近红外分子/纳米荧光探针制备及其在肿瘤分子成像分析中的应用研究

Cancer is one of the most pressing public health concerns. Early detection of localized and disseminated tumor cells in patients is very critical to the success of cancer therapy and improvement of patients' survival rates. Near infrared (NIR) fluorescence imaging is emerging as promising modality for the cancer detection and has been dedicated immense attention. Satisfactory cancer NIR fluorescence imaging needs excellent NIR probes. However, the development of multifunctional agents for simultaneous tumor targeting and NIR fluorescence imaging is still a big challenge. Here in, novel NIR functional fluorescent dyes for cancer targeting and imaging will be designed and synthesized. By using various strategies cancer targeting activatable NIR probes will be developed, and their preferential uptake and rentention in tumor cells and tissues will be investigated, their applications for cancer early detection and fluorescence-guided resection will be explored. We believe these newly developed multifunctional NIR dyes will broaden current concept of tumor targeted imaging and hold promise to make an important contribution to the diagnosis and therapeutics for the treatment of cancer.

恶性肿瘤是当今世界严重威胁人类健康和生存的重大疾病，肿瘤的早期诊断、发现、治疗是关键。近红外光学分子成像备受关注，但肿瘤靶向可激活近红外荧光探针的设计制备面临巨大挑战。本申请项目将设计合成系列GeR或其它（如Cyanine dyes）近红外荧光染料，采取各种策略赋予其可激活性和肿瘤靶向性，建立针对典型肿瘤标志物的高特异性、高灵敏检测方法，应用于肿瘤细胞及组织的成像分析，探索其在肿瘤早期诊断、内窥镜影像分析以及辅助界定肿瘤病灶边缘指导手术切除治疗中的应用。本研究不仅为肿瘤医学基础和应用研究提供有效的手段，其探针设计合成策略也为其它分子影像学试剂的研究提供思路。

本项目基于肿瘤与正常细胞组织在氧化还原/酸度微环境、酶活性、表面受体表达等方面存在的显著差异，设计合成了系列近红外荧光染料GeP/SiP，构建了基于小分子、碳量子点、DNA的肿瘤靶向、可激活近红外分子/纳米荧光探针，建立了肿瘤细胞氧化还原/酸度微环境、透明质酸酶、表面叶酸/透明质酸受体等的高特异性、高灵敏荧光分析方法，应用于肿瘤细胞的特异性标记和生物活性物质分析。项目成果不仅为肿瘤医学基础和应用研究提供有效的手段，其探针设计合成策略也为其它分子影像学试剂的研究提供思路。