缺氧和还原响应的新型近红外荧光探针用于肿瘤微环境成像的研究

Tumor microenvironment plays a crucial role in tumorigenesis, development and metastasis. Tumor cells have obvious heterogeneity, but the tumor microenvironment is relatively stable, with hypoxia, reducing environment, slightly acidic environment and other characteristics. In-depth study of the tumor microenvironment can not only help us better understand the biological behaviors of cancer cells as well as the interaction between cancer cells and tumor microenvironments, but also provide new ideas and directions for drug screening, therapeutic efficacy prediction, cancer diagnosis and treatment. However, there is still a lack of technical tools to real-time quantitatively analyze such tumor micro-environments in vivo. Fluorescence imaging techniques have been widely used in basic research and clinical diagnosis due to their advantages of real-time imaging, high sensitivity, high resolution, small damage and non-radioactivity. In this project, we will develop fluorescence imaging probes that can specifically respond to the factors such as GSH and hypoxia-related reductase in tumor microenvironment to realize the quantitative or semi-quantitative analysis in vitro and in vivo. In addition, we will also develop fluorescent probes that can simultaneously respond to GSH and hypoxia-associated reductase in tumor microenvironment, hoping to obtain multi-dimensional information of cancer cells and the tumor microenvironment, and thus provide new ideas and tools for cancer investigation, diagnosis and therapy.

肿瘤微环境对肿瘤的发生、发展和转移起着重要作用。肿瘤内的癌细胞具有明显的异质性，但肿瘤微环境相对比较稳定，具有乏氧、还原环境等特征。对肿瘤微环境进行深入研究，不仅能够更好地理解癌细胞的各种生物学行为、癌细胞与各种肿瘤微环境的相互作用情况，还能为药物筛选和疗效预测、癌症诊断与治疗提供新的思路和方向。目前比较缺乏在活体上对上述肿瘤微环境进行实时定量分析的技术手段。荧光成像技术具有实时、灵敏度高、分辨率高、损伤小、无放射性等优点，已被广泛应用于基础研究和医学诊断中。本项目拟构建能够特异性响应肿瘤微环境中还原型谷胱甘肽（GSH）、乏氧相关还原酶等特定因素的比率荧光成像探针，从而实现对肿瘤微环境的实时分析与监测。此外，还将构建肿瘤微环境中GSH和乏氧等因素同时响应的荧光成像探针，希望能获得肿瘤内癌细胞和肿瘤微环境的多维信息，从而为癌症研究和诊断治疗提供新的思路和技术手段。

肿瘤微环境对肿瘤的发生、发展和转移起着重要作用。肿瘤内的癌细胞具有明显的异质性，但肿瘤微环境相对比较稳定，具有微酸、乏氧、还原环境等特征。对肿瘤微环境进行深入研究具有重要理论意义与应用前景。目前比较缺乏在活体上对上述肿瘤微环境进行实时定量分析的技术手段。荧光成像技术具有实时、灵敏度高、分辨率高、损伤小、无放射性等优点，已被广泛应用于基础研究和医学诊断中。本项目构建了几种能够特异性响应肿瘤微环境相关因素的响应型荧光成像探针，从而实现对肿瘤微环境的分析与监测。此外，我们构建了几种其他类型的成像与诊疗探针，并进行肿瘤成像与治疗研究。本项目希望能为癌症研究和诊断治疗提供新的思路和手段。