基于聚集诱导发光荧光探针的细胞成像研究进展

doi:10.11944/j.issn.1000-0518.2018.10.170461

摘要/Abstract

摘要：

荧光探针是化学传感技术领域在20世纪末的一项重大发现,具有合成简单、灵敏度高、选择性好、响应时间短、可视化高等优点。将具有聚集诱导发光现象(AIE)特征的荧光基团与具有生物相容性的高分子结合起来,使得荧光材料具有毒性低、光稳定性好、生物相容性好等特点。在分子、离子检测和细胞成像技术中得到广泛的研究和应用。本文综述了细胞质成像、细胞膜成像、线粒体成像、溶酶体成像、脂滴成像、细胞核成像、细胞核和线粒体双靶向性成像的荧光探针,并对其应用前景做了展望。

关键词: 荧光探针, 化学传感, 生物成像, 聚集诱导发光

Abstract:

Fluorescent probes as a major discovery in the field of chemical sensing at the end of the 20th century have the advantages of simple synthesis, high sensitivity, good selectivity, short response time and high visualization. The combination of the fluorescent group with the aggregation-induced emission(AIE) characteristics and the biocompatible polymer makes the fluorescent materials have the characteristics of low toxicity, good light stability and good biocompatibility. In molecular, ion detection and cell imaging technology it has been widely studied and applied. This review summarizes the fluorescence probes for cytoplasmic imaging, cell membrane imaging, mitochondrial imaging, lysosomal imaging, lipid droplet imaging, nuclear imaging, nuclear and mitochondrial dual-targeting imaging and the prospects for their application.

Key words: fluorescence probe, chemical sensing, biological imaging, aggregation-induced emission

王涛,马拉毛草,马恒昌. 基于聚集诱导发光荧光探针的细胞成像研究进展[J]. 应用化学, 2018, 35(10): 1155-1165.

WANG Tao,MA Lamaocao,MA Hengchang. Research Progress on Cell Imaging Based on the Aggregation-induced Emission Fluorescent Probes[J]. Chinese Journal of Applied Chemistry, 2018, 35(10): 1155-1165.

