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Photosensitizing effects and physicochemical properties of chlorophyll a derivatives with hydrophilic oligoethylene glycol fragments at the macrocycle periphery

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Abstract

In this work, screening studies of the cytotoxic effect of chlorins with fragments of di-, tri-, and pentaethylene glycol at the macrocycle periphery in relation to HeLa, A549, and HT29 cells were performed. It is shown that, despite different hydrophobicity, all the compounds studied have a comparable photodynamic effect. The conjugate of chlorin e6 with pentaethylene glycol, which has the lowest tendency to association among the studied compounds with tropism for low density lipoproteins and the best characteristics of the formation of molecular complexes with Tween 80, has a significant difference in dark and photoinduced toxicity (ratio IC50(dark)/IC50(photo) approximately 2 orders of magnitude for all cell lines), which allows to hope for a sufficiently large "therapeutic window". A study of the interaction of this compound with HeLa cells shows that the substance penetrates the cell and, after red light irradiation induces ROS appearance inside the cell, associated, apparently, with the photogeneration of singlet oxygen. These data indicate that photoinduced toxic effects are caused by damage to intracellular structures as a result of oxidative stress. Programmed type of cell death characterized with caspase-3 induction is prevailing. So, the conjugate of chlorin e6 with pentaethylene glycol is a promising antitumor PS that can be successfully solubilized with Tween 80, which makes it suitable for further in vivo studies.

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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was financially supported by the Russian Science Foundation (project No. 21-13-00398). The compounds synthesized were analyzed using the equipment of the Center of Collective Usage (CCU) «Chemistry» at the Institute of Chemistry of the Komi Scientific Centre of the Ural Branch RAS. The studies of biological activity were carried out using the equipment of the Center for Collective Use «Molecular Biology» at the Institute of Biology of the Komi Scientific Centre of the Ural Branch RAS.

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Authors and Affiliations

  1. Institute of Chemistry, Komi Scientific Center, Ural Branch of the Russian Academy of Sciences, 48, Pervomaiskaya St., Syktyvkar, 167982, Russia

    D. V. Belykh

  2. Institute of Biology of Komi Scientific Centre of the Ural Branch of the Russian Academy of Sciences, 28, Kommunisticheskaya St., Syktyvkar, 167982, Russian Federation

    Y. I. Pylina & E. S. Belykh

  3. G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences (ISC RAS), 1, Akademicheskaya St., 153045, Ivanovo, Russian Federation

    A. V. Kustov & N. L. Smirnova

  4. Pitirim Sorokin Syktyvkar State University, 55, Oktyabrskiy Pr., Syktyvkar, 167001, Russian Federation

    O. M. Startseva

  5. Institute of Macroheterocyclic Compounds, Ivanovo State University of Chemistry and Technology (ISUCT), 7, Sheremetevskiy Ave., 153012, Ivanovo, Russian Federation

    O. V. Shukhto & D. B. Berezin

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  1. D. V. Belykh
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Belykh, D.V., Pylina, Y.I., Kustov, A.V. et al. Photosensitizing effects and physicochemical properties of chlorophyll a derivatives with hydrophilic oligoethylene glycol fragments at the macrocycle periphery. Photochem Photobiol Sci 23, 409–420 (2024). https://doi.org/10.1007/s43630-023-00527-w

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