The possibility of monitoring of cancer cells response to photodynamic treatment by the use of porphyrazine photosensitizer as a viscosity sensor is shown. The research was done with tetrapyrrole dye - tetra(4- benzyloxyphenyl)tetracyanoporphyrazine. The dye was shown to demonstrate effective absorption and fluorescence in biological transparent window. In addition, the dye has a molecular rotor properties showing high sensitivity of fluorescence parameters to media viscosity changes. Pre-nuclear region and nuclear membrane or its environment are shown to be the primary space of intracellular accumulation of the dye. The high photodynamic activity of the porphyrazine was detected in relation to epidermoid carcinoma cells of human skin. The significant increase of fluorescence life-time of the dye inside the cells was registered after the photodynamic therapy. It may be concerned as an evidence of the local intracellular viscosity increase and a verification of irreversible degenerative processes onset, leading to the death of cancer cells.
porphyrazine, photosensitizer, photodynamic therapy, fluorescent molecular rotor, intracellular viscosity
1. Uzhinov B.M., Ivanov V.L., Mel'nikov M.Ya. Molekulyarnye rotory - lyuminescentnye sensory lokal'noy vyazkosti i vyazkogo techeniya v rastvorah i biologicheskih sistemah. Uspehi himii, 2011. t. 80, № 12, s. 1231-1243. [Uzhinov B.M., Ivanov V.L., Melnikov M.Ya. Molecular rotors as luminescence sensors of local viscosity and viscous flow in solutions and organized systems. RUSS CHEM REV, 2011, vol. 80, no. 12, pp.1179-1190. (In Russ.)]
2. Shilyagina N.Yu., Plehanov V.I., Shkunov I.V. Svetodiodnyy izluchatel' dlya issledovaniya in vitro svetovoy aktivnosti preparatov dlya fotodinamicheskoy terapii. Sovremennye tehnologii v medicine, 2014, t. 6, № 2, s. 15-24. [Shilyagina N.Y., Plekhanov, V.I., Shkunov I.V., Shilyagin P.A., Dubasova L.V., Brilkina A.A., Sokolova E.A., Turchin I.V., Balalaeva I.V. Sovremennye Tehnologii v Medicine, 2014, vol. 6, no. 2, pp. 15-22. (In Russ.)]
3. DeRosa M.C., Crutchley R.J. Photosensitized singlet oxygen and its applications. Coordination Chemistry Reviews, 2002, vol. 233, pp. 351-371.
4. Förster T., Hoffmann G. Die Viskositatsäbhängigkeit der Fluoreszenzquantenausbeuten einiger Farbstoffsysteme. Z Phys Chem, 1971, vol. 75, p. 6376.
5. Haidekker M., Brady T., Wen K., Okada C., Stevens H., Snell J., Frangos J., Theodorakis E. Effects of solvent polarity and solvent viscosity on the fluorescent properties of molecular rotors and related probes. Bioorganic Chemistry, 2005, vol. 33, no. 6, pp. 415-425.
6. Hamblin M.R., Mroz P. History of PDT: The first hundred years. In: Advances in Photodynamic Therapy: Basic, Translational and Clinical. Norwood, MA: Artech House, Inc, 2008.
7. Izquierdo M. Angeles, Vyšniauskas Aurimas, Lermontova S.A., Grigoryev I.S., Shilyagina N.Y., Balalaeva I.V., Klapshina L.G., Kuimova M.K. Dual use of porphyrazines as sensitizers and viscosity markers during photodynamic therapy. Journal of Materials Chemistry B, 2015, no. 3, pp.1089-1096.
8. Klapshina L.G., Douglas W.E., Grigoryev I.S., Ladilina E.Yu, Shirmanova M.V., Mysyagin S.A., Balalaeva I.V., Zagaynova E.V. Novel PEG-organized biocompatible fluorescent nanoparticles doped with an ytterbium cyanoporphyrazine complex for biophotonic applications. Chem. Commun., 2010, no. 44, pp. 8398-8400.
9. Krasnovskii A.A. Photodynamic activity and singlet oxygen. Biofizika, 2004, vol. 49, no. 2, pp. 305-21.
10. Kuimova M.K., Botchway S.W., Parker A.W., Balaz M., Collins H.A., Anderson H.L., Suhling K., Ogilby P.R. Imaging intracellular viscosity of a single cell during photoinduced cell death. Nat Chem, 2009, vol. 1, pp. 69-73.
11. Kuimova M.K. Mapping viscosity in cells using molecular rotors. Physical Chemistry Chemical Physics, 2012, vol. 14, no. 37, pp. 12671-12686.
12. Lermontova S., Grigorev I. , Shilyagina N., Peskova N., Balalaeva I., Shirmanova M., Klapshina L. New Porphyrazine Macrocycles with High Viscosity-Sensitive Fluorescence Parameters. Russian Journal of General Chemistry, 2016, vol. 86, no. 6, pp. 1011-1018.
13. Lermontova S.A., Grigor’ev I.S., Ladilina E.Y., Balalaeva I.V., Shilyagina N.Y., Klapshina L.G. Porphyrazine Structures with Electron-Withdrawing Substituents as the Base for Materials for Photonics and Biomedicine. Russian Journal of Coordination Chemistry, 2018, vol. 44, no. 4, pp. 301-315.
14. Makarov D.A., Yuzhakova O.A., Slivka L.K., Kuznetsova N.A., Negrimovsky V.M., Kaliya O.L., Lukyanets E.A. Cationic Zn and Al phthalocyanines: synthesis, spectroscopy and photosensitizing properties. Journal of Porhyrins and Phthalocyanines, 2007, vol. 11, no. 8, pp. 586-595.
15. Shilyagina N.Yu., Peskova NN, Lermontova SA, Brilkina AA, Vodeneev VA, Yakimansky AV, Klapshina LG, Balalaeva IV. Effective delivery of porphyrazine photosensitizers to cancer cells by polymer brush nanocontainers. Journal of Biophotonics, 2017, vol. 10, no. 9, pp. 1189-1197.
16. Yoon H., Dakanali M., Lichlyter D., Chang W., Nguyen K,.Nipper M., Haidekker M., Theodorakis E. Synthesis and evaluation of self-calibrating ratiometric viscosity sensors. Org. Biomol. Chem., 2011, vol. 9, no. 9, pp. 3530-3540.