Publication:
Genetically encoded BRET-activated photodynamic therapy for the treatment of deep-seated tumors

Дата
2022
Авторы
Shramova, E. I.
Chumakov, S. P.
Ryabova, A. V.
Telegin, G. B.
Shipunova, V. O.
Kabashin, A. V.
Deyev, S. M.
Journal Title
Journal ISSN
Volume Title
Издатель
Научные группы
Организационные подразделения
OrgUnit Logo
Организационная единица
Инженерно-физический институт биомедицины
Цель ИФИБ и стратегия развития – это подготовка высококвалифицированных кадров на базе передовых исследований и разработок новых перспективных методов и материалов в области инженерно-физической биомедицины. Занятие лидерских позиций в биомедицинских технологиях XXI века и внедрение их в образовательный процесс, что отвечает решению практикоориентированной задачи мирового уровня – диагностике и терапии на клеточном уровне социально-значимых заболеваний человека.
Выпуск журнала
Аннотация
© 2022, The Author(s).Photodynamic therapy (PDT) is one of the most appealing photonic modalities for cancer treatment based on anticancer activity of light-induced photosensitizer-mediated reactive oxygen species (ROS), but a limited depth of light penetration into tissues does not make possible the treatment of deep-seated neoplasms and thus complicates its widespread clinical adoption. Here, we introduce the concept of genetically encoded bioluminescence resonance energy transfer (BRET)-activated PDT, which combines an internal light source and a photosensitizer (PS) in a single-genetic construct, which can be delivered to tumors seated at virtually unlimited depth and then triggered by the injection of a substrate to initiate their treatment. To illustrate the concept, we engineered genetic NanoLuc-miniSOG BRET pair, combining NanoLuc luciferase flashlight and phototoxic flavoprotein miniSOG, which generates ROS under luciferase-substrate injection. We prove the concept feasibility in mice bearing NanoLuc-miniSOG expressing tumor, followed by its elimination under the luciferase-substrate administration. Then, we demonstrate a targeted delivery of NanoLuc-miniSOG gene, via tumor-specific lentiviral particles, into a tumor, followed by its successful elimination, with tumor-growth inhibition (TGI) coefficient exceeding 67%, which confirms a great therapeutic potential of the proposed concept. In conclusion, this study provides proof-of-concept for deep-tissue “photodynamic” therapy without external light source that can be considered as an alternative for traditional PDT.
Описание
Ключевые слова
Цитирование
Genetically encoded BRET-activated photodynamic therapy for the treatment of deep-seated tumors / Shramova, E.I. [et al.] // Light: Science and Applications. - 2022. - 11. - № 1. - 10.1038/s41377-022-00729-4
URI
https://www.doi.org/10.1038/s41377-022-00729-4
 https://www.scopus.com/record/display.uri?eid=2-s2.0-85125385021&origin=resultslist
 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:000758763100001
 https://openrepository.mephi.ru/handle/123456789/28770
Коллекции
Публикации