肿瘤干细胞靶向型光响应多模探测/多重治疗纳米复合探针的构建及应用研究

As the seeds of the tumorigenesis and the driving force of metastases, cancer stem cells have gained great attention in clinical research. To diagnosis in early stage and suppress them has been demonstrated to be one of the most effective measures to reduce cancer mortality, which has important theoretical and practical significance in the diagnostics. In this study, we will design a cancer stem cell-targeted nanoprobe that integrates fluorescence imaging/infrared thermography and photothermal/drug treatment, which possesses the functionality of multimode detection and multipronged therapy. The drug-loaded reconstituted low density lipoprotein (rLDL) will be used as a carrier, and fluorescent quantum dots and photothermal nanomaterials will be then assembled on the surface to obtain a light responsive photothermal/chemotherapeutic collaborative diagnosis and treatment system with visual detection. The specific markers for multi-sites recognition of tumor stem cells will be decorated to improve the therapeutic efficiency. Through the conjugation of the elementary materials with rLDL, the investigation of active targeting system, the visual detection of fluorescence/thermal imaging and the synergistic effect of photothermal/chemotherapeutics, the construction of multifunctional composite probes will be established, which will reveal the internal relationship between the composition/structure and properties of the nanoprobe. This study holds great promise to provide new research ideas and necessary experiments for solving the key scientific problems of early diagnosis, precise localization and radical treatment of colon cancer. Moreover, this project is expected to promote the development for the design and construction of novel theranostic nanoprobes of cancer stem cells.

肿瘤干细胞作为肿瘤形成的根源和转移的动力一直是临床研究的热点，对其进行精准识别和抑制具有重要的理论和实践意义。本项目旨在构建一种结肠癌干细胞靶向型的集荧光/热成像和光热/药物传输多功能于一体、具有多模探测/多重治疗的纳米复合探针。以药物负载的重构低密度脂蛋白（rLDL）为载体，依次组装荧光量子点和光热纳米材料，获得具有可视化探测和近红外光响应的光热/化疗协同诊疗体系；利用对肿瘤干细胞具有多位点识别性的靶向标志物修饰，进而大幅提高其治疗效果。通过基元材料与rLDL的偶联、主动靶向系统检测、荧光/热成像可视化探测以及光热/化疗协同作用等研究，建立靶向多功能探针的构建途径，揭示多模诊断/多重治疗特性与探针组成、结构之间的内在关系，认识其作用机理，有望为解决结肠癌的早期诊断、精确定位、根源性治疗等重要科学问题提供新的研究思路和必要的实验基础，为肿瘤干细胞“诊疗一体化”探针的构建提供新的途径。

肿瘤干细胞作为肿瘤形成的根源和转移的动力一直是临床研究的热点，对其进行多模成像和多重治疗具有重要的理论和实践意义。本项目以结肠癌干细胞为模型，荧光量子点、光热纳米粒子为基元材料，构建具有荧光、光热、靶向、光动力治疗多机制的纳米探针。研制了两类多元无毒量子点，并对其结构和光学性质进行系统表征和调控。通过对量子点的表面官能团化，实现了结肠癌细胞和结肠癌干细胞的可见光和近红外成像。设计了基于低密度脂蛋白和无毒量子点的靶向纳米探针，实现了对结肠癌干细胞的三维荧光成像。利用二元脂肪酸共聚物、多孔二氧化硅纳米粒子和金壳层，构建了具有近红外光响应的药物控释系统。通过其对肿瘤干细胞的多模成像和对细胞增殖抑制效果，研究其多机制抑制细胞增殖的协同性以及分子生物学机制，为结肠癌诊疗一体化提供了新的思路和实验基础。