title: Towards PDT with Genetically Encoded Photosensitizer KillerRed: A Comparison of Continuous and Pulsed Laser Regimens in an Animal Tumor Model.
abstract: The strong phototoxicity of the red fluorescent protein KillerRed allows it to be considered as a potential genetically encoded photosensitizer for the photodynamic therapy (PDT) of cancer. The advantages of KillerRed over chemical photosensitizers are its expression in tumor cells transduced with the appropriate gene and direct killing of cells through precise damage to any desired cell compartment. The ability of KillerRed to affect cell division and to induce cell death has already been demonstrated in cancer cell lines in vitro and HeLa tumor xenografts in vivo. However, the further development of this approach for PDT requires optimization of the method of treatment. In this study we tested the continuous wave (593 nm) and pulsed laser (584 nm, 10 Hz, 18 ns) modes to achieve an antitumor effect. The research was implemented on CT26 subcutaneous mouse tumors expressing KillerRed in fusion with histone H2B. The results showed that the pulsed mode provided a higher rate of photobleaching of KillerRed without any temperature increase on the tumor surface. PDT with the continuous wave laser was ineffective against CT26 tumors in mice, whereas the pulsed laser induced pronounced histopathological changes and inhibition of tumor growth. Therefore, we selected an effective regimen for PDT when using the genetically encoded photosensitizer KillerRed and pulsed laser irradiation.
authors.affiliation: Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia.
authors.forename: Marina
authors.initials: M
authors.lastname: Shirmanova
authors.affiliation: Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia.|Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia.
authors.forename: Diana
authors.initials: D
authors.lastname: Yuzhakova
authors.affiliation: Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Snopova
authors.affiliation: Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia.
authors.forename: Gregory
authors.initials: G
authors.lastname: Perelman
authors.affiliation: Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia.|Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Serebrovskaya
authors.affiliation: Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia.|Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Lukyanov
authors.affiliation: Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod, Russia.
authors.forename: Ilya
authors.initials: I
authors.lastname: Turchin
authors.affiliation: Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod, Russia.
authors.forename: Pavel
authors.initials: P
authors.lastname: Subochev
authors.affiliation: Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia.|Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.|Pirogov Russian National Research Medical University, Moscow, Russia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Lukyanov
authors.affiliation: Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod, Russia.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Kamensky
authors.affiliation: Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Zagaynova
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007834:Lasers; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D061848:Optical Imaging; D010778:Photochemotherapy / Q000295:instrumentation / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D006657:Histones; D017319:Photosensitizing Agents; D011993:Recombinant Fusion Proteins; C508771:killer red protein, Anthomedusae; D049452:Green Fluorescent Proteins