靶向近红外-可见上转换荧光纳米结构的构筑与癌细胞治疗研究

In this proposal, we proposed to synthesize targeted Near IR-Vis upconversion fluorescent nanostructures for chemotherapy and photodynamic therapy of cancer cells and tumor tissue of mice due to the current trend of high incidence of tumors and the characteristics and advantages of photodynamic therapy. High temperature organic solution method would be used to fabricate up-conversion fluorescent (core-shell) nanocrystals with a high fluorescence efficiency (excitation under 800 nm pulsed laser). The upconversion fluorescent nanocrystals would be modified using mesoporous silica layers to fill the anti-cancer drug/ photosensitizer and polymers targeted for the cancer cells resulting into the concentration of the nanoparticles, singlet oxygen and other reactive oxygen species in the cancer cells increased to kill cancer cells under irradiation of Near-infrared light. Furthermore, the anti-cancer drugs would be controlled delivery under irradiation of the near-infrared light; which should improve the treatment of cancer. The upconversion fluorescence, lifetime and nanostructures of upconversion nanoparticles would be investigated via tuning the concentration and composition of co-doped lanthanide ions to clarify the upconversion fluorescent mechanism with higher conversion efficiency. We should demonstrate the action law of the functional nanostructures modified mesoporous silica layer and targeted polymers towards cancer cells. Implementation of the project has important scientific significance and social benefits owing to important reference data for animal experiments and even clinical trials provided.

针对目前肿瘤高发的态势，以及光动力疗法的特点与优点，提出化学制备靶向近红外-可见上转换荧光纳米结构材料，通过化学和光动力治疗癌细胞以及小鼠肿瘤组织。拟采用高温油相法制备具有较高荧光效率（800 nm脉冲激光激发）的上转换荧光纳米晶,在纳米晶表面修饰介孔二氧化硅层用于填充抗癌药物与光敏剂，修饰对肿瘤细胞响应的靶向高分子，促进材料在癌细胞内的富集，提高癌细胞内单线态氧等活性氧自由基的浓度，进而杀死癌细胞（在红外光的照射下）。结合抗癌药物在近红外光照射下的控制释放，抑制癌细胞的生长，提高癌细胞的治疗效果。通过探索镧系元素离子共掺杂，研究上转换荧光纳米颗粒的结构、荧光性质以及寿命,阐明实现较高上转换荧光效率的上转换机制,揭示功能纳米结构经过介孔二氧化硅层与靶向功能化修饰后，与癌细胞以及肿瘤组织的作用规律。项目的实施将为肿瘤的治疗、甚至临床试验提供重要的数据与参考，具有重要的科学意义与社会效益。

本项目已完成了各项研究内容，实现预期的成果。发展了多种合成策略合成不同大小上转换荧光的核壳结构纳米材料，特别是合成了具有较高荧光效率（800 nm脉冲激光激发）的上转换荧光核壳纳米晶。研究了上转换纳米晶的多种改性的方法用于载药或者光敏剂，也发展了策略在上转换纳米晶外面修饰了多种具有催化活性的半导体。制备了近10多种纳米新结构，研究了其在近红外光照射下产生活性氧的功能，并用于肿瘤的活体多模态成像与治疗。项目实施期间发表SCI论文40余篇，基金支持下发表论文26篇以上，申请发明专利13项,授权11项。本项目的成功实施，将为肿瘤的治疗、甚至临床试验提供重要的数据与参考，具有重要的科学意义与社会效益。