БИОХИМИЯ, 2022, том 87, вып. 11, с. 1533–1553

УДК 615.033.1

Биохимические основы селективного накопления и таргетной доставки фотосенсибилизаторов в опухолевые ткани

Обзор

© 2022 В.И. Иванова-Радкевичivanova-radkevich-vi@rudn.ru

Российский университет дружбы народов (РУДН), 117198 Москва, Россия

Поступила в редакцию 01.06.2022
После доработки 17.08.2022
Принята к публикации 06.09.2022

DOI: 10.31857/S032097252211001X

КЛЮЧЕВЫЕ СЛОВА: фотодинамическая терапия, фотосенсибилизатор, таргетная доставка, селективность, хлорин, аминолевулиновая кислота.

Аннотация

Одним из ключевых параметров фотодинамической терапии злокачественных новообразований является селективность накопления фотосенсибилизаторов в опухолевой ткани. Недостаточная избирательность фотосенсибилизаторов по отношению к патологически измененным тканям и генерализованное распространение по организму приводит к развитию тяжелых токсических эффектов, в том числе кожной фототоксичности. Механизмы селективности фотосенсибилизаторов в отношении опухолевой ткани включают избирательное связывание с белками и липопротеинами крови, количество рецепторов к которым увеличено на мембранах опухолевых клеток, поглощение макрофагами в опухоли, лучшую растворимость при низком рН, характерном для опухолевых клеток, и другие механизмы. В настоящее время повышение эффективности фотодинамической терапии во многом связывают с дополнительным нацеливанием фотосенсибилизаторов на ткани опухоли. Стратегии таргетной доставки основываются на различиях в метаболизме и профилях экспрессии опухолевых и здоровых клеток. В этих клетках могут по-разному экспрессироваться рецепторы, протеазы или трансмембранные переносчики. В частности, ускоренный метаболизм у многих типов опухолей приводит к гиперэкспрессии рецепторов эпидермального фактора роста, фолиевой килоты, трансферрина и ряда других соединений. В настоящем обзоре рассмотрены биохимические основы избирательного накопления в опухолях фотосенсибилизаторов разных классов (хлорины, фталоцианины, производные 5‑аминолевулиновой кислоты и др.) и обсуждаются различные стратегии таргетной доставки с акцентом на конъюгацию фотосенсибилизаторов с лигандами рецепторов, гиперэкспрессируемых в опухолевых клетках.

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Конфликт интересов

Автор заявляет об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит описания каких-либо исследований с участием людей или животных в качестве объектов.

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