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H2O2-Mediated Functionalized Fluorescent Dye For Biosensing And Controlled Release

Posted on:2019-11-07Degree:DoctorType:Dissertation
Country:ChinaCandidate:J LiuFull Text:PDF
GTID:1361330542464363Subject:Analytical Chemistry
Abstract/Summary:PDF Full Text Request
Hydrogen peroxide(H2O2),as a vital member of the ROS family,is generated from activation of oxidase complexes,and serves as a major messenger for defense response,reversible oxidation of proteins,oxidative damage,and signaling transduction.It has been reported that numerous fluorescent probes for H2O2 that has the ability to detect the spatial and temporal distribution of biomolecules.However,the localization or non-location of fluorescent probe for H2O2 could be misleading to researchers,due to the diffusibility within the cell.What’s more,It is impolitic to construct these fluorescent systems because of the requirement for efficient quenching,permeability and excellent selectivity.In addition,H2O2-responsive prodrug has chemotherapeutic potential as an activatable fluorogenic probe for target delivery.The diversity of molecular structure provides more strategies into designing a series of fluorophores.Our idiographic works has been summarized four aspects as follows:(1)The constructed fluorescence probe,which can be mobilized the visualization of the intracellular H2O2 through the lysosome windows(pH 4-6),provides valuable guidance to monitor the signal transduction of hydrogen peroxide in cells without potential interference.(2)To fluorescently sense lysosomal H2O2,we develop a lysosomal-localized fluorescent probe for H2O2 constructed by H2O2-responsive boronate moiety and pH-switchable rhodafluor-morpholine fluorophore,Lyso-B-L,to selectively probing H2O2 fluxes within this sensitive organelle.Notably,the ’activatable’ fluorescent can effectively avoids the alkalizing effect on lysosomes in live cells.The good performance of our proposed approach for H2O2 sensing expounds that this strategy might open up new opportunities for the breakthrough of efficient subcellular molecular tools for switched applications.(3)A novel fluorescent probe(Mito-FBN)was developed to explore the activity of mitochondrial H2O2,which based on azobenzene that play an indispensable role in biology study.Mito-FBN is a derivative of rhodamine green that is obtained by appending the triphenylphosphine(TPP)and DABCYL group to increase its multi-functions,thus affording higher cell-membrane permeability.(4)Three distinctive parts of Mito-B-CPT has been designed which is composed of folate moiety as the cancer-targeting ligand,xanthene derivative conjugated with a cleavable borate tag employed as a fluorescent reporter,and camptothecin(CPT)as the cytotoxic anticancer agent.Drug delivery systems(DDS)that allows for the real-time fluorescence imaging of Mito-OH,and affording higher cell-membrane permeability.The skeleton of xanthene was also been constructed,which can lead to 1,4-elimination reaction upon exposure to free H2O2.
Keywords/Search Tags:Fluorescent probe, Hydrogen peroxide, Lysosome, Mitochondria, Drug Controlled release system
PDF Full Text Request
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