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基于功能核酸和聚集诱导荧光的新型荧光探针体系的研究
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摘要
荧光分子探针具有简单直观、灵敏度高、选择性好、有良好的时间和空间分辨能力等优点,已成为包括离子、小分子、生物大分子、病原体等各种与环境、生物、医学相关的分析物检测的重要手段。理想的荧光分子探针需具备高特异性的识别单元以及具有优秀荧光性能的信号响应单元,即荧光团。因此,本文结合功能核酸和聚集诱导荧光分子的优点,构建了新型荧光探针体系。
     首先,本文设计开发了以功能核酸作为识别单元的新型非共价标记催化分子信标荧光分析方法。该方法不仅具备催化分子信标法灵敏度高的优点,同时还具备含有缺碱基位点的非共价标记功能核酸方法操作简便,成本较低廉,对功能核酸的活性干扰较小等优点。通过8-17核酸酶和适体酶,该方法分别实现了对铅离子和有机小分子腺苷的高选择性,高灵敏度的分析检测:对水溶液中铅离子响应的线性范围为0-2.0μM,检测限为3.8nM;对水溶液中有机小分子腺苷的检测限为1.4μM。同时,该方法能够应用于检测生物样品中的铅离子和腺苷小分子。
     其次,本文以聚集诱导荧光分子作为响应单元,构建了两种基于聚集诱导荧光的新型荧光探针:1)比率型pH荧光探针,4-羧基-苯胺-5-氯-水杨醛席夫碱。利用其分子内羧基和羟基能够发生去质子化作用,使得溶液pH值在5.0-7.0变化时,体系在516nm和559nm处荧光强度的比值(I516/I559)随之明显变化,成功的实现了对细胞内pH值变化的原位荧光成像分析。2)铜离子荧光探针,双(2-吡啶基亚甲基)对苯二甲酸二肼。利用在水溶液中探针与铜离子形成2:1的络合物导致荧光淬灭的原理,实现了水溶液中铜离子的分析检测。并且,基于该探针的聚集诱导荧光性质制备了铜离子检测试纸,检测限可达4.2μM。上述两种探针均具有合成简单、选择性好、斯托克斯位移大等优点。
     第三,本文采用溶胶凝胶方法合成了包覆聚集诱导荧光染料的氧化硅纳米粒子。通过控制荧光染料的包覆量和反应条件,可以调控该荧光纳米粒子的量子产率和粒径。进一步将功能核酸对分析物高特异性、高结合力的识别性能与聚集诱导荧光分子高量子产率、大斯托克斯位移等优越的荧光性能相结合,成功地制备了NCL-适配体修饰的包覆聚集诱导荧光染料的氧化硅纳米探针。初步实验结果表明,该荧光纳米探针能够对核仁蛋白过度表达的人乳腺癌细胞系MCF-7细胞进行荧光标记,在癌细胞的识别和荧光标记领域具有潜在的应用价值。
The development of fluorescent sensors for ions, small molecules, biologicalmolecules and pathogens have attracted great attention since fluorescent sesorsshowed advantages of ease in operation, high sensitivity, good selectivity, and hightime and spatial resolution. Ideal fluorescent sensors require both high specificrecognition unit and excellent fluorophores as signal response unit. Hence, the aim ofthis dissertation is to design and develop novel fluorescent sensors based onfunctional nucleic acids (FNAs) and aggregation-induced emission (AIE)fluorophores.
     Firstly, new label-free catalytic and molecular beacon (CAMB) sensors weredeveloped for sensitive fluorescent detection of small inorganic and organicmolecules. The sensor design had the advantages of both the label-free methods,which were low cost and could preserve the activity of the FNAs, and the CAMBmethods, which exhibited signal amplification via multiple-turnover catalyticreactions and ease for the rational design of aptazymes. By using the8-17DNAzyme,the new label-free CAMB sensor showed an approximately linear relationship withPb2+concentration in the range of0-2μM and a detection limit of3.8nM. By usingthe aptazyme for adenosine based on the10-23DNAzyme, our method could alsodetect adenosine successfully with a detection limit of1.4μM. In addition, applicationof this method in biologically relevant sample analysis was successfully achieved.
     Secondly, by the advantages of AIE fluorophores, two novel fluorescent sensorswere developed for monitoring pH fluctuations in live cells and building test paper forCu2+determination in this dissertation, respectively. In the former case, a ratiometricfluorescent pH sensor,4-carboxylaniline-5-chlorosalicylaldehyde Schiff base, wassynthesized via a facile reaction. The integration of hydroxyl and carboxyl groupsprovided the sensor with a significant fluorescence color change from orange to greenand an intensity ratio (I516nm/I559nm) enhancement when the pH increased from5.0to7.0in aqueous solution. Confocal fluorescence imaging of intracellular pH throughratiometric response was successfully achieved by using this sensor in live HepG2cells. In the later case, a novel fluorescent sensor bis (pyridin-2-ylmethylene)terephthalohydrazide for Cu2+determination was developed. The sensor molecule showed high sensitivity and selectivity to Cu2+by forming a1:2metal-to-ligandcomplex in aqueous solution. The fluorescence decrease at516nm was linearlyrelated to the concentration of Cu2+in the range of0.2-8.0μM. In addition, thedevelopment of test paper for Cu2+determination was successfully achieved. Both ofthese sensors showed advantages of ease in preparation, high selectivity and largeStokes shift.
