面向胃癌高分辨成像与精准诊疗纳米探针的基础研究

Gastric cancer remains a high incidence of cancers in China. Normally, the physical and visual symptoms of early gastric cancers in most patients are not obvious. Since perigastric lymphatic system is rich, lymph node metastasis risk is also high. Due to the lack of early diagnostic means and effective therapeutic methods, the mortality of gastric cancers remains high in our country. The current project aims at the construction of nanoprobes integrated with highly sensitive and specific imaging and therapeutic functions, and the development of related theory and experimental methods for high resolution imaging and accurate treatment of gastric cancers. Towards these goals, the following research contents are proposed: Based on magnetic/upconverting rare-earth nanoparticles, tumor-specific magnetic resonance imaging/upconverting optical imaging nanoprobes will be constructed, through photo-sensitizer loading, functional nanoprobes for targeted imaging and photodynamic therapy of gastric cancers will be created; Based on magnetic iron oxide nanoparticles that have bright future with respect to translational medicine, T1/T2 MR imaging probes will be prepared, by loading with chemotherapy drugs, nanoagents with gastric cancer active targeting ability for both imaging and therapy will be constructed; In combination with different tumor animal model studies, methods for high resolution imaging and accurate treatment of gastric cancers will be developed.

胃癌在我国属高发病率癌症之一，其病灶隐蔽，且多数早期患者无明显症状。同时胃周淋巴系统丰富，胃癌淋巴转移风险巨大。由于缺乏灵敏的早期诊断手段和高效的治疗方法，胃癌的死亡率在我国居高不下。本项目以胃癌诊疗为目标，深入研究灵敏度高、特异性强的胃癌成像探针以及诊疗一体化探针的构建方法和在体应用方法，为胃癌的高分辨成像与精准诊疗奠定相关理论和实验基础。具体研究内容包括：依托于先进的稀土纳米颗粒发展胃癌特异性的磁共振/上转换发光多模态分子影像探针，通过光敏剂的可控加载，探索可实施主动靶向成像及光动力治疗的纳米探针的构建方法；依托于临床转化前景广阔的磁性氧化铁纳米颗粒，制备胃癌T1/T2磁共振分子影像探针，并通过肿瘤化疗药物加载，构建可进行胃癌主动靶向成像及靶向治疗的纳米探针；结合合理的动物实验模型，研究发展胃癌高分辨成像及精确诊疗方法。

高分辨成像精准诊疗是本重点项目指南的核心内容，也是开展本重点项目研究的终极目标。本项目深入研究了灵敏度高、特异性强的肿瘤成像探针以及诊疗一体化探针的构建方法和在体应用方法，取得了如下成果：1）发展了多种性能优异的稀土多模态诊疗探针，还建立了稀土生物组织染色检测方法，为稀土探针的医学研究和应用奠定了基础。2）利用肿瘤微环境或外部刺激诱导纳米颗粒在肿瘤内部聚集，发展了肿瘤的高灵敏成像检测和精准诊疗探针；3）借助纳米材料独特的物理性质，发展了纳米探针介导的肿瘤光热、光动力、放射增敏等精准诊疗方法；4）发展了多种肿瘤微环境动态定量可视化方法，为高分辨成像精准诊疗奠定了重要的基础。