RADIATION & RISK
Bulletin of the National Radiation and Epidemiological Registry
since 1992
About the Journal : 2019 : vol.28, No. 4 : Study of efficiency of photodynamic therapy of Earlich carcinoma mice with intravenous introduction of photosensibilizer of liposomal boronated chlorine e6

Study of efficiency of photodynamic therapy of Earlich carcinoma mice with intravenous introduction of photosensibilizer of liposomal boronated chlorine e6

«Radiation and Risk», 2019, vol. 28, No. 4, pp.96-107

DOI: 10.21870/0131-3878-2019-28-4-96-107

Authors

Burmistrova N.V. – Head of Lab., C. Sc., Med.
Drozhzhina V.V. – Researcher. Contacts: 4 Korolyov str., Obninsk, Kaluga region, Russia, 249035. Tel.: + 7 (903) 524-53-13; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Kaplan M.A. – Head of Dep., MD, Prof.
Yuzhakov V.V. – Head of Lab., C. Sc., Med.
Bandurko L.N. – Lead. Researcher, C. Sc., Med.
Tsyganova M.G. – Researcher
Ivanov S.A. – Director, MD, Prof.
Arkhipova L.M. – Research Assistant
Abramova O.B. – Researcher

A. Tsyb MRRC, Obninsk.

Abstract

The article is devoted to the study of the effectiveness of photodynamic therapy (PDT) with the use of new Russian photosensitizer (PS) of liposomal boronated chlorin e6 after its intravenous injection. As an experimental model of the tumor, Ehrlich carcinoma of mice was studied. The aim of the study was to study the effectiveness of PDT with the use of liposomal boronated chlorin e6 as PS. To determine the optimal time for laser irradiation, the kinetics of the distribution of PS in tumor and healthy thigh tissues was studied. The effectiveness of therapy was assessed by the number of animals with complete tumor regression (CR%), by inhibition of tumor growth (TGI%) and by the absolute growth rate (K) in animals with continued tumor growth compared with the control. Control mice were tumor carriers without exposure. The therapeutic potential of PDT for the devitalization of tumor cells was verified by histological studies. It was found that after PDT, which was carried out at the optimal time after the injection of PS, complete tumor regression was observed in 100% of the animals before 21 days of the study at a dose of PS of 1.25 mg/kg, at energy density of 150 J/cm2 and a power density of 0.51 W/cm2 laser radiation. When microscopic examination of tissues in the laser exposure zone, only one animal with visually regressed Ehrlich carcinoma was found to have a relapse of the neoplasm..

Key words
photodynamic therapy, Ehrlich carcinoma, mice, liposomal boronated chlorin e6, photosensitizer accumulation dynamics, contrast index, laser, tumor regression, pathomorphology.

References

1. Tsyb A.F., Kaplan M.A., Romanko Yu.S., Popuchiev V.V. Рhotodynamic therapy. Moscow, Medical Information Agency, 2009. 212 p. (In Russian).

2. Filonenko E.V., Serova L.G. Photodynamic therapy in clinical practice. Biomedical Photonics, 2016, vol. 5, no. 2, pp. 26-37. (In Russian).

3. Stranadko E.P. The main stages of development and the current state of PDT in Russia. Lazernaya meditsina – Laser medicine, 2012, no. 2, pp. 4-14. (In Russian).

4. Bikbov E.N., Privalov V.A., Kurenkov E.L. Dynamics of morphological changes in tumors with PDT in the experiment. Ieroglif – Hieroglyph, 2009, no. 1, pp. 41-59. (In Russian).

5. Allison R.R., Moghissi K. Photodynamic Therapy: PDT mechanisms. Clin. Endos., 2013, vol. 46, no. 1, pp. 24-29.

6. Yuzhakov V.V., Romanko Yu.S., Kaplan M.A., Galkin V.N., Mazhuga A.G., Green M.A., Burmistrova N.V., Fomina N.K., Bandurko L.N., Sevyakkaeva L.E., Yakovleva N.D., Ingel I.E., Moserov S.A., Starovoitova A.V. The effect of photodynamic therapy with bacteriochlorophyll a derivative on the growth and functional morphology of sarcoma M-1 rats. Al'manakh klinicheskoy mediciny – Clinical Medicine Almanac, 2017, vol. 45, no. 4, pp. 333-347. doi: 10.18786/2072-0505-2017-45-4-333-347. (In Russian).

