反应型小分子荧光探针在疾病检测研究中的应用
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摘要
反应型小分子荧光探针能与生物标志物特异性响应而实现荧光"开-关"效应,与传统方法相比具有良好的选择性和更高的灵敏度。阴离子、阳离子、还原性物质、活性氧和酶常用于疾病研究中的生物标志物。综述了反应型小分子荧光探针在疾病标志物检测研究中的应用,介绍了探针类型、作用机理、设计思路以及不足之处,并对这类探针的发展进行展望。这类探针按作用机理主要分为三种类型:"Turn-on"型,"Turn-off"型和比率型。其难点是:实现可逆性检测的同时,保持较好的安全性、稳定性与灵敏度,并使吸收和发射波长达到近红外区域。随着纳米技术的飞速发展,与纳米材料相结合的新型探针将在疾病的预防、诊断与治疗中发挥更为重要的作用。
The reactive small molecule fluorescent probes,which can achieve the fluorescence "on-off" effectwith the specific recognization of biomarker,possess good selectivity and higher sensitivity compared with thetraditional methods. The anions,cations,reducing substances,reactive oxygen species and enzymes areusually used as biomarkers in disease research. We reviewed the applications of reactive small moleculefluorescent probes in disease detection research including the types, mechanism, design strategies,shortcomings and the future prospection. According to the reaction mechanism,the reactive fluorescent probescan be divided into three types: "Turn-on", "Turn-off" and ratio. The pivotal study in the future is to developthe probes with good reversibility detection,security,stability and sensitivity,which can adsorb and emitwavelength in the near infrared region. With the advances of nanomaterials and nanotechnology,novelfluorescence probes will play important roles in the prevention,diagnosis and treatment of diseases.
The reactive small molecule fluorescent probes,which can achieve the fluorescence "on-off" effectwith the specific recognization of biomarker,possess good selectivity and higher sensitivity compared with thetraditional methods. The anions,cations,reducing substances,reactive oxygen species and enzymes areusually used as biomarkers in disease research. We reviewed the applications of reactive small moleculefluorescent probes in disease detection research including the types, mechanism, design strategies,shortcomings and the future prospection. According to the reaction mechanism,the reactive fluorescent probescan be divided into three types: "Turn-on", "Turn-off" and ratio. The pivotal study in the future is to developthe probes with good reversibility detection,security,stability and sensitivity,which can adsorb and emitwavelength in the near infrared region. With the advances of nanomaterials and nanotechnology,novelfluorescence probes will play important roles in the prevention,diagnosis and treatment of diseases.
引文
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[28]G?GGEL R,WINOTO-MORBACH S,VIELHABERG,et al.PAF-mediated pulmonary edema:a new role for acid sphingomyelinase and ceramide[J].Nature Medicine,2004,10:155-160.
[29]PETERSEN N H,OLSEN O D,GROTH-PEDERSENL,et al.Transformation-associated changes in sphingolipid metabolism sensitize cells to lysosomal cell death induced by inhibitors of acid sphingomyelinase[J].Cancer Cell,2013,24:379-393.
[30]CARPINTEIRO A,BECKER K A,JAPTOK L,et al.Regulation of hematogenous tumor metastasis by acid sphingomyelinase[J].EMBO Molecular Medicine,2015,7:714-734.
[31]GULBINS E,PALMADA M,REICHEL M,et al.Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs[J].Nature Medicine,2013,19:934-938.
[32]PINKERT T,FURKERT D,KORTE T,et al.Amplification of a FRET probe by lipid-water partition for the detection of acid sphingomyelinase in live cells[J].Angewandte Chemie International Edition,2017,56:2790-2794.
[33]LORENTE J A,VALENZUELA H,MOROTE J,et al.Serum bone alkaline phosphatase levels enhance the clinical utility of prostate specific antigen in the staging of newly diagnosed prostate cancer patients[J].European Journal of Nuclear Medicine,1999,26(6):625-632.
[34]KINUE O,KATSUYA S,YOSHITAKA M,et al.High-molecular intestinal alkaline phosphatase in chronic liver diseases[J].Journal of Clinical Laboratory Analysis,2007,21:133-139.
[35]COLOMBATTO P,RANDONE A,CIVITICO G,et al.Hepatitis G virus RNA in the serum of patients with elevated gamma glutamyl transpeptidase and alkaline phosphatase:a specific liver disease[J].Journal of Viral Hepatitis,1996(3):301-306.
