Abstract
Objective To study the radiosensitization effect of thio-glucose capped gold nanoparticles (Glu-GNPs) on human lung adenocarcinoma A549 cells in vitro. Methods Human lung adenocarcinoma cell line A549 in logarithmic phase was divided into four groups: control group, drug group (Glu-GNPs), irradiation group (irradiation of 6 MV group and irradiation of 160 kV group), Glu-GNPs combined irradiation group (6 MV + Glu-GNPs group, 160 kV + Glu-GNPs group). Transmission electron microscopy (TEM) was used to observe the distribution of Glu-GNPs in cells. Toxicity of Glu-GNPs on A549 cells and the inhibitory effect of Glu-GNPs combined with irradiation on cell proliferation were determined using crystal violet assay. Clonogenic assay were performed to evaluate radiosensitization of Glu-GNPs on A549 cells. Immunofluorescence assay of γ-H2AX, a biomarker of DNA damage that underlies cellular response to irradiation was used to evaluate radiation-induced DNA double-strand break (DSB). Results TEM images showed that Glu-GNPs were mainly distributed in the cytoplasm of A549 cells, including endosomes and mitochondria. Glu-GNPs had little cytotoxicity toward A549 cells with a concentration lower than 100 nmol/L. Different concentrations(0-100 nmol/L)of Glu-GNPs combined with different energy of X-rays had significant inhibitory effects on A549 cells. Under 160 kV and 6 MV X-ray conditions, the Glu-GNPs treatment further decreased the survival fraction of irradiation group(P<0.05), and the sensitizing enhancement ratio (SER) was 1.41 and 1.15, respectively. Moreover, Glu-GNPs significantly increased radiation-induced γ-H2AX foci in A549 cells, and the number of γ-H2AX foci with 160 kV X-ray radiation was higher than that with 6 MV X-ray radiation(t=12.392, 14.893, 18.947, P<0.05). Conclusions Uptake of Glu-GNPs by A549 cells could enhance radiation effects, especially for kilovolt X-ray radiation. Key words: Gold nanoparticles; A549 cells; Radiosensitization effect
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