具有双光子激发-近红外发射特征的靶向激活型荧光探针用于活体肿瘤的早期成像研究

肿瘤早期成像诊断是降低癌症死亡率最有效的措施之一。双光子具有深层区域聚集、反斯托克斯发光等优势，因此双光子成像技术可以在机体组织中得到更高信噪比的荧光信号，进而实现活体的肿瘤早期诊断。但是，现有双光子荧光小分子探针的最大发射波长普遍位于可见光区域（<650 nm），机体组织的强烈干扰致使发射波长位于该范围的双光子荧光探针无法实现深层高时空分辨成像，限制了双光子成像技术在活体成像中的进一步应用。因此，在本课题组前期研究基础上，本项目拟设计合成一系列最大发射波长位于近红外发射区域（650-900 nm）的双光子荧光分子，并在优选出的荧光分子中同时引入不同机制的肿瘤主动靶向和微环境激活基团，得到具有双光子激发-近红外发射特征的肿瘤靶向激活型荧光分子探针，并利用其对肿瘤的“协同识别”作用实现活体内原位瘤及转移瘤的高精准动态可视化成像监测，为肿瘤的早期诊断、手术导航、药物疗效评价等研究奠定基础。

Early imaging diagnosis of cancer is one of the most effective measures to control cancer mortality. Due to the advantages of deeper region aggregation and anti-Stokes luminescence, two photon imaging technology can obtain the higher signal to noise ration of fluorescence signals in the tissues, thereby realizing early diagnosis of living tumors. However, the emission wavelength of most exist two-photon fluorescence probes generally locate in the visible region (<650 nm) which is strongly interfered by the body tissues. Therefore, the high resolution spatiotemperal imaging can not be obtained which limits the further application of two-photon imaging technology in deep imaging in vivo. Based on the previous result of our group research, this project intends to design and synthesis a series of two-photon dyes which has the properties of near infrared emission（650-900 nm）, After that, we are going to introduce the tumor targeting groups with different mechanism and tumor microenvironment activation groups into the selected dyes for the tumor-targeting and tumor-activation fluorescent probe. Then, the collaborative recognition ability of tumor will be investigated to achieve high-precision dynamic visual imaging of in situ tumor and metastatic tumor, which will lay the foundation for early diagnosis of tumors, surgical navigation, drug efficacy evaluation and other research.