荧光稀土配位聚合物的制备及其靶向监测癌细胞内单线态氧的研究

Target monitoring the level of singlet oxygen in cell is of great scientific and practical importance, because it is benefit to reveal the aging mechanism induced by biological oxidation, and to accurate evaluate the therapeutic efficacy of photodynamic therapy (PDT) and adjust the drug dose in the process of PDT. Nanoscaled coordination polymers (NCPs), particularly fluorescent lanthanide NCPs, have received increasing attention, due to their potential application as a novel fluorescent probe in the detection of biological molecules in cell with highly sensitivity. In this project, we attempt to prepare a series of fluorescent lanthanide NCPs by directly using guanine and its nucleotides as bridge ligands. Auxiliary ligands that can sensitize the fluorescence of lanthanide ions were not added during the synthetic process of NCPs. These fluorescent lanthanide NCPs with excellent biocompatibility and highly emission efficiency were further used to tagert monitor the level of singlet oxygen in cancer cell. More important, the shortcomings of organic fluorescent probe, such as poor water soluble and biocompatible, and tend to be interfered by background fluorescence, can be overcome by using lanthanide NCPs to detect singlet oxygen in cancer cell in the mode of time-resolved fluorescence. Meanwhile, we will investigate the form mechanism of fluorescent lanthanide NCPs,and demonstrate the relationship between the physical properties of lanthanide NCPs, such as shape and size, and their fluorescent properties and detection sensitivity in this project. We believe that the present synthetic strategy constructing special functions from initial building blocks can be extended to the preparation of other lanthanide NCPs. Therefore, they have a wider application in the biomedical field.

细胞内单线态氧的靶向监测对于揭示生物氧化衰老机理、正确评价光动力学治疗效果及其治疗过程中药物剂量的及时调整有着重要的科学意义和实用价值。纳米尺寸的配位聚合物（nanoscaled coordination polymers，NCPs），特别是稀土荧光NCPs，作为一种新型的荧光探针在检测细胞内生物分子方面备受青睐。本课题旨在没有客体发光配体参与的情况下，直接利用生物分子（鸟嘌呤和鸟苷酸）与稀土离子配位制备生物相容性好、发光效率高的NCPs，并以该NCPs为荧光探针通过时间分辨分析技术对癌细胞内的单线态氧进行靶向监测，以克服大多数有机荧光探针本身水溶性差、生物相容性不好以及易受背景荧光干扰等缺陷。同时，通过研究稀土荧光NCPs的形成机理和阐明NCPs的形状、尺寸等物理特征与其荧光性能和分析灵敏度之间的关系，为指导设计合成形貌可控、具有特定功能的NCPs及其在生物医学领域的应用提供理论依据。

在本课题中，我们采用水热法和自组装法制备了多种的荧光稀土配位聚合物。通过以苯丙氨酸为模型，研究了表面活性剂对以生物分子为桥连配体构成的稀土配位聚合物形貌和荧光性能的影响，揭示了氨基酸与稀土离子的成核机制，也实现了稀土配位聚合物的可控制备。在以稀土配位聚合物为直接受体平台构建荧光探针的研究基础上，我们还设计和制备了一些功能化的稀土配位聚合物和具有双发射波长的稀土配位聚合物，以进一步提高稀土配位聚合物荧光探针的传感性能（选择性和灵敏度）；同时其检测对象也得到极大了的丰富，从单线态氧拓展到了有机小分子、生物大分子、金属离子、活性氧（H2O2、羟自由基）等。研究发现，稀土配位聚合物具有良好的生物相容性，可用于肿瘤细胞内单线态氧的比率检测。此外，还研究了基于稀土离子形成的螯合物、G-四链体、双发射硅纳米粒子等荧光材料的传感功能。对于其他功能材料（Fe3O4@C、Cu-MOF及其衍生物）的过氧化物模拟酶活性和DNA传感功能也进行了研究。本课题的开展，不仅为指导合理设计具有特定功能的稀土配位聚合物提供研究思路和理论依据，也为重要生物分子的高灵敏度检测提供了新方法，从而极大地拓展了配位聚合物在生物医学领域的应用范围。