Biocompatibility of Fe3O4@Au composite magnetic nanoparticles in vitro and in vivo

Purpose: This research was conducted to assess the biocompatibility of the core-shell Fe3O4@ Au composite magnetic nanoparticles (MNPs), which have potential application in tumor hyperthermia. Methods: Fe3O4@Au composite MNPs with core-shell structure were synthesized by reduction of Au3+ in the presence of Fe3O4-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 Fe3O4@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 Fe3O4@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. Conclusion: The results indicate that Fe3O4@Au composite MNPs appear to be highly biocompatible and safe nanoparticles that are suitable for further application in tumor hyperthermia.