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11C-radiolabeled aptamer for imaging of tumors and metastases using positron emission tomography-computed tomography / A. V. Ozerskaya, T. N. Zamay, O. S. Kolovskaya [et al.] // Mol. Ther. Nucl. Acids. - 2021. - Vol. 26. - P. 1159-1172, DOI 10.1016/j.omtn.2021.10.020. - Cited References: 44 . - ISSN 2162-2531
Кл.слова (ненормированные):
11C radiolabeling -- radiopharmaceuticals -- PET/CT -- in vivo imaging -- DNA aptamers -- Ehrlich ascites carcinoma -- metastasis
Аннотация: Identification of primary tumors and metastasis sites is an essential step in cancer diagnostics and the following treatment. Positron emission tomography-computed tomography (PET/CT) is one of the most reliable methods for scanning the whole organism for malignancies. In this work, we synthesized an 11C-labeled oligonucleotide primer and hybridized it to an anti-cancer DNA aptamer. The 11C-aptamer was applied for in vivo imaging of Ehrlich ascites carcinoma and its metastases in mice using PET/CT. The imaging experiments with the 11C-aptamer determined very small primary and secondary tumors of 3 mm2 and less. We also compared 11C imaging with the standard radiotracer, 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG), and found better selectivity of the 11C-aptamer to metastatic lesions in the metabolically active organs than 18F-FDG. 11C radionuclide with an ultra-short (20.38 min) half-life is considered safest for PET/CT imaging and does not cause false-positive results in heart imaging. Its combination with aptamers gives us high-specificity and high-contrast imaging of cancer cells and can be applied for PET/CT-guided drug delivery in cancer therapies.

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Держатели документа:
Federal Siberian Research Clinical Centre Under the Federal Medical Biological Agency, Krasnoyarsk, Russian Federation
Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk, Russian Federation
Federal Research Center Krasnoyarsk Science- Center SB RAS, Krasnoyarsk, Russian Federation
Kirensky Institute of Physics, Krasnoyarsk, Russian Federation
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada
Krasnoyarsk Regional Pathology-Anatomic Bureau, Krasnoyarsk, Russian Federation

Доп.точки доступа:
Ozerskaya, A. V.; Zamay, T. N.; Kolovskaya, O. S.; Tokarev, N. A.; Belugin, K. V.; Chanchikova, N. G.; Badmaev, O. N.; Zamay, G. S.; Shchugoreva, I. A.; Moryachkov, R. V.; Морячков, Роман Владимирович; Zabluda, V. N.; Заблуда, Владимир Николаевич; Khorzhevskii, V. A.; Shepelevich, N.; Gappoev, S. V.; Karlova, E. A.; Saveleva, A. S.; Volzhentsev, A. A.; Blagodatova, A. N.; Lukyanenko, K. A.; Veprintsev, D. V.; Smolyarova, T. E.; Смолярова, Татьяна Евгеньевна; Tomilin, F. N.; Томилин, Феликс Николаевич; Zamay, S. S.; Silnikov, V. N.; Berezovski, M. V.; Kichkailo, A. S.
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Investigation of the spatial structure of bionanoconjugates based on DNA aptamers by synchrotron methods / R. V. Moryachkov, V. N. Zabluda, I. A. Shchugoreva [et al.] // International conference "Functional materials" : book of abstracts / ed. V. N. Berzhansky ; org. com. S. G. Ovchinnikov [et al.]. - Simferopol, 2021. - P. 310. - Библиогр.: 3 назв. - The research was carried out with a grant from the Russian Science Foundation № 21-12-00226, https://rscf.ru/project/21-12-00226/

