KillerRed and miniSOG as genetically encoded photosensitizers for photodynamic therapy of cancer

Marina V. Shirmanova, Ekaterina O. Serebrovskaya, Ludmila B. Snopova, Maria M. Kuznetsova, Alina P. Ryumina, Ilya V. Turchin, Ekaterina A. Sergeeva, Nadezhda I. Ignatova, Natalia V. Klementieva, Konstantin A. Lukyanov, Sergey A. Lukyanov, Elena V. Zagaynova

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

2 Citations (Scopus)

Abstract

Despite of the success of photodynamic therapy (PDT) in cancer treatment, the problems of low selective accumulation of a photosensitizer in a tumor and skin phototoxicity have not resolved yet. The idea of encoding of a photosensitizer in genome of cancer cells is attractive, particularly because it can provide highly selective light induced cell killing. This work is aimed at the development of new approach to PDT of cancer, namely to using genetically encoded photosensitizers. A phototoxicity of red fluorescent GFP-like protein KillerRed and FMN-binding protein miniSOG was investigated on HeLa tumor xenografts in nude mice. The tumors were generated by subcutaneous injection of HeLa cells stably expressing the phototoxic proteins. The tumors were irradiated with 594 nm or 473 nm laser at 150 mW/cm2 for 20 or 30 min, repeatedly. Fluorescence intensity of the tumors was measured in vivo before and after each treatment procedure. Detailed pathomorphological analysis was performed 24 h after the therapy. On the epi-fluorescence images in vivo photobleaching of both proteins was observed indicating photodynamic reaction. Substantial pathomorphological abnormalities were found in the treated KillerRed-expressing tumor tissue, such as vacuolization of cytoplasm, cellular and nuclear membrane destruction, activation of apoptosis. In contrast, miniSOG-expressing tumors displayed no reaction to PDT, presumably due to the lack of FMN cofactor needed for fluorescence recovery of the flavoprotein. The results are of interest for photodynamic therapy as a proof of possibility to induce photodamages in cancer cells in vivo using genetically encoded photosensitizers.

Original languageEnglish
Title of host publicationEuropean Conference on Biomedical Optics, ECBO 2013
PublisherOptical Society of America
ISBN (Print)9780819496461
DOIs
Publication statusPublished - 2013
Externally publishedYes
EventEuropean Conference on Biomedical Optics, ECBO 2013 - Munich, Germany
Duration: 12 May 201316 May 2013

Publication series

NameOptics InfoBase Conference Papers
ISSN (Electronic)2162-2701

Conference

ConferenceEuropean Conference on Biomedical Optics, ECBO 2013
Country/TerritoryGermany
CityMunich
Period12/05/1316/05/13

Keywords

  • Genetically encoded photosensitizer
  • KillerRed
  • MiniSOG
  • Photodynamic therapy
  • Phototoxicity
  • Tumor xenograft

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