Biosafety evaluation of Janus [Fe.sub.3][O.sub.4]-Ti[O.sub.2] nanoparticles in Sprague Dawley rats after intravenous injection

Introduction: Newly synthesized Janus-structured [Fe.sub.3][O.sub.4]-Ti[O.sub.2] nanoparticles (NPs) appear to be a promising candidate for the diagnosis and therapy of cancer. Although the toxicity of individual [Fe.sub.3][O.sub.4] or Ti[O.sub.2] NPs has been studied extensively, the toxicity of Janus [Fe.sub.3][O.sub.4]-Ti[O.sub.2] NPs is not clear. Methods: In this study, the biosafety of both Janus [Fe.sub.3][O.sub.4]-Ti[O.sub.2] NPs (20-25 nm) and the maternal material Ti[O.sub.2] 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 [Fe.sub.3][O.sub.4]-Ti[O.sub.2] NP groups (P>0.05 compared with control). However, significant Ti element accumulation in the spleen, lungs, and liver was found in the Ti[O.sub.2] NP-treated rats. Both [Fe.sub.3][O.sub.4]-Ti[O.sub.2] NPs and Ti[O.sub.2] 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 [Fe.sub.3][O.sub.4]-Ti[O.sub.2] NP-treated groups, Ti[O.sub.2] 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 Ti[O.sub.2] 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: [Fe.sub.3][O.sub.4]-Ti[O.sub.2] NPs, Janus structure NPs, Ti[O.sub.2] NPs, accumulation, inductively coupled plasma mass spectrometry, ICP-MS, biodistribution, nanomedicine