| Currently,Magnetic resonance imaging(MRI)is one of the most effective non-invasive diagnostic methods for human diseases.Superparamagnetic nanoparticles,which affect the relaxation of human tissues,can be used as MRI contrast agents to improve the contrast of imaging.In recent years,the study on multifunctional biomolecule probes based on the superparamagnetic nanoparticles has attracted much attention of researchers.The new probes can combine the advantages of enhancing MRI signal,magnetocaloric therapy,drug delivery and target recognition,which make them promising in early diagnosis and treatment of tumors.In this thesis,we designed four kinds of composite nanoparticles based on superparamagnetic Fe3O4 nanoparticles(Fe3O4 NPs)by surface modification.The composite nanoparticles were studied as candidates for biological applications including MRI,fluorescence imaging and iron deficiency anemia(IDA)treatment.The main results are as follows:(1)We prepared Fe3O4@angelica sinensis polysaccharide nanoparticles(Fe3O4@ASP NPs)as MRI contrast agents for liver.The Fe3O4@ASP NPs were fabricated by a two steps approach involving hydrothermal synthesis and esterification.The NPs modified with angelica sinensis polysaccharide have good water solubility and stability,high biocompatibility and low biotoxicity,which can be used as MRI contrast agent in vivo.We injected the Fe3O4@ASP NPs into the mice by the tail vein.The composite nanoparticles were concentrated and metabolized in the liver.MRI studies show a negative-enhanced T2*signal in the liver.Both MRI and pathological tests for mice showed no sign of organ damage or inflammation in the organism.The results prove that Fe3O4@ASP NPs are low biotoxicity and high T2*signal contrast agents for liver MRI applications.(2)We synthesized the Fe3O4@astragalus polysaccharide nanoparticles(Fe3O4@APS NPs)for IDA therapy and MRI contrast agents in vivo.Astragalus polysaccharide is a main content extracted from the traditional Chinese herb astragalus,which possess good biocompatibility and the function of promoting the formation of hematopoietic cells.Cytotoxicity assessment in cells,pathological tests and Fe content in mice tissue justify their high biocompatibility and low toxicity.The IDA treatment in rats shows that the Fe3O4@APS NPs have potent therapeutic effect on IDA after 30 days therapy with a dosage of 2.0 mg/kg/d.Moreover,strong MRI contrast enhancement has been observed for the Fe3O4@APS NPs in vivo.Therefore,the Fe3O4@APS NPs are promising candidates for IDA drugs with the additional functionality as MRI contrast agent.(3)We designed and synthesized Fe3O4@chitosan-graphene quantum dots nanoparticles(Fe3O4@CS-GQDs NPs)as MRI/fluorescent dual-mode biomolecular probes.The probes were fabricated by crosslinking between carboxyl groups of GQDs and amine groups of Fe3O4@CS NPs.It was demonstrated that the Fe3O4@CS-GQDs NPs have good fluorescence performance and MRI T2-weighted imaging.The MTT cytotoxicity experiment proves that the composite nanoparticle has low biological toxicity.Therefore,the Fe3O4@CS-GQDs NPs were demonstrated to be a potential MRI/fluorescent dual-mode biomolecular probe with high biocompatibility in vivo.(4)We prepared a pH-sensitive Fe3O4-rhodamine 6G nanomolecular probe.The fluorescence measurements show that the probe has the best fluorescence imaging in cells with pH?4.The fluorescence performance decreases with the pH increases,and the fluorescence intensity in cancer cells is higher than that in normal cells.The Fe3O4-Rhodamine 6G nanomolecular probe also has an excellent MRI T2-weighted imaging property in both cell and in vivo tests.Therefore,the nanomolecular probe is a pH-sensitive dual-mode probe for fluorescence and MRI,which has obvious advantages for the detection and diagnosis of cancer cells. |
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