Russian Journal of OncologyRussian Journal of OncologyРоссийский онкологический журнал1028-99842412-9119Eco-Vector11522110.17816/onco115221ReviewsНаучные обзорыReview ArticleModern outlook for the use of photosensitizers with aggregation-induced emission in treatment of malignant tumorsСовременные перспективы использования фотосенсибилизаторов с агрегационно-индуцированной эмиссией в лечении злокачественных новообразованийhttps://orcid.org/0000-0002-1199-36995795-0530TseimakhAlexander E.ЦеймахАлександр Евгеньевич
Russian Federation

MD, Cand. Sci. (Med.), Associate Professor

к.м.н., доцент

alevtsei@rambler.ruhttps://orcid.org/0000-0003-1080-52941161-8387LazarevAlexander F.ЛазаревАлександр Федорович
Russian Federation

MD, Dr. Sc. (Med.), Professor

д.м.н., профессор

lazarev@akzs.ruhttps://orcid.org/0000-0002-5253-43256379-3517ShoykhetYakov N.ШойхетЯков Нахманович
Russian Federation

MD, Dr. Sc. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences

д.м.н., профессор, член-корреспондент РАН

starok100@mail.ruAltai State Medical UniversityАлтайский государственный медицинский университет141020222731271350712202206042023Copyright ©; 2022, Eco-VectorCopyright ©; 2022, Эко-Вектор2022Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0/https://rjonco.com/1028-9984/article/view/115221

Photodynamic therapy (PDT) is actively developing, becoming one of the important methods of non-invasive treatment of various oncological and infectious diseases. It is usually carried out using three main components: a photosensitizer, light, and oxygen. The key factors for the effective use of PDT are reactogenic oxygen species, which are produced during the oxidation of photosensitizers under the influence of light irradiation.

To increase the production of reactogenic oxygen species, a technique was proposed for creating photosensitizers with aggregation-induced emission. At the present stage in oncology, the following PDT methods using photosensitizers with aggregation-induced emission are distinguished: PDT, absorbing near infrared radiation; enzyme- or glutathione-activated PDT; hypoxic PDT, and synergistic therapy.

Compared to visible light, near infrared radiation (700–1700 nm) has been shown to be more effective and safer due to reduced photodamage, less scattering, and deeper light penetration. The development of activated photosensitizers is an effective way to overcome the uncontrolled phototoxicity of photosensitizers during long-term PDT in vivo, providing controlled death of tumor cells. The oxygen concentration in tumor tissue varies depending on tumor progression, angiogenesis, metabolism, and metastasis. Therefore, the development of photosensitizers capable of effectively fluorescing under hypoxic conditions, including catalyzing intracellular substrates with the formation of oxygen and stimulating the production of reactogenic oxygen species through the type I mechanism, has become a potential solution to the problem of PDT of solid tumors.

The therapeutic efficacy of a single PDT method, as well as most treatment methods in modern oncology, is limited. Therefore, a significant direction is the development of multifunctional treatment systems for synergistic therapy of tumors. Synergistic chemotherapy and PDT is an important area of treatment in oncology. The combination of PDT and immunotherapy is also a promising direction in the treatment of malignant neoplasms.

There are obvious prospects for PDT in oncology not as a separate method of treatment, but as part of a complex multimodal treatment, including chemotherapy, radiation therapy, surgical treatment, and immunotherapy.

Фотодинамическая терапия (ФДТ) — один из важных методов неинвазивного лечения различных онкологических и инфекционных заболеваний. Она обычно осуществляется с использованием трёх основных компонентов: фотосенсибилизатора, света и кислорода. Ключевыми факторами для эффективного применения ФДТ служат реактогенные формы кислорода, которые вырабатываются при окислении фотосенсибилизаторов под воздействием светового облучения.

Для увеличения продукции реактогенных форм кислорода предложено использовать фотосенсибилизаторы с агрегационно-индуцированной эмиссией. На современном этапе в онкологии выделяют следующие методики ФДТ, в которых применяют фотосенсибилизаторы с агрегационно-индуцированной эмиссией: ФДТ, поглощающую ближнее инфракрасное излучение; активируемую ферментами или глютатионом ФДТ; гипоксическую ФДТ; синергетическую терапию.

По сравнению с видимым светом ближнее инфракрасное излучение (700–1700 нм) продемонстрировало бόльшую эффективность и безопасность за счёт уменьшенного фотоповреждения, меньшего рассеяния и более глубокого проникновения света. Разработка активируемых фотосенсибилизаторов является эффективным направлением преодоления неконтролируемой фототоксичности фотосенсибилизаторов при проведении длительной ФДТ in vivo, что обеспечивает контролируемую гибель опухолевых клеток. Концентрация кислорода в опухолевой ткани варьирует в зависимости от опухолевой прогрессии, ангиогенеза, метаболизма и метастазирования. Поэтому разработка фотосенсибилизаторов, способных эффективно флуоресцировать в условиях гипоксии, в том числе катализируя внутриклеточные субстраты с образованием кислорода и стимуляцией производства реактогенных форм кислорода через механизм типа I, стала потенциальным решением проблемы ФДТ солидных опухолей.

Терапевтическая эффективность одного метода ФДТ, как и большинства методов лечения в современной онкологии, ограничена. Поэтому значимым направлением является разработка многофункциональных лечебных систем для синергетической терапии опухолей. Синергетическая химиотерапия и ФДТ — важное направление лечения в онкологии. Комбинация ФДТ и иммунотерапии также является перспективным направлением лечения злокачественных новообразований.

Очевидны перспективы ФДТ в онкологии не как отдельного метода, а как части комплексного мультимодального лечения, включающего химиотерапию, лучевую терапию, хирургическое лечение и иммунотерапию.

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