Skip to main content
SpringerLink
Log in

In vitro cytotoxicity of a library of BODIPY-anthracene and -pyrene dyads for application in photodynamic therapy

  • Paper
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

The facile synthesis and in vitro activity of a library of heavy atom-free BODIPY-anthracene, -pyrene dyads (BAD-13–BPyrD-19) and a control (BODIPY 20) are reported. We demonstrate that singlet oxygen produced from dyad triplet states formed from charge-separated states is sufficient to induce cytotoxicity in human breast cancer cells (MDA-MB-468) at micromolar concentrations. The compounds in this series are promising candidates for photodynamic therapy, especially BAD-17 which displays significant photo-cytotoxicity (15% cell viability) at a concentration of 5 × 10−7 M, with minimal toxicity (89% cell viability) in the absence of light.

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

Notes and references

  1. (a) T. J. Dougherty, C. J. Gomer, B. W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan and Q. Peng, Photodynamic therapy, J. Natl. Cancer Inst., 1998, 90, 889–905; (b) B. W. Henderson and T. J. Dougherty, How does photodynamic therapy work?, Photochem. Photobiol., 1992, 55(1), 145–157.

  2. (a) S. B. Brown, E. A. Brown and I. Walker, The present and future role of photodynamic therapy in cancer treatment, Lancet Oncol., 2004, 5, 497–508; (b) X. Wen, Y. Li and M. R. Hamblin, Photodynamic therapy in dermatology beyond non-melanoma cancer: an update, Photodiagn. Photodyn. Ther., 2017, 19, 140–152; (c) U. Schmidt-Erfurth and T. Hasan, Mechanisms of action of photodynamic therapy with verteporfin for the treatment of age-related macular degeneration, Surv. Ophthalmol., 2000, 45, 195–214; (d) M. R. Hamblin and T. Hasan, Photodynamic therapy: a new antimicrobial approach to infectious disease?, Photochem. Photobiol. Sci., 2004, 3, 436–450.

  3. (a) A. Treibs and F.-H. Kreuzer, Difluorboryl-Komplexe von Di-und Tripyrrylmethenen, Justus Liebigs Ann. Chem., 1968, 718, 208–223; (b) A. Kamkaew, S. Hui Lim, H. B. Lee, L. V. Kiew, L. Y. Chung and K. Burgess, BODIPY dyes in photodynamic therapy, Chem. Soc. Rev., 2013, 42, 77–88.

    Google Scholar 

  4. S. Callaghan and M. O. Senge, The good, the bad, and the ugly –controlling singlet oxygen through design of photo-sensitizers and delivery systems for photodynamic therapy, Photochem. Photobiol. Sci., 2018, 17, 1490–1514.

    Article  CAS  Google Scholar 

  5. A. Loudet and K. Burgess, BODIPY dyes and their derivatives: syntheses and spectroscopic properties, Chem. Rev., 2007, 107, 4891–4932.

    Article  CAS  Google Scholar 

  6. S. Banfi, E. Caruso, S. Zaza, M. Mancini, M. B. Gariboldi and E. Monti, Synthesis and photodynamic activity of a panel of BODIPY dyes, J. Photochem. Photobiol., B, 2012, 114, 52–60.

    Article  CAS  Google Scholar 

  7. W. Pang, X.-F. Zhang, J. Zhou, C. Yu, E. Hao and L. Jiao, Modulating the singlet oxygen generation property of meso–β directly linked BODIPY dimer, Chem. Commun., 2012, 48, 5437–5439.

    Article  CAS  Google Scholar 

  8. W. Wu, J. Zhao, J. Sun and S. Guo, Light-harvesting fullerene dyads as organic triplet photosensitizers for triplet–triplet annihilation upconversions, J. Org. Chem., 2012, 77, 5305–5312.

    Article  CAS  Google Scholar 

  9. (a) A. Gorman, J. Killoran, C. O’Shea, T. Kenna, W. M. Gallagher and D. F. O’Shea, In vitro demonstration of the heavy-atom effect for photodynamic therapy, J. Am. Chem. Soc., 2004, 126, 10619–10631; (b) A. T. Byrne, A. E. O’Connor, M. Hall, J. Murtagh, K. O’Neill, K. M. Curran, K. Mongrain, J. A. Rousseau, R. Lecomte, S. McGee, J. J. Callanan, D. F. O’Shea and W. M. Gallagher, Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment, Br. J. Cancer, 2009, 101, 1565–1573.

    Article  CAS  Google Scholar 

  10. (a) M. A. Filatov, S. Karuthedath, P. M. Polestshuk, H. Savoie, K. J. Flanagan, C. Sy, E. Sitte, M. Telitchko, F. Laquai, R. W. Boyle and M. O. Senge, Generation of Triplet Excited States via Photoinduced Electron Transfer in meso-anthra-BODIPY: Fluorogenic Response toward Singlet Oxygen in Solution and in Vitro, J. Am. Chem. Soc., 2017, 139, 6282–6285; (b) M. A. Filatov, S. Karuthedath, P. M. Polestshuk, S. Callaghan, K. J. Flanagan, M. Telitchko, T. Wiesner, F. Laquaic and M. O. Senge, Control of triplet state generation in heavy atom-free BODIPY–anthracene dyads by media polarity and structural factors, Phys. Chem. Chem. Phys., 2018, 20, 8016–8031; (c) M. A. Filatov, S. Karuthedath, P. M. Polestshuk, S. Callaghan, T. Wiesner, K. J. Flanagan, F. Laquai and M. O. Senge, BODIPY-Pyrene and Perylene Dyads as Heavy-Atom-Free Singlet Oxygen Sensitizers, ChemPhotoChem, 2018, 2, 1–11.

