biophBiomedical PhotonicsBiomedical Photonics2413-9432Non-profit partnership for development of domestic photodynamic therapy and photodiagnosis10.24931/2413-9432-2023-12-2-34-47bioph-593Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESСпектроскопическое исследование фотофизических свойств метиленового синего в биологических средахSpectroscopic study of methylene blue photophysical properties in biological mediaПоминоваД. В.PominovaD. V.

Москва

Moscow

pominovadv@gmail.comРябоваА. В.RyabovaA. V.

Москва

Moscow

РоманишкинИ. Д.RomanishkinI. D.

Москва

Moscow

МарковаИ. В.MarkovaI. V.

Москва

Moscow

АхлюстинаЕ. В.AkhlustinaE. V.

Москва

Moscow

СкобельцинА. С.SkobeltsinA. S.

Москва

 

Moscow

Институт общей физики им. А. М. Прохорова Российской академии наук; Национальный исследовательский ядерный университет «МИФИ»РоссияProkhorov General Physics Institute of Russian Academy of Sciences; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)Russian FederationИнститут общей физики им. А. М. Прохорова Российской академии наукРоссияProkhorov General Physics Institute of Russian Academy of SciencesRussian FederationНациональный исследовательский ядерный университет «МИФИ»РоссияNational Research Nuclear University MEPhI (Moscow Engineering Physics Institute)Russian Federation20232108202312234–47Copyright © Поминова Д.В., Рябова А.В., Романишкин И.Д., Маркова И.В., Ахлюстина Е.В., Скобельцин А.С., 20232023Поминова Д.В., Рябова А.В., Романишкин И.Д., Маркова И.В., Ахлюстина Е.В., Скобельцин А.С.Pominova D.V., Ryabova A.V., Romanishkin I.D., Markova I.V., Akhlustina E.V., Skobeltsin A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pdt-journal.com/jour/article/view/593

Проведено спектроскопическое исследование фотофизических свойств метиленового синего (МС) в водных растворах и биологических жидкостях. Зарегистрированы спектры поглощения и флуоресценции, а также времена жизни флуоресценции. По зависимости интенсивности и формы спектров от концентрации удалось установить диапазоны концентраций МС для исследований in vitro и in vivo при которых не наблюдается агрегация (до 0,01 мМ, что соответствует 3,2 мг/кг). Исследовано фотообесцвечивание МС под действием лазерного излучения. Исследования фотодеградации в биологических средах показали, что фотообесцвечивание более чем на 80% в плазме и культуральной среде наблюдается уже при дозе 5 Дж/см2 , в то время как в воде при такой концентрации при дозе 5 Дж/см2  фотообесцвечивания еще не наблюдается, а при дозе 50 Дж/см2  фотообесцвечивание МС составляет порядка 30%. Установлено, что в средах, содержащих белки и обладающих щелочным рН, фотообесцвечивание происходит существенно быстрее, чем в нейтральных водных средах. Ионная сила раствора не оказывает влияния на скорость фотообесцвечивания. Такое фотообесцвечивание вызвано фотодеградацией МС, а не переходом в лейкоформу. Проведена оценка эффективности генерации синглетного кислорода и фотодинамической активности in vitro. В исследуемом диапазоне концентраций МС эффективность генерации синглетного кислорода достаточно низкая, так как положительно заряженный МС связывается с негативно заряженными мембранами клеток, что приводит к изменению типа фотодинамической реакции. Продемонстрировано возникновение в клетках других активных форм кислорода (АФК), отличных от синглетного кислорода. Генерация АФК и невысокий квантовом выход генерации синглетного кислорода свидетельствуют о склонности МС к механизму фотосенсибилизации I типа (перенос электрона с образованием полувосстановленных и полуокисленных радикалов MB+), а не к механизму II типа (перенос энергии к кислороду с образованием синглетного кислорода) в биологических средах и in vivo.

A spectroscopic study of the photophysical properties of methylene blue (MB) in aqueous solutions was carried out. Absorption and fluorescence spectra as well as fluorescence lifetime were recorded. The concentration dependence of the intensity and shape of the spectra allowed establishing the ranges of MB concentrations for in vitro and in vivo studies at which aggregation is not observed (up to 0.01 mM, which corresponds to 3.2 mg/kg). Studies of photodegradation in biological media showed that photobleaching of more than 80% in plasma and culture media is observed already at a dose of 5 J/cm2 , while in water at this concentration and dose photobleaching is not yet observed, and at a dose of 50 J/cm2  photobleaching of MB is about 30%. It was found that in media containing proteins and having an alkaline pH, photobleaching occurs significantly faster than in neutral aqueous media. The ionic strength of the solution has no effect on the photobleaching rate. Such photobleaching is caused by the photodegradation of MB rather than the transition to the leucoform.The efficiency of singlet oxygen generation and photodynamic activity were evaluated in vitro. In the investigated range of MB concentrations, the efficiency of singlet oxygen generation is rather low, because positively charged MB binds to negatively charged cell membranes, which leads to a change in the type of photodynamic reaction. The emergence of other reactive oxygen species (ROS), different from singlet oxygen, in cells has been demonstrated. The generation of ROS and the low quantum yield of singlet oxygen generation indicate the tendency of MB to provide the type I photosensitization mechanism (electron transfer with the formation of semi-reduced and semi-oxidized MB+ radicals) rather than to the type II mechanism (energy transfer to oxygen with the formation of singlet oxygen) in biological media and in vivo.

