Fe3O4/含稀土共聚物磁性荧光纳米胶粒的制备及其多模式成像应用

Magnetic fluorescent nanoparticles combining both the magnetic and fluorenscent properties in one entity have attracted much attention in multifuncitonal nanoscale devices, especially in biotechnology and nanomedicine. In the proposal, the Fe3O4 fluids are homogeneously dispersed in water as the seeds, then funcitonal monomers, such as HEMA, GMA, METAC are copolymerizd with polymerizable rare earth complex monomers by emulsifier-free polymerization respectively. The obtained Fe3O4/rare earth containing copolymer colloidal nanoparticles are supposed to have functional groups on the surface, good biocompatibility, excellent magnetic and fluorenscent performance. The main task of this project is searching for a novel method to obtain size-controllable and monodispersed magnetic fluorenscent colloidal nanoparitcles, which overcomes the drawbacks of traditional methods, such as complicated procedure and difficulties in purity. In the scheme, the rare earth ions are steadily and uniformly dipersed in the shell layer of the colloidal nanoparticles by the coordination interaction with polymeric matrix in order to avoid the leakage of the fluorescent substance. Moreover, the polymeric shell layer can effectively preserve the fluorescent effect and improve the fluorescence quantum yield by isolating the rare earth ions and Fe3O4 particles. The relationship between the structure and properties of the nanoparticles, the parameters and conditions of preparation will be investigated. The mechanism and the effect factors such as nanoparticles size, the type of the rare earth, magnetic content on the interaction of colloidal nanoparticles with biomacromolecule and cells will also be investigated. The application of the obtained magnetic fluorescent nanoparticles in cell labeling and cancer diagnosis will be studied by multi-mode imaging technique, which is supposed to provide preliminary work in the field of biomtechnology and nanomedicine.

磁性荧光纳米粒子因其优异性能而受到人们的关注。本项目以均匀分散在水中Fe3O4磁流体作种子，将HEMA、GMA、METAC等功能单体分别与稀土荧光配合物单体进行无皂乳液聚合，制备出生物相容性好、具有磁性和荧光功能、带有功能基团的Fe3O4/含稀土共聚物磁性荧光纳米胶体粒子。探索一种简单易行、可控制备单分散磁性荧光聚合物纳米粒子的方法，避免制备步骤繁琐和不易纯化；实现稀土金属离子在纳米胶体粒子壳层中稳定、均匀分布，避免荧光物质泄露；通过聚合物过渡层保护其荧光效应，提高荧光量子产率。研究磁性荧光纳米胶体粒子结构、性能及其内在关系，探索粒子大小及功能可控的参数和条件。深入研究磁性荧光纳米胶体粒子与生物大分子、细胞的相互作用，考察粒子大小、稀土金属种类、磁流体含量等因素的影响，探讨其作用机理。通过多模式成像技术，研究磁性荧光纳米胶体粒子在细胞显影、肿瘤诊断等方面的作用，了解其在多模式成像中的应用。

摘要：磁性荧光纳米粒子因其优异性能而受到人们的关注。本项目利用共沉淀法制备Fe3O4纳米粒子并对其改性，再通过无皂种子乳液聚合法、自组装包覆和配体交换法制备出具有磁性和荧光功能的Fe3O4/含稀土共聚物磁性荧光纳米胶体粒子。表征了磁性荧光纳米胶体粒子的化学组成、形貌和结构、粒径大小及分布、细胞毒性、磁性和荧光性能，探索了粒子大小及功能可控的参数和条件。深入研究磁性荧光纳米胶体粒子与细胞的相互作用，考察粒子大小、稀土金属种类、磁流体含量等因素的影响。将磁性荧光纳米胶体粒子作为多模式光学/磁共振成像（MRI）探针，通过成像技术研究其在大鼠体内的成像及分布，了解在细胞显影、肿瘤诊断等方面的应用。研究结果如下：. 1. 利用共沉淀法制备Fe3O4纳米粒子，并证实成功被OA和NaUA改性。. 2. 采用种子无皂乳液聚合技术成功制备出含环氧基的磁性荧光纳米胶体粒子。具有超顺磁性和荧光性能、良好的细胞相容性；可作为光学/MRI探针应用于多模式成像之中。. 3. 采用种子无皂乳液聚合技术成功制备出含羟基的磁性荧光纳米胶体粒子。饱和磁化强度为2.85 emu/g ，显示稀土铕的特征发射峰。体外、体内MRI、荧光成像证实其对大鼠肝脏和脾脏组织具有良好的造影效果。. 4. 采用种子无皂乳液聚合技术成功制备出含稀土铕磁性荧光温敏性胶体粒子。在594 nm和619 nm处显示Eu3+的特征发射峰，在双光子激光共聚焦观察到鲜艳的红色荧光；体内和体外MRI表明可作为T2造影剂。. 5. 采用种子无皂乳液聚合技术成功制备出含稀土铽磁性荧光温敏性胶体粒子。饱和磁化强度为7.34 emu/g，能发射出较强的绿光。体内、体外磁共振成像、荧光成像证实粒子对大鼠肝脏和脾脏组织具有良好的造影效果。. 6. 通过自组装包覆技术成功制备出含稀土铕磁性荧光纳米胶体粒子。弛豫率为340 mM-1S-1，显示Eu3+的特征发射峰。MRI显示在肝脏和脾脏位置具有明显的对比效果；双光子激光共聚焦看出肝脏和脾脏具有明显的红色荧光。. 7. 通过自组装包覆技术成功制备出含咔唑基团磁性荧光纳米胶体粒子。体内、体外MRI显示在肝脏与脾脏位置具有加强对比现象，在350 nm和365 nm处显示咔唑的特征发射峰，双光子激光共聚焦看出肝脏和脾脏具有明显的蓝色荧光。