Abstract：Objective To investigate the radiosensitizing effect of mesoporous silica-encapsulated gold nanorods (GNRs@mSiO2) combined with 6 MV X-ray on human triple-negative breast cancer MDA-MB-231 cells and its possible mechanism. Methods A transmission electron microscope was used to analyze the morphology and intracellular distribution of GNRs@mSiO2. An atomic absorption spectrophotometer was used to evaluate the uptake of GNRs@mSiO2 by cells. The CCK-8 assay was used to measure the cytotoxicity of different concentrations of GNRs@mSiO2. The colony formation assay was used to determine the effect of GNRs@mSiO2 on the radiosensitivity of cells. Flow cytometry was used to measure the cell cycle, apoptosis, and the level of reactive oxygen species. Between-group comparison was made by paired t test. Results The uptake of GNRs@mSiO2 by MDA-MB-231 cells reached a peak value at 24 h, which was (7.09±0.26)-fold higher than that in the control group and significantly higher than those in other groups (P=0.002-0.014). After exposure to 12.5-50.0μg/ml GNRs@mSiO2 for 24 h, more than 90% of the cells remained alive. The D0, Dq, and SF2 values in the GNRs@mSiO2+irradiation group were lower than those in the irradiation alone group, yielding a sensitization enhancement radio of 1.27(radio of SF2 values). The apoptosis rate was (30.4±0.68)% in the GNRs@mSiO2+irradiation group. The proportion of cells in G2/M phase was (31.25±0.75)% in the GNRs@mSiO2+irradiation group, which was significantly higher than those in other groups (P=0.003-0.033). Conclusions Mesoporous silica-encapsulated gold nanorods can effectively enhance the radiosensitivity of human triple-negative breast cancer MDA-MB-231 cells to 6 MV X-ray.
Zhao Ning,Li Bingxin,Shi Zeliang et al. Radiosensitizing effect of mesoporous silica-encapsulated gold nanorods on human triple-negative breast cancer cells[J]. Chinese Journal of Radiation Oncology, 2016, 25(9): 1003-1007.
[1] Cho SH,Jones BL,Krishnan S.The dosimetric feasibility of gold nanoparticle-aided radiation therapy (GNRT) via brachytherapy using low-energy gamma-/x-ray sources[J].Phys Med Biol,2009,54(16):4889-4905.DOI:10.1088/0031-9155/54/16/004. [2] Dizdaroglu M.Chemical determination of free radical-induced damageto DNA[J].Free Radic Biol Med,1991,10(3-4):225-242.DOI:10.1016/0891-5849(91)90080-M. [3] 周淑玲,杨文涛.三阴性乳腺癌的临床病理特征及分子研究进展[J].中国癌症杂志,2013,23(8):603-608.DOI:10.3969/j.issn.1007-3969.2013.08.007. Zhou SL,Yang WT.Advance of clinicopathological and molecular research of triple negative breast cancer[J].China Oncol,2013,23(8):603-608.DOI:10.3969/j.issn.1007-3969.2013.08.007. [4] Prise KM,Schettino G,Folkard M,et al. New insights on cell death from radiation exposure[J].Lancet Oncol,2005,6(7):520-528.DOI:10.1016/S1470-2045(05)70246-1. [5] Wu LJ,Randers-Pehrson G,Xu A,et al. Targeted cytoplasmic irradiation with alpha particles induces mutations in mammalian cells[J].Proc Natl Acad Sci USA,1999,96(9):4959-4964.DOI:10.1073/pnas.96.9.4959. [6] Douglass M,Bezak E,Penfold S.Monte Carlo investigation of the increased radiation deposition due to gold nanoparticles using kilovoltage and megavoltage photons in a 3D randomized cell model[J].Med Phys,2013,40(7):071710.DOI:10.1118/1.4808150. [7] Geng F,Song K,Xing JZ,et al. Thio-glucose bound gold nanoparticles enhance radio-cytotoxic targeting of ovarian cancer[J].Nanotechnology,2011,22(28):285101.DOI:10.1088/0957-4484/22/28/285101. [8] Roa W,Zhang XJ,Guo LH,et al. Gold nanoparticle sensitize radiotherapy of prostate cancer cells by regulation of the cell cycle[J].Nanotechnology,2009,20(37):375101.DOI:10.1088/0957-4484/20/37/375101. [9] Mroz RM,Schins RPF,Li H,et al. Nanoparticle-driven DNA damage mimics irradiation-related carcinogenesis pathways[J].Eur Respir J,2008,31(2):241-251.DOI:10.1183/09031936.00006707. [10] Rahman HS,Rasedee A,Abdul AB,et al. Zerumbone-loaded nanostructured lipid carrier induces G2/M cell cycle arrest and apoptosis via mitochondrial pathway in a human lymphoblastic leukemia cell line[J].Int J Nanomedicine,2014,9(1):527-538.DOI:10.2147/IJN.S54346. [11] Meyn RE,Stephens LC,Ang KK,et al. Heterogeneity in the development of apoptosis in irradiated murine tumours of different histologies[J].Int J Radiat Biol,1993,64(5):583-591.DOI:10.1080/09553009314551801. [12] Asharani PV,Sethu S,Lim HK,et al. Differential regulation of intracellular factors mediating cell cycle,DNA repair and inflammation following exposure to silver nanoparticles in human cells[J].Genome Integr,2012,3(1):2.DOI:10.1186/2041-9414-3-2. [13] Yao JX,Yao ZF,Li ZF,et al. Radio-sensitization by piper longumine of human breast adenoma MDA-MB-231 cells in vitro[J].Asian Pac J Cancer Prev,2014,15(7):3211-3217.DOI:10.7314/APJCP.2014.15.7.3211. [14] Bishayee K,Khuda-Bukhsh AR,Huh SO.PLGA-loaded gold-nanoparticles precipitated with quercetin downregulate HDAC-Akt activities controlling proliferation and activate p53-ROS crosstalk to induce apoptosis in hepatocarcinoma cells[J].Mol Cells,2015,38(6):518-527.DOI:10.14348/molcells.2015.2339. [15] Wolfe T,Chatterjee D,Lee J,et al. Targeted gold nanoparticles enhance sensitization of prostate tumors to megavoltage radiation therapy in vivo[J].Nanomedicine,2015,11(5):1277-1283.DOI:10.1016/j.nano.2014.12.016. [16] Shen S,Tang HY,Zhang XT,et al. Targeting mesoporous silica-encapsulated gold nanorods for chemo-photothermal therapy with near-infrared radiation[J].Biomaterials,2013,34(12):3150-3158.DOI:10.1016/j.biomaterials.2013.01.051.
2016, Vol. 25 
