| Superparamagnetic nanoparticle plays a more and more important role in the diagnosis of the cancer of liver and spleen. Superparamagnetic iron oxide nanoparticles (SPION) have a passive targeting effect on liver and spleen. However, SPION without surface modification often suffered from the aggregation problem in aqueous system, leading to insufficiency of blood circulation time, so it’s unable to load drugs or active targeting ligand. It is very important to modify SPION surface with the aim to enhance its stability, biocompatibility and drug loading efficiency. This is the key to the application of SPION in early diagnosis and treatment via MRI contrast agent.According to molecular design principle, several chitosan derivatives were synthesized in this thesis, such as amphiphilic P(EA-MAA), quaternary ammonium salt of chitosan (HTCC) with positive charges which can form complexes with DNA, PEG chitosan (PC) derivative which can prolong blood circulation time, lactose chitosan (GC) derivative which has liver targeting and PEG-lactose chitosan (PGC) derivative which has the merits of both PC and GC. First of all, based on the requirements of the MRI contrast agent, amphiphilic, low protein adsorption and targeted biological polymers were prepared. The self-aggregation behavior, biocompatibility and the interaction with protein of the biopolymers were investigated. Then, the surface modified nano-Fe304with the prepared chitosan derivatives, the stabilizing mechanism and its biocompatibility were studied in detail. As an example, the P(EA-MAA)/CS modified Fe3O4was used in magnetic resonance imaging to evaluate its imaging effect and its side effects on the liver.The structure of these chitosan derivatives was investigated by Fourier Transform infrared spectroscopy (FTIR), hydrogen nuclear magnetic resonance (H-NMR) and elemental analysis. Surface tension, fluorescence spectroscopy, ultraviolet (UV) and other technologies were used to study the aggregation behavior and aggregation mechanism of P(EA-MAA), PC and GC. Interactions between P(EA-MAA), PC, GC and bovine serum albumin (BSA) was investigated by circular dichroism (CD), UV spectroscopy, fluorescence spectroscopy. and impedance techniques. The results showed that P(EA-MAA) has a strong interaction with protein since P(EA-MAA) adsorbed more BSA than PC and GC, but PC and GC can maintain the conformation of BSA, demonstrating good biocompatibility.DNA loaded by HTCC was studied by means of the zeta potential and agarose gel electrophoresis, the efficiency of DNA loaded by HTCC can be controlled by adjusting the ratio of nitrogen to phosphorus. The low-substituted HTCC surface modified Fe3O4can load DNA effectively, which providing an ideal material for immune disease therapy.Fe3O4nanoparticles were successfully synthesized by chemical co-precipitation method. P(EA-MAA)/CS/Fe3O4, HTCC/Fe3O4, PC/Fe3O4, GC/Fe3O4and PGC/Fe3O4suspended dispersion systems were obtained with surface modified by P(EA-MAA), HTCC, PC, GC and PGC on Fe3O4nanoparticles respectively. The morphology, particle size and its distribution and the mechanism of stability were studied by means of FTIR, TEM, X-ray diffraction (XRD) and Dynamic light scattering (DLS). Results indicated that in P(EA-MAA)/CS/Fe3O4dispersion system, modification was done layer by layer by adjusting pH and the driven force were electrostatic interactions; HTCC was adsorbed to the surface of nano-Fe3O4by electrostatic interactions, PC/Fe3O4, GC/Fe3O4and PGC/Fe3O4were prepared mainly by the tnteraction of electrostatic interaction and coordination mechanism. The biopolymer immobilized on the sureface nano-Fe3O4of can successfully stablize the nano-Fe3O4dispersion mainly due to the steric hindrance and electrostatic repulsion.MRI testing of P(EA-MAA)/CS/Fe3O4, HTCC/Fe3O4and PGC/Fe3O4under different sequences and the contrast of animals before and after injection demonstrated that nano-Fe3O4is a T2-sensitive negative contrast agent. The non-alcoholic fatty liver model was established, as an example, P(EA-MAA)/CS surface modified Fe3O4surving as contrast agent, P(EA-MAA)/CS/Fe3O4successfully detected fatty liver. Iron toxicity test showed that the modified nano-Fe3O4will not cause Iron toxicity to liver and is safe to use. |
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