метиленовый синийспектроскопияфлуоресценцияпоглощениефотообесцвечиваниеАФКсинглетный кислородmethylene bluespectroscopyabsorptionfluorescencephotobleachingReferencesBaptista M. S., Indig G. L. Effect of BSA Binding on Photophysical and Photochemical Properties of Triarylmethane Dyes // The Journal of Physical Chemistry B. – 1998. – Vol. 102(23). – Р. 4678-4688. DOI: 10.1021/jp981185n.Baptista M. S., Indig G. L. Effect of BSA Binding on Photophysical and Photochemical Properties of Triarylmethane Dyes. The Journal of Physical Chemistry B, 1998, Vol. 23 (102), pp. 4678-4688. doi: 10.1021/jp981185n.Gabrielli D., Belisle E., Severino D., Kowaltowski A. J., Baptista M. S. Binding, Aggregation and Photochemical Properties of Methylene Blue in Mitochondrial Suspensions // Photochemistry and Photobiology. – 2004. – Vol. 79(3). – Р. 227. DOI: 10.1562/BE-03-27.1.Gabrielli D., Belisle E., Severino D., Kowaltowski A. J., Baptista M. S. Binding, Aggregation and Photochemical Properties of Methylene Blue in Mitochondrial Suspensions. Photochemistry and Photobiology, 2004. Vol, 3 (79), pp. 227. doi: 10.1562/BE-03-27.1.Красновский А. А. Фотодинамическое действие и синглетный кислород // Биофизика. – 2004. – Т. 49, №2. – Р. 305-322.Krasnovsky A. A. Photodynamic action and singlet oxygen. Biophysics, 2004, Vol. 2 (49). pp. 305-322.Foote C. S. Mechanisms of Photosensitized Oxidation: There are several different types of photosensitized oxidation which may be important in biological systems // Science. – 1968. – Vol. 162(3857). – Р. 963-970. DOI: 10.1126/science.162.3857.963.Foote C. S. Mechanisms of Photosensitized Oxidation: There are several different types of photosensitized oxidation which may be important in biological systems. Science, 1968. Vol. 3857 (162), pp. 963-970. doi: 10.1126/science.162.3857.963.Balzani V., Scandola F. Photochemical electron transfer reactions in homogeneous solution под ред. J. S. Connoly // New York: Academic Press. – 1983. – Р. 97-130.Balzani V., Scandola F. Photochemical electron transfer reactions in homogeneous solution edited by J. S. Connoly. New York: Academic Press, 1983. рp. 97-130.Crous A., Abrahamse H. Photodynamic therapy of lung cancer, where arewe? // Frontiers in Pharmacology. – 2022. – Vol. 13. – Р. 932098. DOI: 10.3389/fphar.2022.932098.Crous A., Abrahamse H. Photodynamic therapy of lung cancer, where are we? Frontiers in Pharmacology, 2022, Vol.13, pp. 932098. doi: 10.3389/fphar.2022.932098.Mfouo-Tynga I. S., Mouinga-Ondeme A. G. Photodynamic Therapy: A Prospective Therapeutic Approach for Viral Infections and Induced Neoplasia. // Pharmaceuticals. – 2022. – Vol. 15( №10). – Р. 1273. DOI: 10.3390/ph15101273.Mfouo-Tynga I. S., Mouinga-Ondeme A. G. Photodynamic Therapy: A Prospective Therapeutic Approach for Viral Infections and Induced Neoplasia. Pharmaceuticals, 2022. Vol. 10 (15), pp. 1273. doi: 10.3390/ph15101273.Reshetov I. V., Korenev S. V., Romanko Yu. S. Modern aspects of photodynamic therapy of basal cell skin cancer. // Biomedical Photonics. – 2022. – Vol. 11( №3). – Р. 35-39. DOI: 10.24931/2413-9432-2022-11-3-35-39.Reshetov I. V., Korenev S. V., Romanko Yu. S. Modern aspects of photodynamic therapy of basal cell skin cancer. Biomedical Photonics, 2022, Vol. 3 (11), pp. 35-39. doi: 10.24931/2413-9432-2022-11-3-35-39.Panaseykin Y. A., Kapinus V. N., Filonenko E. V., Polkin V. V., Sevrukov F. E., Isaev P. A., Ivanov S. A., Kaprin A. D. Photodynamic therapy treatment of oral cavity cancer in patients with comorbidities // Biomedical Photonics. – 2023. – Vol. 11(4). – Р. 19-24. DOI: 10.24931/2413-9432-2022-11-4-19-24.Panaseykin Y. A., Kapinus V. N., Filonenko E. V., Polkin V. V., Sevrukov F. E., Isaev P. A., Ivanov S. A., Kaprin A. D. Photodynamic therapy treatment of oral cavity cancer in patients with comorbidities. Biomedical Photonics, 2023, Vol. 4 (11), pp. 19-24. doi: 10.24931/2413-9432-2022-11-4-19-24.Marr H. E., Stewart J. M., Chiu M. F. The crystal structure of methylene blue pentahydrate // Acta Crystallographica Section B: Structural Crystallography and Crystal Chemistry. – 1973. – Vol. 29(4). – Р. 847-853. DOI: 10.1107/S0567740873003432.Marr H. E., Stewart J. M., Chiu M. F. The crystal structure of methylene blue pentahydrate. Acta Crystallographica Section B: Structural Crystallography and Crystal Chemistry, 1973. Vol. 4 (29), pp. 847-853. doi: 10.1107/S0567740873003432.Hamann C. H., Hamnett A., Vielstich W. Electrochemistry / C. H. Hamann, A. Hamnett, W. Vielstich, 