基于Nd3+敏化上转换纳米颗粒/金属纳米团簇复合材料的近红外光响应多功能诊疗体系的研究

Recently, the imaging-guided cancer therapy technology based on the nano-materials has drawn considerable research interest in the field of material and biotechnology. However, there are still some serious concerns to be resolved. Firstly, it is hard to achieve real-time integration of the diagnosis and therapy, due to the diverse operation of these technologies. Secondly, the research of the desired imaging and therapy effect are also difficult to achieve by single imaging or therapeutic technology. The research of multi-mode imaging and cancer therapy is still limited. At last, the interaction mechanism between the multimodal therapies has rarely been studied. Accordingly, to solve these problems, the present proposal is to design and prepare a NIR light-induced multi-functional imaging-guided cancer therapy system based on the upconversion nanoparticles/metal nanoclusters nanoccomposites. Multi-mode imaging and therapeutic technologies will work together upon a single NIR light to achieve true integration of the diagnosis and therapy. The synergy mechanism of these imaging (fluorescence imaging, photoacoustic imaging, photothermal imaging) and therapy (photodynamic therapy and photothermal therapy) technologies will be investigated systematically. The biological safety of as-prepared nanoccomposites in variou cells and living bodies will also be systematically studied based on a series of tests, in order to provide the basic research results and theoretical guidance for the clinic application of this kind of functional nanocomposites in cancer diagnosis and therapy.

近年来，对于以纳米材料为基础的新型癌症诊断、治疗一体化的研究工作成为了材料及生物技术领域内的热点。目前该项技术的研究所存在的问题有：第一，诊断和治疗在实际操作上彼此分离，难以形成真正的实时的一体化；其次，单独成像或治疗手段的效果欠佳，多模式协同成像及治疗研究较少；此外，多种治疗手段共存时的相互作用机制还不明朗，缺乏系统的研究。针对以上问题，本项目提出以上转换纳米颗粒/金属纳米团簇复合材料为基础，形成具有近红外响应的多模式诊疗一体化体系。将多种成像及治疗手段相结合，提高诊断和治疗效果。并且将这些技术在一种近红外光激发下同时实现，形成诊断与治疗技术的真正统一。同时，对近红外光激发下的双重治疗手段(光热治疗及光动力治疗)进行系统研究，获得两者的协同作用机理。项目还将系统地研究复合材料在细胞及小动物体内的病理学及毒理学特征，为该类复合材料在癌症诊疗领域的实际应用提供基础研究数据及理论指导。

项目基于稀土上转换纳米颗粒设计并制备了多种纳米复合材料。同时，面向肿瘤的诊断和治疗，对纳米颗粒的光学、结构、组成、表面等性质进行了深入研究及优化，尤其对Nd3+敏化的稀土纳米颗粒上/下转换荧光及光热性能间的关系进行了细致的研究和分析。通过结构和组成调控所带来的上转换纳米颗粒性质上的优化，能够实现纳米复合材料成像与治疗性能上的兼顾与提高。同时，项目根据肿瘤微环境乏氧、微酸性及特定化学物质过表达等特点，还对纳米复合材料的组成及表面性质修饰，获得了具有肿瘤微环境响应功能的纳米药物，实现了肿瘤治疗效率的进一步提升。项目创新性地提出利用光致多模式成像（包括荧光、光声、光热成像）技术实现肿瘤治疗的实时监控作用，对实现肿瘤的特异性治疗及病灶追踪具有重要意义。项目还对多种纳米复合材料于细胞及小鼠层面的生物毒性进行了细致的研究，所获实验数据对此类材料未来在生物医学领域的应用具有基础支撑作用。