[36]COUTTENYE M M,D'HAESE P C,VAN HOOF VO,et al.Low serum levels of alkaline phosphatase of bone origin:a good marker of adynamic bone disease in haemodialysis patients[J].Nephrology Dialysis Transplantation,1996,11:1065-1072.
[37]LI S J,LI C Y,LI Y F,et al.Facile and sensitive nearinfrared fluorescence probe for the detection of endogenous alkaline phosphatase activity in vivo[J].Analytical Chemistry,2017,89:6854-6860.
[38]FREEMAN R,ELBAZ J,GILL R,et al.Analysis of dopamine and tyrosinase activity on ion-sensitive fieldeffect transistor(ISFET)devices[J].Chemistry AEuropean Journal,2007,13(26):7288-7293.
[39]LI Z P,WANG Y F,ZHANG X,et al.A tyrosinasetriggered oxidative reaction-based"Turn-on"fluorescent probe for imaging in living melanoma cells[J].Sensors and Actuators B:Chemical,2017,242:189-194.
[40]XUE X D,JIN S B,LI Z P,et al.Through-bond energy transfer cassette with dual-stokes shifts for"double checked"cell imaging[J].Advanced Science,2017(4):1700229-1700235.
[41]李志鹏.酪氨酸酶荧光探针的设计、合成及生物学效应研究[D].北京:北京工业大学,2018.
[42]LI Z P,WANG Y F,ZENG C C,et al.Ultrasensitive tyrosinase-activated turn-on near-infrared fluorescent probe with a rationally designed urea bond for selective imaging and photodamage to melanoma cells[J].Analytical Chemistry,2018,90:3666-3669.
[43]YIN C X,HUO F J,ZHANG J J,et al.Thioladdition reactions and their applications in thiol recognition[J].Chemical Society Reviews,2013,42:6032-6059.
[44]TAPIERO H,TOWNSEND D M,TEW K D,et al.The antioxidant role of selenium and seleno-compounds[J].Biomed Pharmacoth,2003,57:134-144.
[45]WANG Z Q,WU H,LIU P L,et al.A self-immolative prodrug nanosystem capable of releasing a drug and a NIR reporter for in vivo imaging and therapy[J].Biomaterials,2017,139:139-150.
[46]JIANG X Q,CHEN J W,BAJIC'A,et al.Quantitative real-time imaging of glutathione[J].Nature Communications,2017,8:16163-16174.
[47]GRIMM J B,ENGLISH B P,CHEN J J,et al.Ageneral method to improve fluorophores for live-cell and single-molecule microscopy[J].Nature Methods,2015,12(3):244-250.
[48]GONG D Y,RU J X,CAO T,et al.Two-stage ratiometric fluorescent responsive probe for rapid glutathione detection based on BODIPY thiol-halogen nucleophilic mono-or disubstitution[J].Sensors and Actuators B:Chemical,2018,258:72-79.
[49]SEDGWICK A C,HAN H H,GARDINER J E,et al.The development of a novel AND logic based fluorescence probe for the detection of peroxynitrite and GSH[J].Chemical Science,2018(9):3672-3676.
[2]HU L M,SUN Y,LI S L,et al.Multifunctional carbon dots with high quantum yield for imaging and gene delivery[J].Carbon,2014,67:508-513.
[3]SUN Y,CAO W P,HU L M,et al.Controlling fluorescence emission from oxygen-doped polyethylenimines and its potential for gene delivery combined with imaging[J].Journal of Controlled Release,2013,172:E122.
[4]TERAI T,NAGANO T.Fluorescent probes for bioimaging applications[J].Current Opinion in Chemical Biology,2008,12(5):515-521.
[5]HERMANSON G T.Bioconjugate techniques[M].Rockford:Academic Press,2013.
[6]YU H B,LI M,WANG W P,et al.High throughput screening technologies for ion channels[J].Acta Pharmacologica Sinica,2016,37(1):34-43.
[7]BAI M,BORNHOP D J.Recent advances in receptortargeted fluorescent probes for in vivo cancer imaging[J].Current Medicinal Chemistry,2012,19(28):4742-4758.
[8]SCHWALL C T,ALDER N N.Site-specific fluorescent probe labeling of mitochondrial membrane proteins[M].Totowa N J:Humana Press,2013:103-120.
[9]CHAN J,DODANI S C,CHANG C J.Reaction-based small-molecule fluorescent probes for chemoselective bioimaging[J].Nature Chemistry,2012,4(12):973-984.
