Metabolic Fate And Subchronic Biological Effects Of Core-shell Structured Fe₃O₄@SiO₂-NH₂ Nanoparticles

As nanomaterials are increasingly entering daily life,they also increase the exposure to the human body,therefore,the potential dangers from such exposure cannot be ignored.Amino-modified core-shell structured Fe3O4@SiO2-NH2 nanoparticles(Fe@Si-NPs),which combine the advantages of magnetic cores and amino functional shells,have shown outstanding potential in drug targeting and medical imaging.However,their unknown potential biological risk limits the popularization and clinical application.Therefore,it is imperative to explore their acute and long-term biological effects.In this thesis,Fe@Si-NH2 nanoparticles with a diameter of about 20 nm were synthesized and characterized.By combining traditional blood biochemical analysis and NMR-based metabonomic analysis,the subchronic biological effects and metabolic fate of Fe@Si-NPs within 12 weeks were investigated by an intravenous rat model.The body fluids(blood and urine)and tissues(liver,kidney,spleen and lung)of the animals were analyzed by NMR,which provided the transportation,absorption and excretion information of Fe@Si-NPs.The results show that Fe@Si-NPs demonstrated strong dose-and time-dependent biological effects.Biofluids(plasma and urine)analysis provided the transportation,absorption and excretion information of Fe@Si-NPs,while tissues(liver,kidney,spleen and lung)analysis provided the biodistribution and bioeffect information.Self-regulation of plasma metabonome leaded to the parallel metabolic trends between dosed and control groups in 12 weeks post-dose,indicating that blood,as a metabolic hub in the body,has strong anti-immune ability.Urinary metabonome displayed a metabolic recovery,in which the fourth week post-dose is the key point of metabolic recovery.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.