Fluorescent probes and functional materials for biomedical applications

Abstract

Due to their simplicity in preparation, sensitivity and selectivity, fluorescent probes have become the analytical tool of choice in a wide range of research and industrial fields, facilitating the rapid detection of chemical substances of interest as well as the study of important physiological and pathological processes at the cellular level. In addition, many long-wavelength fluorescent probes developed have also proven applicable for in vivo biomedical applications including fluorescence-guided disease diagnosis and theranostics (e.g., fluorogenic prodrugs). Impressive progresses have been made in the development of sensing agents and materials for the detection of ions, organic small molecules, and biomacromolecules including enzymes, DNAs/RNAs, lipids, and carbohydrates that play crucial roles in biological and disease-relevant events. Here, we highlight examples of fluorescent probes and functional materials for biological applications selected from the special issues “Fluorescent Probes” and “Molecular Sensors and Logic Gates” recently published in this journal, offering insights into the future development of powerful fluorescence-based chemical tools for basic biological studies and clinical translation.

Graphical abstract

Keywords

fluorescent probes / imaging / cell / biomedicine / biomolecules

References

[1] SinghaS, YongW J, SarkarS, Ahn K H. An endeavor in the reaction-based approach to fluorescent probes for biorelevant analytes: challenges and achievements. Accounts of Chemical Research, 2019, 52( 9): 2571– 2581

[2] Erbas-CakmakS, Kolemen S, SedgwickA C, GunnlaugssonT, JamesT D, Yoon J, AkkayaE U. Molecular logic gates: the past, present and future. Chemical Society Reviews, 2018, 47( 7): 2228– 2248

[3] SedgwickA C, WuL, HanH-H, Bull S D, HeX-P, JamesT D, Sessler J L, TangB Z, TianH, Yoon J. Excited-state intramolecular proton-transfer (ESIPT) based fluorescence sensors and imaging agents. Chemical Society Reviews, 2018, 47( 23): 8842– 8880

[4] WuD, Sedgwick A C, GunnlaugssonT, AkkayaE U, Yoon J, JamesT D. Fluorescent chemosensors: the past, present and future. Chemical Society Reviews, 2017, 46( 23): 7105– 7123

[5] WuL, Sedgwick A C, SunX, BullS D, He X-P, JamesT D. Reaction-based fluorescent probes for the detection and imaging of reactive oxygen, nitrogen, and sulfur species. Accounts of Chemical Research, 2019, 52( 9): 2582– 2597

[6] KolanowskiJ L, LiuF, NewE J. Fluorescent probes for the simultaneous detection of multiple analytes in biology. Chemical Society Reviews, 2018, 47( 1): 195– 208

[7] ChanJ, Dodani S C, ChangC J. Reaction-based small-molecule fluorescent probes for chemoselective bioimaging. Nature Chemistry, 2012, 4( 12): 973– 984

[8] WuL, HanH-H, LiuL, Gardiner J E, SedgwickA C, HuangC, Bull S D, HeX-P, JamesT D. ESIPT-based fluorescence probe for the rapid detection of peroxynitrite ‘AND’ biological thiols. Chemical Communications, 2018, 54( 80): 11336– 11339

[9] SedgwickA C, Gardiner J E, KimG, YevglevskisM, LloydM D, Jenkins A T A, BullS D, YoonJ, James T D. Long-wavelength TCF-based fluorescence probes for the detection and intracellular imaging of biological thiols. Chemical Communications, 2018, 54( 38): 4786– 4789

[10] JiaoX, LiY, NiuJ, XieX, WangX, Tang B. Small-molecule fluorescent probes for imaging and detection of reactive oxygen, nitrogen, and sulfur species in biological systems. Analytical Chemistry, 2017, 90: 533– 555

[11] RomieuA. “AND” luminescent “reactive” molecular logic gates: a gateway to multi-analyte bioimaging and biosensing. Organic & Biomolecular Chemistry, 2015, 13( 5): 1294– 1306

[12] WuD, Durán-Sampedro G, O’SheaD F. Synthesis and properties of water-soluble 1,9-dialkyl-substituted BF2 azadipyrromethene fluorophores. Frontiers of Chemical Science and Engineering, 2020, 14( 1): 97– 104

