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Материалы конференции / Conference proceedings
© ZAMAY S. S., NARODOV A. A., GALEEV R. G., PROKOPENKO V. S., SOKOLOV A. E., BORUS A. A., ZABLUDA V. N. LUKYANENKO A. V., BARON F. A., GARIFULLIN V. F., MASYUGIN A. N., ZELENOV F. V., GREK D. S., VORONKOVSKII I. I., GORBUSHIN A., KOLOVSKAYA O. S., LUKYANENKO K. A., NIKOLAEVA E. D., LUZAN N. A., KICHKAILO A. S. UDC 616-006.04
DOI: 10.20333/25000136-2022-5-109-110
"Smart" nanoscalpel for microsurgery of glial tumors of the human brain
S. S. Zamay1, A. A. Narodov2, R. G. Galeev3, V. S. Prokopenko4, A. E. Sokolov5, A. A. Boras5, V. N. Zabluda5, A. V. Lukyanenko5, F. A. Baron5, V. F. Garifullin3, A. N. Masyugin3, F. V. Zelenov3, D. S. Grek2, I. I. Voronkovskii2, A. Gorbushin2, O. S. Kolovskaya1,2, K. A. Lukyanenko1,2, E. D. Nikolaeva1,2, N. A. Luzan2, A. S. Kichkailo1,2
'Federal Research Center "Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences", Krasnoyarsk 660036, Russian Federation 2Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk 660022, Russian Federation 3JSC «NPP «Radiosviaz», Krasnoyarsk 660021, Russian Federation
4V.P. Astafiev Krasnoyarsk State Pedagogical University, Krasnoyarsk 660049, Russian Federation
5L.V. Kirensky Institute of Physics, Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk 660036, Russian Federation
Abstract. We studied the effectiveness of magnetomechanical therapy in the treatment of brain glial tumors using magnetic nanodiscs functionalized with DNA aptamers to human brain tumor glial cells. • Materials and methods. The formation of a model of human glioblastoma was carried out by intracranial injection of tumor cells of glioblastoma obtained from a patient with glioblastoma. Antitumor therapy was carried out using nanodiscs modified with the Gli233 aptamer. The growth of the glial tumor was monitored using NMR tomography. • Results and discussion. Therapy of a glial tumor during 4 sessions of magnetomechanical therapy using a "smart" nanoscalpel in MF (10Hz, 1000e) led to a significant reduction in its size, while glial tumors in mice that were treated with nanodiscs modified with nonspecific aptamers continued to increase in size. • Conclusion. Microsurgery using three-layer magnetic nanodisks with a quasi-dipole structure (Au/Ni/Au) modified with the specific for glial cells Gli233 aptamer ("smart" nanoscalpel) is effective for the treatment of human glial tumors in the brain.
Key words: aptamers, glial tumor, NMR tomography, «smart» nanoscalpel, nanodiscs, magnetomechanical therapy.
Conflict of interest. The authors declare the absence of obvious and potential conflicts of interest associated with the publication of this article.
Citation: Zamay SS, Narodov AA, Galeev RG, Prokopenko VS, Sokolov AE, Borus AA, Zabluda VN. Lukyanenko AV, Baron FA., Garifullin VF, Masyugin
AN, Zelenov FV, Grek DS, Voronkovskii II, Gorbushin A, Kolovskaya OS, Lukyanenko KA, Nikolaeva ED, Luzan NA, Kichkailo AS. "Smart" nanoscalpel for
microsurgery of glial tumors of the human brain. Siberian Medical Review. 2022;(5):109-110. DOI: 10.20333/25000136-2022-5-109-110
Introduction
Glial tumors are primary human brain tumors with a high mortality rate due to their malignancy [1]. The high invasion of tumor cells into the surrounding tissues makes it impossible to completely resect the tumor, and conventional therapies are ineffective for its treatment. Currently, one of the promising methods for therapy is the cell surgery, where a "smart" nanoscalpel acts as a surgical instrument. A nanoscalpel is a remotely controlled magnetic nanodisc targeted at a tumor with DNA aptamers specific to human brain glial tumors, capable of transforming a magnetic moment into a mechanical one in an alternating magnetic field [2]. Here we evaluated the effectiveness of a "smart" nanoscalpel (unique three-layer magnetic nanodisks with a quasi-dipole structure (Au/Ni/Au) modified with the Gli233 aptamer) under the influence of an alternating magnetic field to destroy a glial brain tumor in vivo.
Material and methods
The objects of the study were laboratory male ICR mice with immunosuppression, weighing 20-25g. The formation of a model of human glioblastoma was carried out by intracranial injection of tumor cells of glioblastoma obtained from a patient with glioblastoma. The growth of the glial tumor was monitored using NMR tomography. Antitumor therapy was carried out using nanodiscs modified with the Gli233 aptamer. The selection of optimal magnetic field parameters for microsurgery with magnetic nanodisks was carried out on ascitic cells of Ehrlich carcinoma.
