Biocompatibility of magnetic Fe 3 O 4 nanoparticles and their cytotoxic effect on MCF-7 cells
Biocompatibility of magnetic Fe 3 O 4 nanoparticles and their cytotoxic effect on MCF-7 cells
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发表时间：
2012
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通讯作者：
Daozhen Chen;Q. Tang;Xiangdong Li;Xiaojin Zhou;Jia Zang;W. Xue;J. Xiang;Cai-qin Guo
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作者：
Daozhen Chen;Q. Tang;Xiangdong Li;Xiaojin Zhou;Jia Zang;W. Xue;J. Xiang;Cai-qin Guo
背景资料：本研究的目的是评价Fe 3 O 4纳米粒子的合成和生物相容性，并研究其与磁流体热疗联合应用对培养的MCF-7癌细胞的治疗作用。方法：采用共沉淀法制备磁性Fe 3 O 4纳米粒子.的外观，结构，相组成，官能团，表面电荷，磁化率，并在体外释放，其特征在于通过透射电子显微镜，X-射线衍射，扫描电子显微镜-能量色散X-射线光谱，和振动样品磁强计。研究了血液毒性、体外毒性和遗传毒性。采用MTT比色法和流式细胞术检测治疗效果。结果如下：透射电子显微镜观察表明，Fe 3 O 4纳米粒子呈近似球形，直径约为26.1 ± 5.2nm。在X射线衍射数据与粉末分级标准联合公司（JCPDS）X射线粉末衍射文件的比较中仅指示尖晶石相。通过扫描电子显微镜-能量色散X射线光谱元素分析确定了Fe 3 O 4的O-Fe比，接近纯Fe 3 O 4。振动样品磁强计的磁滞回线表明，Fe 3 O 4纳米粒子在室温下是超顺磁性的。MTT实验表明，该材料对小鼠成纤维细胞（L-929）细胞系的毒性为0 ~ 1级，无溶血活性。急性毒性LD 50为8.39g/kg。微核试验显示无遗传毒性效应。病理形态学和血液生化学检测表明，Fe 3 O 4纳米粒子对家兔模型的主要脏器和血液生化指标无影响。MTT和流式细胞仪检测结果显示，Fe 3 O 4纳米磁流体热疗对MCF-7细胞增殖有抑制作用，且抑制作用与Fe 3 O 4纳米磁流体浓度呈剂量依赖关系。结论：本研究制备的Fe 3 O 4纳米颗粒具有良好的生物相容性，适合进一步应用于肿瘤热疗。
Background: The objective of this study was to evaluate the synthesis and biocompatibility of Fe 3 O 4 nanoparticles and investigate their therapeutic effects when combined with magnetic fluid hyperthermia on cultured MCF-7 cancer cells. Methods: Magnetic Fe 3 O 4 nanoparticles were prepared using a coprecipitation method. The appearance, structure, phase composition, functional groups, surface charge, magnetic susceptibility, and release in vitro were characterized by transmission electron microscopy, x-ray diffraction, scanning electron microscopy-energy dispersive x-ray spectroscopy, and a vibrating sample magnetometer. Blood toxicity, in vitro toxicity, and genotoxicity were investigated. Therapeutic effects were evaluated by MTT [3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide] and flow cytometry assays. Results: Transmission electron microscopy revealed that the shapes of the Fe 3 O 4 nanoparticles were approximately spherical, with diameters of about 26.1 ± 5.2 nm. Only the spinel phase was indicated in a comparison of the x-ray diffraction data with Joint Corporation of Powder Dif-fraction Standards (JCPDS) X-ray powder diffraction files. The O-to-Fe ratio of the Fe 3 O 4 was determined by scanning electron microscopy-energy dispersive x-ray spectroscopy elemental analysis, and approximated pure Fe 3 O 4 . The vibrating sample magnetometer hysteresis loop suggested that the Fe 3 O 4 nanoparticles were superparamagnetic at room temperature. MTT experiments showed that the toxicity of the material in mouse fibroblast (L-929) cell lines was between Grade 0 to Grade 1, and that the material lacked hemolysis activity. The acute toxicity (LD 50 ) was 8.39 g/kg. Micronucleus testing showed no genotoxic effects. Pathomorphology and blood biochemistry testing demonstrated that the Fe 3 O 4 nanoparticles had no effect on the main organs and blood biochemistry in a rabbit model. MTT and flow cytometry assays revealed that Fe 3 O 4 nano magnetofluid thermotherapy inhibited MCF-7 cell proliferation, and its inhibitory effect was dose-dependent according to the Fe 3 O 4 nano magnetofluid concentration. Conclusion: The Fe 3 O 4 nanoparticles prepared in this study have good biocompatibility and are suitable for further application in tumor hyperthermia.