Synthesis And Properties Of Magnetic Nanoclusters Based Multimodal Probes

Magnetic nanocluster is a secondary structure composed of primary magnetic nanoparticles.Due to its unique nanostructure and excellent magnetic response performance,magnetic nanoclusters have received extensive attention in biomedical fields such as magnetic resonance imaging.It has become an important tool for the diagnosis and treatment of diseases and the separation of specific pathogens and biological species.At present,there are few studies on metal ion-doped magnetic iron oxide nanoparticle clusters and their applications in magnetic resonance imaging.In this paper,a series of multi-modal nanoprobes based on lanthanide metal-doped magnetic iron oxide nanoparticle clusters are prepared,in which the core carrier includes Gd-doped iron oxide nanoparticle clusters(GdIO NCs),Dy-doped iron oxide Nanoparticle clusters(DyIO NCs)and Eu-doped iron oxide nanoparticle clusters(EuIO NCs),etc.The main work includes the following aspects.(1)In this paper,a simple method for synthesizing magnetic nanoparticle clusters is designed.A series of water-soluble,biocompatible,superparamagnetic lanthanide metal(Gd,Dy,Eu)doped iron oxide nanoparticle clusters are synthesized.By adjusting the ratio of metal precursors,reaction temperature and time,the content of doped metal in nanoclusters and the size of nanoclusters can be adjusted.The morphology,size,structure and surface composition of nanoclusters were characterized.(2)This paper discusses the relaxation performance and magnetic resonance imaging performance of magnetic iron oxide nanoparticle clusters doped with different lanthanide metals(Gd,Dy,Eu).Among them,the longitudinal relaxation rate r1 of Gd_0.45Fe_2.55O₄ NCs is 28.1 m M^-1s^-1[Gd],and the lateral relaxation rate r₂ is 859.7 m M^-1s^-1[Fe].For Dy-doped magnetic iron oxide nanoparticle clusters,r₂ increases with the increase of doping amount,and r₁ has no significant change.Among them,r₂ of Dy_0.20Fe_2.80O₄ can reach 485.6 m M^-1s^-1[Dy+Fe].For Eu-doped magnetic iron oxide nanoparticle clusters,r₁ increases with the amount of doping,and r₂ has no significant change.Among them,the r₁ of Eu_0.170Fe_2.830O₄is 4.622 m M^-1s^-1[Eu+Fe].This is much higher than the clinically approved T₁ contrast agent Magnevist(r₁=4.0 m M^-1s^-1)and T₂ contrast agent Feridex(r₂=123.6 m M^-1s-¹).The results show that Gd-doped magnetic iron oxide nanoparticle clusters and Eu-doped magnetic iron oxide nanoparticle clusters can be used as magnetic resonance contrast agents for T₁-T₂bimodal imaging,and Dy-doped magnetic iron oxide nanoparticle clusters can As a highly sensitive T₂ magnetic resonance contrast agent.The evaluation results of colloidal stability,cytotoxicity and blood compatibility show that the nanoparticle clusters have good stability and biocompatibility.In vivo imaging in mice further showed that Gd-doped magnetic iron oxide nanoparticle clusters and Eu-doped magnetic iron oxide nanoparticle clusters all showed excellent T₁ and T₂ bimodal imaging enhancement effects,and Dy-doped magnetic oxidation The iron nanoparticle clusters showed excellent T₂ imaging enhancement effect.(3)The carboxyl functional group is exposed on the surface of the nanoparticle cluster,which provides a reaction site for the functionalization of bioactive molecules.Therefore,fluorescein isothiocyanate(FITC),tumor targeting cyclic peptide c RGD,etc.can be further covalently coupled to the surface of the nanoparticle cluster.FITC modified Gd-doped iron oxide nanoparticle clusters(FITC@GdIO NCs)were injected into mice through the tail vein.In vivo fluorescence imaging shows that this fluorescence/magnetic resonance imaging multimodal nanoprobe can be distributed in various tissues of mice,which lays the foundation for further biological characteristics research and in vivo distribution behavior of specific parts.