Preparation Of Dual-Organelles-Targeted Organic Photosensitizers And Their Application In Tumor Photodynamic Therapy

Due to the aging population,chronic diseases,poor lifestyle and other factors,the incidence and mortality rate of cancer are getting higher,which has become an important factor threatening human life and health.There are many limitations in traditional cancer diagnosis and treatment methods.As a new cancer treatment method,photodynamic therapy has attracted more and more attention with its unique advantages.Design and construct photosensitizers with specific organelle targeting,near-infrared fluorescence emission,large Stokes shift,high singlet oxygen yield and good biocompatibility,and apply them to image-guided photodynamic therapy,which is of great significance for the diagnosis and treatment of cancer.In this dissertation,near-infrared organic photosensitizers with aggregation-induced emission has been designed and synthesized.They have the advantages of lysosomes and mitochondria dual targeting,high singlet oxygen yield,good biocompatibility and two-photon imaging ability,which can be used for fluorescence image-guided photodynamic therapy.The work of this dissertation is mainly divided into the following two parts:(1)Selecting triphenylamine as the electron donor,2,1,3-benzothiadiazole and 2,3-dimethylbenzo[d]thiazole-3-iodonium groups as combined electron acceptors,and thiophene as the π bridge to form a new near-infrared organic photosensitizer ADB with D-A-π-A structure.ADB displays bright near-infrared fluorescence at 736 nm,and has the advantages of dual-organelles targeting mitochondria and lysosomes,large Stokes shift(203 nm),high efficiency of active oxygen generation(0.442),two-photon imaging,good biocompatibility and light stability.In vitro and vivo experiments show that ADB performs high-quality two-photon imaging in cells and tissues,and can effectively inhibit the growth of mouse tumors under white light irradiation.It has the potential to become a efficient two-photon biological imaging and photodynamic therapy photosensitizer for clinical applications.In addition,this work provides a new idea for the design and construction of organic photosensitizers targeting dual organelles.(2)Selecting triphenylamine and 4-(4-ethyl-1-piperazinyl)aniline as the electron donors,2,1,3-benzothiadiazole as the combined electron acceptor,and thiophene as the π bridge to form a Schiff base type near-infrared organic photosensitizer TBA-R with D-A-π-D structure,and packing it in bovine serum albumin to form nanoparticles(TBA-R NPs).TBA-R NPs have the advantages of pH response,dual-organelles targeting,near-infrared emission(720 nm),large Stoke shift(200 nm),two-photon imaging,and high efficiency of active oxygen generation.In vitro experiments show that TBA-R NPs have a good response to intracellular pH changes and it can effectively detect intracellular pH through fluorescence intensity changes.In addition,it can effectively produce reactive oxygen species under white light irradiation to promote cancer cell death,having the potential to become pH fluorescence probe and photosensitizer for effective treatment of cancer.