Zinc ferrate nanoparticles for applications in medicine: synthesis, physicochemical properties, regulation of macrophage functions, andin vivosafety evaluation

Zinc ferrate nanoparticles (ZnFe(2)O(4)NPs) have attracted enormous interest as potential nanomaterials. The purpose of this study was to examine thein vitromacrophages toxicity,in vivosafety, and immunogenicity. Three kinds of ZnFe(2)O(4)NPs with different shapes (round, litchi, and raspberry), nano-sizes, and pores were successfully prepared.In vitroexperiments showed that ZnFe(2)O(4)NPs caused no cytotoxicity against the RAW 264.7 cells up to administered dose of 200 mu g/mL, enhanced proinflammatory cytokine TNF-alpha, and costimulatory marker CD86 expression in the RAW 264.7 cells. Interestingly, ZnFe(2)O(4)NPs reduced ROS expression, which was inconsistent with common metal oxide NPs such as iron oxide (Fe3O4) NPs and zinc oxide (ZnO) NPs. ZnFe(2)O(4)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 ZnFe(2)O(4)NPs in comparison with the blank control. These results demonstrated that ZnFe(2)O(4)NPs slightly enhanced the function of the RAW 264.7 cellsin vitrobut caused no obvious toxicity to macrophages as well as rat blood cells, and low immunogenicity in rats, suggesting that ZnFe(2)O(4)NPs as a biocompatible nanomaterials achieved potential for bioapplication in the future.