Preparation Of The Water Soluble Polymer Ligand Modified Magnetic Fe₃O₄ Nanoparticles And Their Application As A Contrast Agent In Magnetic Resonance Imaging

Iron oxide nanoparticles represented by magnetic nanoparticles have been widely used in biomedical and bioengineering field such as magnetic resonance imaging?MRI?,magnetic separation,biological labeling and drug carrier,due to their excellent properties of superparamagnetism and low toxicity.But they were limited by their high specific surface area and surface energy,which tend to aggregate more easily.We can use polymer ligand with rich functional groups?amino,hydroxyl,carboxyl,thiol?to stable and prepare uniform,nearly monodisperse and stable magnetic nanoparticles.This paper designed and synthesized the polymer ligand with different functional groups to modify magnetic ferroferric oxide nanoparticles and the morphology,particle size,structure,stability,cell toxicity were characterized and further explored the potential as contrast agents in MRI.The details are summarized as follows:?1?Using butyl acetate as solvent,twobenzoyl peroxide?BPO?as an initiator,maleic anhydride?MA?and vinyl acetate?VAc?as monomers,we synthesized water-soluble alternate polymer ligand P?MA-alt-VAc?containing carboxyl groups.Similarly,magnetic iron oxide nanoparticles was synthesized by using high temperature coprecipitation,and further control the synthesis of nanoparticle size and morphology by changing the polymer ligand concentration,adding different amount of chain transfer agent PTMP and changing the MA and VAc monomer molar ratio.The properties of nanoparticles such as morphology,size,chemical composition,structure and magnetic properties were characterized by TEM,DLS,FTIR,XRD,TGA,VSM.In addition,the cytotoxicity of nanoparticles prepared with the monomer molar ratio of 0.5/1 indicates that the magnetic nanoparticles have good biocompatibility.Relaxation in vitro results showed that with the increase of iron ion concentration,the in vitro relaxation signals can increase negatively.The r₁ and r₂ value is7.54 mM^-1s^-1and 24.81 mM^-1s^-1respectively,indicating their potential to be a T₂ contrast agent.?2?using ethanol?EtOH?as solvent,pentaerythritol-four?3-mercapto propionic acid ester??PTMP?as chain transfer agent,N-vinyl-2-pyrrolidone?VP?as the monomer reaction,2-2 azo diisobutyl cyanogen?AIBN?as an initiator,the water-soluble polymer ligand pentaerythritol-four?3-mercapto propionic acid ester?-polyvinyl pyrrolidone?PTMP-PVP?were synthesized by free-radical polymerization.Then,the polymer ligand modified iron oxide nanoparticles?PTMP-PVP@Fe₃O₄?were prepared by high temperature of the precursor solution coprecipitation method at 100?.Their morphology,particle size and size distribution,chemical composition and crystal structure,etc were characterized by transmission electron microscopy?TEM?,dynamic light scattering particle sizer?DLS?,Fourier infrared?FTIR?,X-ray diffraction?XRD?,thermogravimetric analysis?TGA?.Their stability was tested by using different concentrations of salt solution and serum solution.The cytotoxicity of magnetic nanoparticles was characterized by CCK-8,which indicate that the magnetic iron oxide nanoparticles have good biocompatibility on DC2.4 normal cells and MCF-7 tumor cells.In vitro relaxation test indicate the longitudinal relaxation rate?r₁?and transversal relaxation rate values?r₂?were 5.44 mM^-1s^-1and 231.06 mM^-1s^-1,respectively.In vivo magnetic resonance imaging?MRI?results show that the distribution of the magnetic nanoparticles in mice liver has obvious signal change with first increase then decrease,which can be used as T₂ contrast agents.And the histological results indicate the biological safety with no inflammation toxicity at the same time.