[13] ZhangY, LiS, ZhangH, Xu H. Design and application of receptor-targeted fluorescent probes based on small molecular fluorescent dyes. Bioconjugate Chemistry, 2021, 32( 1): 4– 24

[14] VarandasP, CobbA, SegundoM A, Silva E. Emergent glycerophospholipid fluorescent probes: synthesis and applications. Bioconjugate Chemistry, 2019, 31( 3): 417– 435

[15] SinghH, Tiwari K, TiwariR, PramanikS K, Das A. Small molecule as fluorescent probes for monitoring intracellular enzymatic transformations. Chemical Reviews, 2019, 119: 11718– 11760

[16] SedgwickA C, HanH-H, GardinerJ E, Bull S D, HeX-P, JamesT D. The development of a novel AND logicbased fluorescence probe for the detection of peroxynitrite and GSH. Chemical Science, 2018, 9( 15): 3672– 3676

[17] JoseD A, Sakla R, SharmaN, GadiyaramS, Kaushik R, GhoshA. Sensing and bioimaging of the gaseous signaling molecule hydrogen sulfide by near-infrared fluorescent probes. ACS Sensors, 2020, 5( 11): 3365– 3391

[18] TagitO, Hildebrandt N. Fluorescence sensing of circulating diagnostic biomarkers using molecular probes and nanoparticles. ACS Sensors, 2017, 2( 1): 31– 45

[19] SedgwickA C, HanH-H, GardinerJ E, Bull S D, HeX-P, JamesT D. Long-wavelength fluorescent boronate probes for the detection and intracellular imaging of peroxynitrite. Chemical Communications, 2017, 53( 95): 12822– 12825

[20] NketiaT A, Sailem H, RohdeG, MachirajuR, Rittscher J. Analysis of live cell images: methods, tools and opportunities. Methods, 2017, 115: 65– 79

[21] Lopez-AlledC M, Sanchez-Fernandez A, EdlerK J, SedgwickA C, Bull S D, McMullinC L, Kociok-KöhnG, JamesT D, Wenk J, LewisS E. Azulene-boronate esters: colorimetric indicators for fluoride in drinking water. Chemical Communications, 2017, 53( 93): 12580– 12583

[22] DengW, SunP, FanQ, Zhang L, MinamiT. Highly selective detection of copper(II) by a “ligand-free” conjugated copolymer in nucleophilic solvents. Frontiers of Chemical Science and Engineering, 2020, 14( 1): 105– 111

[23] SasakiY, LyuX, ZhangZ, Minami T. A minimized fluorescent chemosensor array utilizing carboxylate-attached polythiophenes on a chip for metal ions detection. Frontiers of Chemical Science and Engineering, 2022, 16( 1): 72– 80

[24] de MolinerF, Biazruchka I, KonsewiczK, BensonS, Singh S, LeeJ S, VendrellM. Near-infrared benzodiazoles as small molecule environmentally-sensitive fluorophores. Frontiers of Chemical Science and Engineering, 2022, 16( 1): 128– 135

[25] OdyniecM L, Sedgwick A C, SwanA H, WeberM, Tang T M S, GardinerJ E, ZhangM, Jiang Y B, Kociok-KohnG, ElmesR B P. . ‘AND’-based fluorescence scaffold for the detection of ROS/RNS and a second analyte. Chemical Communications, 2018, 54( 61): 8466– 8469

[26] MaityS, DasS, SadlowskiC, Zhang J, VegesnabG, MurthyN. Thiophene bridged hydrocyanine—a new fluorogenic ROS probe. Chemical Communications, 2017, 53: 10184– 10187

[27] ChenZ, LiQ, SunQ, ChenH, WangX, Li N, YinM, XieY, LiH, TangB. Simultaneous determination of reactive oxygen and nitrogen species in mitochondrial compartments of apoptotic HepG2 cells and PC12 cells based on microchip electrophoresis-laser-induced fluorescence. Analytical Chemistry, 2012, 84( 11): 4687– 4694

[28] WinterbournC C. Myeloperoxidase as an effective inhibitor of hydroxyl radical production implications for the oxidative reactions of neutrophils. Journal of Clinical Investigation, 1986, 78( 2): 545– 550