2-е изд., Weinheim: Wiley-VCH, 2007. – Р.531.Hamann C. H., Hamnett A., Vielstich W. Electrochemistry / C. H. Hamann, A. Hamnett, W. Vielstich, 2nd ed. Weinheim: Wiley-VCH, 2007, р. 531.Lewis G. N., Goldschmid O., Magel T. T., Bigeleisen J. Dimeric and Other Forms of Methylene Blue: Absorption and Fluorescence of the Pure Monomer // Journal of the American Chemical Society. – 1943. – Vol. 65(6). – Р. 1150-1154. DOI: 10.1021/ja01246a037.Lewis G. N., Goldschmid O., Magel T. T., Bigeleisen J. Dimeric and Other Forms of Methylene Blue: Absorption and Fluorescence of the Pure Monomer. Journal of the American Chemical Society, 1943, Vol. 6 (65). pp. 1150-1154. doi: 10.1021/ja01246a037.Tacconi N. R. de, Carmona J., Rajeshwar K. Reversibility of Photoelectrochromism at the TiO2/Methylene Blue Interface // Journal of The Electrochemical Society. – 1997. – Vol. 144(7). – Р. 2486. DOI: 10.1149/1.1837841.Tacconi N. R. de, Carmona J., Rajeshwar K. Reversibility of Photoelectrochromism at the TiO2/Methylene Blue Interface. Journal of The Electrochemical Society, 1997, Vol. 7 (144). pp. 2486. doi: 10.1149/1.1837841.Wales D. J., Parker R. M., Gates J. C., Grossel M. C., Smith P. G. R. An integrated bragg grating oxygen sensor using a hydrophobic sol-gel layer doped with an organic dye Munich, Germany: IEEE. – 2011. – Р. 1-1. DOI: 10.1109/CLEOE.2011.5943057.Wales D. J., Parker R. M., Gates J. C., Grossel M. C., Smith P. G. R. An integrated bragg grating oxygen sensor using a hydrophobic sol-gel layer doped with an organic dye Munich. Germany: IEEE, 2011, p. 1-1. doi: 10.1109/CLEOE.2011.5943057.Sevcik P., Dunford H. B. Kinetics of the oxidation of NADH by methylene blue in a closed system // The Journal of Physical Chemistry. – 1991. – Vol. 95(6). – Р. 2411-2415. DOI: 10.1021/j100159a054.Sevcik P., Dunford H. B. Kinetics of the oxidation of NADH by methylene blue in a closed system. The Journal of Physical Chemistry, 1991, Vol. 6 (95), pp. 2411-2415. doi: 10.1021/j100159a054.Engbersen J. F. J., Koudijs A., Van Der Plas H. C. Reaction of NADH models with methylene blue // Recueil des Travaux Chimiques des Pays-Bas. – 2010. – Vol. 104(5). – Р. 131-138. DOI: 10.1002/recl.19851040503.16. Engbersen J. F. J., Koudijs A., Van Der Plas H. C. Reaction of NADH models with methylene blue. Recueil des Travaux Chimiques des Pays-Bas, 2010, Vol. 5 (104), pp. 131-138. doi: 10.1002/recl.19851040503.Schirmer R. H., Adler H., Pickhardt M., Mandelkow E. “Lest we forget you — methylene blue …” // Neurobiology of Aging. – 2011. – Vol. 32(12). – Р. 2325.e7-2325.e16. DOI: 10.1016/j.neurobiolaging.2010.12.012.Schirmer R. H., Adler H., Pickhardt M., Mandelkow E. “Lest we forget you — methylene blue …”. Neurobiology of Aging, 2011, Vol. 12 (32), pp. 2325.e7-2325.e16. doi: 10.1016/j.neurobiolaging.2010.12.012.Brooks M. M. The Mechanism of Methylene Blue Action on Blood. // Science. – 1934. – Vol. 80(2062). – Р. 15-16. DOI: 10.1126/science.80.2062.15.b.Brooks M. M. The Mechanism of Methylene Blue Action on Blood. Science, 1934. Vol. 2062 (80), pp. 15-16. doi: 10.1126/science.80.2062.15.b.Komlódi T., Tretter L. Methylene blue stimulates substrate-level phosphorylation catalysed by succinyl-CoA ligase in the citric acid cycle // Neuropharmacology. – 2017. – Vol. 123. – Р. 287-298. DOI: 10.1016/j.neuropharm.2017.05.009.Komlódi T., Tretter L. Methylene blue stimulates substrate-level phosphorylation catalysed by succinyl-CoA ligase in the citric acid cycle. Neuropharmacology, 2017, Vol. 123, pp. 287-298. doi: 10.1016/j.neuropharm.2017.05.009.Herman M. I., Chyka P. A., Butler A. Y., Rieger S. E. Methylene blue by intraosseous infusion for methemoglobinemia // Annals of Emergency Medicine. – 1999. – Vol. 33(1). – Р. 111-113. DOI: 10.1016/s0196-0644(99)70427-0.Herman M. I., Chyka P. A., Butler A. Y., Rieger S. E. Methylene blue by intraosseous infusion for methemoglobinemia. Annals of Emergency Medicine, 1999, Vol. 1 (33), pp. 111-113. doi: 10.1016/s0196-0644(99)70427-0.Boylston M., Beer D. Methemoglobinemia: A Case Study. // Critical Care Nurse. – 2002. – Vol. 22(4). – Р. 50-55. DOI: 10.4037/ccn2002.22.4.50.Boylston M., Beer D. Methemoglobinemia: A Case Study. Critical Care Nurse, 2002, Vol. 4 (22), pp. 50-55. doi: 10.4037/ccn2002.22.4.50.Wendel W. B. The Control of Methemoglobinemia with Methylene Blue // Journal of Clinical Investigation. – 1939. – Vol. 18(2). – Р. 179-185. DOI: 10.1172/JCI101033.Wendel W. B. The Control of Methemoglobinemia with Methylene Blue. Journal of Clinical Investigation, 1939, Vol. 2 (18). pp. 179-185. doi: 10.1172/JCI101033.Tepaev R. F., Vishnevskiy V. A., Kuzin S. A., Sergey I. V., Gordeeva O. B., Pytal A. V., Murashkin N. N. Benzocaine-Induced Methemoglobinemia. A Clinical Case // Pediatric pharmacology. – 2018. – Vol. 15(5). – Р. 396-401. DOI: 10.15690/pf.v15i5.1962.Tepaev R. F., Vishnevskiy V. A., Kuzin S. A., Sergey I. V., Gordeeva O. B., Pytal A. V., Murashkin N. N. Benzocaine-Induced Methemoglobinemia. A Clinical Case. Pediatric pharmacology, 2018, Vol. 5 (15), pp. 396-401. doi: 10.15690/pf.v15i5.1962.Preiser J.