Synthesis And Application Of Near-Infrared Fluorescent Dyes Targeted Biomarkers

In recent years, a growing number of biomarkers have been applied to biological identification, disease diagnosis and medical treatment. It is a kind of special macromolecule related to cell growth and proliferation, which can be served as important indexes of some diseases. Fluorescence imaging has gradually become an effective tool for the localization and dynamic monitoring of biomolecules because of its easy operation, high sensitivity, good selectivity and non-invasive real-time monitoring capabilities. Taking advantage of the specific correlation between biomarkers and corresponding disease signal, we can develop a series of fluorescent probes targeted biomarkers. However, the excitation wavelengths of these probes were short, which results in interference from background auto-fluorescence, thus reducing detection sensitivity and selectivity. In this thesis, we developed two Nile blue based infrared probes targeted biomarkers, and they well solved the above problems in biological imaging.One kind of infrared dye Niblue-C6-IMC was designed and synthesized by using indomethacin as identify group and cyclooxygenase-2 (COX-2) as biomarker. The probe realized the specific combination with COX-2 in cancer cells. Niblue-C6-IMC has good biocompatibility and low cytotoxicity; it can recognize various COX-2 over-expressed cancer cells and locate in the golgi apparatus of cells. Importantly, Niblue-C6-IMC preferentially labeled cancer tissues and the tumors in mouse tumor model with deep tissue penetration capacity. It may be a promising molecular tool for guiding tumor resection during surgery.An infrared probe NBP was developed by using 5-bromobenzofuran-2-carboxylic acid, an inhibitor as the identifying group and protooncogene Pim-1 kinase as the biomarker. There is hydrophobic interaction between the inhibitor and the hydrophobic pocket near hinge region of Pim-1 kinase in cancer cells. NBP has good water solubility, photostability and biocompatibility; thus it can enter into cells at fast speed and distinguish cancer cells from normal ones effectively through fluorescence intensity. In addition, NBP could locate in the mitochondria of living cells, thus providing possibility for visual monitoring of Pim-1 kinase’s specific distribution within cancer cells.