Zinc ferrate nanoparticles for applications in medicine: synthesis, physicochemical properties, regulation of macrophage functions, and in vivo safety evaluation

Abstract

Zinc ferrate nanoparticles (ZnFe₂O₄ NPs) have attracted enormous interest as potential nanomaterials. The purpose of this study was to examine the in vitro macrophages toxicity, in vivo safety, and immunogenicity. Three kinds of ZnFe₂O₄ NPs with different shapes (round, litchi, and raspberry), nano-sizes, and pores were successfully prepared. In vitro experiments showed that ZnFe₂O₄ NPs caused no cytotoxicity against the RAW 264.7 cells up to administered dose of 200 μg/mL, enhanced proinflammatory cytokine TNF-α, and costimulatory marker CD86 expression in the RAW 264.7 cells. Interestingly, ZnFe₂O₄ NPs reduced ROS expression, which was inconsistent with common metal oxide NPs such as iron oxide (Fe₃O₄) NPs and zinc oxide (ZnO) NPs. ZnFe₂O₄ NPs improved the RAW 264.7 cells phagocytosed more neutral red. There was no obvious difference in body weight, the number of immune cells, organ index, and expression of inflammatory factors in serum of rats administrated intravenously and subcutaneously on day 21 after treatment by ZnFe₂O₄ NPs in comparison with the blank control. These results demonstrated that ZnFe₂O₄ NPs slightly enhanced the function of the RAW 264.7 cells in vitro but caused no obvious toxicity to macrophages as well as rat blood cells, and low immunogenicity in rats, suggesting that ZnFe₂O₄ NPs as a biocompatible nanomaterials achieved potential for bioapplication in the future.

Keywords:

• Zinc ferrate
• nanoparticles
• macrophage
• immunotoxicity
• in vivo

Disclosure statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Author contributions

Y.W. designed and performed all the experiments, analyzed the experimental data, and wrote the manuscript. Y.L., J.L., and X.X. provided valuable suggestions to the work. X.L. contributed to revision of the manuscript.