Exclusive: Nanobiomedicine

Application of aggregation-induced emission materials in bioimaging, disease diagnosis and therapy

  • JIANG Meijuan ,
  • KWOK Tsz Kin ,
  • TANG Benzhong
Expand
  • 1. HKUST-Shenzhen Research Institute, Shenzhen 518057, China;
    2. Department of Chemistry, Hong Kong University of Science and Technology;Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction;HKUST Jockey Club Institute for Advanced Study, Clear Water Bay, Kowloon, Hong Kong, China;
    3. State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China

Received date: 2018-05-14

  Revised date: 2018-09-18

  Online published: 2018-12-14

Abstract

The study of the underlying mechanism of aggregation-induced emission (AIE), design and synthesis of novel AIE molecules and their application in various fields of daily life are the current hot research topics. According to AIE mechanism of restriction of intramolecular motions, a variety of AIE probes with "turn-on" sensing feature have been designed to provide much lower background and higher signal reliability, which are particularly attractive and suitable for use in biology. Since the unbound AIE probes have a low background, the use of the AIE bioprobes also has the advantage of not requiring washing steps, which greatly saves the operation time and eliminates the loss of the samples. The formed AIE aggregates have excellent photostability and resistance to photobleaching during detection, allowing long-term tracking and monitoring. AIE bioprobes have been designed and applied to fields of biomolecular detection, cellular structure imaging, bacterial imaging, cell tracking, angiography, in vivo tumor imaging and therapy, etc. With the recently achieved numerous results, herein, we first briefly introduce the origin of AIE, then we discuss the working mechanism of AIE and the construction of AIE probes. Finally we summarize the recent works of AIE in different aspects of bioimaging, disease diagnosis and treatment.

Cite this article

JIANG Meijuan , KWOK Tsz Kin , TANG Benzhong . Application of aggregation-induced emission materials in bioimaging, disease diagnosis and therapy[J]. Science & Technology Review, 2018 , 36(22) : 27 -53 . DOI: 10.3981/j.issn.1000-7857.2018.22.003

References

[1] Michalet X, Pinaud F F, Bentolila L A, et al. Quantum dots for live cells, in vivo imaging, and diagnostics[J]. Science, 2005, 307(5709):538-544.
[2] Medintz I L, Uyeda H T, Goldman E R, et al. Quantum dot bioconjugates for imaging, labelling and sensing[J]. Nature Materials, 2005, 4(6):435-446.
[3] Resch-Genger U, Grabolle M, Cavaliere-Jaricot S, et al. Quantum dots versus organic dyes as fluorescent labels[J]. Nature Methods, 2008, 5(9):763-775.
[4] Chalfie M. Green fluorescent protein[J]. Photochemistry and Photobiology, 1995, 62(4):651-656.
[5] Sample V, Newman R H, Zhang J. The structure and function of fluorescent proteins[J]. Chemical Society Reviews, 2009, 38(10):2852-2864.
[6] Terai T, Nagano T. Small-molecule fluorophores and fluorescent probes for bioimaging[J]. Pflügers Archiv-European Journal of Physiology, 2013, 465(3):347-359.
[7] Noh M, Kim T, Lee H, et al. Fluorescence quenching caused by aggregation of water-soluble CdSe quantum dots[J]. Colloids and Surfaces A:Physicochemical and Engineering Aspects, 2010, 359(1-3):39-44.
[8] Förster T, Kasper K. Ein Konzentrationsumschlag der fluoreszenz des Pyrens[J]. Zeitschrift für Physikalische Chemie, 1955, 59(10):976-980.
[9] Saigusa H, Lim E C. Excimer formation in van der Waals dimers and clusters of aromatic molecules[J]. Accounts of Chemical Research, 1996, 29(4):171-178.
[10] Feng G, Liu B. Multifunctional AIEgens for future theranostics[J]. Small, 2016, 12(47):6528-6535.
[11] Mei J, Hong Y, Lam J W, et al. Aggregation-induced emission:the whole is more brilliant than the parts[J]. Advanced Materials, 2014, 26(31):5429-5479.
[12] Leung N L, Xie N, Yuan W, et al. Restriction of intramolecular motions:The general mechanism behind aggregation-induced emission[J]. Chemistry, 2014, 20(47):15349-15353.
[13] Nishiuchi T, Tanaka K, Kuwatani Y, et al. Solvent-induced crystalline-state emission and multichromism of a bent π-surface system composed of dibenzocyclooctatetraene units[J]. Chemistry, 2013, 19(13):4110-4116.
[14] Yuan C, Saito S, Camacho C, et al. Hybridization of a flexible cyclooctatetraene core and rigid aceneimide wings for multiluminescent flapping π systems[J]. Chemistry, 2014, 20(8):2193-2200.
[15] Mei J, Leung N L, Kwok R T, et al. Aggregation-induced emission:Together we shine, united we soar![J]. Chemical Reviews, 2015, 115(21):11718-11940.
[16] Song Z, Zhang W, Jiang M, et al. Synthesis of imidazolebased AIEgens with wide color tunability and exploration of their biological applications[J]. Advanced Functional Materials, 2016, 26(6):824-832.
[17] Zhao Z, He B and Tang B Z. Aggregation-induced emission of siloles[J]. Chemical Science, 2015, 6(10):5347-5365.
[18] Zhang J B, Ma S Q, Fang H H, et al. Insights into the origin of aggregation enhanced emission of 9,10-distyrylanthracene derivatives[J]. Materials Chemistry Frontiers, 2017, 1(7):1422-1429.
[19] Yamaguchi M, Ito S, Hirose A, et al. Control of aggregationinduced emission versus fluorescence aggregation-caused quenching by bond existence at a single site in boron pyridinoiminate complexes[J]. Materials Chemistry Frontiers, 2017, 1(8):1573-1579.
[20] Chen M, Li L, Nie H, et al. Tetraphenylpyrazine-based AIEgens:Facile preparation and tunable light emission[J]. Chemical Science, 2015, 6(3):1932-1937.