-C., Lejeune P., Roman A., Carlier E., De Backer D., Leeman M., Kahn R. J., Vincent J.-L. Methylene blue administration in septic shock: A clinical trial // Critical Care Medicine. – 1995. – Vol. 23(2). – Р. 259-264. DOI: 10.1097/00003246-199502000-00010.Preiser J.-C., Lejeune P., Roman A., Carlier E., De Backer D., Leeman M., Kahn R. J., Vincent J.-L. Methylene blue administration in septic shock: A clinical trial. Critical Care Medicine, 1995, Vol. 2 (23), pp. 259-264. doi: 10.1097/00003246-199502000-00010.Zhang H., Rogiers P., Preiser J.-C., Spapen H., Manikis P., Metz G., Vincent J.-L. Effects of methylene blue on oxygen availability and regional blood flow during endotoxic shock: // Critical Care Medicine. – 1995. – Vol. 23(10). – Р. 1711-1721. DOI: 10.1097/00003246-199510000-00016.Zhang H., Rogiers P., Preiser J.-C., Spapen H., Manikis P., Metz G., Vincent J.-L. Effects of methylene blue on oxygen availability and regional blood flow during endotoxic shock. Critical Care Medicine, 1995, Vol. 10 (23), pp. 1711-1721. doi: 10.1097/00003246-199510000-00016.Tranquada R. E., Bernstein S., Grant W. J. Intravenous Methylene Blue in The Therapy of Lactic Acidosis. // Archives of Internal Medicine. – 1964. – Vol. 114(1). – Р. 13-25. DOI: 10.1001/archinte.1964.03860070059003.Tranquada R. E., Bernstein S., Grant W. J. Intravenous Methylene Blue in The Therapy of Lactic Acidosis. Archives of Internal Medicine, 1964, Vol. 1 (114), pp. 13-25. doi: 10.1001/archinte.1964.03860070059003.Bell M. A. Methylene Blue in Carbon Monoxide Poisoning. // JAMA: The Journal of the American Medical Association. – 1933. – Vol. 100(18). – Р. 1402. DOI: 10.1001/jama.1933.27420180002007b.Bell M. A. Methylene Blue in Carbon Monoxide Poisoning. JAMA: The Journal of the American Medical Association, 1933, Vol. 18 (100), pp. 1402. doi: 10.1001/jama.1933.27420180002007b.Wendel W. B. The Mechanism of the Antidotal Action of Methylene Blue in Cyanide Poisoning. // Science. – 1934. – Vol. 80(2078). – Р. 381-382. DOI: 10.1126/science.80.2078.381.Wendel W. B. The Mechanism of the Antidotal Action of Methylene Blue in Cyanide Poisoning. Science, 1934, Vol. 2078 (80), pp. 381-382. doi: 10.1126/science.80.2078.381.Chen K. K. Nitrite and Thiosulfate Therapy in Cyanide Poisoning. // Journal of the American Medical Association. – 1952. – Vol. 149(2). – Р. 113. DOI: 10.1001/jama.1952.02930190015004.Chen K. K. Nitrite and Thiosulfate Therapy in Cyanide Poisoning. Journal of the American Medical Association, 1952, Vol. 2 (149), pp. 113. doi: 10.1001/jama.1952.02930190015004.Barron E. S. G. The Catalytic Effect of Methylene Blue on the Oxygen Consumption of Tumors and Normal Tissues. // Journal of Experimental Medicine. – 1930. – Vol. 52(3). – Р. 447-456. DOI: 10.1084/jem.52.3.447.Barron E. S. G. The Catalytic Effect of Methylene Blue on the Oxygen Consumption of Tumors and Normal Tissues. Journal of Experimental Medicine, 1930, Vol. 3 (52), pp. 447-456. doi: 10.1084/jem.52.3.447.Park J., Mroz P., Hamblin M. R., Yaroslavsky A. N. Dye-enhanced multimodal confocal microscopy for noninvasive detection of skin cancers in mouse models // Journal of Biomedical Optics. – 2010. – Vol. 15(2). – Р. 026023. DOI: 10.1117/1.3394301.Park J., Mroz P., Hamblin M. R., Yaroslavsky A. N. Dye-enhanced multimodal confocal microscopy for noninvasive detection of skin cancers in mouse models. Journal of Biomedical Optics, 2010, Vol. 2 (15), pp. 026023. doi: 10.1117/1.3394301.Wainwright M., Crossley K. B. Methylene Blue – a Therapeutic Dye for All Seasons? // Journal of Chemotherapy. – 2002. – Vol. 14(5). – Р. 431-443. DOI: 10.1179/joc.2002.14.5.431.Wainwright M., Crossley K. B. Methylene Blue – a Therapeutic Dye for All Seasons? Journal of Chemotherapy, 2002, Vol. 5 (14), pp. 431-443. doi: 10.1179/joc.2002.14.5.431.Orth K., Russ D., Beck G., Rück A., Beger H. G. Photochemotherapy of