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Intracellular Localization and Phototoxicity Mechanisms of Chlorin e6 Derivatives and their Liposomal Formulations

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Abstract—Confocal microscopy and colocalization analysis using Pearson correlation coefficients were used to show that esterified chlorin e6 derivatives and their liposomal forms are mainly localized in the endoplasmic reticulum, Golgi complexes, cell mitochondria, and levels of their localization in lysosomes are low. Cellular uptake and accumulation kinetics of chlorin e6 derivatives were strongly depended on the type of pharmacological formulation used for photosesitizers administration, while intracellular localization was independent on the formulation. Differences in the photodynamic activity and sensitization mechanisms for chlorin e6 derivatives and their liposomal forms were shown when compared to those of chlorin e6 photosensitizers in K562 cells. It is assumed that the observed differences in the mechanisms of cellular damage are to a greater extent due to specific photosensitizer localization.

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Funding

This study was supported by the Belarusian Republican Foundation for Basic Research, project no. B17-106.

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Correspondence to T. E. Zorina.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Translated by M. Novikova

Abbreviations: PS, photosensitizer; Chl e6, chlorin e6; DChl e6, esterified derivatives of chlorin e6; DME, dimethyl ester of chlorin e6; TME, trimethyl ester of chlorin e6; LF, liposomal form; DMPC, dimyristoyl phosphatidylcholine, FCS, fetal calf serum; PCC, Pearson correlation coefficient; CMXRos, chloromethyl-X-rosamine.

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Zorina, T.E., Yankovsky, I.V., Yakovets, I.V. et al. Intracellular Localization and Phototoxicity Mechanisms of Chlorin e6 Derivatives and their Liposomal Formulations. BIOPHYSICS 64, 533–542 (2019). https://doi.org/10.1134/S0006350919040250

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  • DOI: https://doi.org/10.1134/S0006350919040250

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