[21] Jiang M, Gu X, Kwok R T K, et al. Multifunctional AIEgens:Ready synthesis, tunable emission, mechanochromism, mitochondrial, and bacterial imaging[J]. Advanced Functional Materials, 2018, 28(1):1704589.
[22] Gao M, Tang B Z. Fluorescent sensors based on aggregationinduced emission:recent advances and perspectives[J]. ACS Sensors, 2017, 2(10):1382-1399.
[23] Liang J, Tang B Z, Liu B. Specific light-up bioprobes based on AIEgen conjugates[J]. Chemical Society Reviews, 2015, 44(10):2798-2811.
[24] Gao H, Zhao X and Chen S. AIEgen-based fluorescent nanomaterials:Fabrication and biological applications[J]. Molecules, 2018, 23(2):419.
[25] Mao L C, Liu M Y, Xu D Z, et al. Synthesis, surface modification and biological imaging of aggregation-induced emission (AIE) dye doped silica nanoparticles[J]. Applied Surface Science, 2017, 403:396-402.
[26] Li K, Qin W, Ding D, et al. Photostable fluorescent organic dots with aggregation-induced emission (AIE dots) for noninvasive long-term cell tracing[J]. Scientific Reports, 2013, 3:1150.
[27] Feng G, Tay C Y, Chui Q X, et al. Ultrabright organic dots with aggregation-induced emission characteristics for cell tracking[J]. Biomaterials, 2014, 35(30):8669-8677.
[28] Qin W, Li K, Feng G X, et al. Bright and photostable organic fluorescent dots with aggregation-induced emission characteristics for noninvasive long-term cell imaging[J]. Advanced Functional Materials, 2014, 24(5):635-643.
[29] Yu J, Sun X, Cai F, et al. Low photobleaching and high emission depletion efficiency:The potential of AIE luminogen as fluorescent probe for STED microscopy[J]. Optics Letters, 2015, 40(10):2313-2316.
[30] Fang X F, Chen X Z, Li R Q, et al. Multicolor photo-crosslinkable AIE gens toward compact nanodots for subcellular imaging and STED nanoscopy[J]. Small, 2017, 13(41):1702128.
[31] Li D, Qin W, Xu B, et al. AIE nanoparticles with high stimulated emission depletion efficiency and photobleaching resistance for long-term super-resolution bioimaging[J]. Advanced Materials, 2017, 29(43):1703643.
[32] Stephens D J and Allan V J. Light microscopy techniques for live cell imaging[J]. Science, 2003, 300(5616):82-86.
[33] Hell S W. Far-field optical nanoscopy[J]. Science, 2007, 316(5828):1153-1158.
[34] Ustione A and Piston D W. A simple introduction to multiphoton microscopy[J]. Journal of Microscopy, 2011, 243(3):221-226.
[35] Hell S W, Sahl S J, Bates M, et al. The 2015 super-resolution microscopy roadmap[J]. Journal of Physics D-Applied Physics, 2015, 48(44):443001.
[36] Ding D, Li K, Liu B, et al. Bioprobes based on AIE fluorogens[J]. Accounts of Chemical Research, 2013, 46(11):2441-2453.
[37] Kwok R T, Leung C W, Lam J W, et al. Biosensing by luminogens with aggregation-induced emission characteristics[J]. Chemical Society Reviews, 2015, 44(13):4228-4238.
[38] Yuan Y, Kwok R T, Tang B Z, et al. Smart probe fortracing cancer therapy:Selective cancer cell detection, image-guided ablation, and prediction of therapeutic response in situ[J]. Small, 2015, 11(36):4682-4690.
[39] Hu F and Liu B. Organelle-specific bioprobes based on fluorogens with aggregation-induced emission (AIE) characteristics[J]. Organic & Biomolecular Chemistry, 2016, 14(42):9931-9944.
[40] Gu X, Kwok R T K, Lam J W Y, et al. AIEgens for biological process monitoring and disease theranostics[J]. Biomaterials, 2017, 146:115-135.
[41] Qian J, Tang B Z. AIE luminogens for bioimaging and theranostics:From organelles to animals[J]. Chem, 2017, 3(1):56-91.
[42] Gao M, Tang B Z. Aggregation-induced emission probes for cancer theranostics[J]. Drug Discovery Today, 2017, 22(9):1288-1294.
[43] Mei J, Huang Y, Tian H. Progress and trends in AIE-based bioprobes:A brief overview[J]. ACS Applied Materials & Interfaces, 2018, 10(15):12217-12261.
[44] Song Z, Mao D, Sung S H, et al. Activatable fluorescent nanoprobe with aggregation-induced emission characteristics for selective in vivo imaging of elevated peroxynitrite generation[J]. Advanced Materials, 2016, 28(33):7249-7256.
[45] Seo Y H, Singh A, Cho H J, et al. Rational design for enhancing inflammation-responsive in vivo chemiluminescence via nanophotonic energy relay to near-infrared AIE-active conjugated polymer[J]. Biomaterials, 2016, 84:111-118.
[46] Cheng Y, Dai J, Sun C L, et al. An intracellular H2O2-responsive AIEgen for the peroxidase-mediated selective imaging and inhibition of inflammatory cells[J]. Angewandte ChemieInternational Edition, 2018, 57(12):3123-3127.
[47] Yang J, Liu X L, Wang H L, et al. A turn-on near-infrared fluorescence probe with aggregation-induced emission based on dibenzo[a,c]phenazine for detection of superoxide anions and its application in cell imaging[J]. Analyst, 2018, 143(5):1242-1249.
[48] Gao X, Feng G, Manghnani P N, et al. A two-channel responsive fluorescent probe with AIE characteristics and its application for selective imaging of superoxide anions in living cells[J]. Chemical Communications, 2017, 53(10):1653-1656.
[49] Zhang P, Nie X, Gao M, et al. A highly selective fluorescent nanoprobe based on AIE and ESIPT for imaging hydrogen sulfide in live cells and zebrafish[J]. Materials Chemistry Frontiers, 2017, 1(5):838-845.
[50] Zhan C, Zhang G, Zhang D. Zincke's salt-substituted tetraphenylethylenes for fluorometric turn-on detection of glutathione and fluorescence imaging of cancer cells[J]. ACS Applied Materials & Interfaces, 2018, 10(15):12141-12149.
