Construction Of Aggregation-induced Emission Bioprobes And Their Application In Photodynamic Therapy

Fluorescence imaging is an indispensable technology in biomedical research due to the advantages of good sensitivity,rapidity,real-time and easy operation.It is helpful to reveal the potential rules of biological system.Organic small-molecule bioprobes are widely used in bioimaging owing to their excellent properties,such as precise structure,controllable biocompatibility,and diverse modification strategies.Organic molecules with aggregation-induced emission characteristics do not emit light or emit light weakly in solution,but show strong emission in the aggregation or solid state.They are suitable for biological applications such as high-quality fluorescence imaging and long-term fluorescence tracking in physiological environment.Photodynamic therapy,as a non-invasive treatment method,has the advantages of high spatiotemporal precision,low toxicity,controllable and repeatable treatment.It has been widely concerned in the treatment of solid tumors.Photodynamic therapy requires photosensitizers to produce reactive oxygen species under illumination to play a therapeutic role.In recent years,the emerging photosensitizers with aggregation-induced emission can simultaneously emit strong fluorescence and efficiently produce reactive oxygen species after aggregation in cancer cells,which is easy to achieve image-guided photodynamic therapy,and has attracted the attention of researchers.In this thesis,three types of bioprobes have been designed and synthesized,and their performances in biological imaging and photodynamic therapy have been explored.The research content is mainly divided into the following three parts:（1）Preparation and application of pyridine-based probes.Positively charged hydrophilic pyridinium salt groups are introduced into molecules,which makes the molecules easy to selectively target cancer cells.The UV-Vis test showed that DBTPF₆ had respectable photostability;MTT test showed that DBTPF₆ had good cytocompatibility and could be used for cell imaging research.Under light excitation,DBTPF₆ can be used for photodynamic ablation of cancer cells.（2）Preparation and application of benzothiadiazoletriazole probe TPE-TBZ-TPE and TPA-TBZ-TPA were obtained by Suzuki coupling reaction.Photophysical experiments were used to determine their absorption peaks,emission peaks,and photostability.The twisted intramolecular charge transfer and aggregation-induced emission characteristics of TPE-TBZ-TPE and TPA-TBZ-TPA can be obtained by fluorescence spectroscopy.Cell fluorescence imaging experiments showed that they were located in lipid droplets in cells.Under white light irradiation,they can produce reactive oxygen species,which can be used in photodynamic therapy.（3）Azophenyl probe for the detection of hypoxic tumors.The synthesized TPE-bi-Azo can undergo reversible photoisomerization,which was characterized by UV-Vis absorption.The non-fluorescent TPE-bi-Azo can be reduced by sodium disulfite to produce fluorescent TPE-Am.At the cellular level,it was found that after the TPE-bi-Azo was incubated with cancer cells,the fluorescence of cancer cells gradually increased with the decrease of oxygen concentration,indicating that the azo bond of TPE-bi-Azo could be reduced to TPE-Am by the reductase and light up the cells,which could be used for hypoxia detection of tumor cells.