基于闪烁纳米颗粒/Fe-MOF复合材料的探针构建及其诊疗一体化研究

Currently, there are some problems, including the low uptake of photosensitizer in tumor cells and the separation of image diagnosis and treatment of tumor, in the X-ray inducible photodynamic therapy (X-PDT) of cancer. Aiming at these problems, in this project, we will design a novel probe based on our previous work: the scintillating nanoparticles GdOF:Ce,Tb are firstly coated by a layer of metal-organic framework MIL-100(Fe) to form a nanocomposite, and then the porous structure of MIL-100(Fe) will be utilized to load photodynamic therapy agent rose bengal (RB) and chemotherapy drug doxorubin (DOX) efficiently to realize the theranostic application of the probe. In our study: ①MIL-100(Fe) and GdOF:Ce,Tb will be employed for magnetic resonance imaging and computed tomography imaging, to improve the imaging diagnostic accuracy and sensitivity of tumor; ②The nanocomposite will be modified with aptamer to obtain the probe having targeting ability so as to enhance its cells uptake and improve its curative effect; ③The X-PDT effect will be improved via the efficient energy transfer due to the exact spectrum match of GdOF:Ce,Tb’ emission and RB’s absorption; ④The synergistic therapeutic effect from dual-modal imaging -guided photodynamic therapy and chemotherapy of tumor will be achieved by optimizing the performance of the probe, and the further investigation on the possible mechanism of the treatments will be investigated. The smooth operation of this project will provide a series of scientific problems, including targeted diagnosis, combination therapy, and real-time monitoring curative effect of tumor, with some new thoughts and methods.

针对目前X-射线诱导的光动力治疗(X-PDT)存在光动力治疗剂的肿瘤细胞低摄取量和肿瘤影像诊断与治疗分离等问题，本项目拟构建一种新型纳米探针：首先采用金属有机框架MIL-100(Fe)包覆闪烁纳米颗粒GdOF:Ce,Tb形成复合材料，接着采用MIL-100(Fe)的多孔性高效装载光动力治疗剂孟加拉红(RB)和化疗药DOX以实现探针的肿瘤诊疗一体化应用。本项目将：①利用MIL-100(Fe)和GdOF:Ce,Tb实现肿瘤的磁共振和计算机断层扫描双模态成像诊断，提高成像诊断的准确性；②采用核酸适配体靶向修饰探针，提高肿瘤细胞探针摄取量以增强X-PDT效果；③利用GdOF:Ce,Tb的发射和RB的吸收匹配，通过高效能量转移提高X-PDT效果；④优化探针性能，实现双模态影像指导下的肿瘤X-PDT和化疗协同治疗并探讨治疗机制。本研究将为解决肿瘤靶向诊断、联合治疗，疗效监测等科学问题提供新思路和方法。

针对目前光动力治疗的研究中存在的肿瘤细胞对光敏剂的摄取量低以及肿瘤影像诊断与治疗分离的问题，本项目主要构建了两种新型的基于多功能复合材料的纳米探针，并对它们进行了生物医学方面的研究。一是采用油相Gd2O3纳米片与两亲性聚合物分子(N-Dodecyl-PEI-PEG)组装制备水溶性团簇探针，并对其用于小鼠肿瘤模型的磁共振成像进行了研究。二是将油相闪烁纳米颗粒GdOF:Ce,Tb、光敏剂玫瑰红(RB)和N-Dodecyl-PEI-PEG聚合物分子组装制备水溶性团簇探针，并将其用于X-射线诱导的光动力治疗(X-PDT)方面的研究；由于GdOF:Ce,Tb的发射谱和RB的吸收谱匹配，通过它们之间的有效荧光能量转移获得了X-PDT效果。在以上两种探针中，GdOF:Ce,Tb和Gd2O3使得探针具备磁共振和计算机断层扫描双模态成像功能，这可提高探针用于成像诊断的准确性。此外，本项目同时制备了基于金属有机框架（Fe-MOF等）的复合材料探针以及研究了它们用于生物医学成像和治疗方面的潜力。本项目有助于推进基于复合材料的纳米探针用于肿瘤诊疗一体化方面的基础研究。