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Berzhansky, V. N. \ed.\; Бержанский, Владимир Наумович; Ovchinnikov, S. G. \org. com.\; Овчинников, Сергей Геннадьевич; Moryachkov, R. V.; Морячков, Роман Владимирович; Zabluda, V. N.; Заблуда, Владимир Николаевич; Shchugoreva, Irina A.; Artyushenko, P. V.; Kichkaylo, A.S.; Spiridonova, V. A.; Berlina, A. N.; Sokolov, A. Е.; Соколов, Алексей Эдуардович; "Functional materials", International conference(2021 ; Oct. 4-8 ; Alushta, Russia); Крымский федеральный университет имени В.И. Вернадского
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Structure- and interaction-based design of anti-SARS-CoV-2 Aptamers / V. Mironov, I. A. Shchugoreva, P. V. Artyushenko [et al.] // Chem. - Eur. J. - 2022. - Vol. 28, Is. 12. - Ст. e202104481, DOI 10.1002/chem.202104481. - Cited References: 85. - The authors are grateful to JCSS Joint Super Computer Center of the Russian Academy of Sciences – Branch of Federal State Institution “Scientific Research Institute for System Analysis of the Russian Academy of Sciences” for providing supercomputers for computer simulations. The authors thank the RSC Group (www.rscgroup.ru) and personally Mr. Oleg Gorbachev for the constant support and establishment of “The Good Hope Net Project” (www.thegoodhope.net) multifunctional non-profit anti-CoVID research project. The authors also thank the Helicon Company (www.helicon.ru) and personally Olesya Kucenko, Alexander Kolobov, Leonid Klimov for instrumental support and help with conducting fluorescence polarization assays, which were performed on a demo instrument Clariostar Plus microplate reader (BMG LABTECH, Germany). We thank Dr. Yong-Zhen Zhang for providing the genome sequence of 2019-nCoV and Dr. Xinquan Wang for providing the crystal structure of the binding domain of the SARS-2 Spike protein. The authors are grateful to Aptamerlab LCC financial support (www.aptamerlab.com). Y.A.’s work at Argonne National Laboratory was supported by the U.S. Department of Energy, Office of Science, under contract DE-AC02-06CH11357. The work of D.M. and G.G. has been done as part of the BioExcel CoE (www.bioexcel.eu), a project funded by the European Union contracts H2020-INFRAEDI-02-2018-823830 and H2020-EINFRA-2015-1-675728. D.M. and G.G. also thank the CSC-IT center in Espoo, Finland, as well as PRACE for awarding access to resource Curie-Rome based in France at GENCI. V.M. thanks Russian Foundation for Basic Research (project number 19-03-00043). A.B.’s and N.K.’s work was supported by the Ministry of Science and Higher Education of Russian Federation (state assignment of the Research Center of Biotechnology RAS). V. deF. G.C., N.B and G.O. are grateful to FISR2020 _00177 Shield, Italian Ministry of Education and Research, for funding. GC is grateful to the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement: cONCReTE 872391; PRISAR2 872860. Use of the 13 A BioSAXS beamtime at the Taiwan Photon Source is acknowledged. The work of M.V.B was funded by the Canadian Institutes of Health Research grant OV1-170353. SAXS measurements and PIEDA analyses were funded by the Russian Science Foundation (project No 21-73-20240 for A.S.K.) . - ISSN 0947-6539. - ISSN 1521-3765

РУБ Chemistry, Multidisciplinary
Рубрики:
BIOLOGICAL MACROMOLECULES
   SOLUTION SCATTERING
   BINDING
   SPIKE
Кл.слова (ненормированные):
aptamers -- fragment molecular orbitals method -- molecular dynamics -- SARS-CoV-2 -- SAXS
Аннотация: Aptamer selection against novel infections is a complicated and time-consuming approach. Synergy can be achieved by using computational methods together with experimental procedures. This study aims to develop a reliable methodology for a rational aptamer in silico et vitro design. The new approach combines multiple steps: (1) Molecular design, based on screening in a DNA aptamer library and directed mutagenesis to fit the protein tertiary structure; (2) 3D molecular modeling of the target; (3) Molecular docking of an aptamer with the protein; (4) Molecular dynamics (MD) simulations of the complexes; (5) Quantum-mechanical (QM) evaluation of the interactions between aptamer and target with further analysis; (6) Experimental verification at each cycle for structure and binding affinity by using small-angle X-ray scattering, cytometry, and fluorescence polarization. By using a new iterative design procedure, structure- and interaction-based drug design (SIBDD), a highly specific aptamer to the receptor-binding domain of the SARS-CoV-2 spike protein, was developed and validated. The SIBDD approach enhances speed of the high-affinity aptamers development from scratch, using a target protein structure. The method could be used to improve existing aptamers for stronger binding. This approach brings to an advanced level the development of novel affinity probes, functional nucleic acids. It offers a blueprint for the straightforward design of targeting molecules for new pathogen agents and emerging variants.