[51] Han H, Jin Q, Wang Y, et al. The rational design of a gemcitabine prodrug with AIE-based intracellular light-up characteristics for selective suppression of pancreatic cancer cells[J]. Chemical Communications, 2015, 51(98):17435-17438.
[52] Cheng Y, Huang F, Min X, et al. Protease-responsive prodrug with aggregation-induced emission probe for controlled drug delivery and drug release tracking in living cells[J]. Analytical Chemistry, 2016, 88:8913-8919.
[53] Liu X, Liang G. Dual aggregation-induced emission for enhanced fluorescence sensing of furin activity in vitro and in living cells[J]. Chemical Communications, 2017, 53(6):1037-1040.
[54] Xu G P, Tang Y H, Ma Y Y, et al. A new aggregation-induced emission fluorescent probe for rapid detection of nitroreductase and its application in living cells[J]. Spectrochimica Acta Part a-Molecular and Biomolecular Spectroscopy, 2018, 188:197-201.
[55] Gao M, Hu Q, Feng G, et al. A fluorescent light-up probe with "AIE + ESIPT" characteristics for specific detection of lysosomal esterase[J]. Journal of Materials Chemistry B, 2014, 2(22):3438-3442.
[56] Wang J G, Chen Q Q, Tian N, et al. A fast responsive, highly selective and light-up fluorescent probe for the two-photon imaging of carboxylesterase in living cells[J]. Journal of Materials Chemistry B, 2018, 6(11):1595-1599.
[57] Gu X, Zhang G, Wang Z, et al. A new fluorometric turn-on assay for alkaline phosphatase and inhibitor screening based on aggregation and deaggregation of tetraphenylethylene molecules[J]. Analyst, 2013, 138(8):2427-2431.
[58] Song Z, Kwok R T, Zhao E, et al. A ratiometric fluorescent probe based on ESIPT and AIE processes for alkaline phosphatase activity assay and visualization in living cells[J]. ACS Applied Materials & Interfaces, 2014, 6(19):17245-17254.
[59] Peng L, Gao M, Cai X, et al. A fluorescent light-up probe based on AIE and ESIPT processes for β-galactosidase activity detection and visualization in living cells[J]. Journal of Materials Chemistry B, 2015, 3:9168-9172.
[60] Jiang G, Zeng G, Zhu W, et al. A selective and light-up fluorescent probe for β-galactosidase activity detection and imaging in living cells based on an AIE tetraphenylethylene derivative[J]. Chemical Communications, 2017, 53:4505-4508.
[61] Shi H, Kwok R T, Liu J, et al. Real-time monitoring of cell apoptosis and drug screening using fluorescent light-up probe with aggregation-induced emission characteristics[J]. Journal of the American Chemical Society, 2012, 134(43):17972-17981.
[62] Shi H, Zhao N, Ding D, et al. Fluorescent light-up probe with aggregation-induced emission characteristics for in vivo imaging of cell apoptosis[J]. Organic & Biomolecular Chemistry, 2013, 11(42):7289-7296.
[63] Yuan Y, Zhang C J, Kwok R T K, et al. Light-up probe based on AIEgens:Dual signal turn-on for caspase cascade activation monitoring[J]. Chemical Science, 2017, 8(4):2723-2728.
[64] Yuan Y, Zhang C J, Gao M, et al. Specific light-up bioprobe with aggregation-induced emission and activatable photoactivity for the targeted and image-guided photodynamic ablation of cancer cells[J]. Angewandte Chemie-International Edition, 2015, 54(6):1780-1786.
[65] Shi H, Liu J, Geng J, et al. Specific detection of integrin αvβ3 by light-up bioprobe with aggregation-induced emission characteristics[J]. Journal of the American Chemical Society, 2012, 134:9569-9572.
[66] Ding D, Liang J, Shi H B, et al. Light-up bioprobe with aggregation-induced emission characteristics for real-time apoptosis imaging in target cancer cells[J]. Journal of Materials Chemistry B, 2014, 2(2):231-238.
[67] Gao M, Su H, Lin G, et al. Targeted imaging of EGFR overexpressed cancer cells by brightly fluorescent nanoparticles conjugated with cetuximab[J]. Nanoscale, 2016, 8(32):15027-15032.
[68] Shi X J, Yu C Y Y, Su H, et al. A red-emissive antibodyAIEgen conjugate for turn-on and wash-free imaging of specific cancer cells[J]. Chemical Science, 2017, 8:7014-7024.
[69] Zhao Z, Su H F, Zhang P F, et al. Polyyne bridged AIE luminogens with red emission:Design, synthesis, properties and applications[J]. Journal of Materials Chemistry B, 2017, 5(8):1650-1657.
[70] Zhang P, Zhao Z, Li C, et al. Aptamer-decorated self-assembled aggregation-induced emission organic dots for cancer cell targeting and imaging[J]. Analytical Chemistry, 2018, 90(2):1063-1067.
[71] Zhang R, Sung S H P, Feng G, et al. Aggregation-induced emission probe for specific turn-on quantification of soluble transferrin receptor:An important disease marker for iron deficiency anemia and kidney diseases[J]. Analytical Chemistry, 2018, 90(2):1154-1160.
[72] Wang E J, Zhao E G, Hong Y N, et al. A highly selective AIE fluorogen for lipid droplet imaging in live cells and green algae[J]. Journal of Materials Chemistry B, 2014, 2(14):2013-2019.
[73] Wang Z M, Gui C, Zhao E G, et al. Specific fluorescence probes for lipid droplets based on simple AIEgens[J]. ACS Applied Materials & Interfaces, 2016, 8(16):10193-10200.
[74] Kang M, Gu X, Kwok R T, et al. A near-infrared AIEgen for specific imaging of lipid droplets[J]. Chemical Communications, 2016, 52(35):5957-5960.
[75] Wang D, Su H, Kwok R T K, et al. Facile synthesis of red/NIR AIE luminogens with simple structures, bright emissions, and high photostabilities, and their applications for specific imaging of lipid droplets and image-guided photodynamic therapy[J]. Advanced Functional Materials, 2017, 27(46):1704039.
