biophBiomedical PhotonicsBiomedical Photonics2413-9432Non-profit partnership for development of domestic photodynamic therapy and photodiagnosis10.24931/2413-9432-2017-6-2-4-11bioph-158Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESИССЛЕДОВАНИЕ РАСПРЕДЕЛЕНИЯ ХЛОРИНОВЫХ ФОТОСЕНСИБИЛИЗАТОРОВ В ДВУХМЕРНЫХ И ТРЕХМЕРНЫХ КЛЕТОЧНЫХ КУЛЬТУРАХINVESTIGATION OF CHLORIN PHOTOSENSITIZERS DISTRIBUTION IN MONOLAYER AND SPHEROID CELL CULTURESФарраховаД. С.FarrakhovaD. S.

Москва

Moscow

ЯковецМ. В.YakavetsI. V.

Минск, Nancy, Vandoeuvre-lès-Nancy

Minsk, Nancy, Vandoeuvre-lès-Nancy

ЛощеновВ. Б.LoschenovV. B.

Москва

Moscow

BolotineL. N.BolotineL. N.

Nancy, Vandoeuvre-lès-Nancy

Nancy, Vandoeuvre-lès-Nancy

ЗоринВ. П.ZorinV. P.

Минск

Minsk

vpzorin@mail.ruНациональный исследовательский ядерный университет МИФИ; Институт общей физики им. А.М. Прохорова РАНРоссияNational Research Nuclear University MEPhI (Moscow Engineering Physics Institute); General Physics Institute of the Russian Academy of SciencesRussian FederationБелорусский государственный университет; Centre de Recherche en Automatique de Nancy, Université de Lorraine; Institut de Cancérologie de LorraineБеларусьBelarusian State University; Centre de Recherche en Automatique de Nancy, Université de Lorraine; Institut de Cancérologie de LorraineBelarusCentre de Recherche en Automatique de Nancy, Université de Lorraine; Institut de Cancérologie de LorraineРоссияCentre de Recherche en Automatique de Nancy, Université de Lorraine; Institut de Cancérologie de LorraineRussian FederationБелорусский государственный университет; Международный государственный экологический институт им. А.Д. Сахарова Белорусского государственного университетаБеларусьBelarusian State UniversityBelarus20170409201762411Copyright © Фаррахова Д.С., Яковец М.В., Лощенов В.Б., Bolotine L.N., Зорин В.П., 20172017Фаррахова Д.С., Яковец М.В., Лощенов В.Б., Bolotine L.N., Зорин В.П.Farrakhova D.S., Yakavets I.V., Loschenov V.B., Bolotine L.N., Zorin V.P.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/158

Цель  данного  исследования   заключалась  в  оценке  распределения  хлориновых  фотосенсибилизаторов  –  хлорина  е6    (Ce6) и  его диметилового  эфира  (DME) – в клетках НТ29 аденокарциномы человека  в моделях  монослоя  клеток и мультиклеточных сфероидах. Согласно полученным данным, DME накапливается  в 2,3 раза  более  эффективно в клетках монослоя  по сравнению  с Ce6. Высказано предположение,  что химическая модификация молекул Ce6 приводит к изменению внутриклеточной локализации, а также к увеличению фотосенсибилизирующей активности. Так, проведение фотодинамической терапии на клетках монослоя с использованием DME показало увеличение способности к фотоповреждению  более чем в 2 раза по сравнению с его немодифицированным аналогом.

Процессы распределения DME и Ce6 в опухолевой  ткани были изучены на модели  мультиклеточных опухолевых сфероидов.  Общее количество  DME в опухолевых сфероидах  превышало  накопление  Ce6 в 1,3 раза.  Согласно данным  флуоресцентной  микроскопии, характер  распределения Ce6 и DME в сфероидах  не отличается. Использование  двухи трёхмерных моделей  для анализа  процессов связывания фотосенсибилизаторов может позволить прогнозировать особенности процессов распределения фотосенсибилизаторов при проведении фотодинамической терапии in vivo.

The aim of this study was to analyze the distribution of chlorin type photosensitizers (PS): chlorin e6 (Ce6) and dimethyl ester of chlorin e6 (DME), in human  adenocarcinoma HT29 monolayer and multicellular spheroid cell cultures. There is an assumption,  that the chemical modification of Ce6 molecules  causes a change  of intracellular location and the enhanced photosensitizing activity. Indeed, photodynamic therapy  on monolayer cell culture with DME showed two times higher photokilling ability comparing with that of non-modified analogue.

Ce6 and  DME biodistribution  processes  in tumor  tissue  were studied  on multicellular tumor  spheroids  model. Total amount  of DME in multicellular  tumor  spheroids  exceeded 1,3 times  accumulation  of Ce6. According  to  fluorescence  microscopy  studies, Ce6 and  DME distribution patterns in the spheroids bulk were similar. Application of 2D and 3D tumor models for the analysis of photosensitizer distribution may allow predicting the photosensitizer biodistribution  features for photodynamic therapy in vivo.

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