【作者】 程倩；

【导师】 蔡伟；

【作者基本信息】 哈尔滨工业大学 ， 材料物理与化学， 2013， 博士

【摘要】 稀土掺杂的NaGdF₄纳米粒子具有优异的上转换发光性能和顺磁性，在肿瘤早期诊断和治疗用磁性―荧光双模式分子探针中极具应用潜力。但该类纳米粒子纯六方相的获得和粒径控制、发光强度低和发色光谱单一等仍是制约其发展和应用的主要瓶颈，以稀土掺杂NaGdF₄纳米粒子为磁性―荧光双功能分子探针的研究尚未报道。本文采用改进的热分解法制备NaGdF₄:Yb³⁺,Er³⁺纳米粒子，通过优化反应条件控制相结构和粒径；采用Li⁺离子掺杂和壳包覆等改性手段提高发光强度，研究合成工艺及改性方法和条件对相结构、上转换发光强度、磁性能和分散性的影响规律，揭示改性机理。采用SiO₂包覆和氨基化修饰后接枝Cltx的方法构建胶质瘤靶向磁性―荧光双功能分子探针，研究探针的多模式成像效果。采用热分解法，在油胺溶剂中制备出NaGdF₄:Yb³⁺,Er³⁺纳米粒子，研究了反应条件对相结构、粒径及发光性能和磁性能的影响，结果表明，提高升温速率和反应温度有利于单一β相生成，当升温速率为20℃/min，反应温度为330℃，反应时间为1h时，获得了球形纯β相纳米粒子，平均粒径为13nm，分散性好，呈顺磁性，具有强的上转换荧光发射。采用Li⁺离子掺杂提高β-NaGdF₄: Yb³⁺,Er³⁺纳米粒子的发光性能，研究了Li⁺离子掺杂对相结构、形貌、分散性、上转换发光性能及磁性能的影响，发现，Li⁺离子掺杂对粒径、分散性和磁性能无明显影响，但对相结构和上转换发光性能影响较大。Li⁺离子浓度低于15mol%时，产物为纯β相；Li⁺离子浓度高于15mol%时，除β相外，还有α相生成，Li⁺离子浓度增加，α相增多；当Li⁺离子浓度达60mol%时，产物为纯α相；当Li⁺离子浓度高于60mol%时，获得四方相的LiGdF4:Yb³⁺,Er³⁺和LiF的混合物。Li⁺离子掺杂显著提高了上转换发光强度，Li⁺离子浓度为7mol%时，Li⁺离子主要替代Na+离子进入晶格内部，产生大的晶格畸变，稀土离子局域环境的对称性最低，上转换发光最强，其绿光和红光强度分别提高47倍和23倍。过高的Li⁺离子浓度，生成过量的非β相导致上转换发光强度降低。采用壳包覆对β-NaGdF₄:Yb³⁺,Er³⁺纳米粒子进行改性，研究了钝化壳NaDyF₄和活化壳NaGdF₄: Dy³⁺包覆对发光特性和磁性能的影响，实验结果表明，壳包覆提高了β-NaGdF₄:Yb³⁺,Er³⁺纳米粒子的上转换发光强度和室温磁化强度。钝化壳NaDyF₄包覆后，绿光强度提高2倍，磁化强度提高1倍；活化壳NaGdF₄:0.5%Dy³⁺包覆后，绿光和红光强度分别提高7倍和2倍，磁化强度提高2倍，并呈现出下转换发光特性，在350nm紫外光激发下，发出下转换蓝光和黄光。采用热分解法制备了NaGdF₄:Yb³⁺,Er³⁺,Li⁺@NaGdF₄:Eu³⁺纳米粒子（MFNPs），平均粒径为20nm，呈规则球形，在非极性溶剂中有良好的分散性。同时具有上转换和下转换发光特性，与NaGdF₄:Yb³⁺,Er³⁺,Li⁺纳米粒子相比，其上转换绿光和红光强度分别提高5和4倍；在395nm紫外光激发下，发出强的下转换红色荧光。采用反相微乳液法对MFNPs进行二氧化硅包覆和氨基化修饰，随后通过戊二醛活化再与生物分子Cltx偶联，制备出磁性―荧光多模式胶质瘤细胞靶向分子探针，研究了探针体内和体外多模式成像，结果表明，MFNPs@SiO₂-NH₂的平均粒径为36nm，在水溶液中具有良好的分散性和稳定性、较强的上转换绿光发射和下转换红光发射，并呈现良好的顺磁性，能显著提高其T1加权成像效果。MFNPs@SiO₂-Cltx分子探针对大鼠C6胶质瘤细胞具有特异亲和性，经尾静脉注射老鼠体内，循环2h后，仍呈现出优异的MRI/荧光多模式成像效果。更多还原