[76] Gao M, Su H, Li S, et al. An easily accessible aggregation-induced emission probe for lipid droplet-specific imaging and movement tracking[J]. Chemical Communications, 2017, 53(5):921-924.
[77] Jiang M, Gu X, Lam J W Y, et al. Two-photon AIE bioprobe with large Stokes shift for specific imaging of lipid droplets[J]. Chemical Science, 2017, 8(8):5440-5446.
[78] Gao M, Su H F, Lin Y H, et al. Photoactivatable aggregationinduced emission probes for lipid droplets-specific live cell imaging[J]. Chemical Science, 2017, 8(3):1763-1768.
[79] Leung C W, Hong Y, Chen S, et al. A photostable AIE luminogen for specific mitochondrial imaging and tracking[J]. Journal of the American Chemical Society, 2013, 135(1):62-65.
[80] Li J, Kwon N, Jeong Y, et al. Aggregation-induced fluorescence probe for monitoring membrane potential changes in mitochondria[J]. ACS Applied Materials & Interfaces, 2018, 10(15):12150-12154.
[81] Zhao E G, Deng H Q, Chen S J, et al. A dual functional AEE fluorogen as a mitochondrial-specific bioprobe and an effective photosensitizer for photodynamic therapy[J]. Chemical Communications, 2014, 50(92):14451-14454.
[82] Zhang W, Kwok R T, Chen Y, et al. Real-time monitoring of the mitophagy process by a photostable fluorescent mitochondrion-specific bioprobe with AIE characteristics[J]. Chemical Communications, 2015, 51(43):9022-9025.
[83] Wang Z Y, Gu Y, Liu J Y, et al. A novel pyridinium modified tetraphenylethene:AIE-activity, mechanochromism, DNA detection and mitochondrial imaging[J]. Journal of Materials Chemistry B, 2018, 6(8):1279-1285.
[84] Zhang L, Liu W W, Huang X H, et al. Old is new again:A chemical probe for targeting mitochondria and monitoring mitochondrial membrane potential in cells[J]. Analyst, 2015, 140(17):5849-54.
[85] Zhao N, Chen S J, Hong Y N, et al. A red emitting mitochondria-targeted AIE probe as an indicator for membrane potential and mouse sperm activity[J]. Chemical Communications, 2015, 51(71):13599-13602.
[86] Gu X, Zhao E, Lam J W, et al. Mitochondrion-specific livecell bioprobe operated in a fluorescence turn-on manner and a well-designed photoactivatable mechanism[J]. Advanced Materials, 2015, 27(44):7093-7100.
[87] Gu X, Zhao E, Zhao T, et al. A mitochondrion-specific photoactivatable fluorescence turn-on AIE-based bioprobe for localization super-resolution microscope[J]. Advanced Materials, 2016, 28(25):5064-5071.
[88] Lo C Y, Chen S, Creed S J, et al. Novel super-resolution capable mitochondrial probe, MitoRed AIE, enables assessment of real-time molecular mitochondrial dynamics[J]. Scientific Reports, 2016, 6:30855.
[89] Leung C W, Wang Z, Zhao E, et al. A lysosome-targeting AIEgen for autophagy visualization[J]. Advanced Healthcare Materials, 2016, 5(4):427-431.
[90] Huang Y, Hu F, Zhao R, et al. Tetraphenylethylene conjugated with a specific peptide as a fluorescence turn-on bioprobe for the highly specific detection and tracing of tumor markers in live cancer cells[J]. Chemistry-A European Journal, 2014, 20(1):158-164.
[91] Yu C Y Y, Zhang W J, Kwok R T K, et al. A photostable AIEgen for nucleolus and mitochondria imaging with organelle-specific emission[J]. Journal of Materials Chemistry B, 2016, 4(15):2614-2619.
[92] Ma H C, Yang M Y, Zhang C L, et al. Aggregation-induced emission (AIE)-active fluorescent probes with multiple binding sites toward ATP sensing and live cell imaging[J]. Journal of Materials Chemistry B, 2017, 5(43):8525-8531.
[93] Cheng Y, Sun C, Ou X, et al. Dual-targeted peptide-conjugated multifunctional fluorescent probe with AIEgen for efficient nucleus-specific imaging and long-term tracing of cancer cells[J]. Chemical Science, 2017, 8:4571-4578.
[94] Zhao Y Y, Yu C Y Y, Kwok R T K, et al. Photostable AIE fluorogens for accurate and sensitive detection of S-phase DNA synthesis and cell proliferation[J]. Journal of Materials Chemistry B, 2015, 3(25):4993-4996.
[95] Li Y, Wu Y, Chang J, et al. A bioprobe based on aggregation induced emission (AIE) for cell membrane tracking[J]. Chemical Communications, 2013, 49(96):11335-11337.
[96] Zhang C, Jin S, Yang K, et al. Cell membrane tracker based on restriction of intramolecular rotation[J]. ACS Applied Materials & Interfaces, 2014, 6(12):8971-8975.
[97] Zhang W J, Yu C Y Y, Kwok R T K, et al. A photostable AIE luminogen with near infrared emission for monitoring morphological change of plasma membrane[J]. Journal of Materials Chemistry B, 2018, 6(10):1501-1507.
[98] Chen S, Hong Y, Liu Y, et al. Full-range intracellular pH sensing by an aggregation-induced emission-active two-channel ratiometric fluorogen[J]. Journal of the American Chemical Society, 2013, 135:4926-4929.
[99] Li K, Feng Q, Niu G, et al. Benzothiazole-based AIEgen with tunable excited-state intramolecular proton transfer and restricted intramolecular rotation processes for highly sensitive physiological pH sensing[J]. ACS Sensors, 2018, 3(5):920-928.
[100] Fang M X, Xia S, Bi J H, et al. A cyanine-based fluorescent cassette with aggregation-induced emission for sensitive detection of pH changes in live cells[J]. Chemical Communications, 2018, 54(9):1133-1136.
[101] Chen S, Hong Y, Zeng Y, et al. Mapping live cell viscosity with an aggregation-induced emission fluorogen by means of two-photon fluorescence lifetime imaging[J]. Chemistry, 2015, 21(11):4315-4320.