7. Yuzhakov V.V., Burmistrova N.V., Fomina N.K., Bandurko L.N., Sevanjkaeva L.E., Starovoytova A.V., Yakovleva N.D., Tsyganova M.G., Ingelj I.E., Ostroverkhov P.V., Kaplan M.A., Grin M.A., Mazhuga A.G., Mironov A.F., Galkin V.N., Romanko Yu.S. Morphofunctional characteristics of arterial sarcoma M-1 after photodynamic therapy with bacteriochlorophyll derivatives a. Biomedical Photonics, 2016, vol. 5, no. 4, pp. 4-12. (In Russian).

8. Filonenko E.V. Fluorescent diagnostics and photodynamic therapy – justification of application and possi-bilities in oncology. Fotodinamicheskaya terapiya i fotodiagnostika – Photodynamic Therapy and Photodi-agnostics, 2014, vol. 3, no. 1, pp. 3-7. (In Russian).

9. Abakushina E.V., Romanko Yu.S., Kaplan M.A., Kaprin A.D. Antitumor immune response and photodynamic therapy. Radiaciya i risk – Radiation and Risk, 2014, vol. 23, no. 4, pp. 92-98. (In Russian).

10. Lukiyanets E.A. Search for new photosensitizers in photodynamic therapy. Fotodinamicheskaya terapiya i fotodiagnostika – Photodynamic Therapy and Photodyagnosis, 2013, vol. 2, no. 3, pp. 3-16. (In Russian).

11. Nikitina R.G., Kaplan M.A., Olshevskaya V.A., Rodina J.S., Drozhzhina V.V., Morozova T.G. Photodynam-ic ttherapy with boronated chlorin as a photosensitize photodynamic therapy with boronated chlorin as a photosensitizer. J. Cancer Sci. Ther., 2011, vol. 3, no. 9, pp. 216-219.

12. Zhang J., Jiang C., Longo J.P.F., Azevedo R.B., Zhang H., Muehlmann L.A. An updated overview on the development of new photosensitizers for anticancer photodynamic therapy. Acta Pharm. Sin. B, 2018, vol. 8, no. 2, pp. 137-146. doi: 10.1016/j.apsb.2017.09.003.

13. Raikov A.O., Hashem A., Baryshnikova M.A. Liposomes for the targeted delivery of antitumor drugs. Rossijskij bioterapevticheskij zhurnal – Russian Journal of Biotherapy, 2016, vol. 15, no. 2, pp. 90-96. (In Russian).

14. Weijer R., Broekgaarden M., Kos M., van Vught R., Rauws E.A.J., Breukink E., van Gulik T.M., Storm G., Heger M. Enhancing photodynamic therapy of refractory solid cancers: Combining second-generation photosensitizers with multitargeted liposomal delivery. J. Photochem. Photobiol. C: Photochem. Rev., 2015, vol. 23, pp. 103-131.

15. Muehlmann L.A., Joanitti G.A., Silva J.R., Longo J.P.F., Azevedo R.B. Liposomal photosensitizers: poten-tial platforms for anticancer photodynamic therapy. Braz. J. Med. Biol. Res., 2011, vol. 44, no. 8, pp. 729-737.

16. Machinskaya E.A., Ivanova-Radkevich V.I. Review of selective accumudation of photosensitizers with different chemical structure in tumor tissue. Fotodinamicheskaya terapiya i fotodiagnostika – Photodynamic Therapy and Photodyagnosis, 2013, vol. 2, no. 4, pp. 28-32. (In Russian).

17. Kruglyakova AA. Features of pharmacokinetics of liposomal drugs. Razrabotka i registraciya lekarstvennykh sredstv – Development and Registration of Medicines, 2012, no. 1, pp. 37-40. (In Russian).

18. Loschenov V.B., Linkov K.G., Savelieva T.A., Loschenov M.V., Model S.S., Borodkin A.V. Hardware and tool equipment for fluorescence diagnostics and photodynamic therapy. Fotodinamicheskaya terapiya i fo-todiagnostika – Photodynamic Therapy and Photodyagnosis, 2013, vol. 2, no. 3, pp. 17-25. (In Russian).

19. Inzhevatkin E.V., Slepov E.V., Savchenko A.A. Relationship between the lifespan of mices with as cites carcinoma of Ehrlich with the features of lymphocyte metabolism in tumor growth dynamics. Slozhnye sistemy v ekstremal'nykh usloviyah: Tez. dokl. XV Vserossijskogo simpoziuma s mezhdunarodnym uchastiem – Complex Systems in Extreme Conditions: Abstracts. XV Symposium with International Participation. Krasnoyarsk, 2010, pp. 33-34. (In Russian).

20. Rukovodstvo po provedeniyu doklinicheskikh issledovanij lekarstvennykh sredstv [A guide to preclinical drug research]. Moscow, Grief and K, 2012, Part 1, pp. 640-670.

Full-text article (in Russian)