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The Applications Of Aryl-Substituted Pyrrole With Aggregation-Induced Emission Properties In Biomedicine

Posted on:2018-06-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:D D ChenFull Text:PDF
GTID:1360330596964340Subject:Materials Science and Engineering
Abstract/Summary:PDF Full Text Request
Aggregation-induced emission?Aggregation-induced emission,AIE?phenomenon refers to the molecular that is not emissive in solution but becomes highly fluorescent at aggregated state or solid state.The question about aggregation-caused quenching?Aggregation-caused quenching,ACQ?of traditional fluorescent molecule is solved completely,which broadens the applications of fluorescent materials,such as chemical sensing,biological probe,optoelectronic system,stimulus response system,et al.Therefore,it's of great significance for the developement of science and technology to develop new systems that are AIE-active and investigate the applications.As one of the main components of air,carbon dioxide?CO2?is also an end product of cellular respiration.Different CO2 levels in cells impact or indicate variations of multiple physiological and biological processes.However,existing fluorescent probes have not met to the detection of cell.For clinical diagnosis,a novel CO2 sensor should be specific with high upper detection limit.In addition,serum albumin?SA?and fibrinogen?FIB?has been considered as two important indicators for the evaluations of diseases.The fluorescent probes,reported in the literature,have no power of detecting HSA and FIB without the isolation and purification of serum,which bring some difficulties to the actual test.Therefore,a fluorescent probe for the in-situ detection of these two proteins with one single system should be needed for clinical applications.In this paper,we engaged mainly in enabling the applications of aryl-substituted pyrrole in biomedicine,designed and synthesized two compounds with aggregation-enhancedemission?AEE?features:tris?2-?dimethylamino?ethyl?-4,4',4''-?1H-pyrrole-1,2,5-triyl?tribenzoate?TPP-TMAE?,sodium 4,4',4”-?3,4-diphenyl-1H-pyrrole-1,2,5-triyl?tribenzoate?DP-TPPNa?,and these two compounds had been successfully applied for studying cell metabolic process and specific protein detection,respectively.The results showed that TPP-TMAE exhibited a highly selective to trace amount CO2.Employing this characteristic,TPP-TMAE is ideal to be a biomarker for in-situ monitoring of the CO2 generation rate during the metabolism of single living cell.The distinct responses of TPP-TMAE to CO2 generated from cancer cells and normal cells suggested TPP-TMAE as a useful tool for deeper understanding metabolism process and distinguishing cancer cells from normal cells during the early diagnosis of cancers.And then CO2 generation rate of organelles in single living cell has been detected;the data showed that mitochondrion and endoplasmic reticulum is closely related to cell respiration.Next,we employed TPP-TMAE as a fluorescent probe to study the metabolic rates and survival of stromal cells and tumor cells in co-culture system.The results suggested tumor cells would induce neighboring stromal cells to establish a common protection mechanism against foreign material invasion too,which enhanced the cell activity and drug resistance.In addition,tumor cells in solid carcinoma exhibited delayed growth but less apoptosis in co-culture systems.Taken these results together,a bidirectional signaling pathway theory was proposed between tumor and stromal cells in co-culture system and the results play an important role in designing novel cancer targeted molecule drugs.DP-TPPNa was proposed to determine the concentrations of human serum albumin?HSA?and FIB in human plasma without separation required.HSA level was determined at concentrations lower than 110?g/mL by the selective PL response of DP-TPPNa to HSA and FIB was quantified at high HSA concentrations in the range of 140-200?g/mL by the synergistic effects of FIB and HSA on the PL intensity of DP-TPPNa.Compared with authoritative instruments,the method developed in the present work is rapid,simple,extremely sensitive,highly selective and precise for the quantitative detection of proteins with one single system,which is an ideal detection system candidate for the early diagnosis of diseases.
Keywords/Search Tags:aggregation-induced emission, aryl-substituted pyrrole, carbon dioxide, serum albumin, fibrinogen
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