Research On Ultra-small Fe@Fe₃O₄ Nanoparticles On Targeted MRI

With the development of science,more and more molecular imaging techniques are being used for clinical diagnosis,making medical diagnosis more convenient and more effective.Compared with other molecular imaging techniques,magnetic resonance imaging?MRI?has many advantages such as high penetrability,high spatial resolution,no damage,no radiation,no invasiveness,and the ability to track three-dimensional dynamic imaging.However,due to its low sensitivity in clinical practice,it is impossible to accurately distinguish some normal physiological tissues and diseased tissues.So it is necessary to use intravenous or oral drugs to enhance the contrast between normal tissues and lesions,thereby improving the accuracy of diagnosis.Ferromagnetic nanoparticles are widely used in clinical medical research because they have better biocompatibility and are easily degraded in vivo than Gd and Mn nanomaterials.Iron oxide is widely used in T₂-weighted MR imaging contrast agents because of its high magnetic moment.However,the dark signal of T₂-weighted imaging is not only confused with the signal of hemorrhage,calcification or metal deposits,but also causes the clinical diagnosis to be misleading,and the T₂ contrast agent is easy to induce a local disturbing magnetic field,leading to the so-called"smudge effect",resulting in the marked area exaggerated and blurred images.In order to solve this problem,people can achieve T₁-T₂ bimodal imaging by regulating the particle size,surface ligand and crystal structure of iron oxide,and improve the accuracy of diagnosis by complementary T₁-T₂ bimodal weighted MR images.Based on the above background,we prepared three oil-soluble Fe@Fe₃O₄nanomaterials with different particle sizes,which were modified by macromolecules and small molecule ligands,and the target protein-F56 peptide was ligated to prepare targets to achive functional MRI bimodal contrast agent,as follows:The chapter 1:Briefly summarizes the principles of magnetic resonance imaging,the classification of contrast agents and the principle of imaging,besides,the traditional synthesis of iron-based nanoparticles,the application of nanoparticles in magnetic resonance imaging,and the selection of this paper basis and research content.Chapter 2:Design and prepare three oil-soluble Fe@Fe₃O₄ nanoparticles with different particle sizes?4,8,12 nm?.The material has good monodispersity,uniform particle size,low saturation magnetization,low toxicity and stability and good properties.Then the small molecule ligands?DHCA and ALA?and macromolecular ligands?PEG and PAA?were used to modify the above three oil-soluble Fe@Fe₃O₄nanoparticles with different particle size to obtain good biocompatibility Fe@Fe₃O₄nanoparticles.Next,three different particle sizes modified with four different surface ligands were tested for MR imaging under the same parameters of a 0.5T MRI instrument.The ratio of r₂/r₁ and the observed imaging effect determine the effect of particle size and surface ligand on MR imaging.Finally,the optimal material?8 nm DHCA-NPs?was screened for subsequent in vitro and in vivo experiments.Chapter 3:The successful synthesis of 8 nm DHCA-NPs in the second chapter was coupled to the targeting polypeptide F56,using the target between the F56polypeptide and the VEGFR-1?Flt-1?receptor,which is highly expressed on the surface of tumor vascular endothelial cells.To the specific action,a targeted bimodal Fe@Fe₃O₄ nano contrast agent was prepared.The experiments show that the material not only has a good tumor targeting effect,but also can achieve T₁ and T₂ dual-mode angiography of tumors,providing new material and theoretical support for accurate diagnosis of tumors.