[29] SugiyamaS, Okada Y, SukhovaG K, VirmaniR, Heinecke J W, LibbyP. Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes. American Journal of Pathology, 2001, 158( 3): 879– 891

[30] LiY, YangS, LiQ Y, Ma J P, ZhangS, DongY. UiO-68-ol NMOF-based fluorescent sensor for selective detection of HClO and its application in bioimaging. Inorganic Chemistry, 2017, 56( 21): 13241– 13248

[31] TongP-H, ZhuL, ZangY, Li J, HeX-P, JamesT D. Metal-organic frameworks (MOFs) as host materials for the enhanced delivery of biomacromolecular therapeutics. Chemical Communications, 2021, 57: 12098– 12110

[32] KumarP, DeepA, KimK H. Metal organic frameworks for sensing applications. Trends in Analytical Chemistry, 2015, 73: 39– 53

[33] HashimotoT, Kumai M, MaedaM, MiyoshiK, Tsuchido Y, FujiwaraS, HayashitaT. Structural effect of fluorophore on phenylboronic acid fluorophore/cyclodextrin complex for selective glucose recognition. Frontiers of Chemical Science and Engineering, 2020, 14( 1): 53– 60

[34] XuS, Sedgwick A C, ElfekyS A, ChenW, Jones A S, WilliamsG T, JenkinsT A, Bull S D, FosseyJ S, JamesT D. A boronic acid-based fluorescent hydrogel for monosaccharide detection. Frontiers of Chemical Science and Engineering, 2019, 14( 1): 112– 116

[35] ZhouL, ChenY, ShaoB, Cheng J, LiX. Recent advances of small-molecule fluorescent probes for detecting biological hydrogen sulfide. Frontiers of Chemical Science and Engineering, 2022, 16( 1): 34– 63

[36] ShiY, HuoF, YueY, YinC. N-positive ion activated rapid addition and mitochondrial targeting ratiometric fluorescent probes for in vivo cell H₂S imaging. Frontiers of Chemical Science and Engineering, 2022, 16( 1): 64– 71

[37] Britoda Silva C, GilE, daSilveira Santos F, MorásA, SteffensL, Bruno Gonçalves P, Moura D, LüdtkeD, RodembuschF. Proton-transfer-based azides with fluorescence off−on response for detection of hydrogen sulfide: an experimental, theoretical, and bioimaging study. Journal of Organic Chemistry, 2018, 83: 15210– 15224

[38] XieX, LiM, TangF, Li Y, ZhangL, JiaoX, Wang X, TangB. Combinatorial strategy to identify fluorescent probes for biothiol and thiophenol based on diversified pyrimidine moieties and their biological applications. Analytical Chemistry, 2017, 89( 5): 3015– 3020

[39] LiuH, Zhang X, ZhangJ, WangQ, Hu X, WangP, TanW. Efficient two-photon fluorescent probe with red emission for imaging of thiophenols in living cells and tissues. Analytical Chemistry, 2015, 87: 8896– 8903

[40] ZhangJ, ChaiX, HeX-P, Kim H-J, YoonJ, TianH. Fluorogenic probes for disease-relevant enzymes. Chemical Society Reviews, 2019, 48: 683– 722

[41] GurramB, LiM, FanJ, WangJ, PengX. Near-infrared fluorescent probe for fast track of cyclooxygenase-2 in Golgi apparatus in cancer cells. Frontiers of Chemical Science and Engineering, 2020, 14( 1): 41– 52

[42] OdyniecM L, Gardiner J E, SedgwickA C, HeX-P, Bull S D, JamesT D. Dual enzyme activated fluorescein based fluorescent probe. Frontiers of Chemical Science and Engineering, 2020, 14( 1): 117– 121

[43] ZhuM, TianZ, JinL, HuoX, WangC, Cui J, TianY, TianX, Feng L. A highly selective fluorescent probe for real-time imaging of UDP-glucuronosyltransferase 1A8 in living cells and tissues. Frontiers of Chemical Science and Engineering, 2022, 16( 1): 103– 111

[44] XieY, Zhang J, YangL, ChenQ, Hao Q, ZhangL, SunH. A dual-function chemical probe for detecting erasers of lysine lipoylation. Frontiers of Chemical Science and Engineering, 2022, 16( 1): 121– 127