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Держатели документа:
Lomonosov Moscow State Univ, Dept Chem, Moscow 119991, Russia.
Kyungpook Natl Univ, Dept Chem, Daegu 702701, South Korea.
Fed Res Ctr KSC SB RAS, Lab Digital Controlled Drugs & Theranost, Krasnoyarsk 660036, Russia.
Natl Tsing Hua Univ, Dept Chem Engn, Hsinchu 30013, Taiwan.
Siberian Fed Univ, Sch Nonferrous Met & Mat Sci, Krasnoyarsk 660041, Russia.
IRCCS Neuromed Ist Neurol Mediterraneo Pozzilli, Via Atinense 18, I-86077 Pozzilli, Italy.
Krasnoyarsk State Med Univ, Lab Biomol & Med Technol, Krasnoyarsk 660022, Russia.
Univ Jyvaskyla, Nanosci Ctr, Jyvaskyla 40014, Finland.
Univ Jyvaskyla, Dept Chem, Jyvaskyla 40014, Finland.
Univ Naples Federico II, Dept Pharm, I-80138 Naples, Italy.
Univ Naples Federico II, Dept Mol Med & Med Biotechnol, I-80131 Naples, Italy.
Kirensky Inst Phys, Lab Phys Magnet Phenomena, Krasnoyarsk 660012, Russia.
Siberian Fed Univ, Sch Fundamental Biol & Biotechnol, Krasnoyarsk 660041, Russia.
Xiamen Univ, Coll Chem & Chem Engn, Dept Chem Biol, Xiamen 361005, Peoples R China.
State Res Ctr Virol & Biotechnol Vector, Koltsov 630559, Russia.
NRC Kurchatov Inst, Moscow 117259, Russia.
Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia.
Russian Acad Sci, Res Ctr Biotechnol, AN Bach Inst Biochem, Lab Immunobiochem, Moscow 119071, Russia.
Tomsk State Univ, Lab Adv Mat & Technol, Tomsk 634050, Russia.
Altai State Univ, Barnaul 656049, Russia.
Fed Res Ctr KSC SB RAS, Dept Mol Elect, Krasnoyarsk 660036, Russia.
Krasnoyarsk State Med Univ, Dept Infect Dis & Epidemiol, Krasnoyarsk 660022, Russia.
Natl Pingtung Univ, Dept Appl Chem, Pingtung 900391, Taiwan.
Natl Synchrotron Radiat Res Ctr, Hsinchu Sci Pk, Hsinchu 30076, Taiwan.
Res Natl Council CNR, Inst Genet & Biomed Res IRGB, I-09042 Milan, Italy.
Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Inst Mol Med, Shanghai 200127, Peoples R China.
Natl Inst Adv Ind Sci & Technol, Res Ctr Computat Design Adv Funct Mat, Tsukuba, Ibaraki 3058560, Japan.
Hunan Univ, Coll Chem & Chem Engn, Changsha 410082, Hunan, Peoples R China.
Argonne Natl Lab, Computat Sci Div, Lemont, IL 60439 USA.
Dept Chem & Biomol Sci, Ottawa, ON K1N 6N5, Canada.

