具有强光热/荧光的Au@石墨烯@量子点的制备及其对肝癌干细胞的热疗/标记研究

Cancer stem cells are the source for tumor growth. Targeting tumor stem cell therapy is an important topic at present. The photothermal therapy technology based on the absorption properties of gold nanoparticles provides a new way of thinking for targeting treatment of tumor. But under laser radiation with high power density, Au nanoparticles show less heat stability causing the decrease of the photothermal effect. Aiming at solving these problems, we design Au nanoflower@graphene@quantum dots(QDs) composite structure in this project for forming treatment/tracer multifunctional composite probe with high heat stability, strong photothermal effect and fluorescence properties. Graphene shell with protective effect is used to improve the stability of Au nanoflower. Au nanoflower structure possesses large absorption cross section, which is beneficial for photothermal conversion. At the same time, the surface plasma field enhancement effect of Au nanoflower is used to improve the absorbance of graphene, while the enhanced absorbance of graphene will be used to improve the photothermal effect of composite structures due to the coordination effect. Combined with the theoretical simulation study, the physical mechanism for enhancing the photothermal efficiency of Au nanoflowers with graphene coating is explored. Au nanoflower@graphene@QDs composite structures conjugated with specific antibodies are adopted to cultivate liver cancer stem cells and normal liver cancer cells. By dyeing and photothermal experiment, the difference of the fluorescent tracer ability and treatment effect of composite structures for two kinds of cells will be explored. The researches provide experimental foundation for exploring the materials and method of effective tumor diagnosis and treatment.

肿瘤干细胞是肿瘤生长的源头，目前靶向肿瘤干细胞治疗是一项重要的课题。基于金纳米颗粒吸收性质的光热治疗技术为靶向肿瘤治疗提供了新思路，但是在高功率密度激光辐射下，Au纳米颗粒的热稳定性不足导致光热效果下降。针对此问题，本项目拟设计Au纳米花@石墨烯@量子点复合结构, 形成具有高热稳定性和强光热效果，且兼具荧光性质的治疗/示踪多功能复合探针。通过石墨烯壳的保护作用，提高Au纳米花的稳定性。Au纳米花结构具有大的吸收截面，有利于光热转化，同时其等离子体激元场增强性质可以提高石墨烯的吸收。而石墨烯增强的吸收性质，将协同提高复合结构的光热效果。结合理论模拟研究石墨烯增强Au纳米花光热效率的物理机理。用链接特异性抗体的Au纳米花@石墨烯@量子点复合结构分别培养肝癌干细胞和普通肝癌细胞。通过染色和光热实验，探究复合结构对两种细胞的荧光示踪能力和治疗效果的差异，为探索有效的肿瘤诊疗材料和方法提供实验基础。

复合探针靶向定位治疗肿瘤，具有时间和空间可控性。远远优越于化疗和放疗等传统方法，引起人们广泛关注。本项目通过时域有限元差分法（FDTD）研究了多刺金纳米颗粒的形貌、尺寸等对其电子态密度的分布以及吸收截面的影响。设计找出等离子体激元共振峰在近红外区域并且具有较高局域场的模型, 在实验上制备出来。将其与荧光材料进行复合并连接特异性抗体获得多功能复合探针。通过细胞生物毒性实验发现用复合探针培养的细胞株的凋亡率（2%）与没有复合探针培养的细胞类似（1%）。另外，发现向小鼠体内注射生物探针或生理盐水，两周后取出小鼠的心脏、肝脏、肾脏、肺和脾脏等器官结构都处于正常状态。证明了复合探针的生物兼容性。获得的多功能复合探针可以靶向到细胞质，并在紫外光的照射下发出黄绿色的光，可以监控复合结构的靶向部位。通过优化浓度以及近红外激光的功率密度，复合探针的温度可以稳定在50度。流式细胞术实验展示在光热处理后, 96%的肿瘤细胞可以被杀死，而没有复合探针的对照组，细胞几乎没有损坏，证明了复合探针的光热性能。实验还发现，可以通过在复合探针中引入Fe3O4实现探针的磁成像功能。上述研究为改善现有的肿瘤诊疗模式提供基础的实验依据。此外，我们以石墨烯、金属以及金属化合物为研究对象，通过理论结合实验探究了Co3S4纳米片/rGO、S掺杂的Co3O4/rGO、Co,N-GN-FeNi等复合结构的催化性能，并将其用作电极材料组装成器件探索了其功能特性。为了实现器件的穿戴，我们进一步通过设计优化构型获得了平面柔性功率器件。累计发表SCI论文12篇。授权发明专利1项。