     Thirdly, highly emissive fluorescent silica nanoparticles (FSNPs) encapsulatedby AIE fluorophores were developed by a simple sol-gel reaction in this dissertation.The emission efficiencies and particle diameters of the FSNPs were manipulated bychanging the fluorophore loadings and the reaction conditions. To combine the meritproperties of FNAs and AIE fluorophores, FSNPs were functionalized with NCL-aptamer, which facilitated the nanoparticles for potential applications in targetingnucleolin-overexpressed MCF-7cells.
引文
[1] Wolfbeis O S. Fibre optic chemical sensors and biosensors, Volumes1and2: Boca Raton,CRC Press,1991.
    [2] Cammann G G, Guilbault E A, Hal H, et al. The Cambridge definition of chemical sensors,Cambridge workshop on chemical sensors and biosensors. New York: CambridgeUniversity Press,1996.
    [3] Callan J F, de Silva A P, Magri D C. Luminescent sensors and switches in the early21stcentury. Tetrahedron,2005,61:8551-8588.
    [4] Kiyose K, Kojima H, Nagano T. Functional near-infrared fluorescent probes. Chem. Asian.J.,2008,3:506-515.
    [5] Otsuki J, Akasaka T, Araki K. Molecular switches for electron and energy transferprocesses based on metal complexes. Coord. Chem. Rev.,2008,252:32-56.
    [6] Tang B, Yu F B, Li P, et al. A near-infrared neutral pH fluorescent probe for monitoringminor pH changes: imaging in living HepG2and HL-7702cells. J. Am. Chem. Soc.,2009,131:3016-3023.
    [7] Wu J, Liu W, Ge J, et al. New sensing mechanisms for design of fluorescent chemosensorsemerging in recent years. Chem. Soc. Rev.,2011,40:3483-3495.
    [8] Zhu W P, Xu Y F, Qian X H. Fluorescent molecular sensors for heavy and transitionmetallic cations with biological interests. Prog. Chem.,2007,9:1229-1238.
    [9] Shi W, Sun S N, Li X H, et al. Imaging different interactions of mercury and silver withlive cells by a designed fluorescence probe rhodamine B selenolactone. Inorg. Chem.,2010,49:1206-1210.
    [10] Li H N, Cao Z J, Zhang Y H, et al. Simultaneous detection of two lung cancer biomarkersusing dual-color fluorescence quantum dots. Analyst,2011,136:1399-1405.
    [11] Ellington A D, Szostak J W. In vitro selection of RNA molecules that bind specific ligands.Nature,1990,346:818-822.
    [12] Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligandsto bacteriophage T4DNA polymerase. Science,1990,249:505-510.
    [13] Dass C R, Choong P F M, Khachigian L M. DNAzyme technology and cancer therapy:cleave and let die. Mol. Cancer Ther.,2008,7:243-251.
    [14] Wilson J N, Kool E T. Fluorescent DNA base replacements: reporters and sensors forbiological systems. Org. Biomol. Chem.,2006,23:4265-4274.
    [15] Borisov S M, Wolfbeis O S. Optical sensors. Chem. Rev.,2008,108:423-461.
    [16] Medley C D, Bamrungsap S, Tan W H, et al. Aptamer-conjugated nanoparticles for cancercell detection. Anal. Chem.,2011,83:727-734.
    [17] Turro N J. Modern molecular phytochemistry. Menlo Park CA: Benjamin CummingsPublishing Co.,1978:137.
    [18] Lakowicz J R. Principles of fluorescence spectroscopy.3rd ed. New York: Springer,2006:Chapter1.
    [19] Birks J B. Photophysics of aromatic molecules. London: Wiley,1970.
    [20] Hong Y N, Lam J W Y, Tang B Z. Aggregation-induced emission. Chem. Soc. Rev.,2011,40:5361-5388.
    [21] Cornil J, dos Santos D A, Crispin X, et al. Influence of interchain interactions on theabsorption and luminescence of conjugated oligomers and polymers:a quantum-chemicalcharacterization. J. Am. Chem. Soc.,1998,120:1289-1299.
    [22] Slavík J. Fluorescence microscopy and fluorescent probes. New York: Plenum,1998:Fluorescent probes.
    [23] Valeur B. Molecular fluorescence: principle and applications. Weinheim: Wiley,2001:Chapter4.
    [24] Geddes C D, Lakopwicz J R. Advanced concepts in fluorescence sensing. Springer,Norwell,2005.
    [25] Zhao G S, Shi G X, Guo Z Q, et al. Recent application progress on aggregation-inducedemission. Chinese J. Inorg. Chem.,2012,32:1620-1632.
    [26] Breaker R R, Joyce G F. A DNA enzyme that cleaves RNA. Chem. Biol.,1994,1:223-229.
    [27] Cuenoud B, Szostak J W. A DNA metalloenzyme with DNA ligase activity. Nature,1995,375:611-614.
    [28] Liu J, Cao Z, Lu Y. Functional nucleic acid sensors. Chem. Rev.,2009,109:1948-1998.
    [29] Carmi N, Balkhi H R, Breaker R R. Cleaving DNA with DNA. Proc. Natl. Acad. Sci.U.S.A.,1998,95:2233-2237.
    [30] Huizenga D E, Szostak J W. A DNA Aptamer That Binds Adenosine and ATP.Biochemistry,1995,34:656-665.
