CuS/NaYF4:Yb, Er/SiO2复合纳米胶囊及肿瘤荧光成像诊断和光热消融治疗性能研究

Nanocapsules loaded with functional nanoparticles could achieve the integration of diagnosis and treatment of malignant tumor. This project aimed to utilize high temperature organic phase technique to synthesize NaYF4: Yb, Er and CuS nanoparticles, further use soft template assembling method to fabricate near infrared light-sensitive NaYF4:Yb,Er/CuS/SiO2 composite nanocapsules，explore the influences of chemical composition and concentration on optical absorption and photothermal conversion efficacy of CuS nanomaterial, and reveal the photothermal mechanism of CuS nanomaterial; further investigate the interaction mechanism between hydrophobic nanoparticles and inner core, and assembly mechanism of composite nanocapsules using the molecular dynamics simulation method; investigate the relationship between fluorescence imaging, photothermal properties and load concentration, ratio of different nanoparticles; use confocal laser scanning fluorescence microscopy analysis techniques and MTT methods to optimize the upconversion fluorescence and phtothermal properties,and obtain the most optimal fluorescence imaging and photothermal ablation properties of SiO2 composite nanocapsules. The smooth performance of this project would lay the solid theoretical and practice foundation to the new strategy for integrating of diagnosis and treatment of malignant tumor.

负载功能纳米颗粒的纳米胶囊有望实现恶性肿瘤的诊治一体化。本项目拟采用高温有机相合成技术合成NaYF4:Yb, Er和CuS纳米颗粒，结合软模板法组装近红外光敏型NaYF4:Yb, Er/CuS/SiO2复合纳米胶囊，探明化学组分、颗粒浓度对CuS纳米材料的光热效率的影响规律，阐明CuS纳米材料的光热机理；研究纳米颗粒的负载浓度、比例、SiO2前驱体浓度和pH等因素对胶囊的形貌、尺寸和分散性的影响规律，结合分子动力学理论揭示共负载两种纳米颗粒的复合纳米胶囊的组装机理；建立胶囊的肿瘤靶性能与靶向分子键合率之间的关联; 采用荧光共聚焦显微技术和MTT比色法研究纳米颗粒负载浓度、比例对胶囊的荧光成像和光热消融性能的影响规律，获得一种可用于恶性肿瘤靶向荧光成像诊断和光热消融治疗的SiO2复合纳米胶囊。本项目的顺利实施，将为恶性肿瘤诊治一体化的新方法和新原理的构建提供重要的理论和实验基础。

本项目采用官能化三嵌段聚合物Pluronic F127的胶束为软模板，组装具有上转换荧光和光热性能的近红外光敏型NaYF4:Yb3+, Er3+/CuS/SiO2 复合纳米胶囊。结合高温油相合成技术和热力学理论获得了单分散CuS纳米盘和NaYF4:Yb3+, Er3+纳米颗粒生长的关键技术，探明了CuS 纳米材料的光热机理和NaYF4:Yb3+, Er3+纳米颗粒的荧光特性；研究了疏水抗癌药物、纳米颗粒与疏水内核的相互作用及胶囊的组装机制，获得了复合纳米胶囊的组装技术；在温和条件下，将具有广谱肿瘤靶向性的TRAIL 蛋白与SiO2复合胶囊进行偶联，获得了TRAIL蛋白偶联的关键技术；获得了一种具有对恶性肿瘤具有靶向、上转换荧光成像和光热消融性能的近红外光敏型NaYF4:Yb3+, Er3+/CuS/SiO2 复合纳米胶囊。本项目的顺利实施有望促进具有荧光成像/光热消融/药物缓释多功能的复合纳米胶囊向临床应用的发展，为构建恶性肿瘤诊治一体化的新方法和新技术奠定重要的实践基础。