Intravenously administered iron oxide nanoparticles with different coatings reversibly perturb immune cells in peripheral blood without inducing toxicity in mice

Abstract

Introduction: Iron oxide nanoparticle formulations are widely used in clinical applications and have recently been explored for hyperthermia therapy, cancer imaging and treatment. Here, we report the effects of intravenously injected pegylated or poly acrylic acid decorated iron oxide nanoparticles coated with hydroxyethyl starch (HES) on host immune system and organs. These particles were compared with sucrose coated iron oxide nanoparticle (Venofer®) and the coating compound HES–both FDA approved agents–alongside non-iron oxide polystyrene nanoparticles coated with HES (micromer®). Methods: Toxicity analysis was performed in healthy female normal FVB/NJ mice 60 days after nanoparticle injection, with complete blood analysis conducted at multiple time-points. In a separate cohort, nanoparticle biodistribution 24 h post-intravenous injection was evaluated using a HER2 overexpressing breast cancer mouse model. Results: Toxicity analysis revealed no adverse effects on liver or kidneys with any of the tested formulations after 60 days. Immune cell perturbations were observed at early time points following iron oxide nanoparticle injection but normalized by the study endpoint. Biodistribution analysis demonstrated that the nanoparticle coating dictated their accumulation across various organs, with significant tumor accumulation observed for pegylated iron oxide nanoparticles and Venofer®. Conclusion: Iron oxide nanoparticle formulations exert a transient effect on the host immune system and some exhibit tumor accumulation, suggesting their potential for further development in cancer imaging and treatment.