参考文献

[1]	Shimizu,Yoshinori. Light Emitting Device Having a Nitride Compound Semiconductor and a Phosphor Containing a Garnet Fluorescent Material:US. Patent,5998925A[P].1999-12-07.
[2]	Komoto,Satoshi. Semiconductor Light Emitting Device Including a Fluorescent Material:US Patent,6340824A[P].2002-01-22.
[3]	Xu X,Ray R,Gu Y,et al. Electrophoretic Analysis and Purification of Fluorescent Single-walled Carbon Nanotube Fragments[J]. J Am Chem Soc,2004,126(40):12736-12737.
[4]	Shalon D,Smith S J,Brown P O.A DNA Microarray System for Analyzing Complex DNA Samples Using Two-color Fluorescent Probe Hybridization[J]. Genome Res,1996,6(7):639-645.
[5]	Semisotnov G V,Rodionova N A,Razgulyaev O I,et al. Study of the “Molten Globule” Intermediate State in Protein Folding by a Hydrophobic Fluorescent Probe[J]. Biopolymers,1991,31(1):119-128.
[6]	Betzig E,Patterson G H,Sougrat R,et al. Imaging Intracellular Fluorescent Proteins at Nanometer Resolution[J]. Science,2006,313(5793):1642-1645.
[7]	Kinkhabwala A,Yu Z,Fan S,et al. Large Single-molecule Fluorescence Enhancements Produced by a Bowtie Nanoantenna[J]. Nat Photonics,2009,3(11): 654-657.
[8]	Eggeling C,Ringemann C,et al. Direct Observation of the Nanoscale Dynamics of Membrane Lipids in a Living Cell[J]. Nature,2009,457(7233):1159-1162.
[9]	Luo J,Xie Z,Lam J W Y, et al. Aggregation-induced Emission of 1-Methyl-1,2,3,4,5-Pentaphenylsilole[J]. Chem Commun,2001,(18):1740-1741.
[10]	Hong Y,Lam J W Y,Tang B Z. Aggregation-induced Emission[J]. Chem Soc Rev,2011,40(11):5361-5388.
[11]	Hong Y,Lam J W Y,Tang B Z. Aggregation-induced Emission: Phenomenon, Mechanism and Applications[J]. Chem Commun,2009,(29):4332-4353.
[12]	Lakowicz J R.Topics in Fluorescence Spectroscopy Nonlinear and Two-Photon-Induced Fluorescence[J]. Springer Berlin,2002,6(1):103-121.
[13]	Li M,Hong Y,Wang Z,et al. Fabrication of Chitosan Nanoparticles with Aggregation-Induced Emission Characteristics and Their Applications in Long-Term Live Cell Imaging[J]. Macromol Rapid Commun,2013,34(9):767-771.
[14]	Yan L,Zhang Y,Xu B,et al. Fluorescent Nanoparticles Based on AIE Fluorogens for Bioimaging[J]. Nanoscale,2016,8(5):2471-2487.
[15]	Ding D,Mao D,Li K,et al. Precise and Long-term Tracking of Adipose-derived Stem Cells and Their Regenerative Capacity via Superb Bright and Stable Organic Nanodots[J]. ACS Nano,2014,8(12):12620-12631.
[16]	Zhang X,Zhang X,Wang S,et al. Surfactant Modification of Aggregation-induced Emission Material as Biocompatible Nanoparticles:Facile Preparation and Cell Imaging[J]. Nanoscale,2013,5(1):147-150.
[17]	Shao A,Xie Y,Zhu S,et al. Far-Red and Near-IR AIE-Active Fluorescent Organic Nanoprobes with Enhanced Tumor-Targeting Efficacy:Shape-Specific Effects[J]. Angew Chem Int Ed,2015,127(25):7383-7388
[18]	Lehn J M. Supramolecular Chemistry[M]. SHEN Xinghai,Trans. Beijing:Peking University Press,2002:6-7(in Chinese). Lehn J M. 超分子化学:概念和展望[M]. 沈兴海译. 北京:北京大学出版社,2002:6-7.
[19]	Arai S,Lee S C,Chang Y T,et al. A Molecular Fluorescent Probe for Targeted Visualization of Temperature at the Endoplasmic Reticulum[J]. Sci Rep-UK,2014,4:6701.
[20]	Zhang W,Liu W,Li P,et al. Rapid-Response Fluorescent Probe for Hydrogen Peroxide in Living Cells Based on Increased Polarity of C B Bonds[J]. Anal Chem,2015,87(19):9825-9828.
[21]	Liu T,Liu X,Spring D R,et al. Quantitatively Mapping Cellular Viscosity with Detailed Organelle Information via a Designed PET Fluorescent Probe[J]. Sci Rep-UK,2014,4:5418.
[22]	Cheng J,Ma X,Zhang Y,et al. Optical Chemosensors Based on Transmetalation of Salen-based Schiff Base Complexes[J]. Inorg Chem,2014,53(6):3210-3219.
[23]	Zhou Y,Zhang J F,Yoon J,et al. Fluorescence and Colorimetric Chemosensors for Fluoride-Ion Detection[J]. Chem Rev,2014,114(10):5511-5571.