    [31] Bruno J G, Kiel J L. In vitro selection of DNA aptamers to anthrax spores withelectrochemilumiescence detection. Biosens. Bioelectron.,1999,14:457-464.
    [32] Iqbal S S, Mayo M W, Bruno J G, et al. A review of molecular recognition technologies fordetection of biological threat agents. Biosens. Bioelectron.,2000,15:549-578.
    [33] Takagi Y, Warashina M, Stec W J, et al. Recent advances in the elucidation of themechanisms of action of ribozymes. Nucleic Acids Res.,2001,29:1815-1834.
    [34] Dai N, Kool E T. Fluorescent DNA-based enzyme sensors. Chem. Soc. Rev.,2011,40:5756-5770.
    [35] Doudna J A, Lorsch J R. Ribozyme catalysis: not different, just worse. Nat. Struct. Mol.Biol.,2005,12:395-402.
    [36] Fedor M J, Williamson J R. The catalytic diversity of RNAs. Nat. ReV. Mol. Cell Biol.,2005,6:399-412.
    [37] Santoro S W, Joyce G F, Sakthivel K, et al. RNA cleavage by a DNA enzyme withextended chemical functionality. J. Am. Chem. Soc.,2000,122:2433-2439.
    [38] Liu J, Brown A K, Meng X, et al. A catalytic beacon sensor for uranium withparts-per-trillion sensitivity and millionfold selectivity. Proc. Natl. Acad. Sci. U.S.A.,2007,104:2056-2061.
    [39] Schlosser K, Gu J, Sule L, et al. Sequence-function relationships provide new insight intothe cleavage site selectivity of the8-17RNA-cleaving deoxyribozyme. Nucleic Acids Res.,2008,36:1472-1481.
    [40] Chiuman W, Li Y. Evolution of high-branching deoxyribozymes from a catalytic DNAwith a three-way junction. Chem. Biol.,2006,13:1061-1069.
    [41] Carmi N, Shultz L A, Breaker R R. In vitro selection of self-cleaving DNAs. Chem. Biol.,1996,3:1039-1046.
    [42] Hoadley K A, Purtha W E, Wolf A C, et al. Zn2+-dependent deoxyribozymes that formnatural and unnatural RNA linkages. Biochemistry,2005,44:9217-9231.
    [43] Purtha W E, Coppins R L, Smalley M K, et al. General deoxyribozyme-catalyzed synthesisof native3′-5′RNA linkages. J. Am. Chem. Soc.,2005,127:13124-13125.
    [44] Sreedhara A, Li Y, Breaker R R. Ligating DNA with DNA. J. Am. Chem. Soc.,2004,126:3454-3460.
    [45] Travascio P, Bennet A J, Wang D Y. A ribozyme and a catalytic DNA with peroxidaseactivity: active sites versus cofactor-binding sites. Chem. Biol.,1999,6:779-787.
    [46] Li Y, Sen D. A catalytic DNA for porphyrin metallation. Nat. Struct. Biol.,1996,3:743-747.
    [47] Santoro S W, Joyce G F. A general purpose RNA-cleaving DNA enzyme. Proc. Natl. Acad.Sci. U.S.A.,1997,94:4262-4266.
    [48] Brown A K, Li J, Pavot C M B, et al. A lead-dependent DNAzyme with a two-stepmechanism. Biochemistry,2003,42:7152-7161.
    [49] Cruz R P G, Withers J B, Li, Y. Dinucleotide junction cleavage versatility of8-17deoxyribozyme. Chem. Biol.,2004,11:57-67.
    [50] Liu J, Lu Y. FRET Study of a trifluorophore-labeled DNAzyme. J. Am. Chem. Soc.,2002,124:15208-15216.
    [51] Kim H K, Liu J, Li J, et al. Metal-dependent global folding and activity of the8-17DNAzyme studied by fluorescence resonance energy transfer. J. Am. Chem. Soc.,2007,129:6896-6902.
    [52] Kim H K, Rasnik I, Liu J, et al. Dissecting metal ion dependent folding and catalysis of asingle DNAzyme. Nat. Chem. Biol.,2007,3:763-768.
    [53] Peracchi A, Bonaccio M, Clerici M. A mutational analysis of the8-17deoxyribozyme core.J. Mol. Biol.,2005,352:783-794.
    [54] Robertson D L, Joyce G F. Selection in vitro of an RNA enzyme that specifically cleavessingle-stranded DNA. Nature,1990,344:467-468.
    [55] Wilson D S, Szostak J W. In vitro selection of functional nucleic acids. Annu. Rev.Biochem.,1999,68:611-647.
    [56] Gold L, Polisky B, Uhlenbeck O, et al. Diversity of oligonucleotide functions. Annu. Rev.Biochem.,1995,64:763-797.
    [57] You K M, Lee S H, Im A, et al. Aptamers as functional nucleic acids: In vitro selection andbiotechnological applications. Biotechnol. Bioproc. E.,2003,8:64-75.
    [58] Hermann T, Dinshaw J P. Adaptive recognition by nucleic acid aptamers. Science,2000,287:820-825.
    [59] Chen H W, Medley C D, Sefah K. Molecular recognition of small-cell lung cancer cellsusing aptamers. ChemMedChem.,2008,3:991-1001.
