Skip to main content
SpringerLink
Log in

Ir(III)-based Ratiometric Hypoxic Probe for Cell Imaging

  • Research Article
  • Published:
Chinese Journal of Polymer Science Aims and scope Submit manuscript

Abstract

Two new ratiometric hypoxia probes (Ir-C343 and Ir-GFP) are synthesized by covalently incorporating florescent internal standard molecules coumarin 343 (C343) and green fluorescent protein (GFP) into bis[1-(9,9-dimethyl-9H-fluoren-2-yl)-isoquinoline] (succinylacetone) Ir(III) (Ir-fliq), respectively. After connecting with internal standard molecules, the Ir-fliq moiety still exhibits high sensitivity to oxygen concentration, while the fluorescence intensity of the internal standard remains relatively constant under different oxygen concentrations. As a result, a ratiometric response is realized that is only related to oxygen concentration. In addition, Ir-GFP shows more promising applications in the ratiometric hypoxia imaging of cells due to its long excitation wavelength, good water solubility, high biocompatibility, and low relative fluorescence intensity compared with the phosphorescent emitter Ir-fliq.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Rudin, M.; Weissleder, R. Molecular imaging in drug discovery and development. Nat. Rev. Drug Discov. 2003, 2, 123–131.

    Article  CAS  PubMed  Google Scholar 

  2. Weissleder, R. Molecular imaging in cancer. Science 2006, 312, 1168–1171.

    Article  CAS  PubMed  Google Scholar 

  3. Lee, Y. E. K.; Kopelman, R. Optical nanoparticle sensors for quantitative intracellular imaging. Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol. 2009, 1, 98–110.

    Article  CAS  PubMed  Google Scholar 

  4. Li, Q.; Liu, L.; Liu, J. W.; Jiang, J. H.; Yu, R. Q.; Chu, X. Nanomaterial-based fluorescent probes for live-cell imaging. Trac-Trends Anal. Chem. 2014, 58, 130–144.

    Article  CAS  Google Scholar 

  5. Smith, B. R.; Gambhir, S. S. Nanomaterials for in vivo Imaging. Chem. Rev. 2017, 117, 901–986.

    Article  CAS  PubMed  Google Scholar 

  6. Koo, H.; Huh, M. S.; Ryu, J. H.; Lee, D. E.; Sun, I. C.; Choi, K.; Kim, K.; Kwon, I. C. Nanoprobes for biomedical imaging in living systems. Nano Today 2011, 6, 204–220.

    Article  CAS  Google Scholar 

  7. Wolfbeis, O. S. An overview of nanoparticles commonly used in fluorescent bioimaging. Chem. Soc. Rev. 2015, 44, 4743–68.

    Article  CAS  PubMed  Google Scholar 

  8. Kang, S. Y.; Wang, Y.; Xu, X. C.; Navarro, E.; Tichauer, K. M.; Liu, J. T. C. Microscopic investigation of topically applied nanoparticles for molecular imaging of fresh tissue surfaces. J. Biophoton. 2018, 11, e201700246.

    Article  Google Scholar 

  9. Leigh, S. Y.; Som, M.; Liu, J. T. C. Method for assessing the reliability of molecular diagnostics based on multiplexed SERS-coded nanoparticles. PLoS One 2013, 8, 8.

    Article  Google Scholar 

  10. Wang, Y.; Reder, N. P.; Kang, S.; Glaser, A. K.; Yang, Q.; Wall, M. A.; Javid, S. H.; Dintzis, S. M.; Liu, J. T. C. Raman-encoded molecular imaging with topically applied SERS nanoparticles for intraoperative guidance of lumpectomy. Cancer Res. 2017, 77, 4506–4516.

    Article  CAS  PubMed  Google Scholar 

  11. Wang, Y. W.; Doerksen, J. D.; Kang, S. Y.; Walsh, D.; Yang, Q.; Hong, D.; Liu, J. T. C. Multiplexed molecular imaging of fresh tissue surfaces enabled by convection-enhanced topical staining with SERS-coded nanoparticles. Small 2016, 12, 5612–5621.

    Article  PubMed  Google Scholar 

  12. Papkovsky, D. B.; Dmitriev, R. I. Biological detection by optical oxygen sensing. Chem. Soc. Rev. 2013, 42, 8700–8732.

    Article  CAS  PubMed  Google Scholar 

  13. Tichauer, K. M.; Holt, R. W.; El-Ghussein, F.; Davis, S. C.; Samkoe, K. S.; Gunn, J. R.; Leblond, F.; Pogue, B. W. Dual-tracer background subtraction approach for fluorescent molecular tomography. J. Biomed. Opt. 2013, 18, 11.

    Article  Google Scholar 

  14. Tichauer, K. M.; Wang, Y.; Pogue, B. W.; Liu, J. T. C. Quantitative in vivo cell-surface receptor imaging in oncology: kinetic modeling and paired-agent principles from nuclear medicine and optical imaging. Phys. Med. Biol. 2015, 60, R239–R269.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Haidekker, M. A.; Theodorakis, E. A. Ratiometric mechanosensitive fluorescent dyes: design and applications. J. Mater. Chem. C 2016, 4, 2707–2718.

