Skip to main content
Log in

Development of a Xanthene-Based Red-Emissive Fluorescent Probe for Visualizing H2O2 in Living Cells, Tissues and Animals

  • ORIGINAL ARTICLE
  • Published:
Journal of Fluorescence Aims and scope Submit manuscript

Abstract

Hydrogen peroxide (H2O2) plays important roles in the regulation of many biological processes, and the abnormal level of H2O2 has close relation with the initiation and progression of many diseases. Herein, we describe a novel red-emissive fluorescence probe (RhoB) for the visualization of H2O2 in living cells, tissues and animals. RhoB was constructed on the basis of a xanthene-based red-emissive dye, and displayed nearly no fluorescence. After the treatment with H2O2, RhoB can exhibit red fluorescence with the emission wavelength at 638 nm. RhoB exhibited highly sensitive and selective response to H2O2. Density functional theory (DFT) calculations were conducted to shed light on the optical properties of RhoB, and natural bond orbital (NBO) calculations demonstrate that the boron atom shows the highest positive electricity and further support the response mechanism. RhoB was successfully applied for imaging of exogenous and endogenous H2O2 in living cells, and also can be utilized for visualizing H2O2 in living tissues and animals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Rhee SG (2006) H2O2, a necessary evil for cell signaling. Science 312:1882–1883

    Article  PubMed  Google Scholar 

  2. D’AutrEaux B, Toledano MB (2007) ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8:813–824

    Article  PubMed  CAS  Google Scholar 

  3. Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84

    Article  PubMed  CAS  Google Scholar 

  4. Stone JR, Yang S (2006) Hydrogen peroxide: A signaling messenger. Antioxid Redox Signal 8:243–270

    Article  PubMed  CAS  Google Scholar 

  5. Winterbourn CC (2008) Reconciling the chemistry and biology of reactive oxygen species. Nat Chem Biol 4:278–286

    Article  PubMed  CAS  Google Scholar 

  6. Miller EW, Chang CJ (2007) Fluorescent probes for nitric oxide and hydrogen peroxide in cell signaling. Curr Opin Chem Biol 11:620–625

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Veal EA, Day AM, Morgan BA (2007) Hydrogen peroxide sensing and signaling. Mol Cell 26:1–14

    Article  PubMed  CAS  Google Scholar 

  8. Giorgio M, Trinei M, Migliaccio E, Pelicci PG (2007) Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat Rev Mol Cell Biol 8:722–728

    Article  PubMed  CAS  Google Scholar 

  9. Travasso RDM, dos Aidos FS, Bayani A, Abranches P, Salvador A (2017) Localized redox relays as a privileged mode of cytoplasmic hydrogen peroxide signaling. Redox Biol 12:233–245

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Niethammer P, Grabher C, Look AT, Mitchison TJ (2009) A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature 459:996–999

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Eligini S, Arenaz I, Barbieri SS, Faleri ML, Crisci M, Tremoli E, Colli S (2009) Cyclooxygenase-2 mediates hydrogen peroxide-induced wound repair in human endothelial cells. Free Radic Biol Med 46:1428–1436

    Article  PubMed  CAS  Google Scholar 

  12. Brand MD (2016) Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling. Free Radical Bio Med 100:14–31

    Article  CAS  Google Scholar 

  13. Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H, Nakada K, Honma Y, Hayashi J (2008) ROS-Generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science 320:661–664

    Article  PubMed  CAS  Google Scholar 

  14. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795

    Article  PubMed  CAS  Google Scholar 

  15. DiMauro S, Schon EA (2008) Mitochondrial disorders in the nervous system. Annu Rev Neurosci 31:91–123

    Article  PubMed  CAS  Google Scholar 

  16. Mattson MP (2004) Pathways towards and away from Alzheimer's disease. Nature 430:631–639

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Fruehauf JP, Meysken FL Jr (2007) Reactive oxgen species: A breath of life or death? Clin Cancer Res 448:789–794