experimental colonic tumours with intra-tumorally applied methylene blue. // Langenbeck’s Archives of Surgery. – 1998. – Vol. 383(3-4). – Р. 276-281. DOI: 10.1007/s004230050132.Orth K., Russ D., Beck G., Rück A., Beger H. G. Photochemotherapy of experimental colonic tumours with intra-tumorally applied methylene blue. Langenbeck’s Archives of Surgery, 1998, Vol. 34 (383), pp. 276-281. doi: 10.1007/s004230050132.König K., Bockhorn V., Dietel W., Schubert H. Photochemotherapy of animal tumors with the photosensitizer Methylene Blue using a krypton laser. // Journal of Cancer Research and Clinical Oncology. – 1987. – Vol. 113(3). – Р. 301-303. DOI: 10.1007/BF00396390.König K., Bockhorn V., Dietel W., Schubert H. Photochemotherapy of animal tumors with the photosensitizer Methylene Blue using a krypton laser. Journal of Cancer Research and Clinical Oncology, 1987, Vol. 3 (113). pp. 301-303. doi: 10.1007/BF00396390.Tardivo J. P., Del Giglio A., Paschoal L. H. C., Ito A. S., Baptista M. S. Treatment of melanoma lesions using methylene blue and RL50 light source. // Photodiagnosis and Photodynamic Therapy. – 2004. – Vol. 1(4). – Р. 345-346. DOI: 10.1016/S1572-1000(05)00005-0.35. Tardivo J. P., Del Giglio A., Paschoal L. H. C., Ito A. S., Baptista M. S. Treatment of melanoma lesions using methylene blue and RL50 light source. Photodiagnosis and Photodynamic Therapy, 2004, Vol. 4 (1). pp. 345-346. doi: 10.1016/S1572-1000(05)00005-0.Tardivo J. P., Del Giglio A., De Oliveira C. S., Gabrielli D. S., Junqueira H. C., Tada D. B., Severino D., De Fátima Turchiello R., Baptista M. S. Methylene blue in photodynamic therapy: From basic mechanisms to clinical applications // Photodiagnosis and Photodynamic Therapy. – 2005. – Vol. 2(3). – Р. 175-191. DOI: 10.1016/S1572-1000(05)00097-9.36. Tardivo J. P., Del Giglio A., De Oliveira C. S., Gabrielli D. S., Junqueira H. C., Tada D. B., Severino D., De Fátima Turchiello R., Baptista M. S. Methylene blue in photodynamic therapy: From basic mechanisms to clinical applications. Photodiagnosis and Photodynamic Therapy, 2005, Vol. 3 (2). pp. 175-191. doi: 10.1016/S1572-1000(05)00097-9.Wainwright M. Methylene blue derivatives – suitable photoantimicrobials for blood product disinfection? // International Journal of Antimicrobial Agents. – 2000. – Vol. 16(4). – Р. 381-394. DOI: 10.1016/S0924-8579(00)00207-7.Wainwright M. Methylene blue derivatives – suitable photoantimicrobials for blood product disinfection? International Journal of Antimicrobial Agents, 2000, Vol. 4 (16), pp. 381-394. doi: 10.1016/S0924-8579(00)00207-7.Wagner S. J. Virus inactivation in blood components by photoactive phenothiazine dyes // Transfusion Medicine Reviews. – 2002. – Vol. 16(1). – Р. 61-66. DOI: 10.1053/tmrv.2002.29405.Wagner S. J. Virus inactivation in blood components by photoactive phenothiazine dyes. Transfusion Medicine Reviews, 2002, Vol. 1 (16). pp. 61-66. doi: 10.1053/tmrv.2002.29405.Calderón M., Weitzel T., Rodriguez M. F., Ciapponi A. Methylene blue for treating malaria // Cochrane Database of Systematic Reviews. – 2017. – Vol. 2022(6). DOI: 10.1002/14651858.CD012837.Calderón M., Weitzel T., Rodriguez M. F., Ciapponi A. Methylene blue for treating malaria. Cochrane Database of Systematic Reviews, 2017, Vol. 6 (2022). doi: 10.1002/14651858.CD012837.Dewitt L. M. Preliminary Report of Experiments in the Vital Staining of Tubercles: Studies on the Biochemistry and Chemotherapy of Tuberculosis. IV // Journal of Infectious Diseases. – 1913. – Vol. 12(1). – Р. 68-92. DOI: 10.1093/infdis/12.1.68.Dewitt L. M. Preliminary Report of Experiments in the Vital Staining of Tubercles: Studies on the Biochemistry and Chemotherapy of Tuberculosis. IV. Journal of Infectious Diseases, 1913, Vol. 1 (12), pp. 68-92. doi: 10.1093/infdis/12.1.68.Wainwright M., Phoenix D. A., Laycock S. L., Wareing D. R. A., Wright P. A. Photobactericidal activity of phenothiazinium dyes against methicillin-resistant strains of Staphylococcus aureus // FEMS Microbiology Letters. – 1998. – Vol. 160(2). – Р. 177-181. DOI: 10.1111/j.1574-6968.1998.tb12908.x.Wainwright M., Phoenix D. A., Laycock S. L., Wareing D. R. A., Wright P. A. Photobactericidal activity of phenothiazinium dyes against methicillin-resistant strains of Staphylococcus aureus. FEMS Microbiology Letters, 1998, Vol. 2 (160), pp. 177-181. doi: 10.1111/j.1574-6968.1998.tb12908.xPascual A., Henry M., Briolant S., Charras S., Baret E., Amalvict R., Huyghues Des Etages E., Feraud