    Article  CAS  Google Scholar 

  16. Kumar, S.; Verma, T.; Mukherjee, R.; Ariese, F.; Somasundaram, K.; Umapathy, S. Raman and infra-red microspectroscopy: towards quantitative evaluation for clinical research by ratiometric analysis. Chem. Soc. Rev. 2016, 45, 1879–1900.

    Article  CAS  PubMed  Google Scholar 

  17. Liu, J. T. C.; Helms, M. W.; Mandella, M. J.; Crawford, J. M.; Kino, G. S.; Contag, C. H. Quantifying cell-surface biomarker expression in thick tissues with ratiometric three-dimensional microscopy. Biophys. J. 2009, 96, 2405–2414.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Liu, X.; Yu, Z.; Yu, M.; Zhang, X.; Xu, Y.; Lv, P.; Chu, S.; Liu, C.; Lai, W.; Huang, W. Iridium(III)-complexed polydendrimers for inkjet-printing OLEDs: the influence of solubilizing steric hindrance groups. ACS Appl. Mater. Interfaces 2019, 11, 26174–26184.

    Article  CAS  PubMed  Google Scholar 

  19. Jiang, Y.; Lv, P.; Pan, J.; Li, Y.; Lin, H.; Zhang, X.; Wang, J.; Liu, Y.; Wei, Q.; Xing, G.; Lai, W.; Huang, W. Low-threshold organic semiconductor lasers with the aid of phosphorescent Ir(III) complexes as triplet sensitizers. Adv. Funct. Mater. 2019, 29, 1806719.

    Article  Google Scholar 

  20. Cao, S.; Hao, L.; Lai, W.; Zhang, H.; Yu, Z.; Zhang, X.; Liu, X.; Huang, W. Distinct phosphorescence enhancement of red-emitting iridium(III) complexes with formyl-functionalized phenylpyridine ligands. J. Mater. Chem. C 2016, 4, 4709–4718.

    Article  CAS  Google Scholar 

  21. Liu, J.; Zhou, H.; Wang, Z.; Tang, X.; Wu, H.; Wang, S.; Lai, W.; Li, Y. Distinct Ir(III) complexes containing unsymmetric ligands with fluorene-oxadiazole groups and their performance of organic light-emitting diodes. Dyes and Pigments 2022, 202, 110252.

    Article  CAS  Google Scholar 

  22. Zhang L.; Ding D. Recent advances of transition Ir(III) complexes as photosensitizers for improved photodynamic therapy. VIEW 2020, 2, 20200179.

    Article  Google Scholar 

  23. Ji, S.; Zhou, S.; Zhang, X.; Chen, W.; Jiang, X. An oxygen-sensitive probe and a hydrogel for optical imaging and photodynamic antimicrobial chemotherapy of chronic wounds. Biomater. Sci. 2022, 10, 2054–2061.

    Article  CAS  PubMed  Google Scholar 

  24. Yoshihara, T.; Yamaguchi, Y.; Hosaka, M.; Takeuchi, T.; Tobita, S. Ratiometric molecular sensor for monitoring oxygen levels in living cells. Angew. Chem. Int. Ed. 2012, 51, 4148–51.

    Article  CAS  Google Scholar 

  25. Rodrigues, M.; Kosaric, N.; Bonham, C. A.; Gurtner, G. C. Wound healing: a cellular perspective. Physiol. Rev. 2019, 99, 665–706.

    Article  CAS  PubMed  Google Scholar 

  26. Cooke, J. P. Inflammation and its role in regeneration and repair. Circ. Res. 2019, 124, 1166–1168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rodrigues, M.; Gurtner, G. C. Black, white, and gray: macrophages in skin repair and disease. Curr. Pathobiol. Rep. 2017, 5, 333–342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the National Key R&D Program of China (Nos. 2017YFA0701301 and 2017YFA0205400), the National Natural Science Foundation of China (Nos. 92163214, 51690153, 21720102005 and 51803089), and the Natural Science Foundation of Jiangsu Province (BK20202002).

Author information

Authors and Affiliations

  1. Department of Polymer Science & Engineering, College of Chemistry & Chemical Engineering, Nanjing University, Nanjing, 210093, China

    Shi-Lu Ji, Hua-Min Lan, Sen-Sen Zhou, Xiao-Ke Zhang, Wei-Zhi Chen & Xi-Qun Jiang

  2. College of Science, Nanjing Forestry University, Nanjing, 210037, China

    Shi-Lu Ji

Authors
  1. Shi-Lu Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hua-Min Lan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sen-Sen Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-Ke Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei-Zhi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xi-Qun Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Wei-Zhi Chen or Xi-Qun Jiang.

Additional information

Notes

The authors declare no competing financial interest.

Electronic Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ji, SL., Lan, HM., Zhou, SS. et al. Ir(III)-based Ratiometric Hypoxic Probe for Cell Imaging. Chin J Polym Sci 41, 794–801 (2023). https://doi.org/10.1007/s10118-023-2922-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10118-023-2922-6

Keywords

Search

Navigation