[45] FengB, NiuH, ZhaiH, Shen C, ZhangH. In-situ hydrophobic environment triggering reactive fluorescence probe to real-time monitor mitochondrial DNA damage. Frontiers of Chemical Science and Engineering, 2022, 16( 1): 92– 102

[46] KimD, MoonH, BaikS, Singha S, JunY, WangT, Kim K, ParkB, JungJ, Mook-Jung I, AhnK. Two-photon absorbing dyes with minimal autofluorescence in tissue imaging: application to in vivo imaging of amyloid-β plaques with a negligible background signal. Journal of the American Chemical Society, 2015, 137: 6781– 6789

[47] ChenX, LiuF, ChenB, Wu H, LiK, XieY, Kuang W, LiZ. Novel lysosome-targeted anticancer fluorescent agents used in zebrafish and nude mouse tumour imaging. Frontiers of Chemical Science and Engineering, 2022, 16( 1): 112– 120

[48] WuL, Huang J, PuK Y, JamesT D. Dual-locked spectroscopic probes for sensing and therapy. Nature Reviews Chemistry, 2021, 5( 6): 406– 421

[49] WuL, LiuJ, LiP, TangB, JamesT D. Two-photon small-molecule fluorescence-based agents for sensing, imaging, and therapy within biological systems. Chemical Society Reviews, 2021, 50( 2): 702– 734

[50] YinJ, Huang L, WuL, LiJ, James T D, LinW. Small molecule based fluorescent chemosensors for imaging the microenvironment within specific cellular regions. Chemical Society Reviews, 2021, 50( 21): 12098– 12150

[51] WuL, TianX, GroleauR R, Wang J, HanH-H, ReekstingS B, SedgwickA C, He X-P, BullS D, JamesT D. Coumarin-based fluorescent probe for the rapid detection of peroxynitrite ‘AND’ biological thiols. RSC Advances, 2020, 10( 23): 13496– 13499

[52] WangK, FengB, YangY, Chen Y, WangY, WangY, Yang L, JiangK, JamesT D, Zhang H. Dual-factor synergistically activated ESIPT-based probe: differential fluorescence signals to simultaneously detect α-naphthyl acetate and acid α-naphthyl acetate esterase. Analytical Chemistry, 2021, 93( 43): 14471– 14480

[53] HeX-P, HuX-L, JamesT D, Yoon J, TianH. Multiplexed photoluminescent sensors: towards improved disease diagnostics. Chemical Society Reviews, 2017, 46: 6687– 6696

[54] RaiA, Singh A K, TripathiK, SonkarA K, Chauhan B S, SrikrishnaS, JamesT D, Mishra L. A quick and selective rhodamine based “smart probe” for “signal-on” optical detection of Cu²⁺ and Al³⁺ in water, cell imaging, computational studies and solid state analysis. Sensors and Actuators B: Chemical, 2018, 266: 95– 105

[55] MurfinL C, Weber M, ParkS J, KimW T, Lopez-Alled C M, McMullinC L, Pradaux-CaggianoF, LyallC L, Kociok-Köhn G, WenkJ, BullS D. . Azulene-derived fluorescent probe for bioimaging: detection of reactive oxygen and nitrogen species by two-photon microscopy. Journal of the American Chemical Society, 2019, 141( 49): 19389– 19396

[56] YangM, FanJ, DuJ, PengX. Small-molecule fluorescent probes for imaging gaseous signaling molecules: current progress and future implications. Chemical Science, 2020, 11: 5127– 5141

[57] TranF H, Zheng J J. Modulating the wnt signaling pathway with small molecules. Protein Science, 2017, 26: 650– 661

[58] DongB L, KongX Q, LinW Y. Reaction-based fluorescent probes for the imaging of nitroxyl (HNO) in biological systems. ACS Chemical Biology, 2018, 13: 1714– 1720

[59] ZhouY Q, WangX, ZhangW, Tang B, LiP. Recent advances in small molecule fluorescent probes for simultaneous imaging of two bioactive molecules in live cells and in vivo. Frontiers of Chemical Science and Engineering, 2022, 16( 1): 4– 33

[60] SuY B, YuB, WangS, Cong H, ShenY. NIR-II bioimaging of small organic molecule. Biomaterials, 2021, 271: 120717– 120739