[10]HU W,ZENG L Y,WANG Y Y,et al.A ratiometric two-photon fluorescent probe for fluoride ion imaging in living cells and zebrafish[J].Analyst,2016,141(18):5450-5455.
[11]HAO Y Q,NGUYEN K H,ZHANG Y T,et al.Ahighly selective and ratiometric fluorescent probe for cyanide by rationally altering the susceptible H-atom[J].Talanta,2018,176:234-241.
[12]LIU Y,SU Q Q,CHEN M,et al.Near-infrared upconversion chemodosimeter for in vivo detection of Cu2+in wilson disease[J].Advanced Materials,2016,28(31):6625-6630.
[13]HIRAYAMA T,VAN DE BITTNER G C,GRAY L W,et al.Near-infrared fluorescent sensor for in vivo copper imaging in a murine Wilson disease model[J].Proceedings of the National Academy of Sciences of the United States of America,2012,109(7):2228-2233.
[14]YUAN L,LIN W Y,ZHENG K B,et al.ChemInform abstract:far-red to near infrared analyte-responsive fluorescent probes based on organic fluorophore platforms for fluorescence imaging[J].Cheminform,2013,44(20):622-661.
[15]IDRIS N M,JAYAKUMAR M K,BANSAL A,et al.Upconversion nanoparticles as versatile light nanotransducers for photoactivation applications[J].Chemical Society Reviews,2015,44(6):1449-1478.
[16]LIU Q,FENG W,YANG T S,et al.Upconversion luminescence imaging of cells and small animals[J].Nature Protocols,2013,8(10):2033-2044.
[17]ZHOU B,SHI B Y,JIN D C,et al.Controlling upconversion nanocrystals for emerging applications.[J].Nature Nanotechnology,2015,10(11):924-936.
[18]ZHANG Y J,WANG X,ZHOU Y,et al.Influence of donor on the sensing performance of a series of throughbond energy transfer-based two-photon fluorescent Cu2+probes[J].Photochemistry&Photobiology,2016,92(4):528-536.
[19]HUANG R,ZHENG X L,WANG C C,et al.Reaction based two-photon fluorescent probe for turnon mercury(II)sensing and imaging in live cells[J].Chemistry an Asian Journal,2012,7(5):915-918.
[20]SUI B L,TANG S M,LIU T H,et al.Novel BODIPY-based fluorescence turn-on sensor for Fe3+and its bioimaging application in living cells[J].ACSApplied Materials&Interfaces,2014,6(21):18408-184012.
[21]HUANG X,LI Z,CAO T,et al.A methylene bluebased near-infrared fluorescent probe for rapid detection of hypochlorite in tap water and living cells[J].RSC Advances,2018,8:14603-14608.
[22]后际挺,李坤,覃彩芹,等.活性氧簇的小分子荧光探针研究进展[J].有机化学,2018,38(3):612-628.
[23]DONG B L,SONG X Z,KONG X Q,et al.Simultaneous near-infrared and two-photon in vivo imaging of H2O2 using a ratiometric fluorescent probe based on the unique oxidative rearrangement of oxonium[J].Advanced Materials,2016,28(39):8755-8759.
[24]ZHOU X Q,LESIAK L,LAI R,et al.Chemoselective alteration of fluorophore scaffolds as a strategy for the development of ratiometric chemodosimeters[J].Angewandte Chemie,2017,129(15):4197-4200.
[25]LIU F,DU J,SONG D,et al.A sensitive fluorescent sensor for the detection of endogenous hydroxyl radicals in living cells and bacteria and direct imaging with respect to its ecotoxicity in living zebra fish[J].Chemical Communications,2016,52(25):4636-4639.
[26]CAI Q,FEI Y,AN H W,et al.Macrophage-instructed intracellular S.aureus killing by targeting photodynamic dimers[J].ACS Applied Materials Interfaces,2018,10:9197-9202.
[27]CAI Q,FEI Y,HU L M,et al.Chemotaxis-instructed intracellular S.aureus infection detection by a targeting and self-assembly signal enhanced photoacoustic probe[J].Nano Letters,2018,18(10):6229-6236.
[28]G?GGEL R,WINOTO-MORBACH S,VIELHABERG,et al.PAF-mediated pulmonary edema:a new role for acid sphingomyelinase and ceramide[J].Nature Medicine,2004,10:155-160.
[29]PETERSEN N H,OLSEN O D,GROTH-PEDERSENL,et al.Transformation-associated changes in sphingolipid metabolism sensitize cells to lysosomal cell death induced by inhibitors of acid sphingomyelinase[J].Cancer Cell,2013,24:379-393.
