稀土上转换纳米探针用于癌症转移淋巴结精准示踪和成像导航手术的应用研究

Precision surgical resection of cancer-related lymph nodes is a significant issue in clinic. The most important thing is to achieve 'seeing clearly and cutting accurately'. At present, radiolabeling small molecule fluorescent probes are commonly used in surgical navigation. However real-time information cannot be obtained from the above techniques about whether lymph nodes are invaded by cancer cells, which seriously affects the operation and prognosis. In order to explore new methods for diagnosis and treatment of metastatic lymph nodes, this project proposes a new strategy for precise tracing and imaging of lymph nodes based on micro-temperature sensitivity of upconverted luminescence signals based on rare-earth upconversion nanomaterials. By studying the correlation between upconverted optical temperature sensing and the physiological state of cancer metastasis microenvironment, an optimized micro-area temperature detection and multi-mode imaging probe is constructed. This project tries to solve the problem of "seeing clearly and cutting accurately" through the establishment of lymph node dissection platform under imaging navigation, and realize the precise resection of lesions at millimeter scale, which will provide a new strategy for imaging navigated surgery.

癌症相关淋巴结的精准手术切除是临床医学研究中的一项重要课题，其中最核心的是要做到“看得清、切的准”。目前临床手术导航多用放射性标记和小分子荧光探针结合的技术，难以实时获得淋巴结被癌症细胞转移的信息，严重影响了手术顺利进行和预后效果。本项目提出以稀土上转换纳米材料为基础的癌症转移淋巴结精准示踪新策略。利用上转换发光温度敏感这一特点，通过研究上转换光学温度传感与癌症转移微环境生理状态之间的相关性，构建优化的纳米微区温度检测和多模式成像于一体的探针，实现对癌症转移淋巴结的快速实时示踪和导航切除，解决“看得清、切的准”的关键问题，为癌症转移诊断提供新方法，为成像导航手术提供新策略。

生物体炎症反应引起的微区升温与许多重大疾病都有强烈的相关性，对其进行精准示踪对研究各种生理病理过程背后机制具有重大意义。稀土纳米发光材料由于其独特的发光过程，在生物成像领域具有显著优势，但是开发能够简单合成的、主动靶向的稀土纳米微区温度传感器依然是一个极大的挑战。本项目通过研究精准调控材料结构、表界面性质、温敏性能等科学问题，成功设计合成了多模态耦合的稀土纳米复合结构，基本掌握了结构参数与光学性质、温度传感性能的内在关系，成功探索了靶向性配体修饰新方法，实现了对癌症转移淋巴结的快速实时示踪和导航切除的应用。本项目的研究为设计合成炎症微区示踪的稀土纳米复合材料提供了重要实验依据，建立了微区温度快速精准检测方法。通过本项目的实施，目前已在国内外重要学术期刊上发表相关SCI论文3篇，影响因子均大于10.0，其中影响因子大于30.0的1篇。研究成果得到了国内外同行学者的广泛关注和肯定。项目博士生参与人员4名，其中已顺利毕业3名，在读1名。指导本科生2名，均顺利毕业。