    Article  CAS  Google Scholar 

  11. (a) M. R. Wasielewski, Photoinduced electron transfer in supramolecular systems for artificial photosynthesis, Chem. Rev., 1992, 92, 435–461; (b) T. Kowada, H. Maeda and K. Kikuchi, BODIPY-based probes for the fluorescence imaging of biomolecules in living cells, Chem. Soc. Rev., 2015, 44, 4953–4972.

    Article  CAS  Google Scholar 

  12. N. Kiseleva, M. A. Filatov, M. Oldenburg, D. Busko, M. Jakoby, I. A. Howard, B. S. Richards, M. O. Senge, S. M. Borisov and A. Turshatov, The Janus-faced chromophore: a donor–acceptor dyad with dual performance in photon up-conversion, Chem. Commun., 2018, 54, 1607–1610.

    Article  CAS  Google Scholar 

  13. S. L. Niu, G. Ulrich, R. Ziessel, A. Kiss, P.-Y. Renard and A. Romieu, Water-soluble BODIPY derivatives, Org. Lett., 2009, 11, 2049–2052.

    Article  CAS  Google Scholar 

  14. J. R. Lakowicz, Principles of Fluorescence Spectroscopy, Kluwer Academic/Plenum Publishers, New York, London, Moscow, Dordrecht, 2nd edn, 1999.

  15. Y. Cakmak, S. Kolemen, S. Duman, Y. Dede, Y. Dolen, B. Kilic, Z. Kostereli, L. T. Yildirim, A. L. Dogan, D. Guc and E. U. Akkaya, Designing Excited States: Theory-Guided Access to Efficient Photosensitizers for Photodynamic Action, Angew. Chem., Int. Ed., 2011, 50, 11937–11941.

    Article  CAS  Google Scholar 

  16. T. Mosman, Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays, J. Immunol. Methods, 1983, 65, 55–63.

  17. J.-M. Aubry, C. Pierlot, J. Rigaudy and R. Schmidt, Acc. Chem. Res., 2003, 36, 668–675.

  18. (a) D. V. Ash and B. Brown, New drugs and future developments in photodynamic therapy, Eur. J. Cancer, 1983, 29, 1781–1783; (b) S.-I. Moriwaki, J. Misawa, Y. Yoshinari, I. Yamada, M. Takigawa and Y. Tokura, Analysis of photosensitivity in Japanese cancer-bearing patients receiving photodynamic therapy with porfimer sodium (PhotofrinTM), Photodermatol., Photoimmunol. Photomed., 2001,17, 241–243.

  19. H. Sunahara, Y. Urano, H. Kojima and T. Nagano, Design and synthesis of a library of BODIPY-based environmental polarity sensors utilizing photoinduced electron-transfer-controlled fluorescence ON/OFF switching, J. Am. Chem. Soc., 2007, 129, 5597–5604.

    Article  CAS  Google Scholar 

  20. P. A. Liddell, T. P. Forsyth, M. O. Senge and K. M. Smith, Chemical synthesis of a “GSA-pyrrole” and its reaction with Ehrlich’s reagent, Tetrahedron, 1993, 49,1343–1350.

  21. M. A. Filatov, R. Guilard and P. D. Harvey, Selective Stepwise Suzuki Cross-Coupling Reaction for the Modelling of Photosynthetic Donor— Acceptor Systems, Org. Lett., 2010, 12, 196–199.

    Article  CAS  Google Scholar 

  22. Y. Gabe, Y. Urano, K. Kikuchi, H. Kojima and T. Nagano, Highly sensitive fluorescence probes for nitric oxide based on boron dipyrromethene chromophore rational design of potentially useful bioimaging fluorescence probe, J. Am. Chem. Soc., 2004, 126, 3357–3367.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity Biomedical Sciences Institute, Trinity College Dublin, The University of Dublin, 152-160 Pearse Street, Dublin 2, Ireland

    Susan Callaghan & Mikhail A. Filatov

  2. Department of Chemistry, University of Hull, Cottingham Road, Kingston-upon-Hull, HU6 7RX, UK

    Huguette Savoie & Ross W. Boyle

  3. Medicinal Chemistry, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, Trinity College Dublin, The University of Dublin, St. James’s Hospital, Dublin 8, Ireland

    Mathias O. Senge

Authors
  1. Susan Callaghan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mikhail A. Filatov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huguette Savoie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ross W. Boyle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mathias O. Senge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ross W. Boyle.

Additional information

Electronic supplementary information (ESI) available: Details of experimental protocols, synthetic procedures and spectra. See DOI: 10.1039/c8pp00402a

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Callaghan, S., Filatov, M.A., Savoie, H. et al. In vitro cytotoxicity of a library of BODIPY-anthracene and -pyrene dyads for application in photodynamic therapy. Photochem Photobiol Sci 18, 495–504 (2019). https://doi.org/10.1039/c8pp00402a

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/c8pp00402a

Search

Navigation