M., Rogier C., Pradines B. In Vitro Activity of Proveblue (Methylene Blue) on Plasmodium falciparum Strains Resistant to Standard Antimalarial Drugs // Antimicrobial Agents and Chemotherapy. – 2011. – Vol. 55(5). – Р. 2472-2474. DOI: 10.1128/AAC.01466-10.Pascual A., Henry M., Briolant S., Charras S., Baret E., Amalvict R., Huyghues Des Etages E., Feraud M., Rogier C., Pradines B. In Vitro Activity of Proveblue (Methylene Blue) on Plasmodium falciparum Strains Resistant to Standard Antimalarial Drugs. Antimicrobial Agents and Chemotherapy, 2011, Vol. 5 (55), pp. 2472-2474. doi: 10.1128/AAC.01466-10.Tiganova I. G., Meerovich G. A., Zulufova I. D., Akhlyustina E. V., Ovchinnikov R. S., Solovyev A. I., Romanishkin I. D., Kozlikina E. I., Nekhoroshev A. V., Glechik D. A., Parshin A. V., Parshin V. D., Romanova Y. M., Loschenov V. B. On the possibility of photodynamic inactivation of tracheobronchial tree pathogenic microbiota using methylene blue (in vitro study) // Photodiagnosis and Photodynamic Therapy. – 2022. – Vol. 38. – Р. 102753. DOI: 10.1016/j.pdpdt.2022.102753.Tiganova I. G., Meerovich G. A., Zulufova I. D., Akhlyustina E. V., Ovchinnikov R. S., Solovyev A. I., Romanishkin I. D., Kozlikina E. I., Nekhoroshev A. V., Glechik D. A., Parshin A. V., Parshin V. D., Romanova Y. M., Loschenov V. B. On the possibility of photodynamic inactivation of tracheobronchial tree pathogenic microbiota using methylene blue (in vitro study). Photodiagnosis and Photodynamic Therapy, 2022, Vol. 38, pp. 102753. doi: 10.1016/j.pdpdt.2022.102753.Shen X., Dong L., He X., Zhao C., Zhang W., Li X., Lu Y. Treatment of infected wounds with methylene blue photodynamic therapy: An effective and safe treatment method // Photodiagnosis and Photodynamic Therapy. – 2020. – Vol. 32. – Р. 102051. DOI: 10.1016/j.pdpdt.2020.102051.Shen X., Dong L., He X., Zhao C., Zhang W., Li X., Lu Y. Treatment of infected wounds with methylene blue photodynamic therapy: An effective and safe treatment method. Photodiagnosis and Photodynamic Therapy, 2020, Vol. 32, pp. 102051. doi: 10.1016/j.pdpdt.2020.102051.Severino D., Junqueira H. C., Gugliotti M., Gabrielli D. S., Baptista M. S. Influence of Negatively Charged Interfaces on the Ground and Excited State Properties of Methylene Blue. // Photochemistry and Photobiology. – 2003. – Vol. 77(5). – Р. 459-468. DOI: 10.1562/0031-8655(2003)0770459IONCIO2.0.CO2.Severino D., Junqueira H. C., Gugliotti M., Gabrielli D. S., Baptista M. S. Influence of Negatively Charged Interfaces on the Ground and Excited State Properties of Methylene Blue. Photochemistry and Photobiology, 2003, Vol. 5 (77), pp. 459-468. doi: 10.1562/0031-8655(2003)0770459IONCIO2.0.CO2.Murov S. L., Hug G. L., Carmichael I. Handbook of photochemistry / S. L. Murov, G. L. Hug, I. Carmichael, 2-е изд., New York: M. Dekker. – 1993. – Р. 420.Murov S. L., Hug G. L., Carmichael I. Handbook of photochemistry / S. L. Murov, G. L. Hug, I. Carmichael, 2 ed. New York: M. Dekker, 1993, p. 420.Wang W., Zhang W., Sun H., Du Q., Bai J., Ge X., Li C. Enhanced photodynamic efficiency of methylene blue with controlled aggregation state in silica-methylene bule-acetate@tannic acidiron(III) ions complexes // Dyes and Pigments. – 2019. – Vol. 160. – Р. 663-670. DOI: 10.1016/j.dyepig.2018.08.068.Wang W., Zhang W., Sun H., Du Q., Bai J., Ge X., Li C. Enhanced photodynamic efficiency of methylene blue with controlled aggregation state in silica-methylene bule-acetate@tannic acidiron(III) ions complexes. Dyes and Pigments, 2019, Vol. 160, pp. 663-670. doi: 10.1016/j.dyepig.2018.08.068.Dean J. C., Oblinsky D. G., Rafiq S., Scholes G. D. Methylene Blue Exciton States Steer Nonradiative Relaxation: Ultrafast Spectroscopy of Methylene Blue Dimer. // The Journal of Physical Chemistry B. – 2016. – Vol. 120(3). – Р. 440-454. DOI: 10.1021/acs.jpcb.5b11847.Dean J. C., Oblinsky D. G., Rafiq S., Scholes G. D. Methylene Blue Exciton States Steer Nonradiative Relaxation: Ultrafast Spectroscopy of Methylene Blue Dimer. The Journal of Physical Chemistry B, 2016, Vol. 3 (120), pp. 440-454. doi: 10.1021/acs.jpcb.5b11847.Coronel A., Catalán-Toledo J., Fernández-Jaramillo H., GodoyMartínez P., Flores M. E., Moreno-Villoslada I. Photodynamic action of methylene blue subjected to aromatic-aromatic interactions with poly(sodium 4-styrenesulfonate) in solution and supported in solid, highly porous alginate sponges. // Dyes and Pigments. – 2017. – Vol. 147. – Р. 455-464. DOI: 10.1016/j.dyepig.2017.08.042.Coronel