Specific Biological Responses Following Dextran-coated USPIO Administration In Mice

In recent years,ultra-small superparamagnetic particles of iron oxides(USPIO)have been widely applied to clinical medicine especially as MRI contrast agents.However,with their expanded applications in biomedical field,the potential bio-related risks and side effects following administration have attracted special attention from scientists and the public.In this paper,pertinent information regarding metabolic responses and disturbed biochemical pathways of dextran-coated USPIO in BALB/C mice was obtained using 1H-NMR spectroscopy-based metabolomic strategy combined with the traditional biochemical assay in an intravenous model.In the first part of this thesis,principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were performed on the 1H NMR data of body fluids(plasma and urine)and major organs(liver,kidney and spleen)of mice,and significant differential metabolites in each metabolome were identified between the control and USPIO groups.Combined with serum biochemical parameters and histopathological evaluation,metabolomic analysis revealed that the disturbance,impairment and recovery of the physiological functions of these organs were related to the metabolic response to USPIO administration.Furthermore,the specific effects of dextran-coated USPIO on the metabolism and function of two body fluids and three tissues of mice were analyzed.In the second part of this thesis,hierarchical PCA(H-PCA)was performed on the NMR data of plasma,urine,liver,kidney,and spleen metabolomes at 6 h and 48 h post-dose of USPIO to get the corresponding metabolic pathway networks.Disturbed metabolic pathways(including energy,lipid,glucose,and amino acid metabolisms)following USPIO administration as well as the correlations between the biofluids and tissue metabolomes were derived,and the specific metabolic information of USPIO was related to their in vivo transportation,absorption,biodistribution and excretion.Moreover,such a full suite of metabolomic analysis provides preliminary validation of the potential use of USPIO and their derivatives as MRI contrast agents in clinical medicine,and a feasible method and platform was provided for preclinical research on targeted organs and biosafety of similar nanoparticles in the field of clinical imaging.