Доп.точки доступа:
Mironov, Vladimir; Shchugoreva, I. A.; Artyushenko, P. V.; Артюшенко, Полина Владимировна; Morozov, D. I.; Морозов, Дмитрий И.; Borbone, N.; Oliviero, G.; Zamay, T. N.; Замай, Т. Н.; Moryachkov, R. V.; Морячков, Роман Владимирович; Kolovskaya, .; Коловская О. С.; Lukyanenko, K. A.; Лукьяненко Кирилл А.; Song, Y. L.; Merkuleva, I. A.; Zabluda, V. N.; Заблуда, Владимир Николаевич; Peters, G.; Koroleva, L. S.; Veprintsev, D. V.; Glazyrin, Y. E.; Volosnikova, E. A.; Belenkaya, S. V.; Esina, T. I.; Isaeva, A. A.; Nesmeyanova, .; Shanshin, D. V.; Berlina, A. N.; Komova, N. S.; Svetlichnyi, V. A.; Silnikov, V. N.; Shcherbakov, D. N.; Zamay, G. S.; Замай, Галина Сергеевна; Zamay, S. S.; Замай, С. С.; Smolyarova, T. E.; Смолярова, Татьяна Евгеньевна; Tikhonova, E. P.; Chen, U. S.; Jeng, G.; Condorelli, V.; Franciscis, G.; Groenhof, C. Y.; Yang, A. A.; Moskovsky, D. G.; Fedorov, F. N.; Tomilin, F. N.; Томилин, Феликс Николаевич; Tan, Y.; Alexeev, M. V.; Berezovski, A. S.; Kichkailo, A.S.; Aptamerlab LCC; U.S. Department of Energy, Office of ScienceUnited States Department of Energy (DOE) [DE-AC02-06CH11357]; European UnionEuropean Commission [H2020-INFRAEDI-02-2018-823830, H2020-EINFRA-2015-1-675728, 872391, PRISAR2 872860]; CSC-IT center in Espoo, Finland; PRACE; Russian Foundation for Basic ResearchRussian Foundation for Basic Research (RFBR) [19-03-00043]; Ministry of Science and Higher Education of Russian Federation (state assignment of the Research Center of Biotechnology RAS); Italian Ministry of Education and ResearchMinistry of Education, Universities and Research (MIUR) [FISR2020 _00177]; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR) [OV1-170353]; Russian Science FoundationRussian Science Foundation (RSF) [21-73-20240]
}
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Moryachkov, R. V.
Structure approaches to study of DNA aptamers in solution / R. V. Moryachkov, P. A. Nikolaeva, V. A. Spiridonova // Sib. Med. Rev. - 2021. - Vol. 2021, Is. 2. - P. 76-78 ; Сиб. мед. обозрение, DOI 10.20333/2500136-2021-2-76-78. - Cited References: 5. - The reported study was funded by RFBR, project number 19-32-90266 . - ISSN 1819-9496
Кл.слова (ненормированные):
biomolecules in solution -- tertiary structure -- small-angle X-ray scattering (SAXS) -- structure analysis
Аннотация: The high potential of aptamers – specific molecular agents based on short single-stranded nucleic acids – makes high demands on the molecules under development for the efficiency of interaction with target biomolecules. In this work, approaches are considered for studying the spatial structure of DNA aptamers in solution using various complementary methods, which make it possible to obtain a more complete picture of the formation of the structure and conformational changes, to track the interaction with the target protein, the tendency to oligomerization, and to characterize the spatial structure of both individual molecules and complexes.

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Держатели документа:
Federal Research Center “Krasnoyarsk Science Center SB RAS”, 50, Akademgorodok St., Krasnoyarsk, 660036, Russian Federation
Kirensky Institute of Physics, Bld. 38, 50, Akademgorodok St., Krasnoyarsk, 660036, Russian Federation
Lomonosov Moscow State University, 1, Leninskie Gory St., Moscow, 119992, Russian Federation
A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Bld. 40, 1, Leninskie Gory St., Moscow, 119992, Russian Federation

Доп.точки доступа:
Nikolaeva, P. A.; Spiridonova, V. A.; Морячков, Роман Владимирович

}
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Magnetic properties of iron oxide nanoparticles to create aptamer bionanoconjugates / A. Е. Sokolov, V. N. Zabluda, A. V. Sherepa [et al.] // Molecular Therapy - Nucleic Acids : book of abstracts of the 1st Int. conf. "Aptamers in Russia 2019". - 2019. - Vol. 17, Suppl. 1. - P. 12

