基于“上转换光遗传技术”精准可控纳米递送系统的肿瘤诊疗一体化研究

肿瘤早期由于诊断准确性低、治疗可控性差、诊治环节分离等问题，导致贻误了肿瘤治疗最佳时机。针对上述问题，本项目拟将多模态诊断成像与光遗传凋亡操控相结合，以核壳多模上转换纳米晶（NaYF4:Yb,Tm@Lu@Gd）为诊断要素、光敏促凋亡蛋白基因（Cry2-Bax）为治疗要素、功能化聚丙交酯接枝聚氧乙烯共聚物（PLA-g-PEO）和碳酸氢钠为基质要素，利用纳米乳液组装方法，构建基于“上转换光遗传”机制的肿瘤一体诊治递送系统。该系统利用多模纳米晶实施MRI、CT、荧光三模态成像诊断，实现对组织结构与功能精准分析，有效改善诊断准确性；利用近红外光选择性激活促凋亡蛋白，实现对肿瘤杀伤的特异调控，有效提高治疗可控性；利用共聚物和碳酸氢钠进行有效递送与敏感释放，实现对诊治双功能承载衔接，有效融合一体诊治。项目通过细胞动物实验对其安全性、准确性、可控性等进行验证，为实现肿瘤早期一体诊治提供重要依据。

Now the early diagnosis and treatment of tumor have some major defects, including low diagnostic accuracy, poor treatment controllability, separation of diagnosis and treatment and so on, all of which lead to miss the best time for curing malignant tumor. In this proposal, based on near-infrared excitationtechnique and polymeric liposome technique, a synergetic nano-delivery system for tumor theragnosis is designed on the basis of multimode imaging technology and photocontrolled apoptosis technology. In this system, there are three parts including upconverting nanocrystals, apoptosis protein A and PLA-g-PEO. The upconverting nanocrystals can conduct tri-modal imagings for improving the diagnostic accuracy; The apoptosis protein A can be activated by NIR light to promote cell apoptosis which can improve the treatment controllability; The PLA-g-PEO and sodium bicarbonate can be used for loading the upconverting nanocrystals and apoptosis protein A gene, which combines the diagnosis and treatment together. The final purpose is to optimize all these parameters to get the synergetic nano-delivery system with good safety, accuracy and controllability. This study will be of great significance to expand ideas for tumor theragnosis.