    [60] Raddatz M S, Dolf A, Endl E, et al. Enrichment of cell-targeting and population-specificaptamers by fluorescence-activated cell sorting. Angew. Chem., Int. Ed.,2008,47:5190-5193.
    [61] Clark S L, Remcho V T. Aptamers as analytical reagents. Electrophoresis,2002,23:1335-1340.
    [62] Brody E N, Gold L. Aptamers as therapeutic and diagnostic agents. J. Biotechnol.,2000,74:5-13.
    [63] Walter N G, Burke J M. Real-time monitoring of hairpin ribozyme kinetics throughbase-specific quenching of fluorescein-labeled substrates. RNA,1997,3:392-404.
    [64] Hanne A, Ramanujam M V, Rucker T, et al. Fluorescence resonance energy-transfer(FRET) to follow ribozyme reactions in real-time. Nucleotides Nucleotides,1998,17:1835-1850.
    [65] Li H, Huang X X, Kong D M, et al. Ultrasensitive, high temperature and ionic strengthvariation-tolerant Cu2+fluorescent sensor based on reconstructed Cu2+-dependentDNAzyme/substratecomplex. Biosens. Bioelectron.,2013,42:225-228.
    [66] Jenne A, Gmelin W, Raffler N, et al. Real-time characterization of Ribozymes byfluorescence resonance energy transfer (FRET). Angew. Chem. Int. Ed.,1999,38:1300-1303.
    [67] Jenne A, Hartig J S, Piganeau N, et al. Rapid identification and characterization ofhammerhead-ribozyme inhibitors using fluorescence-based technology. Nat. Biotechnol.,2001,19:56-61.
    [68] Liu J, Lu Y. A DNAzyme catalytic beacon sensor for paramagnetic Cu2+ions in aqueoussolution with high sensitivity and selectivity. J. Am. Chem. Soc.,2007,129:9838-9839.
    [69] Zhang X B, Wang Z D, Xing H, et al. Catalytic and molecular beacons for amplifieddetection of metal ions and organic molecules with high sensitivity. Anal. Chem.,2010,82:5005-5011.
    [70] Li B L, Qin C J, Li T, et al. Flourescent switch constructed based on hemin-sensitiveanionic conjugated polymer and its applications in DNA-related sensors. J. Anal. Chem.,2009,81:3544‐3550.
    [71] Ho H A, Leclerc M. Optical sensors based on hybrid aptamer/conjugated polymercomplexes. J. Am. Chem. Soc.,2004,126:1384‐1387.
    [72] Zhou Z X, Du Y, Zhang L B, et al. A label-free, G-quadruplex DNAzyme-basedfluorescent probe for signal-amplified DNA detection and turn-on assay of endonuclease.Biosens. Bioelectron.,2012,34:100-105.
    [73] Wang Y, Liu B. ATP detection using a label-free DNA aptamer and a cationictetrahedralfluorene. Analyst,2008,133:1593-1598.
    [74] Zhang L B, Han B Y, Li T, et al. Label-free DNAzyme-based fluorescing molecular switchfor sensitive and selective detection of lead ions. Chem. Commun.,2011,47:3099-3101.
    [75] Guo Q, Lu M, Marky L A, et al. Interaction of the dye ethidium bromide with DNAcontaining guanine repeats. Biochemistry,1992,31:2451-2455.
    [76] Shida T, Ikeda Sekiguchi N J. Drug binding to higher ordered DNA structures: Ethidiumbromide complexation with parallel quadruple-stranded DNA. Nucleosides Nucleotides,1996,15:599-605.
    [77] Byren C D, de Mello A J. Photophysics of ethidium bromide complexed to ct-DNA: amaximum entropy study. Biophys. Chem.,1998,70:173-184.
    [78] Pal S K, Mandal D, Bhattacharyya K. Photophysical processes of ethidium bromide inmicelles and reverse micelles. J. Phys. Chem. B,1998,102:11017-11023.
    [79] Arthanari H, Basu S, Kawano T L, et al. Fluorescent dyes specific for quadruplex DNA.Nucleic Acids Res.,1998,26:3724-3728.
    [80] Li B, Wei H, Dong S J. Sensitive detection of protein by an aptamer-based label-freefluorescing molecular switch. Chem. Commun.,2007,73-75.
    [81] Xiang Y, Wang Z D, Xing H, et al. Label-free fluorescent functional DNA sensors usingunmodified DNA: A vacant site approach. Anal. Chem.,2010,82:4122-4129.
    [82] Mohanty J, Barooah N, Dhamodharan V, et al. Thioflavin T as an efficient inducer andselective fluorescent sensor for the human telomeric G-quadruplex DNA. J. Am. Chem.Soc.,2013,135:367-376.
    [83] Yoshimoto K, Nishizawa S, Minagawa M, et al. Use of abasic site-containing DNA strandsfor nucleobase recognition in water. J. Am. Chem. Soc.,2003,125:8982-8983.
    [84] Sato Y, Nishizawa S, Teramae N. Label-free molecular beacon system based on DNAscontaining abasic sites and fluorescent ligands that bind abasic sites. Chem. Eur. J.,2011,17:11650-11656.
    [85] Xu Z A, Sato Y, Nishizawa S, et al. Signal-off and signal-on design for a label-freeaptasensor based on target-induced self-assembly and abasic-site-binding ligands. Chem.Eur. J.,2009,15:10375-10378.