[24]	Zhou X,Lee S,Xu Z,et al. Recent Progress on the Development of Chemosensors for Gases[J]. Chem Rev,2015,115(15):7944-8000.
[25]	Goswami S,Das S,Aich K,et al. A Chemodosimeter for the Ratiometric Detection of Hydrazine Based on Return of ESIPT and Its Application in Live-cell Imaging[J]. Org Lett,2013,15(21):5412-5415.
[26]	Yin J,Kwon Y,Kim D,et al. Cyanine-based Fluorescent Probe for Highly Selective Detection of Glutathione in Cell Cultures and Live Mouse Tissues[J]. J Am Chem Soc,2014,136(14):5351-5358.
[27]	Liu B,Wang J,Zhang G,et al. Flavone-based ESIPT Ratiometric Chemodosimeter for Detection of Cysteine in Living Cells[J]. ACS Appl Mater Interfaces,2014,6(6):4402-4407.
[28]	Aigner D,Borisov S M,Fern ndez F J O, et al. New Fluorescent pH Sensors Based on Covalently Linkable PET Rhodamines[J]. Talanta,2012,99:194-201.
[29]	Park B W,Philippe B,Gustafsson T,et al. Enhanced Crystallinity in Organic Inorganic Lead Halide Perovskites on Mesoporous TiO2 via Disorder-Order Phase Transition[J]. Chem Mater,2014,2(15):4466-4471.
[30]	Liu Z,He W,Guo Z,et al. Metal Coordination in Photoluminescent Sensing[J]. Chem Soc Rev,2013,42(4):1568-1600.
[31]	Xu Z,Yoon J,Spring D R.A Selective and Ratiometric Cu2+ Fluorescent Probe Based on Naphthalimide Excimer Monomer Switching[J]. Chem Commun,2010,46(15):2563-2565.
[32]	Wu J,Liu W,Ge J,et al. New Sensing Mechanisms for Design of Fluorescent Chemosensors Emerging in Recent Years[J]. Chem Soc Rev,2011,40(7):3483-3495.
[33]	Kim T I,Kang H J,Han G,et al. A Highly Selective Fluorescent ESIPT Probe for the Dual Specificity Phosphatase MKP-6[J]. Chem Commun,2009,(39):5895-5897.
[34]	Mei J,Hong Y,Lam J W Y, et al. Aggregation-Induced Emission:The Whole is More Brilliant Than the Parts[J]. Adv Mater,2014,26(31):5429-5479
[35]	Chang Z F,Jing L M,Liu Y Y,et al. Constructing Small Molecular AIE Luminophores Through a 2,2-(2,2-Diphenylethene-1,1-diyl) Dithiophene Core and Peripheral Triphenylamine with Applications in Piezofluorochromism, Optical Waveguides, and Explosive Detection[J]. J Mater Chem C,2016,4(36):8407-8415.
[36]	Miyanari Y,Atsuzawa K,Usuda N,et al. The Lipid Droplet is an Important Organelle for Hepatitis C Virus Production[J]. Nat Cell Biol,2007,9(9):1089-1097.
[37]	Berezney R.The Nuclear Matrix:A Heuristic Model for Investigating Genomic Organization and Function in the Cell Nucleus[J]. J Cell Biochem,1991,47(2):109-123.
[38]	Vendrell M,Zhai D,Er J C,et al. Combinatorial Strategies in Fluorescent Probe Development[J]. Chem Rev,2012,112(8):4391-4420.
[39]	Xu W,Zeng Z,Jiang J H,et al. Discerning the Chemistry in Individual Organelles with Small-Molecule Fluorescent Probes[J]. Angew Chem Int Ed,2016,55(44):13658-13699.
[40]	Li Y,Shao A,Wang Y,et al. Tumor Bioimaging: Morphology-Tailoring of a Red AIEgen from Microsized Rods to Nanospheres for Tumor-Targeted Bioimaging[J]. Adv Mater,2016,28(16):3224-3224.
[41]	Li Y,Shao A,Wang Y,et al. Morphology-Tailoring of a Red AIEgen from Microsized Rods to Nanospheres for Tumor-Targeted Bioimaging[J]. Adv Mater,2016,28(16):3187-3193.
[42]	Umezawa K,Yoshida M,Kamiya J M,et al. Rational Design of Reversible Fluorescent Probes for Live-cell Imaging and Quantification of Fast Glutathione Dynamics[J]. Nat Chem,2017,9(3):279-286.
[43]	Ma H,Yang M,Zhang C,et al. Aggregation-induced Emission(AIE)-active Fluorescent Probes with Multiple Binding Sites Toward ATP Sensing and Live Cell Imaging[J]. J Mater Chem B,2017,5(43):8525-8531.
[44]	Pedram P,Mahani M,Torkzadeh-Mahani M,et al. Cadmium Sulfide Quantum Dots Modified with the Human Transferrin Protein Siderophiline for Targeted Imaging of Breast Cancer Cells[J]. Microchim Acta,2016,183(1):67-71.
