Photodynamic activity of the boronated chlorin e6 amide in artificial and cellular membranes |
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| Authors: | Yuri N. Antonenko Elena A. Kotova Elena O. Omarova Tatyana I. Rokitskaya Valentina A. Ol'shevskaya Valery N. Kalinin Roza G. Nikitina Julia S. Osipchuk Mikhail A. Kaplan Alla A. Ramonova Mikhail M. Moisenovich Igor I. Agapov Mikhail P. Kirpichnikov |
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| Affiliation: | 1. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian Federation;2. Biological Department, Lomonosov Moscow State University, Moscow, Russian Federation;3. Nesmeyanov Institute of Organoelement Compounds, Moscow, Russian Federation;4. Medical Radiological Research Center, Obninsk, Russian Federation;5. Shumakov Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation |
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| Abstract: | Photodynamic tumor-destroying activity of the boronated chlorin e6 derivative BACE (chlorin e6 13(1)-N-{2-[N-(1-carba-closo-dodecaboran-1-yl)methyl]aminoethyl}amide-15(2), 17(3)-dimethyl ester), previously described in Moisenovich et al. (2010) PLoS ONE 5(9) e12717, was shown here to be enormously higher than that of unsubstituted chlorin e6, being supported by the data on much higher photocytotoxicity of BACE in M-1 sarcoma cell culture. To validate membrane damaging effect as the basis of the enhanced tumoricidal activity, BACE was compared with unsubstituted chlorin e6 in the potency to photosensitize dye leakage from liposomes, transbilayer lipid flip-flop, inactivation of gramicidin A ionic channels in planar lipid membranes and erythrocyte hemolysis. In all the models comprising artificial and cellular membranes, the photodynamic effect of BACE exceeded that of chlorin e6. BACE substantially differed from chlorin e6 in the affinity to liposomes and erythrocytes, as monitored by fluorescence spectroscopy, flow cytometry and centrifugation. The results support the key role of membrane binding in the photodynamic effect of the boronated chlorin e6 amide. |
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| Keywords: | PDT, photodynamic therapy BACE, chlorin e6 13(1)-N-{2-[N-(1-carba-closo-dodecaboran-1-yl)methyl]aminoethyl}amide-15(2), 17(3)-dimethyl ester sodium DPhPC, diphytanoylphosphatidylcholine EggPC, egg yolk phosphatidylcholine Chol, cholesterol pyPC, 1-lauroyl-2-(1&prime pyrenebutyroyl)-sn-glycero-3-phosphocholine gA, gramicidin A CF, 5(6)-carboxyfluorescein BLM, bilayer lipid membrane RBC, red blood cell MTT, 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide PBS, phosphate buffer solution |
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