| Organic fluorescent dyes,especially organic small molecule fluorescent dyes,are playing crucial role in the detection of disease-related biomarkers due to their biocompatibility,good selectivity and high sensitivity.This has gradually become one of the important methods for early clinical diagnosis of diseases.Aggregation-induced emission luminogens(AIEgens),with excellent photophysics,photochemical properties and low toxicity bio-tissue in high concentrations,which will be widely applied in the biological field,such as fluorescence imaging and organelle tracking,disease diagnosis and treatment.Importantly,the development of AIEgens provides a novel research method for fluorescence-guided photodynamic therapy of malignant tumors.In this thesis,four series of fluorescent dyes with unique properties were prepared by using molecular functionalization design strategy,and their application values in biomarker detection,organelle tracking and tumor photodynamic ablation were explored.The research contents are as follows:1.Two near-infrared(NIR)fluorescent dyes,TCF-Cys and AXPI-Cys,were prepared based on the reactivity between acrylyl and cysteine(Cys).The excitation and emission wavelengths of TCF-Cys were located in 650-900 nm,which could not only avoid the damage of excitation light to biological tissues but also reduce the influence of autofluorescence of tissues in biological imaging.AXPI-Cys was successfully used for rapidly colorimetric and fluorescence detection of Cys in urine samples due to its good water solubility.They all showed high selectivity and sensitivity,short response time(about 7 min)and low detection limit(TCF-Cys: 0.1323 ?M;AXPI-Cys: 0.0489 ?M)for Cys.The living cells imaging studies have shown that two probes could be used for online and real-time monitoring of intracellular endogenous and exogenous Cys.Finally,TCF-Cys and AXPI-Cys were applied for In Situ detection of Cys in vivo.2.A series of AIEgens(MPAA,MPAN and MPAT)were prepared by functionalizing triphenylamine derivatives with morpholine rings,which could specifically stain intracellular lysosomes.On the basis of MPAA,acrylonitrile and 1,3-indenone were introduced for obtaining MPAN and MPAT,respectively,and the conjugated systems were increased.Resulting in the maximum emission wavelength of MPAN and MPAT was redshifted from530 nm to 614 nm and 677 nm relative to MPAA,respectively.The AIEgens were used for specific staining and tracing of lysosomes,respectively,due to excellent biocompatibility,high light stability and brightness,which was of great significance for the physiological and pathological studies of lysosomal-related diseases.Excitedly,the MPAT under light irradiation could quickly produce reactive oxygen species(ROS),and MPAT(40 ?M)could inhibit cancer cells activity as high as 89% under light irradiation for 30 min.3.A series of NIR AIEgens(TTI,MTTI and MOTTI)were prepared by three-fragment molecular assembly engineering.TTI was used for high fidelity dynamic tracking lipid droplets(LDs,Pearson’s coefficient is 0.95)due to its strong lipophilic(Clogp of 8.34),large Stokes shift(170 nm),excellent photophysical properties and biocompatibility.At the same time,TTI self-assembled into particles with an average diameter of 196.57 nm in PBS solution,and had a high ROS generation efficiency under white light irradiation.The viability of Hep G2 cells was inhibited more than 80% with TTI(10 ?M)under white light irradiation for 30 min.The cell migration and apoptosis assay showed that TTI could effectively inhibit wound healing and eventually lead to the death of Hep G2 cells under light condition.4.Amphiphilic AIEgens(Me DCTPy-OH,Hy DCTPy-OH,Me DCTPy-ET and Hy DCTPy-OH)containing TPA and pyridinium salt units were designed and prepared.The These AIEgens have typical AIE properties,excellent photophysical properties and photochemical properties in solution.Amphiphilic AIEgens hardly emit light in aqueous solution,and have red fluorescence emission after co-assembly with liposomes.Cell imaging studies have shown that amphiphilic AIEgens can specifically stain cell membranes and have a high efficiency of ROS generation in cells under light irradiation.Cell migration and apoptosis experiments show that AIEgens can effectively inhibit the migration of living cells under light,and cause cell membrane lysis and cause cell necrosis.Finally,the MTT experiment showed that AIEgens has a high inhibitory rate on the activity of common cancer cells under light irradiation. |
