Background:Gold nanoparticles (GNPs) have been conceived to cause increased cytotoxicity of radiotherapy in human malignant cells. Greater uptake of GNPs by cells may induce increased radiation effects. Here we report the radiosensitization effect of glucose-capped GNPs (Glu-GNPs) with different sizes (16 nm and 49 nm) on MDA-MB-231 cells in the presence of megavoltage X-rays.
Methods:Transmission electron microscopy (TEM) was used to observe the distribution of Glu-GNPs in cells. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used to measure the quantities of Glu-GNPs absorbed by cells. After treatment of Glu-GNPs with a series of concentrations, we used the MTT and clonogenic assays to confirm the radiation enhancement effect of Glu-GNPs on MDA-MB-231 cells. The cell cycle distribution was analyzed by flow cytometry to further explore the mechanisms of enhanced radiosensitivity of Glu-GNPs.
Results:TEM showed that Glu-GNPs are mainly distributed in the cytoplasm of cells, including endosomes and lysosomes. ICP-AES indicates that MDA-MB-231 cells absorb more 49-nm Glu-GNPs than 16-nm Glu-GNPs in number (P < 0.05). Glu-GNPs have little cytotoxicity toward MDA-MB-231 cells with a concentration below 20 nM. In the clonogenic assay, the combination of Glu-GNPs with radiation induced a significant growth inhibition, compared with radiation alone (P < 0.05). Moreover 49-nm Glu-GNPs induced much greater radiation effects than 16-nm Glu-GNPs (P < 0.05). Flow cytometry shows that Glu-GNPs can help radiation arrest more cells in the G2/M phase, with greater effect with 49-nm Glu-GNPs than 16-nm Glu-GNPs.
Conclusions:Glu-GNPs can increase the cytotoxicity of radiation toward MDA-MB-231 cells, probably by regulating the distribution of the cell cycle, with more cells in the G2/M phase. The effect of radiation enhancement may be related to the quantities of Glu-GNPs in the cells.
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