Preparation And Application Of Up-conversion,Timed-gated,Magnetic Resonance Imaging Multi-mode Fluorescent Probes

Compared with a single imaging technology,Multi-mode imaging technology combines the advantages of various imaging technologies to obtain more accurate information of the lesion tissue,while up-conversion nanoparticles have special optical properties,which are often used as the basic luminous materials for multi-mode imaging and applied in biomedical and other fields.In this paper,multi-mode nano-fluorescent probes designed for up-conversion luminescence,time-gated fluorescence,steady-state fluorescence and magnetic resonance imaging were used as the starting point,and hydrophobic up-conversion nanoparticles were prepared by taking Gd³⁺as a paramagnetic T₁ contrast agent,using NaGdF₄ as the matrix and oleic acid as the surfactant.In order to make the nanoparticles biocompatible,the core-shell structure nanoparticles with amino groups on the surface were synthesized by adding the precursor of europium ion complexes in the reverse microemulsion method,and then the folic acid molecules were bonded on the surface to prepare multi-mode nano-fluorescence probes for up-conversion,time-gated,steady-state fluorescence and magnetic resonance imaging.The main contents are as follows:?1?Preparation and application of UCNPs@SiO₂-FA multi-mode nano-fluorescent probes.Doping Mn²⁺in upconversion nanoparticles can effectively improve the luminous efficiency of upconversion.Therefore,in the first part of this paper,Mn²⁺-doped NaGdF₄:Nd³⁺/Yb³⁺/Er³⁺up-conversion nanoparticles were prepared by hydrothermal method.The structure,morphology and optical properties of the nanoparticles were characterized by XRD,TEM,EDS and FT-IR,indicating that Mn²⁺ions were successfully doped in NaGdF₄:Nd³⁺/Yb³⁺/Er³⁺nanoparticles,and the morphology of the nanoparticles was not significantly affected.At the same time,the doping amount of each ion was optimized,and the optimal doping ratio of nano-particle luminescence performance was summarized.Then using reverse microemulsion method,APS-BHHBCB-Eu³⁺,TEOS and APS as the main raw materials,the core-shell structure up-conversion nanoparticles?UCNPs@SiO₂?were prepared and characterized by morphology and fluorescence properties,indicating that silica was successfully coated on the surface of bare-core particles with small particle size and uniform dispersion,and UCNPs@SiO₂ nanoparticles had good luminescence performance.Finally UCNPs@SiO₂ nanoparticles were bonded with folic acid to prepare UCNPs@SiO₂-FA multi-mode nano-fluorescent probes.The results of the experiments showed the luminous stability of the UCNPs@SiO₂-FA in a wide pH range,and the probe concentration had a good linear relationship with luminous intensity,Moreover,the results of multi-mode imaging measurement were abtainted in HeLa cells.?2?Optimization of preparation conditions and biological application of TUM-NPs-FA multi-mode nano-fluorescent probes.The reverse microemulsion method was used to optimize the core-shell structure of NaGdF₄:Nd³⁺/Yb³⁺/Ho³⁺nanoparticles prepared in the previous stage.The core-shell structure of TUM-NPs had a small particle size of about 50 nm.Then,after linking folic acid,the TUM-NPs-FA Multi-mode nano-fluorescent probes were prepared.The probes had stable fluorescence properties,and the imaging assays in HeLa cells were achieved.