[102] Soleimaninejad H, Chen M Z, Lou X D, et al. Measuring macromolecular crowding in cells through fluorescence anisotropy imaging with an AIE fluorogene[J]. Chemical Communications, 2017, 53(19):2874-2877.
[103] Hu Q, Gao M, Feng G, et al. A cell apoptosis probe based on fluorogen with aggregation induced emission characteristics[J]. ACS Applied Materials & Interfaces, 2015, 7(8):4875-4882.
[104] Leung A C S, Zhao E G, Kwok R T K, et al. An AIE-based bioprobe for differentiating the early and late stages of apoptosis mediated by H2O2[J]. Journal of Materials Chemistry B, 2016, 4(33):5510-5514.
[105] Hu Y, Shi L, Su Y, et al. A fluorescent light-up aggregationinduced emission probe for screening gefitinib-sensitive non-small cell lung carcinoma[J]. Biomaterials Science, 2017, 5:792-799.
[106] Li M, Hong Y N, Wang Z K, et al. Fabrication of chitosan nanoparticles with aggregation-induced emission characteristics and their applications in long-term live cell imaging[J]. Macromolecular Rapid Communications, 2013, 34(9):767-771.
[107] Mondal N, Sarkar J, Ghosh S. Fluorescent PEGlated oligourethane nanoparticles for long-term cellular tracing[J]. Chemistry-A European Journal, 2016, 22:10930-10936.
[108] Ma H, Qi C, Cheng C, et al. AIE-active tetraphenylethylene cross-linked n-isopropylacrylamide polymer:A long-term fluorescent cellular tracker[J]. ACS Applied Materials & Interfaces, 2016, 8(13):8341-8348.
[109] Wang Z K, Yang L, Liu Y L, et al. Ultra long-term cellular tracing by a fluorescent AIE bioconjugate with good water solubility over a wide pH range[J]. Journal of Materials Chemistry B, 2017, 5(25):4981-4987.
[110] Li K, Zhu Z S, Cai P Q, et al. Organic dots with aggregationinduced emission (AIE dots) characteristics for dual-color cell tracing[J]. Chemistry of Materials, 2013, 25(21):4181-4187.
[111] 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.
[112] Cai X, Zhang C J, Ting Wei Lim F, et al. Organic nanoparticles with aggregation-induced emission for bone marrow stromal cell tracking in a rat PTI model[J]. Small, 2016, 12(47):6576-6585.
[113] Lin G W, Manghnani P N, Mao D, et al. Robust red organic nanoparticles for in vivo fluorescence imaging of cancer cell progression in xenografted zebrafish[J]. Advanced Functional Materials, 2017, 27(31):1701418.
[114] Zhao E G, Hong Y, Chen S J, et al. Highly fluorescent and photostable probe for long-term bacterial viability assay based on aggregation-induced emission[J]. Advanced Healthcare Materials, 2014, 3(1):88-96.
[115] Zhao E G, Chen Y L, Chen S J, et al. A luminogen with aggregation-induced emission characteristics for wash-free bacterial imaging, high-throughput antibiotics screening and bacterial susceptibility evaluation[J]. Advanced Materials, 2015, 27(33):4931-4937.
[116] Chen W W, Li Q Z, Zheng W S, et al. Identification of bacteria in water by a fluorescent array[J]. Angewandte ChemieInternational Edition, 2014, 53(50):13734-13739.
[117] Liu G J, Tian S N, Li C Y, et al. Aggregation-induced-emission materials with different electric charges as an artificial tongue:Design, construction, and assembly with various pathogenic bacteria for effective bacterial imaging and discrimination[J]. ACS Applied Materials & Interfaces, 2017, 9(34):28331-28338.
[118] Zhao E G, Chen Y L, Wang H, et al. Light-enhanced bacterial killing and wash-free imaging based on AIE fluorogen[J]. ACS Applied Materials & Interfaces, 2015, 7(13):7180-7188.
[119] Chen J J, Gao M, Wang L, et al. Aggregation-induced emission probe for study of the bactericidal mechanism of antimicrobial peptides[J]. ACS Applied Materials & Interfaces, 2018, 10(14):11436-11442.
[120] Gao T, Zeng H L, Xu H, et al. Novel self-assembled organic nanoprobe for molecular imaging and treatment of gram-positive bacterial infection[J]. Theranostics, 2018, 8(7):1911-1922.
[121] Gao M, Hu Q L, Feng G X, et al. A multifunctional probe with aggregation-induced emission characteristics for selective fluorescence imaging and photodynamic killing of bacteria over mammalian cells[J]. Advanced Healthcare Materials, 2015, 4(5):659-663.
[122] Zhao L, Chen Y F, Yuan J, et al. Electrospun fibrous mats with conjugated tetraphenylethylene and mannose for sensitive turn-on fluorescent sensing of Escherichia coli[J]. ACS Applied Materials & Interfaces, 2015, 7(9):5177-5186.
[123] Feng G, Yuan Y, Fang H, et al. A light-up probe with aggregation-induced emission characteristics (AIE) for selective imaging, naked-eye detection and photodynamic killing of Gram-positive bacteria[J]. Chemical Communications, 2015, 51(62):12490-12493.
[124] Zhao Q and Sun J Z. Red and near infrared emission materials with AIE characteristics[J]. Journal of Materials Chemistry C, 2016, 4:10588-10609.
[125] Zhao Q L, Li K, Chen S J, et al. Aggregation-induced redNIR emission organic nanoparticles as effective and photostable fluorescent probes for bioimaging[J]. Journal of Materials Chemistry, 2012, 22(30):15128-15135.
[126] Zhang Y, Chang K W, Xu B, et al. Highly efficient near-infrared organic dots based on novel AEE fluorogen for specific cancer cell imaging[J]. RSC Advances, 2015, 5(46):36837-36844.
[127] Wang Y J, Shi Y, Wang Z, et al. A red to Near-IR fluorogen:Aggregation-induced emission, large Stokes shift, high solid efficiency and application in cell-imaging[J]. Chemistry, 2016, 22(28):9784-9791.
