Design,Synthesis And Biomedical Application Of Aggregation-induced Emission Molecules

The unique features of aggregation-induced emission(AIE)molecules which are non-emissive or faintly emissive in solution,while highly emissive in the aggregated or solid state,can efficiently confront the aggregation-caused quenching(ACQ)of emission and are attracting much interest in recent years.Moreover,AIE-active molecules are usually characterized by their excellent photostability,bright luminescence and large Stoke shift and thus are widely applied in the field of bio/chemosensors,bioimaging,disease diagnosis and therapy,et al.Based on the unique properties of AIE molecules,here in this dissertation,we designed and synthesized three types of AIE-active functional molecules.Their applications in chemosensing,bioimaging,photodynamic therapy(PDT)of cancer and bacteria,and photothermal therapy(PTT)of cancer are studied.The main results are listed below:1)In view of that traditional fluorescent probes show quenched emission when used as test strips in visual detection,we designed and synthesized an AIE-active fluorescent probe(TM)with D-?-A structure.The probe TM shows large Stokes shift of 220 nm and good biocompatibility.TM exhibited high sensitivity and good selectivity to N₂H₄,and can be applied in fluorescent imaging of N₂H₄ in living MCF-7 cells.Additionally,thanks to the AIE characteristic of probe TM,visual detection of N₂H₄solution or vapor can be realized on test strips,which provide a good solution to the ACQ effect of traditional probes faced.2)A new strategy for constructing new AIE-active photosensitizers by oxidation enhanced reactive oxygen species(ROS)generation was proposed.By varying the oxygen numbers on the sulfur atom,three new AIE-active photosensitizers,namely,SF-2TPA,SFO-2TPA and SF2O-2TPA were obtained.The singlet oxygen(¹O₂)quantum yield increased gradually as the number of oxygen atom numbers increase on the sulfur atom.The ¹O₂ quantum yields of SF-2TPA,SFO-2TPA and SF2O-2TPA were measured to be 0.029,0.099 and 0.52 respectively.Among the obtained three new photosensitizers,SF2O-2TPA exhibited the highest ¹O₂ quantum yield and showed the strongest binding ability to proteins(the main target of ¹O₂ in cells),making it the most promising photosensitizer in PDT.Moreover,SF2O-2TPA also displayed high photodynamic antibacterial activity against gram(+)Staphylococcus aureus after activated by light.To enhance the water solubility and cell compatibility,SF2O-2TPA NPs were obtained by encapsulating of SF2O-2TPA into DSPE-PEG2000.Cell imaging results indicated that SF2O-2TPA NPs can penetrated cell membrane and efficiently generate inside living cells.SF2O-2TPA NPs exhibited certain photocytotoxicity,which make it promising to act as an anticancer agent in PDT.3)By introducing triphenylamine as the electron donor into traditional perylene diimide(PDI)or naphthalimide(NDI)skeleton with ACQ characteristic,new AIE-active PDI-2TPA and NDA-2TPA were obtained through a simple one-step synthetic process.Both PDI-2TPA and NDA-2TPA featured with D-A-D structure show strong near-infrared emission.Then PDI-2TPA and NDA-2TPA were encapsulated with DSPE-PEG2000 respectively to obtain AIE nanoparticles PDI-2TPA NPs and NDI-2TPA NPs.Results indicated that PDI-2TPA NPs and NDI-2TPA NPs remain their strong emission in the NIR region and exhibited high photothermal conversion efficiency.PDI-2TPA NPs can penetrate cell membrane and act as a NIR bioimaging probe for cancer cells.Additionally,after activated by light,PDI-2TPA NPs can be used to kill cancer cells by PTT process.The work here provides a facile and efficient strategy for NIR-guided photothermal therapy of cancer and may find great promise in the clinical application of cancer diagnosis and treatment.