biophBiomedical PhotonicsBiomedical Photonics2413-9432Non-profit partnership for development of domestic photodynamic therapy and photodiagnosis10.24931/2413-9432-2024-13-2-9-18bioph-648Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESФотодинамическая терапия с фотосенсибилизаторами метиленовый синий и хлорин е6: исследование на мышиной модели карциномы ЭрлихаPhotodynamic therapy with methylene blue and chlorin e6 photosensitizers: study on Ehrlich carcinoma mice modelПоминоваД. В.PominovaD. V.

Москва

Moscow

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

Москва

Moscow

СкобельцинА. С.SkobeltsinA. S.

Москва

Moscow

МарковаИ. В.MarkovaI. V.

Москва

Moscow

РоманишкинИ. Д.RomanishkinI. D.

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 Federation202431072024132918Copyright © Поминова Д.В., Рябова А.В., Скобельцин А.С., Маркова И.В., Романишкин И.Д., 20242024Поминова Д.В., Рябова А.В., Скобельцин А.С., Маркова И.В., Романишкин И.Д.Pominova D.V., Ryabova A.V., Skobeltsin A.S., Markova I.V., Romanishkin I.D.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/648

Гипоксия негативно влияет на эффективность всех видов противоопухолевой терапии, в частности фотодинамической терапии (ФДТ).

В связи с этим в литературе широко обсуждаются разные подходы для преодоления ограничений, связанных с гипоксией. Одним из них является использование фотосенсибилизаторов (ФС), работающих по первому механизму фотодинамической реакции, таких как метиленовый синий (МС). Ранее нами было показано, что МС может положительно влиять на оксигенацию опухоли. В данной работе мы провели исследование фотодинамической активности МС и МС в комбинации с хлорином е6 на опухоли in vivo на модели карциномы Эрлиха. Была исследована ФДТ при совместном и раздельном введении хлорина е6 и МC. Выполнена оценка накопления и локализации МС и МС в комбинации с хлорином е6 in vivo при помощи видеофлуоресцентных и спектроскопических методов, проанализировано влияние лазерного воздействия на накопление. После проведения ФДТ с хлорином е6, МС и комбинации МС с хлорином е6 отмечен хороший терапевтический эффект и уменьшение скорости роста опухоли по сравнению с контролем, особеннов группах с ФДТ с МС и при одновременном введении хлорина е6 и МС. Уровень оксигенации опухоли на 3-е и 5-е сутки после ФДТ был выше в группах с облучением, самая высока оксигенация на 5-е сутки после ФДТ отмечена в группе с ФДТ с МC. На фазорных диаграммах опухолей после проведения ФДТ наблюдается отклонение от метаболической траектории и сдвиг в сторону более длинного времени жизни по сравнению с контрольной опухолью, что указывает на наличие продуктов перекисного окисления липидов.

Следовательно, регрессия опухоли после ФДТ связана с прямым разрушением опухолевых клеток под воздействием активных форм кислорода, образующихся при ФДТ. Таким образом, продемонстрирована эффективность ФДТ при совместном применении МВ и хлорина е6 и исследованы основные механизмы противоопухолевого действия комбинации этих ФС.

Hypoxia negatively affcts the effctiveness of all types of anticancer therapy, in particular photodynamic therapy (PDT). In this regard, various approaches to overcome the limitations associated with hypoxia are widely discussed in the literature, one of them is the use of photosensitizers (PS) operating through the fist mechanism of the photodynamic reaction, such as methylene blue (MB). Previously, we have demonstrated that MB can have a positive effect on tumor oxygenation. In this work, we investigated the photodynamic activity of MB and a combination of MB with chlorin e6 on a tumor in vivo using a model of Ehrlich carcinoma. PDT was studied with the joint and separate administration of chlorin e6 and MB. The accumulation and localization of MB and its combination with chlorin e6 in vivo was assessed using video ˛uorescence and spectroscopic methods, and the effect of laser exposure on accumulation was analyzed. After the PDT with chlorin e6, MB and a combination of MB with chlorin e6, a good therapeutic effect and a decrease in the tumor growth rate were observed compared to the control, especially in groups with PDT with MB and with the simultaneous administration of chlorin e6 and MB. The level of tumor oxygenation on days 3 and 5 after PDT was higher for groups with irradiation, the highest oxygenation on the 5th day after PDT was observed in the group with PDT only with MB. Phasor diagrams of tumors after PDT show a deviation from the metabolic trajectory and a shift towards a longer lifetimes compared to the control tumor, which indicates the presence of lipid peroxidation products. Thus, tumor regression after PDT is associated with the direct destruction of tumor cells under the in˛uence of reactive oxygen species formed during PDT. Thus, the effectiveness of PDT with the combined use of MB and chlorin e6 has been demonstrated, and the main mechanisms of the antitumor effect of the combination of these PS have been studied.

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