[128] Nicol A, Qin W, Kwok R T K, et al. Functionalized AIE nanoparticles with efficient deep-red emission, mitochondrial specificity, cancer cell selectivity and multiphoton susceptibility[J]. Chemical Science, 2017, 8(6):4634-4643.
[129] Feng G, Mao D, Liu J, et al. Polymeric nanorods with aggregation-induced emission characteristics for enhanced cancer targeting and imaging[J]. Nanoscale, 2018, 10(13):5869-5874.
[130] Qi J, Sun C, Zebibula A, et al. Real-time and high-resolution bioimaging with bright aggregation-induced emission dots in short-wave infrared region[J]. Advanced Materials, 2018, 30(12):1706856.
[131] Geng J, Zhu Z, Qin W, et al. Near-infrared fluorescence amplified organic nanoparticles with aggregation-induced emission characteristics for in vivo imaging[J]. Nanoscale, 2014, 6(2):939-945.
[132] Qian J, Zhu Z, Leung C W T, et al. Long-term two-photon neuroimaging with a photostable AIE luminogen[J]. Biomedical Optics Express, 2015, 6(4):1477-1486.
[133] Qian J, Zhu Z, Qin A, et al. High-order non-linear optical effects in organic luminogens with aggregation-induced emission[J]. Advanced Materials, 2015, 27(14):2332-2339.
[134] Wang Y, Chen M, Alifu N, et al. Aggregation-induced emission luminogen with deep-red emission for through-skull three-photon fluorescence imaging of mouse[J]. ACS Nano, 2017, 11(10):10452-10461.
[135] Zhang H, Alifu N, Jiang T, et al. Biocompatible aggregationinduced emission nanoparticles with red emission for in vivo three-photon brain vascular imaging[J]. Journal of Materials Chemistry B, 2017, 5:2757-2762.
[136] Wang Y L, Han X, Xi W, et al. Bright AIE nanoparticles with F127 encapsulation for deep-tissue three-photon intravital brain angiography[J]. Advanced Healthcare Materials, 2017, 6(21):1700685.
[137] Cai X, Bandla A, Mao D, et al. Biocompatible red fluorescent organic nanoparticles with tunable size and aggregationinduced emission for evaluation of blood-brain barrier damage[J]. Advanced Materials, 2016, 28(39):8760-8765.
[138] Geng J, Goh C C, Qin W, et al. Silica shelled and block copolymer encapsulated red-emissive AIE nanoparticles with 50% quantum yield for two-photon excited vascular imaging[J]. Chemical Communications, 2015, 51(69):13416-13419.
[139] Gao Y, Feng G, Jiang T, et al. Biocompatible nanoparticles based on diketo-pyrrolo-pyrrole (DPP) with aggregation-induced red/NIR emission for in vivo two-photon fluorescence imaging[J]. Advanced Functional Materials, 2015, 25(19):2857-2866.
[140] Wang Y, Hu R, Xi W, et al. Red emissive AIE nanodots with high two-photon absorption efficiency at 1040 nm for deep-tissue in vivo imaging[J]. Biomedical Optics Express, 2015, 6(10):3783-3794.
[141] Xiang J Y, Cai X L, Lou X D, et al. Biocompatible green and red Fluorescent organic dots with remarkably large twophoton action cross sections for targeted cellular imaging and real-time intravital blood vascular visualization[J]. ACS Applied Materials & Interfaces, 2015, 7(27):14965-14974.
[142] Qin W, Zhang P F, Li H, et al. Ultrabright red AIEgens for two-photon vascular imaging with high resolution and deep penetration[J]. Chemical Science, 2018, 9(10):2705-2710.
[143] Xu W F, He L Y, Xia Q, et al. A far-red-emissive AIE active fluorescent probe with large stokes shift for detection of inflammatory bowel disease in vivo[J]. Journal of Materials Chemistry B, 2018, 6(5):809-815.
[144] Yue X, Morales A R, Githaiga G W, et al. RGD-conjugated two-photon absorbing near-IR emitting fluorescent probes for tumor vasculature imaging[J]. Organic & Biomolecular Chemistry, 2015, 13(43):10716-10725.
[145] Li M, Lam J W Y, Mahtab F, et al. Biotin-ddecorated fluorescent silica nanoparticles with aggregation-induced emission characteristics:Fabrication, cytotoxicity and biological applications[J]. Journal of Materials Chemistry B, 2013, 1:676-684.
[146] Geng J L, Li K, Ding D, et al. Lipid-PEG-folate encapsulated nanoparticles with aggregation induced emission characteristics:Cellular uptake mechanism and two-photon fluorescence imaging[J]. Small, 2012, 8(23):3655-3663.
[147] Liu J, Chen C, Ji S L, et al. Long wavelength excitable nearinfrared fluorescent nanoparticles with aggregation-induced emission characteristics for image-guided tumor resection[J]. Chemical Science, 2017, 8(4):2782-2789.
[148] Situ B, Chen S J, Zhao E G, et al. Real-time imaging of cell behaviors in living organisms by a mitochondria-targeting AIE fluorogen[J]. Advanced Functional Materials, 2016, 26(39):7132-7138.
[149] Li D Y, Zhao X Y, Qin W, et al. Toxicity assessment and long-term three-photon fluorescence imaging of bright aggregation-induced emission nanodots in zebrafish[J]. Nano Research, 2016, 9(7):1921-1933.
[150] Zou J L, Lu H G, Zhao X W, et al. A multi-functional fluorescent probe with aggregation-induced emission characteristics:Mitochondrial imaging, photodynamic therapy and visualizing therapeutic process in zebrafish model[J]. Dyes and Pigments, 2018, 151:45-53.
[151] Li X, Jiang M, Lam J W Y, et al. Mitochondrial imaging with combined fluorescence and stimulated Raman scattering microscopy using a probe of the aggregation-induced emission characteristic[J]. Journal of the American Chemical Society, 2017, 139(47):17022-17030.
[152] Geng J, Liao L D, Qin W, et al. Fluorogens with aggregation induced emission:Ideal photoacoustic contrast reagents due to intramolecular rotation[J]. Journal of Nanoscience and Nanotechnology, 2015, 15(2):1864-1868.
