基于新型复合纳米探针的多模式成像分析

Imaging, as a powerful visualization tool for diagnosis of disease, is capable of providing detailed information on anatomical structures and functional activities inside body. The combination of various imaging modalities facilitates to obtain comprehensive imaging information data, which is of vital importance for improving accuracy of diagnosis and efficiency of therapy. As a matter of fact, the design and constructing of multimodal imaging probes have gained more and more research interest. This proposal that aims at high-resolution imaging will be performed to design and synthesize novel composite nanoprobes prior to commercial products and to carry on multimodal imaging, including the design and synthesis of lanthanide upconversion luminescence nanoparticles for fluorescence imaging(FI), Gd or Mn nanoparticles with T1-relaxivity for magnetic resonance imaging(MRI), gold and tantalum oxide nanoparticles with high absorpance ratio of X-ray for computed tomography(CT) imaging; to construct excellent composite nanoprobes such as FI-MRI and FI-CT via co-encapsulation or doping; to disclose the optimization relationship between imaging signal with the composition, structure and synthesis parameter of composite nanoprobes via bioimaging analysis, to research the targeting, distribution and metabolization of composite nanoprobes and to conclude the general law between imaging and probes.

成像能够提供人体病变部位详细的解剖和功能信息，是一种强有力的、可视化的疾病诊断技术。不同成像模式的结合使用能够获取全面的影像信息，对于提高疾病诊断的准确性以及防治的有效性非常重要。事实上，设计构筑多模式成像探针已经引起人们越来越多的研究兴趣。本项目以获取多模式高清晰影像为目标，开发几种性能优于商品化产品的新型复合纳米探针并开展多模式成像分析。具体内容包括：设计合成用于荧光成像(FI)的近红外发射、稀土上转换发光纳米粒子，用于磁共振成像(MRI)的掺钆或者锰等元素、纵向弛豫的纳米粒子，用于计算机断层扫描(CT)成像的X-射线高吸收率的金纳米粒子、氧化钽纳米粒子；以包敷法或者掺杂法构建性能优异的FI-MRI、FI-CT等复合纳米探针；通过复合纳米探针的生物成像揭示成像信号与探针的组成、结构和合成条件的最优化关系以及复合纳米探针在体内的靶向性、分布情况和代谢过程，探索成像与探针之间的一般性规律。

成像能够提供人体病变部位详细的解剖和功能信息，不同成像模式的结合使用能够获取全面的影像信息。因此，设计构筑多模式成像探针获取全面、准确影像信息的关键。本项目以获取多模式高清晰影像为目标，合成了几种新型纳米探针，表征了其结构和性质，结果显示这些材料适合进行成像研究。所合成的NaYbF4: Er3+, Tm3+纳米粒子（UCNPs）具有较满意的上转换发光性质、较高的分散性和结晶性，最强的发射峰位于801 nm（即Tm3+离子的3H4-3H6跃迁）。优化所得的NaYb0.96Er0.02Tm0.02F4纳米粒子具有较纯的发射谱线（NIR/weak光谱纯度比值，Snw，大于0.7）和较强的近红外-近红外上转换发光（激发和发射波长分别为980和801 nm；激光光源的激发功率低至3.8 W）。改变稀土离子Y3+、Yb3+ 和Tm3+ 的摩尔进料比，采用高温热分解法合成铥含量不同的四种β-NaYF4 :Yb3+ , Tm3+ 纳米粒子（UCNPs），NaY0.75Yb0.25Tm0.003F4， NaY0.78Yb0.20Tm0.02F4, NaY0.78Yb0.21Tm0.01F4和NaY0.78Yb0.17Tm0.05F4纳米粒子，并研究了它们在980 nm 近红外光激发下的上转换发光性质。采用高温溶剂热法合成NaYF4：Yb3+，Ho3+上转换纳米粒子（UCNPs），采用反相微乳液将SiO2包覆在纳米颗粒外，形成NaYF4：Yb3+，Ho3+@SiO2核壳结构(UCNPs@SiO2)。通过XRD、TEM、傅里叶红外光谱及荧光光谱对产品进行表征。结果表明，UCNPs晶相为纯六方相，粒径约45nm，SiO2成功包覆在UCNPs上，壳层厚约15nm；在980 nm红外光的激发下发射542nm绿光。