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

Abstract

Yuntao Li1,2, Jing Liu1, Yuejiao Zhong3, Jia Zhang1, Ziyu Wang1, Li Wang1, Yanli An1, Mei Lin1, Zhiqiang Gao2, Dongsheng Zhang11School of Medicine, Southeast University, Nanjing, Jiangsu Province, People's Republic of China; 2Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China; 3Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, Jiangsu Province, People's Republic of ChinaPurpose: 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. Keywords: toxicity, hyperthermia, core-shell