Light Sci Appl, 2022, 11(1):38

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

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.

IBCH: 9916
Ссылка на статью в журнале: https://www.nature.com/articles/s41377-022-00729-4
Кол-во цитирований на 04.2023: 11
Данные статьи проверены модераторами 2022-03-15

Список научных проектов, где отмечена публикация

  1. Разработка системы прижизненного биоимиджинга HER2-положительных опухолей модельных животных на основе векторных наноконтейнеров c генетически кодируемым BRET-сенсором (4 Сентября 2018 года — 4 Сентября 2021 года). Прошкина Г.М.. Грант, РФФИ.
  2. 21-74-30016. . Внебюджетное финансирование.
  3. МНТИ: Разработка новых технологий для специфического уничтожения раковых клеток и опухолей (6 Января 2019 года — 31 Декабря 2022 года). Деев С.М.. Грант, РФФИ.
  4. 3-16495. . Внебюджетное финансирование.
  5. 74834. . Внебюджетное финансирование.