    [86] Sato Y, Kageyama T, Nishizawa S, et al. Competitive binding of abasic site-binding ligandsand masking ligands to DNA duplexes for the analysis of single-base mutation. Anal. Sci.,2013,29:15-19.
    [87] Xu Z A, Morita K, Sato Y. Label-free aptamer-based sensor using abasic site-containingDNA and a nucleobase-specific fluorescent ligand. Chem. Commun.,2009,6445-6447.
    [88] Xiang Y, Tong A J, Lu Y. Abasic site-containing DNAzyme and aptamer for label-freefluorescent detection of Pb2+and adenosine with high sensitivity, selectivity, and tunabledynamic range. J. Am. Chem. Soc.,2009,131:15352-15357.
    [89] Luo J, Xie Z, Lam J W Y, et al. Aggregation-induced emission of1-methyl-1,2,3,4,5-pentaphenylsilole. Chem. Commun.,2001,1740-1741.
    [90] Tang B Z, Zhan X, Yu G, et al. Efficient blue emission from siloles. J. Mater. Chem.,2001,11:2974-2978.
    [91] Choi J K, Jang S, Kim K J, et al. Observation of negative charge rrapping and investigationof its physicochemical origin in newly synthesized poly(tetraphenyl)silole siloxane thinfilms. J. Am. Chem. Soc.,2011,133:7764-7785.
    [92] Du X B, Wang Z Y. Donor-acceptor type silole compounds with aggregation-induceddeep-red emission enhancement: synthesis and application for significant intensification ofnear-infrared photoluminescence. Chem. Commun.,2011,47:4276-4278.
    [93] Sartin M M, Boydston A J, Pagenkopf B L, et al. Electrochemistry, spectroscopy, andelectrogenerated chemiluminescence of silole-based chromophoes. J. Am. Chem. Soc.,2006,128:10163-10170.
    [94] Ren Y, Lam J W Y, Dong Y Q, et al. Enhanced emission efficiency and excited statelifetime due to restricted intramolecular motion in silole aggregated. J. Phys. Chem. B,2005,109:1135-1140.
    [95] Qi X Y, Li H, Lam J W Y, et al. Graphene oxide as a novel nanoplatform for enhancementof aggregation-induced emission of silole fluorophores. Adv. Mater.,2012,24:4191-4195.
    [96] Wang Z, Shao H, Ye J, et al. Dibenzosuberenylidene-ended fluorophores rapid and efficientsynthesis characterization and aggregation-induced emissions. J. Phys. Chem. B,2005,109:19627-19633.
    [97] Dong Y Q, Lam J W Y, Qin A J, et al. Aggregation-induced and crystallization-enhancedemissions of1,2-diphenyl-3,4-bis(diphenylmethylene)-1-cyclobutene. Chem. Commun.,2007,3255-3257.
    [98] Gao X, Peng Q, Niu Y L, et al. Theoretical insight into the aggregation induced emissionphenomena of diphenyldibenzofulvene: a nonadiabatic molecular dynamics study. Phys.Chem. Chem. Phys.,2012,14:14207-14216.
    [99] Gu X G, Yao J J, Zhang G X, et al. Controllable self-assembly ofdi(p-methoxylphenyl)dibenzofulvene into three different emission forms. Small,2012,8:3406-3411.
    [100] Gu X G, Yao J J, Zhang G X, et al. Polymorphism-dependent emission fordi(p-methoxylphenyl)dibenzofulvene and analogues: optical waveguide/amplifiedspontaneous emission behaviors. Adv. Funct. Mater.,2012,22:4862-4872.
    [101] Li Z, Dong Y, Lam J W Y, et al. Functionalized siloles: Versatile synthesis,aggregation-induced emission, and sensory and device applications. Adv. Funct. Mater.,2009,19:905-917.
    [102] Shi J Q, Chang N, Li C H et al. Locking the phenyl rings of tetraphenylethene step by step:understanding the mechanism of aggregation-induced emission. Chem. Commun.,2012,48:10675-10677.
    [103] Tong H, Hong Y, Dong Y, et al. Fluorescent “light-up” bioprobes based ontetraphenylethylene derivatives with aggregation-induced emission characteristics. Chem.Commun.,2006,35:3705-3707.
    [104] Guo Z Q, Zhu W H, Tian H. Dicyanomethylene-4H-pyran chromophores for OLEDemitters, logic gates and optical chemosensors. Chem. Commun.,2012,48:6073-6084.
    [105] Tong H, Hong Y N, Dong Y Q, et al. Color-tunable, aggregation-induced emission of abutterfly-shaped molecule comprising a pyran skeleton and two cholesteryl wings. J. Phys.Chem. B,2007,111:2000-2007.
    [106] Tong H, Haussler M, Dong Y Q, et al. Aggregation-induced emission of4-dicyanomethylene-2,6-distyryl-4H-pyran. J. Chin. Chem. Soc.,2006,53:243-246.
    [107] Zeng Q, Li Z, Dong Y Q, et al. Fluorescence enhancements of benzene-cored luminophorsby restricted intramolecular rotations: AIE and AIEE effects. Chem. Commun.,2007,70-72.
    [108] Zhang H Q, Yang B, Zheng Y. et al. New biphenyl derivative with planar phenyl phenylconformation in crystal at room temperature exhibits highly efficient UV light-emitting. J.Phys. Chem. B,2004,108:9571-9573.
