Amphiphilic Fluorescent Materials With Aggregation-induced Emission Characteristic For Cell Imaging And Photodynamic Therapy

Aggregation Induced Emission（AIE）materials have solved the problem of traditional fluorophore aggregation-induced quenching（ACQ）in biological systems,opened up the application of fluorescent materials in the field of biomedicine.Because of the unique properties of AIE fluorescent probes,a large number of AIE molecular probes and nanoprobes（NP）have been developed for the fields of biosensors,cell imaging,photodynamic and photothermal therapy.Relevant studies have shown that the occurrence of cancer is closely related to bacterial infection,while the application of traditional chemotherapy drugs and antibiotics in clinical practice is restricted by drug resistance.Photodynamic therapy（PDT）has become a promising method for antibacterial and cancer treatment due to its advantages of non-drug resistance,non-invasion,low cytotoxicity and selective targeting.In recent years,it has been found that some red emission AIE dyes not only have good imaging ability,but also produce singlet oxygen under light conditions,which are new PDT photosensitive reagents.In this paper,based on tetraphenyl ethylene molecules with AIE properties,several red emission fluorescence probes with amphiphilic properties were synthesized through different molecular designs,and we studied its applications in biosensors,cell imaging,organelle targeted cancer therapy and antimicrobial.The specific contents are as follows:（1）Taking typical AIE fluorophore tetraphenyl ethylene as the basic unit,according to the push-pull electronic effect,a near-infrared amphiphilic fluorescent probe TPETHPy-PEG with high ROS production capacity and long wavelength emission was designed and synthesized.The modified pyridine cation enhanced the targeting ability to mitochondria and bacterial membrane,and the introduction of polyethylene glycol（PEG）enhanced the hydrophilicity and biocompatibility.DLS test showed that TPETHPy-PEG could self-assemble into nanoparticles with good dispersion in aqueous solution.Fluorescence spectrum data show that the maximum emission peak is located in the near infrared region of 640nm and has a large Stokes shift.Therefore,it can be used for cell imaging targeting mitochondria under the interference of low background fluorescence.Based on the fact that TPETHPy-PEG has higher singlet oxygen generation capacity than commercial photosensitizer RB,we studied the photosensitivity of TPETHPy-PEG.The experimental results showed that it not only has a good photodynamic therapy effect on cancer cells,but also has a good photodynamic antibacterial effect on Staphylococcus aureus and Escherichia coli at a low working concentration（5μM）.It can be used as an excellent broad-spectrum bactericidal photosensitizer.（2）In the third chapter,we designed and synthesized two amphiphilic dyes,TPEPy-Al and TPEPy-PEG,containing hydrophobic C12 alkyl and hydrophilic polyethylene glycol（PEG）respectively,using methoxy and tetraphenyl ethylene as electron donors and pyridine salt cation as electron acceptant.Nanoparticles with spherical morphology can be formed by self-assembly in aqueous phase with an emission peak of 625nm.The modified alkyl chain on the molecule TPEPy-Al increases its solubility in organic solvents and forms nanoparticles with abundant positive charge on the surface and weak luminescence in water.After combining with negatively charged ATP,they gather to enhance the fluorescence,which can be used for specific recognition of ATP anions.In addition,both probes can produce cytotoxic singlet oxygen（¹O₂）under light conditions,which can be used as an excellent photosensitizer for targeting mitochondria-guided photodynamic therapy of cancer cells.The antibacterial activity of Escherichia coli and Staphylococcus aureus was further investigated,the experimental results show that TPEPy-Al and TPEPy-PEG with positive charge and amphiphilic property can target the bacterial membrane surface with a lot of negative charge,and produce ¹O₂ under light to destroy the bacterial membrane,which can realize the fluorescence imaging of bacteria and good bacteriostatic effect.