A., Catalán-Toledo J., Fernández-Jaramillo H., GodoyMartínez P., Flores M. E., Moreno-Villoslada I. Photodynamic action of methylene blue subjected to aromatic-aromatic interactions with poly(sodium 4-styrenesulfonate) in solution and supported in solid, highly porous alginate sponges. Dyes and Pigments, 2017, Vol. 147, pp. 455-464. doi: 10.1016/j.dyepig.2017.08.042.Junqueira H. C., Severino D., Dias L. G., Gugliotti M. S., Baptista M. S. Modulation of methylene blue photochemical properties based on adsorption at aqueous micelle interfaces. // Physical Chemistry Chemical Physics. – 2002. – Vol. 4(11). – Р. 2320-2328. DOI: 10.1039/b109753a.50. Junqueira H. C., Severino D., Dias L. G., Gugliotti M. S., Baptista M. S. Modulation of methylene blue photochemical properties based on adsorption at aqueous micelle interfaces. Physical Chemistry Chemical Physics, 2002, Vol. 11 (4), pp. 2320-2328. doi: 10.1039/b109753a.Bonneau R., Pottier R., Bagno O., Joussot-Dubien J. pH Dependence of Singlet Oxygen Production in Aqueous Solutions Using Thiazine Dyes as Photosensitizers. // Photochemistry and Photobiology. – 1975. – Vol. 21(3). – Р. 159-163. DOI: 10.1111/j.1751-1097.1975.tb06646.x.Bonneau R., Pottier R., Bagno O., Joussot-Dubien J. pH Dependence of Singlet Oxygen Production in Aqueous Solutions Using Thiazine Dyes as Photosensitizers. Photochemistry and Photobiology, 1975, Vol. 3 (21), pp. 159-163. doi: 10.1111/j.1751-1097.1975.tb06646.x.Patil K., Pawar R., Talap P. Self-aggregation of Methylene Blue in aqueous medium and aqueous solutions of Bu4NBr and urea. // Physical Chemistry Chemical Physics. – 2000. – Vol. 2(19). – Р. 4313-4317. DOI: 10.1039/b005370h.Patil K., Pawar R., Talap P. Self-aggregation of Methylene Blue in aqueous medium and aqueous solutions of Bu4NBr and urea. Physical Chemistry Chemical Physics, 2000, Vol. 19 (2), pp. 4313-4317. doi: 10.1039/b005370h.Zhao Z., Malinowski E. R. Determination of the Hydration of Methylene Blue Aggregates and Their Dissociation Constants Using Visible Spectroscopy. // Applied Spectroscopy. – 1999. – Vol. 53(12). – Р. 1567-1574. DOI: 10.1366/0003702991946028.Zhao Z., Malinowski E. R. Determination of the Hydration of Methylene Blue Aggregates and Their Dissociation Constants Using Visible Spectroscopy. Applied Spectroscopy, 1999, Vol. 12 (53), pp. 1567-1574. doi: 10.1366/0003702991946028.Moreno-Villoslada I., Torres C., González F., Shibue T., Nishide H. Binding of Methylene Blue to Polyelectrolytes Containing Sulfonate Groups: Binding of Methylene Blue to Polyelectrolytes Containing …. // Macromolecular Chemistry and Physics. – 2009. – Vol. 210(13-14). – Р. 1167-1175. DOI: 10.1002/macp.200900042.54. Moreno-Villoslada I., Torres C., González F., Shibue T., Nishide H. Binding of Methylene Blue to Polyelectrolytes Containing Sulfonate Groups: Binding of Methylene Blue to Polyelectrolytes Containing … Macromolecular Chemistry and Physics, 2009, Vol. 13-14 (210), pp. 1167-1175. doi: 10.1002/macp.200900042.Moreno-Villoslada I., Torres-Gallegos C., Araya-Hermosilla R., Nishide H. Influence of the Linear Aromatic Density on Methylene Blue Aggregation around Polyanions Containing Sulfonate Groups. // The Journal of Physical Chemistry B. – 2010. – Vol. 114(12). – Р. 4151-4158. DOI: 10.1021/jp909105r.55. Moreno-Villoslada I., Torres-Gallegos C., Araya-Hermosilla R., Nishide H. Influence of the Linear Aromatic Density on Methylene Blue Aggregation around Polyanions Containing Sulfonate Groups. The Journal of Physical Chemistry B, 2010, Vol. 12 (114), pp. 4151-4158. doi: 10.1021/jp909105r.Aznar A. J., Casal B., Ruiz-Hitzky E., Lopez-Arbeloa I., LopezArbeloa F., Santaren J., Alvarez A. Adsorption of methylene blue on sepiolite gels: spectroscopic and rheological studies. // Clay Minerals. – 1992. – Vol. 27(1). – Р. 101-108. DOI: 10.1180/claymin.1992.027.1.10.Aznar A. J., Casal B., Ruiz-Hitzky E., Lopez-Arbeloa I., LopezArbeloa F., Santaren J., Alvarez A. Adsorption of methylene blue on sepiolite gels: spectroscopic and rheological studies. Clay Minerals, 1992, Vol. 1 (27), pp. 101-108. doi: 10.1180/claymin.1992.027.1.10.Bergmann K., O’Konski C. T. A Spectroscopic Study of Methylene Blue Monomer, Dimer, and Complexes with Montmorillonite. // The Journal of Physical Chemistry. – 1963. – Vol. 67(10). – Р. 2169-2177. DOI: 10.1021/j100804a048.Bergmann K., O’Konski C. T. A Spectroscopic Study of Methylene Blue Monomer, Dimer, and Complexes with Montmorillonite. The Journal