Abstract
High atomic number molecules, such as gold and platinum, are known to be able to enhance the biological effect of X-irradiation. It is generally thought to be due to the increase of DNA damage mainly by Photoelectric and Compton effects when cells are irradiated in the kilo-voltage range. Herold et al. (INT. J. RADIAT. Biol.,76:1357, 2000) demonstrated radiosensitization by the gold particles (3 μm diameter) in mouse tumor EMT-6 cells. However, for application of in vivo tumor cells, there are some problems such as their toxicity for normal tissues and delivery of the gold particle to tumor cells. To solve these issues, we newly synthesized gold-nanogel (GNG) consisting of polyamine, polyethylene glycol, and gold-nanoparticles (6 nm diameter). The diameter of this GNG was determined as 148 nm by transmission electron microscopy (TEM). In this study, we investigated whether GNG enhances the cell death induced by X-irradiation and studied the mechanism of the radiosensitization. Mouse squamous carcinoma SCCVII cells, human lung adenocarcinoma A549 cells, and Chinese hamster V79 cells were incubated without or with various concentration of GNG for 14 h. After X-irradiation at 200 kV, the cytotoxicity and the reproductive cell death were evaluated by colony formation assay. In all cell lines, GNG treatment increased the reproductive cell death after irradiation without a marked cytotoxicity. PI staining also revealed that GNG enhanced apoptosis in SCCVII cells induced by irradiation. Futhermore, results obtained by immunofluorescence analysis, western blotting and pulsed-field gel electrophoresis indicated that GNG decreased DNA double-strand break in cells irradiated. In addition, TEM images revealed that GNGs were distributed in cytoplasm after uptake by endocytosis. These results suggested that GNG induced radiosensitization not by enhancing the damage of nuclear DNA but by targeting other organellars.
