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Recently, we developed iron oxide (Fe<jats:sub>3<\/jats:sub>O<jats:sub>4<\/jats:sub>)\u2013zinc oxide (ZnO) core\u2010shell nanoparticles (CSNPs) as carriers for antigen delivery into dendritic cells (DCs), and the CSNPs were injected subcutaneously into C57BL\/6 mice to examine the systemic toxicity, tissue distribution and excretion of the CSNPs. The doses injected were 0, 4, 20 and 200\u2009mg\u2009kg<jats:sup>\u20131<\/jats:sup> weekly for 4\u2009weeks. No significant changes were observed after the CSNPs administration with respect to mortality, clinical observations, body weight, food intake, water consumption, urinalysis, haematology, serum biochemistry,and organ weights. A dose\u2010dependent increase in granulomatous inflammation was observed at the injection site of the CSNP\u2010treated animals, but no other histopathological lesions in other organs could be attributed to the CSNPs. The Zn concentration, which is an indicator for CSNPs, was not significantly higher in the sampled tissues, urine, or faeces after the CSNP injection. In contrast, the Zn concentration at the subcutaneous skin of the site injected with the CSNPs increased in a dose\u2010dependent manner, along with a macroscopic deposition of the CSNPs. The CSNP residue at the injection site resulted in a foreign body response with the appearance of macrophage infiltration, but otherwise did not show any systemic distribution or toxicity at up to 200\u2009mg\u2009kg<jats:sup>\u20131<\/jats:sup> during this study. In conclusion, CSNPs could be used as good antigen carriers for DC\u2010based immunotherapy, although further study is needed to completely clear the residue of the CSNPs at the injection site. 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