Biocompatibility of magnetic Fe₃O₄ nanoparticles and their cytotoxic effect on MCF-7 cells

• Published in: International journal of nanomedicine 2012-01, Vol.7 (default), p.4973-4982
• Main Authors: Chen, Daozhen, Tang, Qiusha, Li, Xiangdong, Zhou, Xiaojin, Zang, Jia, Xue, Wen-qun, Xiang, Jing-ying, Guo, Cai-qin
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biocompatibility; Biocompatible Materials - toxicity; Cell Survival - drug effects; characterization; Dose-Response Relationship, Drug; Fe3O4; Flow cytometry; Humans; Hyperthermia; Lethal Dose 50; magnetic nanoparticles; Magnetite Nanoparticles - chemistry; Magnetite Nanoparticles - toxicity; MCF-7 Cells; Mice; Nanoparticles; Original Research; Scanning electron microscopy; Spectrum analysis; Survival Analysis; Survival Rate; Transmission electron microscopy
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S35140

The objective of this study was to evaluate the synthesis and biocompatibility of Fe₃O₄ nanoparticles and investigate their therapeutic effects when combined with magnetic fluid hyperthermia on cultured MCF-7 cancer cells. Magnetic Fe₃O₄ 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. Transmission electron microscopy revealed that the shapes of the Fe₃O₄ 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 Diffraction Standards (JCPDS) X-ray powder diffraction files. The O-to-Fe ratio of the Fe₃O₄was determined by scanning electron microscopy-energy dispersive x-ray spectroscopy elemental analysis, and approximated pure Fe₃O₄. The vibrating sample magnetometer hysteresis loop suggested that the Fe₃O₄nanoparticles 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 Fe₃O₄ nanoparticles had no effect on the main organs and blood biochemistry in a rabbit model. MTT and flow cytometry assays revealed that Fe₃O₄ nano magnetofluid thermotherapy inhibited MCF-7 cell proliferation, and its inhibitory effect was dose-dependent according to the Fe₃O₄ nano magnetofluid concentration. The Fe₃O₄ nanoparticles prepared in this study have good biocompatibility and are suitable for further application in tumor hyperthermia.