[30]CARPINTEIRO A,BECKER K A,JAPTOK L,et al.Regulation of hematogenous tumor metastasis by acid sphingomyelinase[J].EMBO Molecular Medicine,2015,7:714-734.
[31]GULBINS E,PALMADA M,REICHEL M,et al.Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs[J].Nature Medicine,2013,19:934-938.
[32]PINKERT T,FURKERT D,KORTE T,et al.Amplification of a FRET probe by lipid-water partition for the detection of acid sphingomyelinase in live cells[J].Angewandte Chemie International Edition,2017,56:2790-2794.
[33]LORENTE J A,VALENZUELA H,MOROTE J,et al.Serum bone alkaline phosphatase levels enhance the clinical utility of prostate specific antigen in the staging of newly diagnosed prostate cancer patients[J].European Journal of Nuclear Medicine,1999,26(6):625-632.
[34]KINUE O,KATSUYA S,YOSHITAKA M,et al.High-molecular intestinal alkaline phosphatase in chronic liver diseases[J].Journal of Clinical Laboratory Analysis,2007,21:133-139.
[35]COLOMBATTO P,RANDONE A,CIVITICO G,et al.Hepatitis G virus RNA in the serum of patients with elevated gamma glutamyl transpeptidase and alkaline phosphatase:a specific liver disease[J].Journal of Viral Hepatitis,1996(3):301-306.
[36]COUTTENYE M M,D'HAESE P C,VAN HOOF VO,et al.Low serum levels of alkaline phosphatase of bone origin:a good marker of adynamic bone disease in haemodialysis patients[J].Nephrology Dialysis Transplantation,1996,11:1065-1072.
[37]LI S J,LI C Y,LI Y F,et al.Facile and sensitive nearinfrared fluorescence probe for the detection of endogenous alkaline phosphatase activity in vivo[J].Analytical Chemistry,2017,89:6854-6860.
[38]FREEMAN R,ELBAZ J,GILL R,et al.Analysis of dopamine and tyrosinase activity on ion-sensitive fieldeffect transistor(ISFET)devices[J].Chemistry AEuropean Journal,2007,13(26):7288-7293.
[39]LI Z P,WANG Y F,ZHANG X,et al.A tyrosinasetriggered oxidative reaction-based"Turn-on"fluorescent probe for imaging in living melanoma cells[J].Sensors and Actuators B:Chemical,2017,242:189-194.
[40]XUE X D,JIN S B,LI Z P,et al.Through-bond energy transfer cassette with dual-stokes shifts for"double checked"cell imaging[J].Advanced Science,2017(4):1700229-1700235.
[41]李志鹏.酪氨酸酶荧光探针的设计、合成及生物学效应研究[D].北京:北京工业大学,2018.
[42]LI Z P,WANG Y F,ZENG C C,et al.Ultrasensitive tyrosinase-activated turn-on near-infrared fluorescent probe with a rationally designed urea bond for selective imaging and photodamage to melanoma cells[J].Analytical Chemistry,2018,90:3666-3669.
[43]YIN C X,HUO F J,ZHANG J J,et al.Thioladdition reactions and their applications in thiol recognition[J].Chemical Society Reviews,2013,42:6032-6059.
[44]TAPIERO H,TOWNSEND D M,TEW K D,et al.The antioxidant role of selenium and seleno-compounds[J].Biomed Pharmacoth,2003,57:134-144.
[45]WANG Z Q,WU H,LIU P L,et al.A self-immolative prodrug nanosystem capable of releasing a drug and a NIR reporter for in vivo imaging and therapy[J].Biomaterials,2017,139:139-150.
[46]JIANG X Q,CHEN J W,BAJIC'A,et al.Quantitative real-time imaging of glutathione[J].Nature Communications,2017,8:16163-16174.
[47]GRIMM J B,ENGLISH B P,CHEN J J,et al.Ageneral method to improve fluorophores for live-cell and single-molecule microscopy[J].Nature Methods,2015,12(3):244-250.
[48]GONG D Y,RU J X,CAO T,et al.Two-stage ratiometric fluorescent responsive probe for rapid glutathione detection based on BODIPY thiol-halogen nucleophilic mono-or disubstitution[J].Sensors and Actuators B:Chemical,2018,258:72-79.
[49]SEDGWICK A C,HAN H H,GARDINER J E,et al.The development of a novel AND logic based fluorescence probe for the detection of peroxynitrite and GSH[J].Chemical Science,2018(9):3672-3676.