[45]	Sun L,Ding J,Xing W,et al. Novel Strategy for Preparing Dual-modality Optical/PET Imaging Probes via Photo-click Chemistry[J]. Biol Chem,2016,27(5):1200-1204.
[46]	Domaille D W,Que E L,Chang C J.Synthetic Fluorescent Sensors for Studying the Cell Biology of Metals[J]. Nat Chem Biol,2008,4(3):168-175.
[47]	Liang J,Li K,Liu B.Visual Sensing with Conjugated Polyelectrolytes[J]. Chem Soc,2013,4(4):1377-1394.
[48]	Ma H,Qi C,Cheng C,et al. AIE-active Tetraphenylethylene Cross-linked N-Isopropylacrylamide Polymer:A Long-term Fluorescent Cellular Tracker[J]. ACS Appl Mater Interfaces,2016,8(13):8341-8348.
[49]	Wang B,Zhu C,Liu L,et al. Synthesis of a New Conjugated Polymer for Cell Membrane Imaging by Using an Intracellular Targeting Strategy[J]. Polym Chem-UK,2013,4(20):5212-5215.
[50]	Zhang C,Jin S,Yang K,et al. Cell Membrane Tracker Based on Restriction of Intramolecular Rotation[J]. ACS Appl Mater Interfaces,2014,6(12):8971-8975.
[51]	Jouaville L S,Pinton P,Bastianutto C,et al. Regulation of Mitochondrial ATP Synthesis by Calcium:Evidence for a Long-term Metabolic Priming[J]. PNAS,1999,96(24):13807-13812.
[52]	Suen D F,Norris K L,Youle R J.Mitochondrial Dynamics and Apoptosis[J]. Gene Dev,2008,22(12):1577-1590.
[53]	Leung C W T,Hong Y,Chen S,et al. A Photostable AIE Luminogen for Specific Mitochondrial Imaging and Tracking[J]. J Am Chem Soc,2013,135(1):62-65.
[54]	Van Meel E,Klumperman J.Imaging and Imagination:Understanding the Endo-lysosomal System[J]. Histo Chem Cell Biol,2008,129(3):253-266.
[55]	Gao M,Hu Q,Feng G,et al. A Fluorescent Light-up Probe with “AIE+ ESIPT” Characteristics for Specific Detection of Lyssomal Esterase[J]. J Mater Chem B,2014,2(22):3438-3442.
[56]	Martin S,Parton R G.Opinion: Lipid Droplets:A Unified View of a Dynamic Organelle[J]. Nat Rev Mol Cell Biol,2006,7(5):373-378.
[57]	Alberti K G M M,Zimmet P,Shaw J. Metabolic Syndrome-A New World-wide Definition. A Consensus Statement from the International Diabetes Federation[J]. Diabetic Med,2006,23(5):469-480.
[58]	Wang Z,Gui C,Zhao E,et al Specific Fluorescence Probes for Lipid Droplets Based on Simple AIEgens[J]. ACS Appl Mater Interfaces,2016,8(16):10193-10200.
[59]	Kobayashi H,Ogawa M,Alford R,et al. New Strategies for Fluorescent Probe Design in Medical Diagnostic Imaging[J]. Chem Rev,2009,110(5):2620-2640.
[60]	Horobin R W,Stockert J C,Rashid-Doubell F.Fluorescent Cationic Probes for Nuclei of Living Cells:Why Are They Selective? A Quantitative Structure-Activity Relations Analysis[J]. Histochem Cell Biol,2006,126(2):165-175
[61]	Collas P,Aleström P.Rapid Targeting of Plasmid DNA to Zebrafish Embryo Nuclei by the Nuclear Localization Signal of SV 40T Antigen[J]. Mol Mar Biol Biotechnol,1997,6(1):48-58.
[62]	Wade W,Grabow,Luc J.RNA Self-Assembly and RNA Nanotechnology[J]. Acc Chem Res,2014,47:1871-1880.
[63]	Chris Y Y,Kwok R T K,Tang B Z, et al. A Photostable AIEgen for Nucleolus and Mitochondria Imaging with Organelle-specific Emission[J]. J Mater Chem B,2016,4(15):2614-2619.
[64]	Ma H,Yang M,Zhang C,et al. Aggregation-induced Emission(AIE)-active Fluorescent Probes with Multiple Binding Sites Toward ATP Sensing and Live Cell Imaging[J]. J Mater Chem B,2017,5(43):8525-8531.
[65]	Haugland R P.Handbook of Fluorescent Probes and Research Products[M]. 9th Edn. Eugene OR:Molecular Probes,USA,2002.
[66]	Giepmans B N,Adams S R,Ellisman M H,et al. The Fluorescent Toolbox for Assessing Protein Location and Function[J]. Science,2006,312(5771):217-224.
[67]	Ashkenazi A.Targeting Death and Decoy Receptors of the Tumour-necrosis Factor Superfamily[J]. Nat Rev Cancer,2002,2(6):420-430.
[68]	Ma H,Yang Z,Cao H,et al. One Bioprobe:A Fluorescent and AIE-active Macromolecule; Two Targets:Nucleolus and Mitochondria with Long Term Tracking[J]. J Mater Chem B,2017,5(4):655-660.