Preparation Of Fe₃O₄ Nanoparticles And Its Application As A Brain-targeted Contrast Agent

Magnetic nanoparticles have broad application prospects in the field of biomedicine due to their unique magnetic properties,excellent chemical stability,and biological safety.As a magnetic material,iron oxide nanoparticles have great potential in cell separation,targeted drug delivery,hyperthermia,magnetic resonance imaging,and so on.When superparamagnetic iron oxide is used in MRI,it has the advantages of low toxicity,long internal circulation time,and good stability.Modification of nanomaterials with inorganic molecules,polymers,etc.can further improve nanoparticle dispersion and biocompatibility.In vivo tumor imaging,the contrast agent is required to accumulate in the tumor,so the nanoparticles are linked to the targeting molecule to improve its tumor targeting.In this thesis,we synthesized RGERPPR-targeted,liposome-coated magnetic nanoparticles based on iron oxide nanoparticles,which were able to penetrate tumor tissue and enhance magnetic resonance imaging.And we developed an MRI-fluorescence dual-modality imaging probe and studied its performance in the field of biological imaging.Meanwhile,we have preliminarily fabricated a nanoprobe for targeting?-amyloid plaques.First,we prepared oleic acid-coated iron oxide nanoparticles by solvothermal method.The hysteresis loops of the materials were characterized,and the effect of zinc doping amount on the magnetic properties of the nanoparticles was studied.Nanoparticles with optimal doping ratio are subsequently selected for subsequent modification,improving water solubility and biocompatibility of magnetic NPs.Subsequently,Zn_0.4Fe_2.6O₄-RGERPPR nanomaterials were synthesized through link of the targeting molecules on the surface of Zn_0.4Fe_2.6O₄@lipid,and the morphology,particle size,and potential were characterized.In vitro cytotoxicity experiments proved that DSPE-PEG-coated nanomaterials have good biocompatibility.In vitro assays verified more nanoparticles are engulfed by the cells with the ligation of targeting peptide.In addition,we explored the imaging properties of nanomaterials.The relaxation rate and in vitro angiography of the nanomaterials were tested,and the results showed that the materials can enhance the effect of MRI.After the fluorescent molecules were connected,the detection in vivo showed that the nanoparticles accumulated in the tumor.Afterwards,a 1,2-stilbene derivative was attached to the surface of Zn_0.4Fe_2.6O₄@SiO₂,with the specific affinity to?-amyloid plaques,an early diagnosis probe of Alzheimer's disease was fabricated,and the morphology,particle size and infrared spectrum have also been characterized to clarify successful ligation of targeting ligand to nanocarrier.The research showed that zinc doping is related to the magnetic properties of magnetic nanoparticles,and the magnetic properties of nanoparticles are improved by controlling the amount of zinc doping.Magnetic particles with core-shell structure were prepared.After coating and modification,the obtained materials had good biocompatibility and brain targeting ability.And the tumor-targeted MRI-fluorescence dual-modality imaging probe was achieved.