yoonhee [1 ]
Song, Su Jeong [2 ]
Mun, Ji Young [3 ,4 ]
Ko, Kyung Soo [5 ]
Han, Jin [1 ]
Choi, Joon Sig [2 ]
机构
[1] Inje Univ, Dept Hlth Sci & Technol, Coll Med,Natl Res Lab Mitochondrial Signaling,Dep, Cardiovasc & Metab Dis Ctr,Plus Project Team BK21, Busan 614735, South Korea
[2] Chungnam Natl Univ, Coll Nat Sci, Dept Biochem, Taejon 305764, South Korea
[3] Eulji Univ, Coll Hlth Sci, Dept Biomed Lab Sci, Seongnam 461713, Gyeonggi Do, South Korea
[4] Eulji Univ, Grad Sch, Dept Senior Healthcare, Program BK21Plus, Taejon 305764, South Korea
[5] Inje Univ, Dept Internal Med, Sanggye Paik Hosp, Cardiovasc & Metab Dis Ctr, Seoul 139707, South Korea
基金
新加坡国家研究基金会;
关键词
apoptin; nonviral gene delivery; apoptosis; polyamidoamine dendrimer; gene therapy; PLASMID DNA; THERAPY; NANOPARTICLES; POLYCATION; TOXICITY; VECTOR;
D O I
10.3390/polym9060197
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
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.
引用
收藏
页数:18
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