Cyanine Derivatives For Cysteine Detection And Design And Synthesis Of New Photosensitizers

Due to the advantages of high sensitivity,high selection,low cost,and easy operation,organic small molecule fluorescent dyes have reported more and more new organic small molecule fluorescent dyes in recent years.Fluorescent probes have been widely used in the fields of quality inspection,environmental protection and biomedicine.Among the small organic fluorescent dyes,cyanine dyes have become the most studied in the field of bioanalysis and bioimaging due to their large molar extinction coefficient,many modification sites,long absorption and emission wavelengths,and low biotoxicity.Potential and development prospects of a class of organic fluorescent dyes designed for cyanine probes that can be used for biological detection and imaging in living cells and organisms have high chemical and biological applications.Cysteine,as an important biological thiol in the human body,participates in a variety of physiological processes.According to previous research reports,the imbalance of cysteine levels in the human body is related to liver injury,cardiovascular disease and cancer.Disease related.Therefore,it is of great significance to develop probes capable of detecting and biological imaging cysteine in vivo.In addition,photodynamic therapy(PDT)has become an emerging tumor treatment program due to its good targeting and low normal tissue damage,but the effect of photodynamic therapy is limited by tissue penetration depth and The activation of cell protection mechanisms,so the development of new photosensitizers is very important for improving the therapeutic effect of PDT on tumors.In this paper,five-membered ring cyanine dyes are used as fluorophores,and the design and synthesis of cysteine probe in vitro detection,bioimaging,and p H-responsive photosensitizers are achieved through different structural modifications.It mainly includes the following work:1.Cysteine(Cys),as one of the biological thiols with high content in the body,participates in various physiological processes including intracellular redox reaction,cell proliferation and signal transduction.Cys level imbalance has become one of the hallmarks of many diseases.Here,we designed and synthesized a water-soluble near-infrared fluorescent probe NIR-Cy2 for detecting the endogenous and exogenous Cys of cells.The skeleton of the probe is composed of a five-membered ring cyanine dye,and two sulfonic acid chains are modified,which greatly increases thehydrophilicity of the probe and solves the disadvantage of poor water solubility of cyanine derivatives.Before the reaction of Cys with the probe,the emission wavelength of the probe is about 865 nm.When the thiol group on Cys attacks the chlorine atom on the probe,due to the influence of thermodynamic factors,the intramolecular N,S exchange reaction will occur quickly.The emission wavelength of the laser is blue shifted to about 725 nm,and the ratio of the fluorescence intensity of the probe at these two places is linearly related to the concentration of Cys.The probe can respond to Cys with high sensitivity and selectivity,and can image the endogenous and exogenous Cys of cells.2.Photodynamic therapy(PDT),as an emerging tumor treatment program,has the advantages of high targeting,controllable treatment area,and small damage to normal tissues compared with traditional treatments such as surgery,radiotherapy and chemotherapy.It has become a hot research direction in the field of biomedicine in recent years.However,the therapeutic effect of PDT is limited by the excitation and emission wavelengths of the photosensitizer,which cannot reach deep tissue penetration depth;and the activation of the tumor cell protection mechanism,the photosensitizer is degraded or cleared by the cells.Therefore,it is of great significance to develop a near-infrared photosensitizer that can inhibit the protective mechanism of tumor cells.Therefore,we designed and synthesized a near-infrared photosensitizer PDT-Cy that can enhance the therapeutic effect of PDT by inhibiting cell autophagy,using a five-membered ring cyanine dye as a fluorophore,modified on the indole of the cyanine dye Heavy atomic iodine increases its singlet oxygen quantum yield.The probe can respond according to the p H of the environment.After entering the cell,the probe can be selectively enriched in the mitochondria.When the autophagy process occurs,the probe forms the autophagosome with the damaged mitochondria and is transported to the solution.In the enzyme body,the emission wavelength of the probe red-shifted from 630 nm at physiological p H to 750 nm in the low p H environment of the lysosome.After the probe enters the lysosome,PDT treatment generates singlet oxygen to inhibit the cell autophagy pathway,thereby enhancing the therapeutic effect of PDT.Our work provides new ideas for the design of photosensitizers that inhibit cell autophagy to enhance the therapeutic effect of PDT.I believe that the photosensitizers we design can become a meaningful tool in tumor treatment.