title: Gene delivery to carcinoma cells via novel non-viral vectors: nanoparticle tracking analysis and suicide gene therapy.
abstract: Suicide gene therapy of oral squamous cell carcinoma (OSCC) may be a viable approach to the treatment of this cancer. However, human OSCC cells are relatively resistant to efficient transfection by non-viral vectors. To identify an optimal vector for gene delivery, we compared the transfection activities and efficiencies of Glycofect, Metafectene, Metafectene Pro, Metafectene Easy and FuGENE HD, using the OSCC cell line, HSC-3, and the cervical carcinoma cell line, HeLa. The size distribution and ζ-potential of the complexes of these vectors with plasmid DNA were assessed by nanoparticle tracking analysis and electrophoretic mobility measurements, respectively. Metafectene Easy and FuGENE HD mediated the highest transfection activity (measured as luciferase expression) and efficiency (measured as the percentage of cells transfected with ß-galactosidase). These vectors were used to deliver a plasmid encoding herpes simplex virus thymidine kinase, followed by ganciclovir treatment. By day 9, HeLa cell viability was 22±3% of controls with FuGENE HD and 26±3% with Metafectene Easy. The viability of HSC-3 cells was 42±25% with FuGENE HD, and 58±28% with Metafectene Easy. The reduction in viability was statistically significant in both cases (p⩽0.005; average of 3 independent experiments), although there was considerable variability between experiments with the HSC-3 cells.
authors.affiliation: Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA 94115, USA.
authors.forename: Senait
authors.initials: S
authors.lastname: Gebremedhin
authors.affiliation: Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA 94115, USA.
authors.forename: Aruna
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA 94115, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Koons
authors.affiliation: Particle Characterization Laboratories, Novato, CA 94945, USA.
authors.forename: William
authors.initials: W
authors.lastname: Bernt
authors.affiliation: Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA 94115, USA.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Konopka
authors.affiliation: Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA 94115, USA. Electronic address: nduzgune@pacific.edu.
authors.forename: Nejat
authors.initials: N
authors.lastname: Duzgunes
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D015774:Ganciclovir / Q000494:pharmacology*; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008156:Luciferases / Q000235:genetics; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010957:Plasmids; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D014162:Transfection / Q000379:methods*; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D004247:DNA; D008156:Luciferases; D013937:Thymidine Kinase; D001616:beta-Galactosidase; D015774:Ganciclovir
keywords: Cancer gene therapy; Cervical cancer; FuGENE HD; Metafectene Easy; Nanoparticle tracking analysis; Oral cancer