Study On The Construction And Properties Of Novel Gadolinium-based Multifunctional Contrast Agents

Magnetic resonance imaging(MRI)is one of the most important imaging tools widely used in life science research and clinical diagnosis at present.It has the characteristics of no ionizing radiation,high soft tissue contrast,no injury,and high spaial resolution.Computed tomography(CT)is one of the most powerful imaging techniques in the field of biomedicine.With high density resolution and excellent tissue penetration,it can provide three-dimensional anatomical images of tissues and organs with high resolution.The combination of MRI and CT has important clinical significance.Upconversion nanoparticles doped with rare earth are a new kind of luminescent materials,which are widely used because of their unique luminescent properties.They can achieve upconversion fluorescence emission in ultraviolet or visible light under the excitation of 808 nm and 980 nm near infrared light.The upconversion fluorescence has good properties such as long fluorescence lifetime,deep penetration of biological tissue,good chemical stability,little light damage to biological samples,and no interference of background fluorescence.Therefore,upconversion nanoparticles have great application prospects in biomarkers,imaging,immunoanalysis,infrared sensors and other aspects.Gadolinium-based contrast agent is a kind of magnetic resonance imaging contrast agent which is widely used in clinical disease diagnosis and related research.However,the relaxation efficiency of current gadolinium-based contrast agents is not high.Moreoer,the imaging ability,selectivity and biocompatibility of current gadolinium-based contrast agents need to be improved.Therefore,the preparation of multifunctional contrast agents has become a new prospect in the field of gadolinium-based contrast agents.In this paper,based on the characteristics of rare earth doped upconversion luminescence(UCL),computed tomography(CT),magnetic resonance imaging(MRI)and other molecular imaging technologies containing gadolinium contrast agent,the following aspects of work were carried out:In the second chapter of this thesis,a new MRI contrast agents system based on organic gadolinium(Gd)nanoparticles was designed,synthesized and tested.Based on a biocompatible condensation reaction between a 1,2-aminothiol and cyano group,organic Gd nanoparticles with well-controlled diameter in the range of 8～23 nm were successfully synthesized.When used as the MRI contrast agents,the organic Gd nanoparticle exhibited slowly weakened longitudinal relaxivity with time.Meanwhile,its transverse relaxivity was observed to be enhanced firstly,and then gradually weakened,attributed to the diameter increase of the Gd-nanoparticles.The time-dependant properties of the longitudinal and transverse relaxation of organic gadolinium nanoparticles indicate that it has the potential to be an advanced T1-T2 bimodal MRI contrast agent.In the third chapter of this paper,two methods for the preparation of NaErF4@NaGdF4 core-shell nanoparticles,which were chloride solvothermal method and oxide solvothermal method.The hexagonal rare earth fluoride synthesized by solvothermal method of chloride is more stable.In addition,we also discussed the effects of different core-shell ratio NaErF4@NaGdF4 on the luminescence properties,magnetic resonance imaging and CT imaging ability of core-shell structure nanoparticles,and screened out the best core-shell ratio of nanoparticle.The forth chapter of this paper is based on the research work in the third chapter,the NaErF4@NaGdF4 core-shell structure nanoparticles screened in the third chapter are used in UCL,MRI and CT imaging.In order to make up for the deficiency of a single imaging mode,it is necessary to combine a variety of biological imaging technologies to achieve comprehensive monitoring of diseases.The NaErF4@NaGdF4 core-shell nanoparticles designed by us introduce Gd in the coating of active shells,which provides the possibility for MRI imaging.CT angiography efficiency is effectively enhanced because Er has appropriate K-edge binding energy.Secondly,Er has abundant energy levels and unique 4f electronic structure,so the nucleus of NaErF4 is ideal for studying upconversion luminescence The probe can be used for UCL,MRI and CT imaging.In summary,we have designed and constructed a multifunctional nanocomposite probe based on dynamic organic gadolinium nanoparticles and NaErF4@NaGdF4 nanoparticles,which can perform bimodal or multimodal imaging for disease detection.