title: Biocompatibility of magnetic Fe₃O₄ nanoparticles and their cytotoxic effect on MCF-7 cells.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The Fe₃O₄ nanoparticles prepared in this study have good biocompatibility and are suitable for further application in tumor hyperthermia.
authors.affiliation: Central Laboratory, Wuxi Hospital for Matemaland Child Health Care Affiliated Medical School of Nanjing, Jiangsu Province, China.
authors.forename: Daozhen
authors.initials: D
authors.lastname: Chen
authors.forename: Qiusha
authors.initials: Q
authors.lastname: Tang
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Li
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhou
authors.forename: Jia
authors.initials: J
authors.lastname: Zang
authors.forename: Wen-qun
authors.initials: WQ
authors.lastname: Xue
authors.forename: Jing-ying
authors.initials: JY
authors.lastname: Xiang
authors.forename: Cai-qin
authors.initials: CQ
authors.lastname: Guo
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007928:Lethal Dose 50; D061986:MCF-7 Cells; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D016019:Survival Analysis; D015996:Survival Rate
chemical_list: D001672:Biocompatible Materials; D058185:Magnetite Nanoparticles