    Article  Google Scholar 

  18. Finkel T, Serrano M, Blasco MA (2007) The common biology of cancer and ageing. Nature 448:767–774

    Article  PubMed  CAS  Google Scholar 

  19. Lakowicz JR (2006) Principles of Fluorescence Spectroscopy. Springer, New York

    Book  Google Scholar 

  20. Lee MH, Kim JS, Sessler JL (2015) Small molecule-based ratiometric fluorescence probes for cations, anions, and biomolecules. Chem Soc Rev 44:4185–4191

    Article  PubMed  CAS  Google Scholar 

  21. Zelmer A, Ward TH (2013) Noninvasive fluorescence imaging of small animals. J Microsc 252:8–15

    Article  PubMed  CAS  Google Scholar 

  22. Chan J, Dodani SC, Chang CJ (2012) Reaction-based small-molecule fluorescent probes for chemoselective bioimaging. Nat Chem 4:973–984

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Yuan L, Lin W, Zheng K, He L, Huang W (2013) Far-red to near infrared analyte-responsive fluorescent probes based on organic fluorophore platforms for fluorescence imaging. Chem Soc Rev 42:622–661

    Article  PubMed  CAS  Google Scholar 

  24. Chen X, Wang F, Hyun JY, Wei T, Qiang J, Ren X, Shin I, Yoon J (2016) Recent progress in the development of fluorescent, luminescent and colorimetric probes for detection of reactive oxygen and nitrogen species. Chem Soc Rev 45:2976–3016

    Article  PubMed  CAS  Google Scholar 

  25. Wardman P (2007) Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: Progress, pitfalls, and prospects. Free Radic Biol Med 43:995–1022

    Article  PubMed  CAS  Google Scholar 

  26. Yuan L, Lin W, Zhao S, Gao W, Chen B, He L, Zhu S (2012) A Unique Approach to Development of Near-Infrared Fluorescent Sensors for in Vivo Imaging. J Am Chem Soc 134:13510–13523

    Article  PubMed  CAS  Google Scholar 

  27. Wang P, Wang K, Chen D, Mao Y, Gu Y (2015) A novel colorimetric and near-infrared fluorescent probe for hydrogen peroxide imaging in vitro and in vivo. RSC Adv 5:85957–85963

    Article  CAS  Google Scholar 

  28. Dong B, Song X, Kong X, Wang C, Tang Y, Liu Y, Lin W (2016) Simultaneous Near-Infrared and Two-Photon In Vivo Imaging of H2O2 Using a Ratiometric Fluorescent Probe based on the Unique Oxidative Rearrangement of Oxonium. Adv Mater 28:8755–8759

    Article  PubMed  CAS  Google Scholar 

  29. Liu K, Shang H, Kong X, Ren M, Wang JY, Liu Y, Lin W (2016) A novel near-infrared fluorescent probe for H2O2 in alkaline environment and the application for H2O2 imaging in vitro and in vivo. Biomaterials 100:162–171

    Article  PubMed  CAS  Google Scholar 

  30. Song X, Dong B, Kong X, Wang C, Zhang N, Lin W (2017) A sensitive and selective red fluorescent probe for imaging of cysteine in living cells and animals. Anal Methods 9:1891–1896

    Article  CAS  Google Scholar 

  31. Hilborn RC (1982) Einstein coefficients, cross sections, f values, dipole moments, and all that. Am J Phys 50:982–986

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was financially supported by NSFC (21472067, 21672083, 51602127), Taishan Scholar Foundation (TS 201511041), and the startup fund of the University of Jinan (309-10004).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Weiying Lin.

Electronic Supplementary Material

ESM 1

(DOCX 2271 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, N., Dong, B., Kong, X. et al. Development of a Xanthene-Based Red-Emissive Fluorescent Probe for Visualizing H2O2 in Living Cells, Tissues and Animals. J Fluoresc 28, 681–687 (2018). https://doi.org/10.1007/s10895-018-2231-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10895-018-2231-6

Keywords

Navigation