[61] YangQ, MaH, LiangY, Dai H. Rational design of high brightness NIR-II organic dyes with S-D-A-D-S structure. Accounts of Materials Research, 2021, 2: 170– 183

[62] ZhaoJ, ChenJ, MaS, LiuQ, HuangL, Chen X, LouK, WangW. Recent developments in multimodality fluorescence imaging probes. Acta Pharmaceutica Sinica B, 2018, 8: 320– 338

[63] GuoX, Huang J, WangM, WangL. A dual-emission water-soluble g-C₃N₄@AuNCs-based fluorescent probe for label-free and sensitive analysis of trace amounts of ferrous(II) and copper(II) ions. Sensors and Actuators B: Chemical, 2020, 309: 127766– 127776

[64] HanH-H, TianH Jr. , Zang Y, Sedgwick A C, Li J, Sessler J L, He X-P, James T D. Small-molecule fluorescence-based probes for interrogating major organ diseases. Chemical Society Reviews, 2021, 50: 9391– 9429

[65] ChaiX, HanH-H, SedgwickA C, Li N, ZangY, JamesT D, Zhang J, HuX-L, YuY, LiY. . Photochromic fluorescent probe strategy for the super-resolution imaging of biologically important biomarkers. Journal of the American Chemical Society, 2020, 142: 18005– 18013

[66] YangF, Zhang Q, HuangS, MaD. Recent advances of near infrared inorganic fluorescent probes for biomedical applications. Journal of Materials Chemistry B: Materials for Biology and Medicine, 2020, 8: 7856– 7879

[67] MiaoQ, YeoD C, WirajaC, Zhang J, NingX, XuC, PuK. Near-infrared fluorescent molecular probe for sensitive imaging of keloid. Angewandte Chemie International Edition, 2018, 57: 1256– 1260

[68] ChenW, XuS, DayJ J, Wang D, XianM. A general strategy for development of near-infrared fluorescent probes for bioimaging. Angewandte Chemie International Edition, 2017, 56: 16611– 16615

[69] FuY, HanH-H, ZhangJ, He X-P, FeringaB L, TianH. Photocontrolled fluorescence “Double-Check” bioimaging enabled by a glycoprobe—protein hybrid. Journal of the American Chemical Society, 2018, 140: 8671– 8674

[70] ShaoA, GuoZ, ZhuS J, Zhu S, ShiP, TianH, Zhu W. Insight into aggregation-induced emission characteristics of red-emissive quinoline-malononitrile by cell tracking and real-time trypsin detection. Chemical Science, 2014, 5: 1383– 1389

[71] ThomasB, YanK-C, HuX-L, Donnier-Maréchal M, ChenG-R, HeX-P, Vidal S. Fluorescent glycoconjugates and their applications. Chemical Society Reviews, 2020, 49: 593– 641

[72] HeX-P, ZangY, JamesT D, Li J, ChenG-R, XieJ. Fluorescent glycoprobes: a sweet addition for improved sensing. Chemical Communications, 2017, 53: 82– 90

[73] DouW-T WangX LiuT T Zhao S W LiuJ-J YanY LiJ ZhangC-Y Sedgwick A C TianH SesslerJ L ZhouD-M HeX-P. A homogeneous high-throughput array for the detection and discrimination of influenza A viruses. Chem, 2022, doi: org/10.1016/j.chempr.2022.03.012 (in press)

[74] DouW-T, HanH-H, SedgwickA C, Zhu G-B, ZangY, YangX-R, Yoon J Y, JamesT D, LiJ, HeX-P. Fluorescent probes for the detection of disease-associated biomarkers. Science Bulletin, 2022, 67: 853– 878

Acknowledgements

The authors thank the National Natural Science Foundation of China (Grant Nos. 21907030 and 22108077) and the International Cooperation Program of Shanghai Science and Technology Committee (Grant No. 19410712600). De-Tai Shi would like to thank the Natural Science Foundation of Jiangxi (Grant No. 20161BAB213067) and the Scientific Research Fund of Jiangxi Provincial Education Department (Grant No. GJJ170807). Tony D. James wishes to thank the Royal Society for a Wolfson Research Merit Award and the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University for support (Grant No. 2020ZD01).

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