Design,Synthesis And Bioapplications Of B,O-Chelated Azadipyrromethene Organic Phototherapy Agents

Near-infrared organic small molecule phototherapy reagents have been widely used in the field of optical cancer treatment due to their natural degradability,good biocompatibility,simple synthesis,and rich variety.Among them,Aza-BODIPY organic dye molecules are outstanding among many organic phototherapy reagents due to their excellent light and thermal stability,obvious red-shift absorption,high molar extinction coefficient,good biocompatibility and multiple functional modification sites.They are widely used in bioimaging,photodynamic therapy,photothermal therapy and multimodal imaging guided diagnosis and treatment integration.In this study,by rationally modifying the structure of Aza-BODIPY,we designed and synthesized B,O chelated Aza-BODIPY derivatives with different cancer treatment methods.Their molecular structure,photophysical properties and biological applications were characterized to explore their in vitro cancer cell killing effect as well as in vitro and in vivo imaging diagnostic capabilities.The research contents of this thesis mainly include the following two parts:(1)Based on the multi-functional reaction sites of Aza-BODIPY dye molecules and the strong electron-donating ability of 2-methylthiophene,a single thiophene modified B,O chelating Aza-BODIPY organic phototherapy reagent A-BDP with D-A structure was designed and synthesized,which laid the foundation for its use in near-infrared photothermal therapy.The halogen-substituted Aza-BODIPY derivative IA-BDP was obtained by introducing heavy atom iodine at its 2,6 positions,which effectively promoted the rate of photon intersystem crossing and induced the molecule to produce singlet oxygen,thereby enhancing the photodynamic therapy effect.The water-soluble nanoparticles IA-BDP NPs were prepared by coating the amphiphilic polymer F127.Under the near-infrared light irradiation of 808 nm,the photothermal conversion efficiency of 55.2% and the singlet oxygen quantum yield of8.36% were obtained.It can be used for photothermal and photodynamic synergistic therapy of cancer cells.(2)Based on the π-conjugated planarity and strong electron-donating ability of the dithienyl group,the D-A type B,O chelating Aza-BODIPY derivative BTA-BDP with a large π-conjugated structure was further designed,and a flexible long alkyl chain with a certain steric hindrance effect was introduced to avoid the face-to-face stacking between the molecules of the large conjugated structure,so that the BTA-BDP molecules formed a J-aggregate with absorption and emission maximum redshift in a sliding stacking arrangement.The BTA-BDP NPs prepared by F127 encapsulation have a photothermal conversion efficiency of 69.6% and a NIR-II fluorescence quantum yield of 4.37% under 808 nm laser irradiation,which can achieve good photothermal killing effect in cancer cells under the guidance of photothermal and NIR-II fluorescence dual-mode imaging.