Design,Synthesis And Photodynamic Activity Of BODIPY-based Photosensitizers

Photodynamic therapy（PDT）is a new clinical treatment for cancer and non-malignant lesions in recent years.Under irradiation by the light with a specific wavelength,the photosensitizers accumulated in tumors react with oxygen（³O₂）to produce reactive oxygen species（ROS）,which oxidize and then k ill the tumor cells.PDT is a potential technology of treating cancers.The systemic toxicity can be greatly reduced by tumor-targeting of the photosensitizer and local irradiation on the tumor sites.Photothermal therapy（PTT）is also a new treatment for cancer,which allow local tumor temperature to reache a certain temperature（above 42oC）by photothermal conversion effect to kill anti-tumor cells.Continuous consumption of oxygen during PDT aggravate hypoxia of the tumor cells and reduce therapeutic effect.PTT can make up this disadventage of PDT because of its independence of oxygen.Therefore,PTT will greatly improve the therapeutic effect when it synergizes with PDT.Photosensitizer plays a vital role during PDT process.Boron dipyrromethene（BODIPY）is a kind of novel photosensitizer because of high extinction coefficient,high singlet oxygen yield,and high resistance to photo-bleaching and light-dark toxicity.In this thesis,BODIPY core was modified by different substitution in the styrene part to achieve a regulation of molecular basicity.We studied their photodynamic activity,photothermal effect and subcellular localization in the tumor cells.Moreover,polymeric photosensitizers poly-BODIPY with different conjugation were designed and synthesized.We evaluated their photophysical and photochemical properties,such as absorption spectra,fluorescence spectra,singlet oxygen generation and photothermal effect.In this paper,the specific contents are summarized as follow:In Chapter 1 we briefly describe the mechanism,research development of the photosensitizer and their application in PDT and PTT.Organelle-targeting research is also demonstrated.The basis and research content of this paper is clarified on this basis.In C hapter 2 we design and synthesize organelle-targeting BODIPY photosensitizers.Four kinds of BODIPY photosensitizers were synthesized by introducing three basic groups or a non-basic group in the styrene part.Their photophysical and photochemical properties were measured.The result shows that introduction of basic group can enhance the singlet oxygen generation capacity.According to the data of cytological evaluation in vitro,we found that introduction of basic group can enhance the cellular uptake,photodynamic activity,photothermal effect,lysosomal colocalization and photocytoto-xicity.In Chapter 3 we design and synthesize two kinds of polymeric photosensitizers poly-BO DIPY via a sonogashira coupling reaction.Poly-BODIPY 1 and 2 are synthesized from iodinated BODIPY 1’and 2’,respectively.The results show that poly-BODIPY exhibited the longer maximum absorption and fluorescence emission wavelength.Poly-BODIPY 2 exhibited the longest maximum absorption and fluorescence emission wavelength,which is in near-infrared region（NIR）.It also exhibited the higher singlet oxygen and better photothermal conversion effect when using NIR light.