Synthesis and Bioimaging Applications of Several Rare Earth Flourides Nanocrystals

Author:Feng Yang

Supervisor:you hong peng


Degree Year:2019





Rare earth fluoride nanoparticles have received extensive attention in biomedical fields as bioimaging contrast agents.Compared with traditional medical contrast agents,rare earth fluoride nanomaterials have many obvious advantages,such as multifunction,large specific surface area,good biocompatibility,and stable physical and chemical properties.However,it is still a major research difficulty and hotspot to prepare highly efficient and multi-functional rare earth fluoride nanoparticles and their application in the field of bioimaging.To meet the demand for rare earth fluoride nanomaterials in the biomedical field,it is of great significance to synthesize nanomaterials with good stability,high fluorescence intensity,rapid metabolism in vivo,multifunctional integration and biosafety by using green environmental protection methods.In this thesis,a series of rare earth fluoride nanomaterials were designed and synthesized,and their structures and properties were characterized.Furthermore,these nanomaterials were applied in vitro and in vivo imaging.The main points of this thesis are outlines as follows:The first chapter introduces the research background of this thesis,including the significance of bioimaging,the main biological imaging modes,the advantages and disadvantages of different imaging methods,the luminescence properties of rare earth nanomaterials,the synthesis methods of rare earth fluorides and advantages and disadvantages of each method,the application prospects of rare earth fluoride nanomaterials in the field of bioimaging,etc..The second chapter presents fast synthesis of β-NaYF4:Ln3+(Ln=Yb/Er,Yb/Tm)upconversion nanocrystals via topotactic transformation route.We introduced one of the most effective substrates for the upconversion of fluorescent materials,β-NaYF4.The Y2(OH)5(NO3)·1.4H2O precursor was selected as the precursor to synthesizeβ-NaYF4.It can avoid α-NaYF4 in the process.The β-NaYF4 nanoparticles were successfully transformed from Y2(OH)5(NO3)·1.4H2O by topological transformation method.Importantly,the β-NaYF4 nanoparticles were synthesized by aqueous phase without any surfactants and organic reagents,which is very friendly to the environment.The morphology of β-NaYF4 nanoparticles can be effectively regulated by controlling the ratio of NaF/Y(NO3)3.The rare earth luminescent ions(Yb3+,Er3+,Tm3+)were doped in the β-NaYF4 nanoparticles,which finally proved that theβ-NaYF4:Yb3+,Er3+/Tm3+ is an effective rare earth upconversion luminescent material.The third chapter is devoted to surfactant-free aqueous synthesis of novel Ba3Gd2F12:Ln3+nanocrystals with luminescence properties.A novel rare earth fluoride nanoparticle was designed-Ba3Gd2F12.It was successfully synthesized by friendly hydrothermal synthesis method without any surfactants and organic solvents.The obtained Ba3Gd2F12 nanoparticles containing rare earth ions(Eu,Dy,Tb,Ce,Er,Tm,and Yb)exhibit excellent luminescent properties,indicating that the new rare earth fluoride Ba3Gd2F12 is an effective luminescent host material.The fourth chapter is focused on surfactant-free aqueous synthesis of novel Ba2Gd0.8F7:0.18Yb3+,0.02Er3+@PEG upconversion nanoparticles for in vivo trimodality imaging.The monodisperse and uniform Ba2Gd0.8F7:0.18Yb3+,0.02Er3+upconversion nanoparticles were synthesized by using hydrothermal method without the addition of any surfactants or organic reagents.Subsequently,polyethylene glycol(PEG)was coated on the surface of the nanoparticle.The Ba2Gd0.8F7:0.18Yb3+,0.02Er3+@PEG nanomaterial emits bright red light and has good fluorescence imaging,MR imaging,and CT imaging signal.More importantly,the in vitro and in vivo biotoxicity results prove that the Ba2Gd0.8F7:0.18Yb3+,0.02Er3+@PEG the nanoparticles have low biotoxicity.Therefore,Ba2Gd0.8F7:0.18Yb3+,0.02Er3+@PEG has potential applications as a contrast agent for multimodal imaging.The fifth chapter is concentrated on renal clearable peptide functionalized Ba2GdF7 nanoparticles for positive tumor-targeting dual-mode bioimaging.The obtained nanoparticle size was 6.5 nm.The phase transfer from hydrophobic oleic acid-coated Ba2GdF7 to hydrophilic pEGFR-Ba2GdF7 nanoparticles was achieved by the coordination between Gd3+ ions and phosphate ions.At the same time,the EGFR targeting peptide was modified on the nanoparticle.The preprared pEGFR-Ba2GdF7 nanoparticles had the active targeting ability for A549 tumor site and the excellent MR/CT dual-mode imaging function.The nanoparticles were applied on the mouse model with A549 tumors.The in vivo experiments demonstrated that pEGFR-Ba2GdF7 nanoparticles have good biocompatibility,effective renal clearance,active tumor targeting,and good MR and CT imaging function.