Results and discussion
The effectiveness of magnetomechanical therapy was evaluated on cell cultures of Ehrlich's ascitic carcinoma in vitro at the following frequencies of an alternating magnetic field (MF): 1, 5, 10, 20, and 50 Hz (MF intensity was 100 Oe). As-citic cells were destroyed using magnetic nanodiscs modified with a AS42 aptamer, which was specific to ascitic cells. Studies have shown that MF with a frequency of10 Hz led to the maximum death of ascitic cells. MF with a frequency of 10 Hz was used for microsurgery of a glial brain tumor in vivo.
The development and treatment of glial tumors in mice was monitored using NMR imaging. Studies have shown that within 14 days the tumor has increased to a large size (Fig. 1, a, d). Therapy of a glial tumor during 4 sessions of magnetomechanical therapy using a "smart" nanoscalpel in MF (10Hz, 100üe) led to a significant reduction in its size (Fig. 1, b-c), while glial tumors in mice that were treated with nanodiscs modified with nonspecific aptamers continued to increase in size (Fig. d-f).
Conclusion
Microsurgery using three-layer magnetic nanodisks with a quasi-dipole structure (Au/Ni/Au) modified with the specific for glial cells Gli233 aptamer ("smart" nanoscalpel) is effective for the treatment of human glial tumors in the brain.
This research was funded by the Regional State Autonomous Institution "Krasnoyarsk Regional Fund for Support of Scientific and Scientific and Technical Activities", Competition of scientific, technical and innovative projects in the interests of the first world-class climate scientific and educa-
Сибирское медицинское обозрение. 2022;(5):109-110
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Zamay S. S., Narodov A. A., Galeev R. G. et al.
"Smart" nanoscalpel for microsurgery of glial tumors of the human brain
After 1st session After 3rd session
Before therapy therapy therapy
JÍ-tumor
Figure. Efficiency of "smart" nanoscalpel in microsurgery of glial tumors: a) and d) the tumors before treatment; b) and c) treatment with nanodisks modified with Gli233 aptamer; e) and f) treatment with nanodisks modified with nonspecific aptamer.
tional center "Yenisei Siberia", grant "Carrying out applied research and development aimed at creating technologies for the production of nanoscalpels based on magnetic nanodisks for microsurgery of glial brain tumors" № 2022060108781 and with the support of a partner company JSC «NPP «Ra-diosviaz».
References
1. WirschingH-G, Galanis E, Weller M. Glioblastoma. Handbook of Clinical Neurology. 2016;(134):381-97. DOI: 10.1016/B978-0-12-802997-8.00023-2
2. Zamay TN, Prokopenko VS, Zamay SS, Lukyanenko KA, Kolovskaya OS, Orlov VA, Zamay GS, Galeev RG, Narodov AA, Kichkailo AS. Magnetic nanodiscs - a new promising tool for microsurgery of malignant neoplasms. Nanoma-terials. 2021;11(6):1459-147.
Author information
Sergey S. Zamay, Senior Researcher, Federal Research Center"Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences"; Address: 50, Akademgorodok 660036, Krasnoyarsk, Russian Federation; Phone: +7(391)2201893; e-mail: sergey-zamay@ yandex.ru, https:llorcid.org/0000-0002-4828-7077
Andrey A. Narodov, Dr. of Med. Sci., Professor, Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Address: 1, Partizan Zheleznyak Str., Krasnoyarsk, Russian Federation 660022; Phone: +7(391)2201893; e-mail: narodov_a@mail.ru
Rinat G. Galeev, Professor, director JSC «NPP «Radiosviaz»; Address: 19, Dekabristov Str., Krasnoyarsk 660021, Russian Federation; Phone: +7(391)2201893; e-mail: info@krtz.su.
