Design,Synthesis And Biological Applications Of Reactive Fluorescent Probes For Hydrogen Peroxide And Polyamine

Aggregation-induced emission(AIE)-based reactive probes have received a lot of attention in the biomedical field due to their low background interference,high signal-to-noise ratio and good photostability,which have obtained many good achievements in the research.Reactive oxygen species(ROS),such as hydrogen peroxide(H₂O₂),are important products of oxygen metabolism that can accumulate and lead to intracellular oxidative stress if not properly regulated.Many diseases associated with human ageing,including cancer,vascular disease and neurodegenerative disorders have a strong oxidative stress component.Polyamines are prevalent and important components of mammalian cells,and they have multiple functions,playing key roles in nucleic acid and protein synthesis,gene expression,protein function,protection against oxidative damage,regulation of ion channels,and maintenance of cellular macromolecular structure.In cancer and other hyperproliferative diseases,the metabolism of polyamines is often dysregulated,causing elevated levels of polyamines and leading to excessive tumour transformation and progression.Based on the important role of H₂O₂ and polyamines in physiological processes,probes capable of detecting H₂O₂ and polyamines with the responsive phenotype of AIE have promising applications in the diagnosis and treatment of related diseases.In this paper,AIE-based reactive probes were rationally designed and successfully synthesized for the detection of H₂O₂ and polyamines.Based on a detailed study of the detection mechanism,they were used for cell imaging as well as photodynamic therapy.In Chapter 2,an H₂O₂-activated and near-infrared AIE fluorescent probe(TPYS)was successfully synthesized for the specific imaging of lipid droplets(LDs)based on an ingenious molecular structure design.TPYS showed almost no fluorescence in DMSO/PBS buffer(1:1,v/v,p H 7.4),the emission peak at 590 nm was significantly enhanced and the solution emitted bright yellow fluorescence after the addition of H₂O₂.TPYS has a high sensitivity for H₂O₂,the limit of detection was 0.83?M.It has good selectivity for H₂O₂,and other 16 kinds of anions,5 kinds of amino acids and 4 kinds of reactive oxygen/nitrogen species do not interfere with the detection of H₂O₂.The reaction mechanism is the in situ release of the AIE-active molecule TPY after the oxidation of TPYS by H₂O₂.After TPYS is precisely located at LDs by electrostatic interaction,highly efficient H₂O₂-mediated reaction would liberate a hydrophobic AIEgen(TPY),generating in situ nanoaggregates at LDs with intensive emission and facilitating LDs imaging with high selectivity and sensitivity.TPY exhibits good biocompatibility and excellent photostability,allowing tracking of the dynamic motion of LDs.In addition,TPY can be used to monitor changes in intracellular LDs content in response to oleic acid stimulation.This work not only provides a powerful tool for the study of the biological function of LDs to standardise the visualisation of LDs,but also provides a general reference for the design of high-fidelity AIE probes with ultra-high selectivity for future applications.In Chapter 3,a new polyamine depletion therapy,in which polyamines are effectively depleted by irreversible chemical reactions,is explored.A new strategy combining polyamine and photodynamic therapy(PDT)for cancer treatment is also proposed.The photosensitizer has near-infrared absorption and emission and can be used as a reactive fluorescent probe for the selective detection of biogenic amines(biogenic diamines such as spermidine,spermidine,putrescine and cadaverine)and aliphatic primary amines,while other secondary amines,tertiary amines,aromatic amines,glutathione,hydrogen peroxide,metal ions(K⁺and Na⁺)and anions(NO₃^-and NO₂^-)do not interfere with the detection of the probe.PPAB-Py S showed high sensitivity for spermine,spermidine and putrescine,with minimum detection limits of 0.193?M,0.326?M and 0.602?M,respectively.And it has a high ability to produce reactive oxygen species(ROS)with a yield of 87.5%for ¹O₂.The nanoparticles(PPAB-Py S NPs)obtained after compound encapsulation with Pluronics F127 have good stability in water and could ratio fluorescence imaging of overexpressed polyamines in cells.In addition,the reaction of the photosensitizer with polyamines generated two reactive oxygen species(ROS)-enhanced photosensitizers that combined with polyamine depletion to synergistically destroy cancer cells,showing a significant killing effect on prostate cancer DU145 cells.In addition,the chemical reaction of this photosensitizer with polyamines generates two photosensitizers that can produce more reactive oxygen species(ROS)for synergistic cancer destruction.Therefore,this combination polyamine consumption via chemical reaction can provide a new modality to enable polyamine detection along with photodynamic therapy as well as a depletion of polyamines for cancer treatment and prevention.In Chapter 4,three pyrroloazo-BODIPY compounds with AIE activity,namely PPAB-TPE-1,PPAB-TPE-2 and PPAB-TPE-3,were successfully synthesized by modifying PPAB on the vertical axis.All three compounds exhibited typical AIE activity and NIR emission.The detection of amines by compound PPAB-TPE-1 was investigated,and it was showed high sensitivity and selectivity for biogenic amines,with the lowest detection limits of 0.143?M,0.161?M,0.083?M,0.058?M and 0.053?M for putrescine,cadaverine,1,3-propanediamine,spermidine and spermine,respectively.Moreover,compound PPAB-TPE-1 was capable of qualitative detection of putrescine gas.In addition,the filter paper loaded with the compound PPAB-TPE-1 can be used as a writing material.The nanoparticles(PPAB-TPE-1 NPs,PPAB-TPE-2 NPs,and PPAB-TPE-3 NPs)obtained after compound encapsulation with Pluronics F127 have NIR emission,indicating that the three nanoparticles have potential NIR imaging capabilities.The three nanoparticles have the ability to produce ROS under light,and the PPAB-TPE-1 NPs has the strongest ability to produce ROS,indicating that this nanoparticle has the potential ability for photodynamic therapy.