    [109] An B K, Lee D S, Lee J S, et al. Strongly fluorescent organogel system comprising fibrillarself-assembly of a trifluoromethyl-based cyanostilbene derivative. J. Am. Chem. Soc.,2004,126:10232-10233.
    [110] An B K, Gierschner J, Park S Y. pi-Conjugated cyanostilbene derivatives: A uniqueself-assembly motif for molecular nanostructures with enhanced emission and transport.Accounts Chem. Res.,2012,45:544-554.
    [111] Zhu L L, Zhao Y L. Cyanostilbene-based intelligent organic optoelectronic materials. J.Mater. Chem. C,2013,1:1059-1065.
    [112] Tang W X, Xiang Y, Tong A J. Salicylaldehyde azines as fluorophores ofaggregation-induced emission enhancement characteristics. J. Org. Chem.,2009,74:2163-2166.
    [113] Chen X T, Xiang Y, Li N, et al. Fluorescence turn-on detection of protamine based onaggregation-induced emission enhancement characteristics of4-(6'-carboxyl)hexyloxysalicyl aldehyde azine. Analyst,2010,135:1098-1105.
    [114] Chen X T, Wei R R, Xiang Y, et al. Organic crystalline solids response to piezo/thermostimulus: Donor-Acceptor (D-A) attached salicylaldehyde azine derivatives. J. Phys. Chem.C,2011,115:14353-14359.
    [115] Wei R R, Song P S, Tong A J. Reversible thermochromism of aggregation-inducedemission-active benzophenone azine based on polymorph-dependent excited-stateintramolecular proton transfer fluorescence. J. Phys. Chem. C,2013,117:3467-3474.
    [116] Zhang S, Qin A J, Sun J Z, et al. Mechanism study of Aggregation-induced emission. Prog.Chem.,2011,23:623-636.
    [117] Chan C Y K, ZhaoZ J, Lam J W Y, et al. Efficient light emitters in the solid state: synthesis,aggregation-induced emission, electroluminescence, and sensory properties of luminogenswith benzene cores and multiple triarylvinyl peripherals. Adv. Funct. Mater.,2012,22:378-389.
    [118] Qin A J, Lam J W Y, Tang B Z. Luminogenic polymers with aggregation-induced emissioncharacteristics. Prog. Polym. Sci.,2012,37:182-209.
    [119] Zhao Z, Wang Z, Lu P, et al. Structural Modulation of Solid-State Emission of2,5-Bis(trialkylsilylethynyl)-3,4-diphenylsiloles. Angew. Chem. Int. Ed.,2009,48:7608-7611.
    [120] Liu J, Meng Q, Zhang X T, et al. Aggregation-induced emission enhancement based on11,11,12,12,-tetracyano-9,10-anthraquinodimethane. Chem. Commun.,2013,49:1199-1201.
    [121] Chen J, Law C C W, Lam J W Y, et al. Synthesis, light emission, nanoaggregation, andrestricted intramolecular rotation of1,1-substituted2,3,4,5-tetraphenylsiloles. Chem. Mater.,2003,15:1535-1546.
    [122] Fan X, Sun J, Wang F, et al. Photoluminescence and electroluminescence ofhexaphenylsilole are enhanced by pressurization in the solid state. Chem. Commun.,2008,2989-2991.
    [123] Huang G, Ma B, Chen J, et al. Dendron-containing tetraphenylethylene compounds:Dependence of fluorescence and photocyclization reactivity on the dendron generation.Chem. Eur. J.,2012,18:3886-3892.
    [124] Kim T H, Choi M S, Sohn B H, et al. Gelation-induced fluorescence enhancement ofbenzoxazole-based organogel and its naked-eye fluoride detection. Chem. Commun.,2008,2364-2366.
    [125] Sun Y Y, Liao J H, Fang J M, et al. Fluorescent organic nanoparticles ofbenzofuran naphthyridine linked molecules: Formation and fluorescence enhancement inaqueous media. Org. Lett.,2006,8:3713-3716.
    [126] An B K, Kwon S K, Jung S D, et al. Enhanced emission and its switching in fluorescentorganic nanoparticles. J. Am. Chem. Soc.,2002,124:14410-14415.
    [127] Zhang P, Wang H T, Liu H M, et al. Fluorescence-enhanced organogels and mesomorphicsuperstructure based on hydrazine derivatives. Langmuir,2010,26:10183-10190.
    [128] Hu R R, Lager E, Aguilar-Aguilar A, et al. Twisted intramolecular charge transfer andaggregation-induced emission of BODIPY derivatives, J. Phys. Chem. C,2009,113:15845-15853.
    [129] Yuan C X, Tao X T, Ren Y, et al. Synthesis, structure, and aggregation-induced emissionof a novel Lambda (Λ)-shaped pyridinium salt based on Tr ger's base. J. Phys. Chem. C,2007,111:12811-12816.
    [130] Lamere J-F, Saffon N, Dos S I, et al. Aggregation-induced emission enhancement inorganic ion pairs. Langmuir,2010,26:10210-10217.
    [131] Toal S J, Jones K A, Magde D, et al. Luminescent silole nanoparticles as chemoselectivesensors for Cr(VI),J. Am. Chem. Soc.,2005,127:11661-11665.
