1. Photophysical properties and in vitro photocytotoxicity of disodium salt 2.4-di(alpha-methoxyethyl)-deuteroporphyrin-IX (Dimegine).
- Author
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Dadeko AV, Lilge L, Kaspler P, Murav'eva TD, Starodubtcev AM, Kiselev VM, Zarubaev VV, and Ponomarev GV
- Subjects
- Animals, Cell Line, Tumor, Dose-Response Relationship, Drug, Humans, Hydrogen-Ion Concentration, Methylene Blue pharmacology, Microscopy, Fluorescence, Photobleaching drug effects, Protoporphyrins pharmacology, Rats, Deuteroporphyrins pharmacology, Photochemotherapy methods, Photosensitizing Agents pharmacology, Singlet Oxygen metabolism
- Abstract
Photophysical and in vitro photocytotoxicity studies were performed for the photosensitizer Dimegine, a disodium salt 2.4-di(alpha-methoxyethyl)-deuteroporphyrin-IX with very low systemic toxicity. The singlet oxygen and luminescence quantum yield were Φ
Δ = 0,65 ± 0,06, and Φƒ =0,11 ± 0,01 respectively, and were independent of the excitation wavelength. The photobleaching coefficients for Dimegine dissolved in phosphate buffer (pH 7.4), and DMEM medium at concentration 2 μM/l and in phosphate buffer (pH 7.0) at concentration 10 μM/l were 16·10-5 , 9·10-5 and 2·10-5 respectively. In vitro cellular distribution and photocytotoxicity was studied in two human (U87 - primary glioblastoma and HT1376 - bladder cancer) and two rat cell lines (RG2 - glioma, and AY27 - bladder carcinoma). Fluorescence microscopy analysis shows primary Dimegine accumulation as small fluorescent inclusion bodies around the nuclei, suggesting an apoptotic over a necrotic cell death mechanism. The PDT efficacy was slightly higher for the rat cell lines over the human-derived cell lines, with LD50 values of 2,5 μM/l, 2.8 μM/l, 4.5 μM/l, 2.8 μM/l using 530 nm excitation wavelength for AY27, RG2, HT1376 and U87 respectively, and 1.8 μM/l, 2 μM/l, 5 μM/l, 2.4 μM/l using 625 nm excitation wavelength for AY27, RG2, HT1376 and U87 respectively. Comparison to literature data showed that Dimegine demonstrated improved phototherapeutic characteristics comparing to PpIX-mediated PDT., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2019
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