Vladimir S. Prokopenko, professor, V.P. Astafiev Krasnoyarsk State Pedagogical University; Address: 89, A. Lebedeva Str., Krasnoyarsk 660049, Russian Federation; Phone: +7(391)2171777; e-mail: plufe@yandex.ru, https:llorcid.org/0000-0002-6125-9353
Aleksey E. Sokolov, Senior Researcher, L. V. Kirensky Institute of Physics, Siberian Branch of the Russian Academy of Sciences, Address: 50, Akademgorodok, Krasnoyarsk 660036, Russian Federation; Phone: +7(391)2201893; e-mail: alexeys@iph.krasn.ru
Andrey A. Borus, student PhD, L. V. Kirensky Institute of Physics, Siberian Branch of the Russian Academy of Sciences, Address: 50, Akademgorodok, Krasnoyarsk 660036, Russian Federation; Phone: +7(391)2201893; e-mail: borus@andrew-foto.ru
Vladimir N. Zabluda, Senior Researcher, L. V. Kirensky Institute of Physics, Siberian Branch of the Russian Academy of Sciences, Address: 50, Akademgorodok, Krasnoyarsk 660036, Russian Federation; Phone: +7(391)2201893; e-mail: zvn@iph.krasn.ru
Anna V. Lukyanenko, Senior Researcher, L. V. Kirensky Institute of Physics, Siberian Branch of the Russian Academy of Sciences, Address: 50, Akademgorodok, Krasnoyarsk 660036, Russian Federation; Phone: +7(391)2201893; e-mail: lav@iph.krasn.ru
Filipp A. Baron, Senior Researcher, L. V. Kirensky Institute of Physics, Siberian Branch of the Russian Academy of Sciences, Address: 50, Akademgorodok, Krasnoyarsk 660036, Russian Federation; Phone: +7(391)2201893; e-mail: filippbaron@mail.ru
Vadim F. Garifullin, Head of the project office, JSC «NPP «Radiosviaz». Address: 19, Dekabristov, Krasnoyarsk, 660021; Phone +7(391)204-12-07; e-mail: vadimgar@mail.ru
Albert N. Masyugin, Deputy Chief Technologist, JSC «NPP «Radiosviaz». Address: 19, Dekabristov, Krasnoyarsk 660021, Russian Federation; Phone: +7(391)2201893; e-mail: albert. masyugin@mail.ru
Fedor V. Zelenov, Leading Microelectronics Specialist, JSC «NPP «Radiosviaz». Address: 19, Dekabristov, Krasnoyarsk 660021, Russian Federation; Phone: +7(391)2201893; e-mail: fyodor. zelenov@yandex.ru
Daniil S. Grek, student, Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Address: 1, Partizan Zheleznyak Str., Krasnoyarsk, Russian Federation 660022; Phone: +7(391)2201893; e-mail: daniilgrek@gmail.com
Ivan I. Voronkovskii, student, Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Address: 1, Partizan Zheleznyak Str., Krasnoyarsk, Russian Federation 660022; Phone: +7(391)2201893; e-mail: ivoronkovskiy@bk.ru.
Anton K. Gorbushin, PhD student, Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University, Address: 1, Partizan Zheleznyak Str., Krasnoyarsk, Russian Federation 660022; Phone:+7(391)2201893; e-mail: senior.gorak93@yandex.ru.
Olga S. Kolovskaya, PhD, senior researcher, Federal Research Center "Krasnoyarsk Research Center" Siberian Branch of Russian Academy of Science; Address: 50, Akademgorodok, Krasnoyarsk, Russian Federation 660036; Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Address: 1, Partizan Zheleznyak Str., Krasnoyarsk, Russian Federation 660022; Phone: +7(391)2201893; e-mail: olga.kolovskaya@gmail.com, http://orcid.org/0000-0002-2494-2313
Kirill A. Lukyanenko, researcher, Federal Research Center"Krasnoyarsk Research Center" Siberian Branch of Russian Academy of Science; Address: 50, Akademgorodok, Krasnoyarsk, Russian Federation 660036; Professor V. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Address: 1, Partizan Zheleznyak Str., Krasnoyarsk, Russian Federation 660022; Phone: +7(391)2201893; e-mail: k.a.lukyanenko@yandex.ru, http:llorcid.org/0001-0001-5845-588E
Elena D. Nikolaeva, senior researcher, Federal Research Center"Krasnoyarsk Research Center" Siberian Branch of Russian Academy of Science; Address: 50, Akademgorodok, Krasnoyarsk, Russian Federation 660036; Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Address: 1, Partizan Zheleznyak Str., Krasnoyarsk, Russian Federation 660022; Phone: +7(391)2201893; e-mail: nikolaeva-lena@mail.ru
Natalia A. Luzan, researcher, Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Address: 1, Partizan Zheleznyak Str., Krasnoyarsk, Russian Federation 660022; Phone: +7(391)2201893; e-mail: laskimo@mail.ru
Anna S. Kichkailo, Dr.Bio.Sci., leading researcher, Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University; Address: 1, Partizan Zheleznyak Str., Krasnoyarsk, Russian Federation 660022; Federal Research Center"Krasnoyarsk Research Center" Siberian Branch of Russian Academy of Science; Address: 50, Akademgorodok, Krasnoyarsk, Russian Federation 660036; e-mail: annazamay@yandex.ru, http:llorcid.org/0000-0003-0690-7837
Received 17 June 2022 Revision Received 20 August 2022 Accepted 30 August 2022
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