[153] Mahtab F, Yu Y, Lam J W Y, et al. Fabrication of silica nanoparticles with both efficient fluorescence and strong magnetization, and exploration of their biological applications[J]. Advanced Functional Materials, 2011, 21(9):1733-1740.
[154] Yan L, Zhang Y, Ji G, et al. Multifunctional polymer nanoparticles:Ultra bright near-infrared fluorescence and strong magnetization and their biological applications[J]. RSC Advances, 2016, 6(70):65426-65433.
[155] Chen Y, Li M, Hong Y, et al. Dual-modal MRI contrast agent with aggregation-induced emission characteristic for liver specific imaging with long circulation lifetime[J]. ACS Applied Materials & Interfaces, 2014, 6(13):10783-10791.
[156] Feng G, Li J L Y, Claser C, et al. Dual modal ultra-bright nanodots with aggregation-induced emission and gadolinium-chelation for vascular integrity and leakage detection[J]. Biomaterials, 2018, 152:77-85.
[157] Zhao Y, Kwok R T, Lam J W, et al. A highly fluorescent AIE-active theranostic agent with anti-tumor activity to specific cancer cells[J]. Nanoscale, 2016, 8(25):12520-12523.
[158] Hu Q L, Gao M, Feng G X, et al. Mitochondria-targeted cancer therapy using a light-up probe with aggregation-induced-emission characteristics[J]. Angewandte Chemie-International Edition, 2014, 53(51):14225-14229.
[159] Huang Y Y, Zhang G X, Hu F, et al. Emissive nanoparticles from pyridinium-substituted tetraphenylethylene salts:Imaging and selective cytotoxicity towards cancer cells in vitro and in vivo by varying counter anions[J]. Chemical Science, 2016, 7(12):7013-7019.
[160] Reedy J L, Hedlund D K, Gabr M T, et al. Synthesis and evaluation of tetraarylethylene-based mono-, bis-, and tris (pyridinium) derivatives for image-guided mitochondria-specific targeting and cytotoxicity of metastatic melanoma cells[J]. Bioconjugate Chemistry, 2016, 27(10):2424-2430.
[161] Shin W S, Lee M G, Verwilst P, et al. Mitochondria-targeted aggregation induced emission theranostics:Crucial importance of in situ activation[J]. Chemical Science, 2016, 7(9):6050-6059.
[162] Kim K Y, Jin H, Park J, et al. Mitochondria-targeting selfassembled nanoparticles derived from triphenylphosphoniumconjugated cyanostilbene enable site-specific imaging and anticancer drug delivery[J]. Nano Research, 2018, 11(2):1082-1098.
[163] Xue X, Zhao Y, Dai L, et al. Spatiotemporal drug release visualized through a drug delivery system with tunable aggregation-induced emission[J]. Advanced Materials, 2014, 26(5):712-717.
[164] Zhang C Q, Jin S B, Li S L, et al. Imaging intracellular anticancer drug delivery by self-assembly micelles with aggregation-induced emission (AIE micelles)[J]. ACS Applied Materials & Interfaces, 2014, 6(7):5212-5220.
[165] Chen Y, Han H, Tong H, et al. Zwitterionic phosphorylcholine-TPE conjugate for pH-responsive drug delivery and AIE active imaging[J]. ACS Applied Materials & Interfaces, 2016, 8(33):21185-21192.
[166] Wang H B, Liu G Y, Gao H Q, et al. A pH-responsive drug delivery system with an aggregation-induced emission feature for cell imaging and intracellular drug delivery[J]. Polymer Chemistry, 2015, 6(26):4715-4718.
[167] Wang X, Yang Y, Zhuang Y, et al. Fabrication of pH-responsive nanoparticles with an AIE feature for imaging intracellular drug delivery[J]. Biomacromolecules, 2016, 17(9):2920-2929.
[168] Ding D, Kwok R T K, Yuan Y Y, et al. A fluorescent lightup nanoparticle probe with aggregation-induced emission characteristics and tumor-acidity responsiveness for targeted imaging and selective suppression of cancer cells[J]. Materials Horizons, 2015, 2(1):100-105.
[169] Wu X M, Sun X R, Guo Z Q, et al. In vivo and in situ tracking cancer chemotherapy by highly photostable NIR fluorescent theranostic prodrug[J]. Journal of the American Chemical Society, 2014, 136(9):3579-3588.
[170] Yuan Y, Chen Y, Tang B Z, et al. A targeted theranostic platinum(IV) prodrug containing a luminogen with aggregation-induced emission (AIE) characteristics for in situ monitoring of drug activation[J]. Chemical Communications, 2014, 50(29):3868-3870.
[171] Yuan Y, Kwok R T, Tang B Z, et al. Targeted theranostic platinum(IV) prodrug with a built-in aggregation-induced emission light-up apoptosis sensor for noninvasive early evaluation of its therapeutic responses in situ[J]. Journal of the American Chemical Society, 2014, 136(6):2546-2554.
[172] Yuan Y, Kwok R T, Zhang R, et al. Targeted theranostic prodrugs based on an aggregation-induced emission (AIE) luminogen for real-time dual-drug tracking[J]. Chemical Communications, 2014, 50(78):11465-11468.
[173] Yu G, Cook T R, Li Y, et al. Tetraphenylethene-based highly emissive metallacage as a component of theranostic supramolecular nanoparticles[J]. PNAS, 2016, 113(48):13720-13725.
[174] Gui C, Zhao E G, Kwok R T K, et al. AIE-active theranostic system:Selective staining and killing of cancer cells[J]. Chemical Science, 2017, 8(3):1822-1830.
[175] Jiang M, Kwok R T K, Li X, et al. A simple mitochondrial targeting AIEgen for image-guided two-photon excited photodynamic therapy[J]. Journal of Materials Chemistry B, 2018, 6(17):2557-2565.
[176] Zhang C J, Hu Q L, Feng G X, et al. Image-guided combination chemotherapy and photodynamic therapy using a mitochondria-targeted molecular probe with aggregation-induced emission characteristics[J]. Chemical Science, 2015, 6(8):4580-4586.