    [132] Han T Y, Feng X, Tong B, et al. A novel ‘‘turn-on’’ fluorescent chemosensor for theselective detection of Al3+based on aggregation-induced emission. Chem. Commun.,2012,48:416-418.
    [133] Xie D X, Ran Z J, Jin Z, et al. A simple fluorescent probe for Zn(II) based on theaggregation-induced emission, Dyes and pigments,2013,96:495-499.
    [134] Xie Y Z, Shan G G, Guo G, et al. A novel class of Zn(II) schiff base complexes withaggregation-induced emission enhancement (AIEE) properties: synthesis, characterizationand photophysical/electrochemical properties. Dyes Pigments,2013,96:467-474.
    [135] Liu L, Zhang G X, Xiang J F, et al. Fluorescence “turn on” chemosensors for Ag+and Hg2+based on tetraphenylethylene motif featuring adenine and thymine moieties. Org. Lett.,2008,10:4581-4584.
    [136] Zhang H, Qu Y, Gao Y T, et al. A red fluorescent “turn-on” chemosensor for Hg2+based ontriphenylamine–triazines derivatives with aggregation-induced emission characteristics.Tetrahedron Lett.,2013,54:909-912.
    [137] Yan Y Y, Che Z P, Yu X, et al. Fluorescence “on-off-on” chemosensor for sequentialrecognition of Fe3+and Hg2+in water based on tetraphenylethylene motif. Bioorg. Med.Chem.,2013,21:508-513.
    [138] Sun F, Zhang G X, Zhang D Q, et al. Aqueous fluorescence turn-on sensor for Zn2+with atetraphenylethylene compound. Org. Lett.,2011,13:6378-6381.
    [139] Tong H, Hong Y N, Dong Y Q, Protein detection and quantitation bytetraphenylethene-based fluorescent probes with aggregation-induced emissioncharacteristics. J. Phys. Chem. B,2007,111:11817-11823.
    [140] Wang M, Zhang D Q, Zhang G X, et al. Fluorescence turn-on detection of DNA andlabel-free fluorescence nuclease assay based on the aggregation-induced emission of silole,Anal. Chem.,2008,80:6443-6448.
    [141] Huang J, Wang M, Zhou Y Y, et al. Visual observation of G-quadruplex DNA with thelabel-free fluorescent probe silole with aggregation-induced emission, Bioorg. Med. Chem.,2009,17:7743-7748.
    [142] Faisal M, Hong Y N, Liu J Z, et al. Fabrication of fluorescent silica nanoparticleshybridized with AIE luminogens and exploration of their applications as nanobiosensors inintracellular imaging. Chem.-Eur. J.,2010,16:4266-4272.
    [143] Mahtab F, Yu Y, Lam J W Y, et al. Fabrication of silica nanoparticles with both efficientfluorescence and strong magnetization, and exploration of their biological applications. Adv.Funct. Mater.,2011,21:1733-1740.
    [144] Mahta F, Lam J W Y, Yu Y, et al. Covalent immobilization of aggregation-induced emissionluminogens in silica nanoparticles through click reaction. Small,2011,7:1448-1455.
    [145] Wu W C, Chen C Y, Tian Y Q, et al. Enhancement of aggregation-induced emission indye-encapsulating polymeric micelles for bioimaging. Adv. Funct. Mater.,2010,20:1413-1423.
    [146] Zhu W H, Huang X M, Guo Z Q, et al. A novel NIR fluorescent turn-on sensor for thedetection of pyrophosphate anion in complete water system. Chem. Commum.,2012,48:1784-1786.
    [147] Guo Z Q, Zhu W H, Zhu M M, et al. Near-infrared cell-permeable Hg2+-selectiveratiometric fluorescent chemodosimeters and fast indicator paper for MeHg+based ontricarbocyanines. Chem. Eur. J.,2010,16:14424-14432.
    [148] Yu Y, Feng C, Hong Y N. Cytophilic fluorescent bioprobes for long-term cell tracking. Adv.Mater.,2011,23:3298-3302.
    [149] Qin W, Ding D, Liu J Z. Biocompatible nanoparticles with aggregation-induced emissioncharacteristics as far-red/near-infrared fluorescent bioprobes for in vitro and in vivoimaging applications. Adv. Funct. Mater.,2012,22:771-779.
    [150] Martinez A W, Phillips S T, Butte M J, et al. Patterned paper as a platform for inexpensive,low-volume, portable bioassays. Angew. Chem. Int. Ed.,2007,119:1340-1342.
    [151] Martinez A W, Phillips S T, Whitesides G M, et al. E. Diagnostics for the developing world:microfluidic paper-based analytical devices. Anal. Chem.,2010,82:3-10.
    [152] Liu Y, Yu Y, Lam J W Y. et al. Y. Hong, M. Faisal, W. Zhang Yuan, B. Z. Tang, SimpleBiosensor with High Selectivity and Sensitivity: Thiol-Specific Biomolecular Probing andIntracellular Imaging by AIE Fluorogen on a TLC Plate through a Thiol-Ene ClickMechanism. Chem. Eur. J.2010,16:8433-8438.
    [153] Leino A, Loo B M. Comparison of three commercial tests for buprenorphine screening inurine. Ann. Clin. Biochem.,2007,44:563-565.
    [154] Sanji T, Nakamura M, Kawamata S. Fluorescence “turn-on” detection of melamine withaggregation-induced-emission-active tetraphenylethene. Chem. Eur. J.,2012,18:15254-15257.
