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.
Highlights
Various types of cancers plague the world today and have a major impact on society because of the associated morbidity and mortality
We showed that the modification of the surface functional groups of PAMAM dendrimers using basic amino acids such as histidine and arginine increased the proton buffer effect, improved the transfection efficiency, and had low cytotoxicity when used as gene delivery carriers [19]
We investigated a gene therapy-based approach using apoptin, a known tumor-selective killer gene, using nonviral gene delivery vectors, namely, PAMAM-O
Summary
Various types of cancers plague the world today and have a major impact on society because of the associated morbidity and mortality. Cancer is characterized by uncontrolled proliferation, metastasis, cellular invasion, and angiogenesis [1,2]. The conventional therapeutic approaches for malignant tumor include surgery, chemotherapy, and radiotherapy These tumor therapies have several drawbacks, such as systemic toxicity, side effects, and drug resistance, and might cause tumor recurrence and metastasis [3,4]. This necessitates the development and improvement of therapeutic strategies to tackle malignant tumors. Gene therapy aims to treat human disorders by Polymers 2017, 9, 197; doi:10.3390/polym9060197 www.mdpi.com/journal/polymers
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