International Journal of Nanomedicine (Oct 2018)
Biosafety evaluation of Janus Fe3O4-TiO2 nanoparticles in Sprague Dawley rats after intravenous injection
Abstract
Hong Su,1 Xin Song,1 Juan Li,2 Muhammad Zubair Iqbal,2 Samuel Selorm Fiati Kenston,1 Zhen Li,1 Aiguo Wu,2 Min Ding,3 Jinshun Zhao1 1Department of Preventative Medicine, Zhejiang Key Laboratory of Pathophysiology, Medicine School of Ningbo University, Ningbo, Zhejiang, 315211, People’s Republic of China; 2Key Laboratory of Magnetic Materials and Devices, Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Division of Functional Materials and Nanodevices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang, 315201, People’s Republic of China; 3Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA Introduction: Newly synthesized Janus-structured Fe3O4-TiO2 nanoparticles (NPs) appear to be a promising candidate for the diagnosis and therapy of cancer. Although the toxicity of individual Fe3O4 or TiO2 NPs has been studied extensively, the toxicity of Janus Fe3O4-TiO2 NPs is not clear. Methods: In this study, the biosafety of both Janus Fe3O4-TiO2 NPs (20–25 nm) and the maternal material TiO2 NPs (7–10 nm) were evaluated in Sprague Dawley rats after one intravenous injection into the tail vein. Healthy rats were randomly divided into one control group and six experimental groups. Thirty days after treatment, rats were killed, then blood and tissue samples were collected for hematological, biochemical, element-content, histopathological, and Western blot analysis. Results: The results show that only a slight Ti element accumulation in the heart, spleen, and liver could be found in the Janus Fe3O4-TiO2 NP groups (P>0.05 compared with control). However, significant Ti element accumulation in the spleen, lungs, and liver was found in the TiO2 NP-treated rats. Both Fe3O4-TiO2 NPs and TiO2 NPs could induce certain histopathological abnormalities. Western blot analysis showed that both NPs could induce certain apoptotic or inflammatory-related molecular protein upregulation in rat livers. A certain degree of alterations in liver function and electrolyte and lipid parameters was also observed in rats treated with both materials. However, compared to Janus structure Fe3O4-TiO2 NP-treated groups, TiO2 NPs at 30 mg/kg showed more severe adverse effects. Conclusion: Our results showed that under a low dose (5 mg/kg), both NP types had no significant toxicity in rats. Janus NPs certainly seem less toxic than TiO2 NPs in rats at 30 mg/kg. To ensure safe use of these newly developed Janus NPs in cancer diagnosis and therapy, further animal studies are needed to evaluate long-term bioeffects. Keywords: Fe3O4-TiO2 NPs, Janus structure NPs, TiO2 NPs, accumulation, inductively coupled plasma mass spectrometry, ICP-MS, biodistribution, nanomedicine