of Physical Chemistry, 1963, Vol. 10 (67), pp. 2169-2177. doi: 10.1021/j100804a048.Lemin D. R., Vickerstaff T. The aggregation of direct dyes and of Methylene Blue 2B in aqueous solution. // Transactions of the Faraday Society. – 1947. – Vol. 43. – №0. – Р. 491-502. DOI: 10.1039/TF9474300491.Lemin D. R., Vickerstaff T. The aggregation of direct dyes and of Methylene Blue 2B in aqueous solution. Transactions of the Faraday Society, 1947, Vol. 0 (43), pp. 491-502. doi: 10.1039/TF9474300491.Heger D., Jirkovský J., Klán P. Aggregation of Methylene Blue in Frozen Aqueous Solutions Studied by Absorption Spectroscopy. // The Journal of Physical Chemistry A. – 2005. – Vol. 109(30). – Р. 6702-6709. DOI: 10.1021/jp050439j.Heger D., Jirkovský J., Klán P. Aggregation of Methylene Blue in Frozen Aqueous Solutions Studied by Absorption Spectroscopy. The Journal of Physical Chemistry A, 2005, Vol. 30 (109), pp. 6702-6709. doi: 10.1021/jp050439j.Braswell E. Evidence for trimerization in aqueous solutions of methylene blue. // The Journal of Physical Chemistry. – 1968. – Vol. 72(7). – Р. 2477-2483. DOI: 10.1021/j100853a035.Braswell E. Evidence for trimerization in aqueous solutions of methylene blue. The Journal of Physical Chemistry, 1968, Vol. 7 (72), pp. 2477-2483. doi: 10.1021/j100853a035.Klika Z., Čapková P., Horáková P., Valášková M., Malý P., Macháň R., Pospíšil M. Composition, structure, and luminescence of montmorillonites saturated with different aggregates of methylene blue. // Journal of Colloid and Interface Science. – 2007. – Vol. 311(1). – Р. 14-23. DOI: 10.1016/j.jcis.2007.02.034.Klika Z., Čapková P., Horáková P., Valášková M., Malý P., Macháň R., Pospíšil M. Composition, structure, and luminescence of montmorillonites saturated with different aggregates of methylene blue. Journal of Colloid and Interface Science, 2007, Vol. 1 (311), pp. 14-23. doi: 10.1016/j.jcis.2007.02.034.Zhikhoreva A. A., Belashov A. V., Serebryakov E. B., Semenova I. V., Vasyutinskii O. S. Photophysical properties of methylene blue in aqueous solution sprayed onto biological surfaces. // Dyes and Pigments. – 2022. – Vol. 208. – Р. 110789. DOI: 10.1016/j.dyepig.2022.110789.Zhikhoreva A. A., Belashov A. V., Serebryakov E. B., Semenova I. V., Vasyutinskii O. S. Photophysical properties of methylene blue in aqueous solution sprayed onto biological surfaces. Dyes and Pigments, 2022, Vol. 208, pp. 110789. doi: 10.1016/j.dyepig.2022.110789.Walter-Sack I., Rengelshausen J., Oberwittler H., Burhenne J., Mueller O., Meissner P., Mikus G. High absolute bioavailability of methylene blue given as an aqueous oral formulation. // European Journal of Clinical Pharmacology. – 2009. – Vol. 65(2). – Р. 179-189. DOI: 10.1007/s00228-008-0563-x.Walter-Sack I., Rengelshausen J., Oberwittler H., Burhenne J., Mueller O., Meissner P., Mikus G. High absolute bioavailability of methylene blue given as an aqueous oral formulation. European Journal of Clinical Pharmacology, 2009, Vol. 2 (65), pp. 179-189. doi: 10.1007/s00228-008-0563-x.Peter C., Hongwan D., Küpfer A., Lauterburg B. H. Pharmacokinetics and organ distribution of intravenous and oral methylene blue. // European Journal of Clinical Pharmacology. – 2000. – Vol. 56(3). – Р. 247-250. DOI: 10.1007/s002280000124.Peter C., Hongwan D., Küpfer A., Lauterburg B. H. Pharmacokinetics and organ distribution of intravenous and oral methylene blue. European Journal of Clinical Pharmacology, 2000, Vol. 3 (56), pp. 247-250. doi: 10.1007/s002280000124.Ryabova A. V., Stratonnikov A. A., Loshchenov V. B. Laser spectroscopy technique for estimating the efficiency of photosensitisers in biological media. // Quantum Electronics. – 2006. – Vol. 36(6). – Р. 562-568. DOI: 10.1070/ QE2006v036n06Ryabova A. V., Stratonnikov A. A., Loshchenov V. B. Laser spectroscopy technique for estimating the efficiency of photosensitisers in biological media. Quantum Electronics, 2006, Vol. 6 (36), pp. 562-568. doi: 10.1070/QE2006v036n06ABEH013291.ABEH013291.Redmond R. W., Gamlin J. N. A Compilation of Singlet Oxygen Yields from Biologically Relevant Molecules. // Photochemistry and Photobiology. – 1999. – Vol. 70(4). – Р. 391-475. DOI: 10.1111/j.1751-1097.1999.tb08240.x.Redmond R. W., Gamlin J. N. A Compilation of Singlet Oxygen Yields from Biologically Relevant Molecules. Photochemistry and Photobiology, 1999, Vol. 4 (70), pp. 391-475. doi: 10.1111/j.1751-1097.1999.tb08240.x.

The authors declare that there are no conflicts of interest present.