title: Biocompatibility of Fe₃O₄@Au composite magnetic nanoparticles in vitro and in vivo.
abstract: OBJECTIVE
  This research was conducted to assess the biocompatibility of the core-shell Fe(3)O(4)@ Au composite magnetic nanoparticles (MNPs), which have potential application in tumor hyperthermia.
  
  
  METHODS
  Fe(3)O(4)@Au composite MNPs with core-shell structure were synthesized by reduction of Au(3+) in the presence of Fe(3)O(4)-MNPs prepared by improved co-precipitation. Cytotoxicity assay, hemolysis test, micronucleus (MN) assay, and detection of acute toxicity in mice and beagle dogs were then carried out.
  
  
  RESULTS
  The result of cytotoxicity assay showed that the toxicity grade of this material on mouse fibroblast cell line (L-929) was classified as grade 1, which belongs to no cytotoxicity. Hemolysis rates showed 0.278%, 0.232%, and 0.197%, far less than 5%, after treatment with different concentrations of Fe(3)O(4)@Au composite MNPs. In the MN assay, there was no significant difference in MN formation rates between the experimental groups and negative control (P > 0.05), but there was a significant difference between the experimental groups and the positive control (P < 0.05). The median lethal dose of the Fe(3)O(4)@Au composite MNPs after intraperitoneal administration in mice was 8.39 g/kg, and the 95% confidence interval was 6.58-10.72 g/kg, suggesting that these nanoparticles have a wide safety margin. Acute toxicity testing in beagle dogs also showed no significant difference in body weight between the treatment groups at 1, 2, 3, and 4 weeks after liver injection and no behavioral changes. Furthermore, blood parameters, autopsy, and histopathological studies in the experimental group showed no significant difference compared with the control group.
  
  
  CONCLUSIONS
  The results indicate that Fe(3)O(4)@Au composite MNPs appear to be highly biocompatible and safe nanoparticles that are suitable for further application in tumor hyperthermia.
authors: School of Medicine, Southeast University, Nanjing, Jiangsu Province, People's Republic of China.
authors: Yuntao
authors: Y
authors: Li
authors: Jing
authors: J
authors: Liu
authors: Yuejiao
authors: Y
authors: Zhong
authors: Jia
authors: J
authors: Zhang
authors: Ziyu
authors: Z
authors: Wang
authors: Li
authors: L
authors: Wang
authors: Yanli
authors: Y
authors: An
authors: Mei
authors: M
authors: Lin
authors: Zhiqiang
authors: Z
authors: Gao
authors: Dongsheng
authors: D
authors: Zhang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D004285:Dogs; D005260:Female; D006046:Gold / Q000008:administration & dosage / Q000633:toxicity*; D006461:Hemolysis; D006651:Histocytochemistry; D006979:Hyperthermia, Induced / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects; D007677:Kidney Function Tests; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects; D008111:Liver Function Tests; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008422:Materials Testing; D051379:Mice; D015162:Micronucleus Tests; D023382:Toxicity Tests, Acute
chemical_list: D001672:Biocompatible Materials; D058185:Magnetite Nanoparticles; D006046:Gold