Preparation And Properties Of Multifunctional Magnetic Iron Oxide Nanoparticles By Layer-by-Layer Self-Assembly

In recent years,with the intersection of nanotechnology and biotechnology,some new diagnosis and treatment methods for diseases based on nanomaterials have emerged.Among them,magnetic iron oxide nanoparticles have attracted much attention in the biomedical field because of their superparamagnetic properties,low toxicity and easy surface modification.Magnetic iron oxide nanoparticles can be used not only as drug or gene delivery carriers,but also as contrast agents for cancer diagnosis,which makes it promising as a multifunctional platform combining multiple treatment methods guided by imaging diagnosis to achieve efficient treatment of major diseases.The preparation of multifunctional magnetic iron oxide nanoparticles,magnetic resonance imaging properties and preliminary applications in tumor therapy are investigated in this paper,mainly as follows:The well-dispersed Fe₃O₄ nanoparticles（MNPs）prepared by polyol method were used as a template to prepare multifunctional Fe₃O₄ nanoparticles alternately coated with polyethyleneimine（PEI）and fucoidan（Fuc）by layer-by-layer self-assembly method.It was shown that surface pretreatment of MNPs with sodium tripolyphosphate to make MNPs strongly negatively charged in aqueous solution and maintain a good monodisperse state is the key to obtain a good subsequent coating effect.PEI with a molecular weight of 10,000 is better than PEI with a molecular weight of 1,800 in terms of coating effect.The optimal p H for PEI coating is 7 and for Fuc coating is 5.The optimal polyelectrolyte solution concentration was 1.0 mg/m L for PEI and 0.5 mg/m L for Fuc.The adjustment of the thickness of the polyelectrolyte coating layer on the surface of MNPs can be achieved by adjusting the ionic strength in the solution.TEM,DLS,XPS,TGA and zeta potential measurements were used to demonstrate that the polyelectrolyte was successfully coated on the surface of Fe₃O₄ nanoparticles,and the obtained composite Fe₃O₄ nanoparticles were uniformly dispersed in aqueous solution and had a well-defined core-shell structure.The relationship between the thickness of the surface polyelectrolyte coating layer and the number of coating layers with the relaxometric efficiency of Fe₃O₄ nanoparticles was investigated.The relaxometric properties of MNPs with different coating thickness and number of layers were tested at a magnetic field strength of 1.41 T.The results showed that both the thickness of the polyelectrolyte coating layer and the number of coating layers had significant effects on the relaxometric performance of Fe₃O₄nanoparticles.The r₁ and r₂ values of MNPs gradually decreased with the increase of the thickness of polyelectrolyte coating layer and the number of coating layers on the surface.This indicates that the polyelectrolyte coating layer on the surface of MNPs hinders the water molecules from approaching MNPs and attenuates the contribution of MNPs to the inner sphere relaxometric and outer sphere relaxometric of surrounding water molecules.Meanwhile,the r₂/r₁ ratio gradually increases with the increase of the polyelectrolyte coating layer,indicating that the polyelectrolyte coating layer has a more significant effect on the inner spherical relaxometric of water molecules around MNPs.The application of layer-by-layer self-assembled Fe₃O₄ nanoparticles as immunomodulators and gene carriers in tumor therapy was initially explored by in vitro cellular experiments.The experimental results showed that sodium tripolyphosphate,PEI and Fuc-modified Fe₃O₄ nanoparticles had no effect on the growth of normal cells in the tested concentration range,but PEI-and Fuc-modified Fe₃O₄ nanoparticles had a slight inhibitory effect on the growth of tumor cells.Fuc-coated Fe₃O₄ nanoparticles can induce immune responses in macrophages RAW 264.7 cells and have good immunomodulatory activity.PEI-coated Fe₃O₄ nanoparticles could effectively load mi RNA129 with 64.80μg/m L when mi RNA129:MNPs@2^nd layer was 1:1.Fe₃O₄nanoparticles loaded with mi RNA129 had a significant inhibitory effect on the growth of tumor cells.Fluorescence imaging experiments showed that Fe₃O₄ nanoparticles loaded with mi RNA129 could be effectively taken up by tumor cells.