Core-shell structured Fe3O4@SiO2-NH2 nanoparticles (Fe@Si-NPs) demonstrated outstanding potentials in drug targeting and delivery and medical imaging. However, they have limited clinical applications due to unknown chronic bio-effects and potential bio-related risks. In this study, the subchronic biological effects and metabolic fate of 20 nm Fe@Si-NPs in Sprague-Dawley rats in 12 weeks were investigated by the biochemical assay and NMR-based metabonomic analysis using an intravenous model. Biofluids (plasma and urine) analysis provided the transportation, absorption, and excretion information of Fe@Si-NPs. Urine metabonome displayed a metabolic recovery while self-regulation of plasma metabonome leaded to the parallel metabolic trends between dosed and control groups in 12 weeks. And biological tissues (spleen, liver, kidney, and lung) analysis indicated liver and spleen are the targeted-organs of Fe@Si-NPs. The obvious metabolic variations responding to the biodistribution were induced by Fe@Si-NPs although no visible toxic effects were observed in these tissues. Besides the common energy metabolism response to the xenobiotics, Fe@Si-NPs also disturbed the metabolic pathways in glycerophospholipid and sphingolipid metabolism, metabolisms of purine, pyrimidine, and nicotinate. Our results provide preliminary validation for the potential use of Fe@Si-NPs in clinical medicine and give identifiable ground for the dose selection and bio-nanoagent optimization.
Keywords: Core–shell structure; biomedical nanoparticles; metabonomics; subchronic biological effect.