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Intracellular Localization and the Mechanisms of Photodynamic Action of 131-[2-(Guanidinyl)ethylamino] Chlorin e6 Dimethyl Ester

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Abstract—

It has been found that the photosensitizer 131-[2-(guanidinyl)ethylamino] chlorin e6 dimethyl ester accumulates predominantly in lysosomes, partially in endosomes, and does not accumulate in mitochondria of human lung adenocarcinoma A549 cells. The primary photocytotoxic effect of the photosensitizer is associated with the damage to lysosomes and its release into the cytoplasm. In the cytoplasm, the photosensitizer is uniformly distributed in complexes with membrane structures, which serve as the secondary targets of its photoinduced effect. Time-dependent morphological signs of the development of paraptosis have been revealed, which indicate the photodynamic damage to the endoplasmic reticulum as the secondary mechanism of the photocytotoxic effect of the photosensitizer. At this stage, one more change in the potential cellular targets of the photosensitizer occurs: it concentrates in cytoplasmic and nuclear membranes, in the membranes of numerous vacuoles, and in lysosomes, which apparently continue to form during the development of paraptosis. Thus, the chlorin е6 derivative, as a representative of hydrophobic photosensitizers with the intracellular targeting to lysosomes, has a two- or three-stage process of photodynamic action with consecutive changes in cellular targets.

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Funding

The study was supported by the Russian Foundation for Basic Research (project no. 19-04-00854).

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Authors and Affiliations

  1. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia

    A. V. Efremenko, E. D. Dyakova & A. V. Feofanov

  2. Faculty of Biology, Moscow State University, 119234, Moscow, Russia

    A. V. Efremenko & A. V. Feofanov

  3. MIREA–Russian Technological University, Lomonosov Institute of Fine Chemical Technologies, 119571, Moscow, Russia

    E. D. Dyakova, P. V. Ostroverkhov, N. S. Kirin, A. F. Mironov & M. A. Grin

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  1. A. V. Efremenko
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Correspondence to A. V. Feofanov.

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Translated by S. Sidorova

Abbreviations: DMSO, dimethyl sulfoxide; DIPEA, diisopropylethylamine; LSCM laser scanning confocal microscopy; PS, photosensitizer; PDT, photodynamic therapy; ER, endoplasmic reticulum; CrEL, cremophore EL; LTG, LysoTracker Green; Rh 123, rhodamine 123; TOG488, a conjugate of transferrin with the dye Oregon Green 488.

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Efremenko, A.V., Dyakova, E.D., Ostroverkhov, P.V. et al. Intracellular Localization and the Mechanisms of Photodynamic Action of 131-[2-(Guanidinyl)ethylamino] Chlorin e6 Dimethyl Ester. Russ J Bioorg Chem 47, 845–853 (2021). https://doi.org/10.1134/S1068162021040087

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