Near-infrared Fluorescent Dyes:Construction、 Fluorescence Imaging And Photodynamic Therapy

In recent years,with the development of science life,due to the feature of non-destructive,visualization,high sensitivity and real-time imaging,fluorescence imaging technology is loved by many researchers.The development of fluorescent imaging technology is restricted by fluorescent dyes.Classical fluorophores such as coumarin,anthracene,fluoroboron dipyrrole,rhodamine B and cyanine have excellent photochemical properties,good stability,large molar extinction coefficient,easy modification,wide range of applications and other characteristics.They are widely used in fluorescence immunity,fluorescent probes(recognition of biologically active small molecules),organic photosensitizers(photodynamic therapy),solar cells,light-emitting diodes.NIR fluorescent dyes are widely used among many fluorescent dyes.This can be attributed to the strong tissue penetration ability of NIR light,which can weaken the background fluorescence of organisms and causes little damage to biological tissues.Among the above fluorescent dyes,the fluoroboron dipyrrole(BODIPY)fluorophore has excellent chemical properties,many structural sites that can be modified,high molar absorption coefficient,high fluorescence quantum yield,excellent photophysical and chemical properties and it is not easily affected by the external environment.(temperature,viscosity,p H,etc.).Many researchers are committed to the development of BODIPY in the direction of fluorescent probes and photosensitizers due to the above advantage.The most important thing is that fluoroboron dipyrrole can achieve near-infrared emission through 3,5 Knoevenagel condensation.While the absorption and emission wavelength of cyanine is within the NIR region.It is a relatively mature NIR fluorophore and has an irreplaceable position in the field of NIR fluorescence imaging.In this paper,based on fluoroboron dipyrrole skeleton,lysosome targeted photosensitizers were constructed and evaluated its photodynamic therapy effect.Then,an NIR and pure water-soluble fluorescent probe based on cyanine skeleton were constructed and evaluated its biological thiol recognition performance at cellular level.The main work is as follows:Chapter 2: Three basic NIR fluorescent molecules are synthesized.Firstly,based on quinoline BODIPY fluorophore,the NIR lysosome targeted photosensitizer BDP-lyso was synthesized by free radical reaction and Knoevenagel condensation reaction.Secondly,based on thiophene BODIPY fluorophore,the NIR lysosome targeted photosensitizer SBDP-Lyso was constructed by Knoevenagel condensation reaction.Finally,based on cyanine fluorophore,the pure water-soluble NIR fluorescent probe Hecy-NBD was synthesized by nucleophilic Aromatic substitution reaction and retro-Knoevenagel condensation reaction.Chapter 3: Photodynamic therapy is the process which uses light to activate photosensitizers to produce highly reactive oxygen species and it is a new method of tumor treatment.With quinoline BODIPY as the core,an NIR lysosome targeted photosensitizer BDP-Lyso was constructed for photodynamic therapy of cancer cells.Under NIR light excitation,BDP-Lyso could rapidly produce singlet oxygen.DCFH-DA confirmed BDP-Lyso could efficiently generate ROS in living cells.BDP-Lyso had low dark toxicity and high phototoxicity,which was verified by AO/EB double staining experiment.BDP-Lyso had good lysosomal co-localization ability.Scratch test showed that BDP-Lyso could effectively inhibit SGC-7901 cells migration.In a word,BDP-Lyso showed excellent results in intracellular photodynamic therapy.Chapter 4: With thiophene BODIPY as the core,a novel NIR and lysosome targeted photosensitizer SBDP-Lyso was synthesized and explored its potential application in photodynamic therapy of cancer cells and zebrafish.Under NIR irradiation,the singlet oxygen yield of SBDP-Lyso is as high as 44.1% with S atom and I atom double promotion of ISC.SBDP-Lyso had negligible dark toxicity and excellent phototoxicity.Singlet oxygen produced by SBDP-Lyso during PDT could effectively induce cancer cell apoptosis and inhibit A549 cell migration.As an excellent lysosomal targeted photosensitizer,SBDP-Lyso will show unlimited potential in photodynamic therapy of cancer cells.Chapter 5: The content of thiols in human body is closely related to diseases.With cyanine as the core,in this chapter,an NIR water-soluble and ratiometric fluorescence probe Hecy-NBD was designed and synthesized for real-time detection of Cysteine/Homocysteine/Glutathione.Hemicyanine was selected as the main fluorophore,nitrooxadiazole(NBD)was used as the recognition unit and fluorescence quenching group.Probe showed weak red fluorescence.With the addition of biothiols,probe showed ratiometric fluorescence change and showed low detection limit(GSH:50 nm;Cys: 81 nm;Hcy: 130 nm).Hecy-NBD had negligible cytotoxicity and been successfully applied to cell fluorescence imaging.In short,it would play an irreplaceable role in detection of biothiol related to diseases.