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Effects of zinc porphyrin and zinc phthalocyanine derivatives in photodynamic anticancer therapy under different partial pressures of oxygen in vitro

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Summary

Photodynamic therapy (PDT) is gradually becoming an alternative method in the treatment of several diseases. Here, we investigated the role of oxygen in photodynamically treated cervical cancer cells (HeLa). The effect of PDT on HeLa cells was assessed by exposing cultured cells to disulphonated zinc phthalocyanine (ZnPcS2) and tetrasulphonated zinc tetraphenylporphyrin (ZnTPPS4). Fluorescence microscopy revealed their different localizations within the cells. ZnTPPS4 seems to be mostly limited to the cytosol and lysosomes, whereas ZnPcS2 is most likely predominantly attached to membrane structures, including plasmalemma and the mitochondrial membrane. Phototoxicity assays of PDT-treated cells carried out under different partial pressures of oxygen showed dose-dependent responses. Interestingly, ZnPcS2 was also photodynamically effective at a minimal level of oxygen, under a nitrogen atmosphere. On the other hand, hyperbaric oxygenation did not lead to a higher PDT efficiency of either photosensitizer. Although both photosensitizers can induce a significant drop in mitochondrial membrane potential, ZnPcS2 has a markedly higher effect on mitochondrial respiration that was completely blocked after two short light cycles. In conclusion, our observations suggest that PDT can be effective even in hypoxic conditions if a suitable sensitizer is chosen, such as ZnPcS2, which can inhibit mitochondrial respiration.

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Acknowledgements

We would like to thank American Journal Experts (http://aje.com) for proofreading our manuscript.

Funding

This work was supported by the grants from the Ministry of Education, Youth and Sports of the Czech Republic LO1304, LM2015062, European Regional Development Fund CZ.02.1.01/0.0/0.0/16_019/0000868.

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Authors and Affiliations

  1. Department of Medical Biophysics, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Hnevotinska 3, 775 15, Olomouc, Czech Republic

    Martin Pola, Hana Kolarova, Jiri Ruzicka & Robert Bajgar

  2. Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Hnevotinska 3, 775 15, Olomouc, Czech Republic

    Aleksey Zholobenko & Martin Modriansky

  3. Department of Inorganic Chemistry, Faculty of Science, Charles University, Hlavova 2030, 128 43, Prague 2, Czech Republic

    Jiri Mosinger

  4. Institute of Inorganic Chemistry of the Czech Academy of Sciences, v.v.i., Husinec-Rez 1001, 250 68, Rez, Czech Republic

    Jiri Mosinger

  5. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Hnevotinska 3, 775 15, Olomouc, Czech Republic

    Robert Bajgar

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  1. Martin Pola
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  2. Hana Kolarova
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  7. Robert Bajgar
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Contributions

M.P. performed most of the experiments and analyzed the data. J.R. developed the small hyperbaric chamber and assisted in experiments carried out under hyperbaric conditions. A.Z. and M.M. performed the measurements of cellular respiration and analyzed the acquired data. J.M. synthetized the photosensitizers. R.B. and H.K. designed the study, interpreted the results and wrote the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Robert Bajgar.

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Pola, M., Kolarova, H., Ruzicka, J. et al. Effects of zinc porphyrin and zinc phthalocyanine derivatives in photodynamic anticancer therapy under different partial pressures of oxygen in vitro. Invest New Drugs 39, 89–97 (2021). https://doi.org/10.1007/s10637-020-00990-7

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  • DOI: https://doi.org/10.1007/s10637-020-00990-7

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