【Abstract】 Rare-earth doped NaGdF₄nanoparticles have large potential application for themagnetic-fluorescence bimodal molecular probe in the early diagnosis of cancer andtreatment, due to their outstanding upconversion luminescence and theparamagnetic properties. Unfortunately, there are several serious problems,including obtaintion of pure β phase, controllable size, low upconversion intensity,single emission spectra etc, which are major bottleneck restricting the developmentand application. Moreover, studies on rare-earth doped NaGdF₄nanoparticlesapplied to magnetic-fluorescence bimodal molecular probe have not been reported.In this dissertation, NaGdF₄:Yb³⁺,Er³⁺nanoparticles with controlled phase structureand size have been prepared via modified high temperature thermal decompositionmethod by optimizing reaction condition. Modified methods, such as Li⁺ionsdoping and shell-coating, have been employed to improve the intensity ofupconversion luminescence. The effect of the synthetic technology, modifiedmethod and condition on phase structure, the intensity of upconversionluminescence and magnetic properties as well as dispersibility is investigated toclarify the mechanism. Glioma targeting probe with magnetic-fluorescencebifunctional properties has been built by SiO₂coating and amination modificationas well as Cltx grafting. The effect of multimodality imaging has been studied.NaGdF₄:Yb³⁺,Er³⁺nanoparticles have been prepared in oleylamine by hightemperature thermal decomposition method. The effect of reaction conditions on thephase structure, particle size, upconversion luminescence and magnetic properties isexplored. The experimental results show that enhancing heating rate and reactiontemperature as well as prolong reaction time are favourable for formation of pure βphase structure. Pure β phase nanoparticles are obtained at heating rate of20℃/min,reaction temperature of330℃and reaction time of1.5h. The as-preparednanoparticles with13nm are spherical and display excellent dispersibility in thenonpolar solvent, strong upconversion luminescence and paramagnetic properties atroom temperature.The intensity of upconversion luminescence has been enhanced by codopingLi⁺ions. The effect of Li⁺ion concentration on the phase structure, morphology,dispersibility, upconversion luminescence and magnetic properties ofβ-NaGdF₄:Yb³⁺,Er³⁺nanoparticles is investigated in detail. It is found that the phasestructure and upconversion luminescence properties are changed obviously, whilethe morphology and the dispersibility are almost unchanged by codoping of Li⁺ions.When the concentration of the codoping Li⁺ions is lower than15mol%, the structure of the nanoparticles is pure β phase, When the Li⁺ions concentration is inthe range from15mol%to60mol%, the mixture of α phase and β phase is obtained.Pure α phase is formed when the Li⁺ions concentration is60mol%. With thefurther increase of the Li⁺ions concentration, the mixture of tetragonal LiGdF4andLiF is obtained. The intensity of upconversion emission has been significantlyenhanced by codoping of Li⁺ions. When the concentration of the codoping Li⁺ionsis7mol%, the obviously improvement can be attributed to the lowest localsymmetry of the rare earth caused by lattice distortion due to the substitution of Na+ions by Li⁺ions. It should be note that the intensity of green and red UC emissionsis enhanced by about47and23times. When the concentration of the codoping Li⁺ions is too high, the intensity of upconversion luminescence is weakened due to theformation of excessive non-β phase.NaGdF₄:Yb³⁺,Er³⁺nanoparticles are modified by coating a passive shell ofNaDyF₄and an active shell of the Dy³⁺ions doped NaGdF₄. The effects of passiveand active shell on the luminescence and magnetic properties are investigated. Theexperimental results show that the intensity of upconversion luminescence andmagnetization are both enhanced by the shell, and the paramagnetic charactersremain unchanged. The intensity of green UC emission and magnezation of thenanoparticles are enhanced by about2and1times respectively by the passive shell.By coating active shell NaGdF₄: Dy³⁺, NaGdF₄: Yb³⁺,Er³⁺@NaGdF₄:Dy³⁺nanocomposites possess excellent upconversion （UC） luminescence,downconversion （DC） and paramagnetic characters. The intensities of green and redUC emission and the magnezation of the nanoparticles were enhanced by about7,2times and2times, respectively. The blue and yellow luminescence is also observedunder UV excitation at350nm.NaGdF₄:Yb³⁺,Er³⁺,Li⁺@NaGdF₄:Eu³⁺nanoparticles（MFNPs） are prepared byhigh temperature thermal decomposition method. The as-prepared nanoparticleswith mean size of20nm are uniform spherical and exibits excellent dispersibility inthe nonpolar solvent. These nanoparticles possess excellent upconversionluminescence and downconversion luminescence. The intensity of green and red isenhanced by5times and4times compared to NaGdF₄:Yb³⁺,Er³⁺,Li⁺nanoparticles.In addition, the strong red luminescence is observed under UV excitation at395nm.MFNPs@SiO₂-NH₂multifunctional nanoparticles are prepared by reversemicroemusion method. The as-prepared multifunctional nanoparticles are activatedby glutaraldehyde and then coupled using the Cltx to synthesis magnetic-fluorescence multifunctional gliomas targeting probe. MRI/optical multimodalityimaging in vivo and viro are investigated. The results show that theMFNPs@SiO₂-NH₂nanoparticles with36nm have excellent dispersibility andstablity in water. High-performance upconversion and downcoversion luminescence as well as good paramagnetic properties are simultaneously observed, and the effectof T1weighted image was obviously enhanced. MFNPs@SiO₂-Cltx molecular probehas special affinity to C6gliomas cells and no cytotxieity. The excellent effect ofMRI/optical mutimodal imaging is observed after circulating in vivo for2h.更多还原