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Доп.точки доступа:
Sokolov, A. Е.; Соколов, Алексей Эдуардович; Zabluda, V. N.; Заблуда, Владимир Николаевич; Sherepa, A. V.; Knyazev, Yu. V.; Князев, Юрий Владимирович; Volochaev, M. N.; Волочаев, Михаил Николаевич; Kurilina, A.; Velikanov, D. A.; Великанов, Дмитрий Анатольевич; Goncharova, D. A.; Shabalina, A.; Шабалина Анастасия; Svetlichnyi, V.; Светличный В.; Aptamers in Russia, international conference(1 ; 2019 ; Aug. 27-30 ; Krasnoyarsk)
}
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Magnetic sorting of tumor cells with attached magnetic nanoparticles in a microchannel / P. Denissenko, V. V. Denisenko, I. Denisov [et al.] // Molecular Therapy - Nucleic Acids : book of abstracts of the 1st Int. conf. "Aptamers in Russia 2019". - 2019. - Vol. 17, Suppl. 1. - P. 14

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Доп.точки доступа:
Denissenko, P.; Denisenko, V. V.; Denisov, I.; Kantsler, V.; Kolovskaya, O. S.; Коловская, О. С.; Lapin, I. N.; Sokolov, A. Е.; Соколов, Алексей Эдуардович; Svetlichnyi, V.; Светличный, В. А.; Zabluda, V. N.; Заблуда, Владимир Николаевич; Zamay, S. S.; Замай, С. С.; Kichkailo, A.S.; Кичкайло, Анна Сергеевна; Aptamers in Russia, international conference(1 ; 2019 ; Aug. 27-30 ; Krasnoyarsk)
}
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Computational approach to design of aptamers to the receptor binding domain of sars-cov-2 / P. V. Artyushenko, V. A. Mironov, D. I. Morozov [et al.] // Sib. Med. Rev. - 2021. - Vol. 2021, Is. 2. - P. 66-67 ; Сиб. мед. обозрение, DOI 10.20333/2500136-2021-2-66-67. - Cited References: 5 . - ISSN 1819-9496
Кл.слова (ненормированные):
selection -- aptamer -- receptor-binding domain -- SARS-CoV-2
Аннотация: The aim of the research. In this work, in silico selection of DNA-aptamers to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was performed using molecular modeling methods. Material and methods. A new computational approach to aptamer in silico selection is based on a cycle of simulations, including the stages of molecular modeling, molecular docking, molecular dynamic simulations, and quantum chemical calculations. To verify the obtained calculated results flow cytometry, fluorescence polarization, and small-angle X-ray scattering methods were applied. Results. An initial library consisted of 256 16-mer oligonucleotides was modeled. Based on molecular docking results, the only one aptamer (Apt16) was selected from the library as a starting aptamer to the RBD protein. For Apt16/RBD complex, molecular dynamic and quantum chemical calculations revealed the pairs of nucleotides and amino acids whose contribution to the binding between aptamer and RBD is the largest. Taking into account these data, Apt16 was subjected to the structure modifications in order to increase the binding with the RBD. Thus, a new aptamer Apt25 was designed. The procedure of 1) aptamer structure modeling/modification, 2) molecular docking, 3) molecular dynamic simulations, 4) quantum chemical calculations was performed sev-eral times. As a result, four aptamers (Apt16, Apt25, Apt27, Apt31) to the RBD were designed in silico without any preliminary experimental data. Binding of the each modeled aptamer to the RBD was studied in terms of interactions between residues in protein and nucleotides in the aptamers. Based on the simulation results, the strongest binding with the RBD was predicted for two Apt27 and Apt31aptamers. The calculated results are in good agreement with experimental data obtained by flow cytometry, fluorescence polarization, and small-angle X-ray scattering methods. Conclusion. The proposed computational approach to selection and refinement of aptamers is universal and can be used for wide range of molecular ligands and targets.

