Biosafety evaluation of Janus Fe3O4-TiO2 nanoparticles in Sprague Dawley rats after intravenous injection

Abstract

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; ICP-MS; Janus structure NPs; TiO2 NPs; accumulation; biodistribution; inductively coupled plasma mass spectrometry; nanomedicine.