[177] Feng G, Qin W, Hu Q, et al. Cellular and mitochondrial dual-targeted organic dots with aggregation-induced emission characteristics for image-guided photodynamic therapy[J]. Advanced Healthcare Materials, 2015, 4(17):2667-2676.
[178] Wang D, Su H, Kwok R T K, et al. Rational design of a water-soluble NIR AIEgen, and its application in ultrafast wash-free cellular imaging and photodynamic cancer cell ablation[J]. Chemical Science, 2018, 9(15):3685-3693.
[179] Han K, Wang S B, Lei Q, et al. Ratiometric biosensor for aggregation-induced emission-guided precise photodynamic therapy[J]. ACS Nano, 2015, 9(10):10268-10277.
[180] Hu F, Huang Y Y, Zhang G X, et al. Targeted bioimaging and photodynamic therapy of cancer cells with an activatable red fluorescent bioprobe[J]. Analytical Chemistry, 2014, 86(15):7987-7995.
[181] Zhang R, Feng G, Zhang C J, et al. Real-time specific lightup sensing of transferrin receptor:Image-guided photodynamic ablation of cancer cells through controlled cytomembrane disintegration[J]. Analytical Chemistry, 2016, 88(9):4841-4848.
[182] Yuan Y, Feng G, Qin W, et al. Targeted and image-guided photodynamic cancer therapy based on organic nanoparticles with aggregation-induced emission characteristics[J]. Chemical Communications, 2014, 50(63):8757-8760.
[183] Wu W B, Feng G X, Xu S D, et al. A photostable far-red/near-infrared conjugated polymer photosensitizer with aggregation-induced emission for image-guided cancer cell ablation[J]. Macromolecules, 2016, 49(14):5017-5025.
[184] Zhen S, Wang S, Li S, et al. Efficient red/near-infrared fluorophores based on benzo[1,2-b:4,5-b']dithiophene 1,1,5,5-tetraoxide for targeted photodynamic therapy and in vivo two-photon fluorescence bioimaging[J]. Advanced Functional Materials, 2018, 28(13):1706945.
[185] Li M, Gao Y Y, Yuan Y, et al. One-step formulation of targeted aggregation-induced emission dots for image-guided photodynamic therapy of cholangiocarcinoma[J]. ACS Nano, 2017, 11(4):3922-3932.
[186] Yuan Y Y, Xu S D, Cheng X M, et al. Bioorthogonal turnon probe based on aggregation-induced emission characteristics for cancer cell imaging and ablation[J]. Angewandte Chemie-International Edition, 2016, 55(22):6457-6461.
[187] Wu W B, Mao D, Xu S D, et al. High performance photosensitizers with aggregation-induced emission for image-guided photodynamic anticancer therapy[J]. Materials Horizons, 2017, 4(6):1110-1114.
[188] Zang Q G, Yu J Y, Yu W B, et al. Red-emissive azabenzanthrone derivatives for photodynamic therapy irradiated with ultralow light power density and two-photon imaging[J]. Chemical Science, 2018, 9(23):5165-5171.
[189] Wu W B, Mao D, Hu F, et al. A highly efficient and photostable photosensitizer with near-infrared aggregation-induced emission for image-guided photodynamic anticancer therapy[J]. Advanced Materials, 2017, 29(33):1700548.
[190] Feng G X, Wu W B, Xu S D, et al. Far red/near-infrared AIE dots for image-guided photodynamic cancer cell ablation[J]. ACS Applied Materials & Interfaces, 2016, 8(33):21193-21200.
[191] Yuan Y Y, Zhang C J, Xu S D, et al. A self-reporting AIE probe with a built-in singlet oxygen sensor for targeted photodynamic ablation of cancer cells[J]. Chemical Science, 2016, 7(3):1862-1866.
[192] Hu R, Yang C B, Wang Y C, et al. Aggregation-induced emission (AIE) dye loaded polymer nanoparticles for gene silencing in pancreatic cancer and their in vitro and in vivo biocompatibility evaluation[J]. Nano Research, 2015, 8(5):1563-1576.
[193] Jin G, Feng G, Qin W, et al. Multifunctional organic nanoparticles with aggregation-induced emission (AIE) characteristics for targeted photodynamic therapy and RNA interference therapy[J]. Chemical Communications, 2016, 52(13):2752-2755.
[194] Yuan Y, Zhang C J, Liu B. A photoactivatable AIE polymer for light-controlled gene delivery:Concurrent endo/lysosomal escape and DNA unpacking[J]. Angewandte Chemie-International Edition, 2015, 54(39):11419-11423.
[195] Li J, Leung C W T, Wong D S H, et al. Photocontrolled siRNA delivery and biomarker-triggered luminogens of aggregation-induced emission by up-conversion NaYF4:Yb3+ Tm3+@SiO2 nanoparticles for inducing and monitoring stem-cell differentiation[J]. ACS Applied Materials & Interfaces, doi:2017, 10.1021/acsami.7b00845.
[196] Wang K, Fan X, Zhao L, et al. Aggregation induced emission fluorogens based nanotheranostics for targeted and imaging-guided chemo-photothermal combination therapy[J]. Small, 2016, 12(47):6568-6575.
[197] Chen C, Song Z G, Zheng X Y, et al. AIEgen-based theranostic system:targeted imaging of cancer cells and adjuvant amplification of antitumor efficacy of paclitaxel[J]. Chemical Science, 2017, 8(3):2191-2198.
[198] Feng G X, Liu J, Zhang C J, et al. Artemisinin and AlEgen conjugate for mitochondria-targeted and image-guided chemo-and photodynamic cancer cell ablation[J]. ACS Applied Materials & Interfaces, 2018, 10(14):11546-11553.
[199] Mao D, Wu W B, Ji S L, et al. Chemiluminescence-guided cancer therapy using a chemiexcited photosensitizer[J]. Chem, 2017, 3(6):991-1007.
[200] Yu C Y, Xu H, Ji S, et al. Mitochondrion-anchoring photosensitizer with aggregation-induced emission characteristics synergistically boosts the radiosensitivity of cancer cells to ionizing radiation[J]. Advanced Materials, 2017, 29(15):1606167.
Outlines

/