| Malignant tumours are a highly life-threatening disease. Recently, many molecular imaging technologies have been applied to clinical detection of tumors, such as magnetic resonance imaging (MRI), positron emission tomography (PET), optical imaging, etc. But there are pros and cons for a mono-modal imaging technology in tumor diagnosis. Therefore, multi-modal molecular imaging techniques have being obtained much attention, which can simultaneously get tumor images with improved accuracy and sensitivity by several kinds of different techniques.Fe3O4 nanoparticles have used as contrast agents for MRI due to their advantages such as good biocompatibility and low toxicity. Carboxymethyl chitosan (CMCTS) is a hydrophilic and biocompatible polymer owning animo groups and carboxylic groups. Both of them are facile to be coupled with functional molecules. Polyethylene glycol (PEG) as a coating material of nanoparticles can suppress the nonspecific adsorption of protein and prolong the blood circulation of nanodrugs. In the dissertation, Fe3O4/CMCTS nanocomposites were synthesized, modified with PEG derivatives, and coupled by arginine-glycine-aspartic peptides (RGD), fluorescein (FLS) or 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The obtained products were then characterized and assessed whether they are applicable to be MRI/optical or MRI/PET dual-modal contrast agents (precursor) in tumor imaging. The concrete research contents were as follows:Firstly, Fe3O4/CMCTS nanocomposites was prepared by a reduction & co-precipitation method. The results show that Fe3O4/CMCTS with mean hydrodynamic diameter (HD) of 70.77 nm behaves quasi-superparamagnetic and the saturation magnetization (Ms) is 35.7 emu/g and the transverse relaxation rate (r2) is about 173.1 mmol-L-1·s-1. MTT test shows that the sample is relatively low toxic to MCF-7 cells. Furthermore, the feasibility of coupling RGD and FLS to the surface of Fe3O4/CMCTS was confirmed. Therefore, Fe3O4/CMCTS has been demonstrated as a good substrate to build a negative contrast agent for MRI imaging.Secondly, two kinds of PEG derivatives were used to modify Fe3O4/CMCTS to improve the colloidal stability of the magnetic nanocomposites. PEG-modified nanocomposites (Fe3O4/CMCTS-g-pmPEGMA) were prepared by photochemical grafting of methoxy polyethylene glycol methacrylate onto Fe3O4/CMCTS due to their enhanced properties. And effects of irradiation time, acetone concentration and monomer concentration on HD and zeta potential of Fe3O4/CMCTS-g-pmPEGMA were also investigated. In addition, RGD was coupled directly and indirectly via streptavidin-biotin system to the PEGylated nanocomposites, respectively, followed by the coupling of FLS. The results show that both the two products showed low cytotoxicity, but the product obtained from the direct coupling method has the smaller HD, the higher loading amount of RGD and stronger fluorescence intensity than another.Finally, both RGD and NOTA was immobilized onto Fe3O4/CMCTS-g-pmPEGMA using the direct and indirect methods mentioned above. The two products also have low cytotoxicity. But the product from the indirect method is smaller in size yet has a stronger capacity to combine of Al ions, although the concentration of the combined F ions is too low to be detected. To enhance the concentration of Al and F ions anchored on the products may makes them promising to be a precursor of PET/MRI dual-modal contrast agent to target integrin avβ3 expressed on tumor cells. |
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