    [155] DeBoeck M, Kirsch-Volders M, Lison, D. Cobalt and antimony: genotoxicity andcarcinogenicity. Mutat. Res.,2003,533:135-152.
    [156] Lead and Copper Rule Minor Revision; EPA815-F-899-010; Environmental ProtectionAgency: Washington, DC,1999.
    [157] Li J, Lu Y. A general method to convert DNAzymes into fluorescent sensors using catalyticbeacon. J. Am. Chem. Soc.,2000,122:10466-10467.
    [158] Liu J, Lu Y. Improving fluorescent DNAzyme biosensors by combining inter-andintramolecular quenchers. Anal. Chem.,2003,75:6666-6672.
    [159] Liu J, Lu Y. Fluorescent DNAzyme biosensors for metal ions based on catalytic molecularbeacons. Methods Mol. Biol.,2006,335:275-288.
    [160] Elbaz J, Moshe M, Shlyahovsky B, et al. Cooperative multicomponent self-assembly ofnucleic acid structures for the activation of DNAzyme cascades: a paradigm for DNAsensors and aptasensors. Chem. Eur. J.,2009,15:3411-3418.
    [161] Martinez-Zaguilan R, Chinock B F, Wald-Hopkins S, et al.[Ca2+]Iand pHInhomeostasis inkaposi sarcoma cells. Cell. Physiol. Biochem.,1996,6:169-184.
    [162] Xu K, Klibanov A M. pH control of the catalytic activity of cross-linked enzyme crystals inorganic solvents. J. Am. Chem. Soc.,1996,118:9815-9819.
    [163] Han J Y, Burgess K. Fluorescent indicators for intracellular pH. Chem. Rev.,2010,5:2709-2728.
    [164] Han J Y, Loudet A, Barhoumi R, et al. A ratiometric pH reporter for imaging protein-dyeconjugates in living cells. J. Am. Chem. Soc.,2009,131:1642-1643.
    [165] Peng X Y, Du J J, Fan J L, et al. A selective fluorescent sensor for imaging Cd2+in livingcells. J. Am. Chem. Soc.,2007,129:1500-1501.
    [166] High B, Bruce D, Richter M M. Determining copper ions in water usingelectrochemiluminescence. Anal. Chim. Acta,2001,449:17-22.
    [167] Tapia L, Suazo M, Hodar C, et al. Copper exposure modifies the content and distribution oftrace metals in mammalian cultured cells. Biometals,2003,16:169-174.
    [168] Janzen D E, Burand M W, Ewbank P C, et al. Preparation and characterization ofπ-stacking quinodimethane oligothiophenes. Predicting semiconductor behavior andbandwidths from crystal structures and molecular orbital calculations. J. Am. Chem. Soc.,2004,126:15295-15308.
    [169] Ning Z J, Zhou Y C, Zhang Q, et al. Bisindolylmaleimide derivatives as non-doped redorganic light-emitting materials. J. Photochem. Photobiol. A,2007,192:8-16.
    [170] Tang B Z, Geng Y, Lam J W Y, et al. Processible nanostructured materials with electricalconductivity and magnetic susceptibility: preparation and properties ofmaghemite/polyaniline nanocomposite films. Chem. Mater.,1999,11:1581-1589.
    [171] Llopis J, McCaffery J M, Miyawaki A, et al. Measurement of cytosolic, mitochondrial, andGolgi pH in single living cells with green fluorescent proteins. Proc. Natl. Acad. Sci.U.S.A.,1998,95:6803-6808.
    [172] Yang X, Wang E K. A nanoparticle autocatalytic sensor for Ag+and Cu2+ions in aqueoussolution with high sensitivity and selectivity and its application in test paper. Anal. Chem.,2011,83:5005-5011.
    [173] Burns A, Owb H, Wiesner U. Fluorescent core–shell silica nanoparticles: towards “Lab on aParticle” architectures for nanobiotechnology. Chem. Soc. Rev.,2006,35:1028-1042.
    [174] Shi H, He X X, Yuan Y, et al. Nanoparticle-based biocompatible and long-life marker forlysosome labeling and tracking. Anal. Chem.,2010,82:2213-2220.
    [175] Song Y J, Zhao C, Ren J S, et al. Rapid and ultra-sensitive detection of AMP using afluorescent and magnetic nano-silica sandwich complex. Chem. Comm.,2009,1975-1977.
    [176] He X X, Wang Y S, Wang K M, et al. Fluorescence resonance energy transfer mediatedlarge stokes shifting near-infrared fluorescent silica nanoparticles for in vivo small-animalimaging. Anal. Chem.,2012,84:9056-9064.
    [177] Bates P J, Kahlon J B, Thomas S D, et al. Antiproliferative activity of G-richoligonucleotides correlates with protein binding. J. Biol. Chem.,1999,274:26369-26377.
    [178] Soundararajan S, Chen W, Spicer E K, et al. The nucleolin targeting aptamer AS1411destabilizes Bcl-2messenger RNA in human breast cancer cells. Cancer Res.,2008,68,2358-2365.
    [179] Li L L, Yin Q, Cheng J J, et al. Polyvalent mesoporous silica nanoparticle-aptamerbioconjugates target breast cancer cells. Adv. Healthc. Mater.,2012,1:567-572.

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