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Держатели документа:
Federal Research Center KSC SB RAS, Krasnoyarsk, 660036, Russian Federation
Siberian Federal University, Krasnoyarsk, 660041, Russian Federation
Lomonosov Moscow State University, Moscow, 119991, Russian Federation
University of Jyvaskyla, Jyvaskyla, 40014, Finland
University of Naples Federico II, Naples, 80138, Italy
Kirensky Institute of Physics KSC SB RAS, Krasnoyarsk, 660036, Russian Federation

Доп.точки доступа:
Artyushenko, P. V.; Mironov, V. A.; Morozov, D. I.; Shchugoreva, I. A.; Borbone, N.; Tomilin, F. N.; Томилин, Феликс Николаевич; Kichkailo, A. S.

}
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Structural analysis of thrombin-binding G-aptamers in presence of bivalent ions / P. A. Nikolaeva, R. V. Moryachkov, V. N. Raldugina [et al.] // Sib. Med. Rev. - 2022. - Is. 5. - P. 111-113 ; Сиб. мед. обозрение, DOI 10.20333/25000136-2022-5-111-113. - Cited References: 4. - The study was supported by a grant from the Russian Science Foundation (project number 21-73-20240) . - ISSN 1819-9496
Кл.слова (ненормированные):
3D structures -- DNA aptamers -- thrombin inhibitors -- G-quadruplexes
Аннотация: The aim of this study was to examine 3D structures of DNA aptamers, thrombin inhibitors. The main objective was to study 3D structure 15TBA, RE31, NU172 aptamers using the small-angle X-ray scattering method. The size of 15TBA was 4.5 nm, which corresponds to a partially unfolded conformation. The CD spectrum of Nu172 in the presence of 50 mM strontium ions indicates the presence of an antiparallel G-quadruplex, the concentration o f which drops at 50°C. NU172 does not have a rigid structure, apparently due to the presence of a guanine residue in the GT loop. The NU172 aptamer does not form a stable conformation in solution either without ions or with Ba2+ and Sr2+ ions. It was shown that there is possibility of aptamers transition from one conformation to another dependently on concentration and temperature confirms that the potassium ion is a unique stabilizing ion of natural molecules containing G-quadruplexes.

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Держатели документа:
Department bioimformatics and bioengineery, Lomonosov Moscow State University, Moscow, 119992, Russian Federation
Federal Research Center «Krasnoyarsk Science Center SB RAS», Krasnoyarsk, 660036, Russian Federation
Kirensky Institute of Physics, Krasnoyarsk, 660036, Russian Federation
Belozersky Institute of physical chemical biology, Lomonosov Moscow State University, Moscow, 119992, Russian Federation

Доп.точки доступа:
Nikolaeva, P. A.; Moryachkov, R. V.; Морячков, Роман Владимирович; Raldugina, V. N.; Naumova, Iu. O.; Novikova, T. M.; Spiridonova, V. A.

}
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Magnetic nanoscalpel for the effective treatment of ascites tumors / T. Zamay, S. Zamay, N. Luzan [et al.] // J. Funct. Biomater. - 2023. - Vol. 14, Is. 4. - Ст. 179, DOI 10.3390/jfb14040179. - Cited References: 36. - 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 educational 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” No. 2022060108781 and with the support of a partner company JSC «NPP «Radiosviaz» . - ISSN 2079-4983
Кл.слова (ненормированные):
magnetic nanodisks -- ascitic tumor -- magneto-mechanical therapy -- “smart nanoscalpel” -- DNA aptamers -- apoptosis -- necrosis
Аннотация: One of the promising novel methods for radical tumor resection at a single-cell level is magneto-mechanical microsurgery (MMM) with magnetic nano- or microdisks modified with cancer-recognizing molecules. A low-frequency alternating magnetic field (AMF) remotely drives and controls the procedure. Here, we present characterization and application of magnetic nanodisks (MNDs) as a surgical instrument (“smart nanoscalpel”) at a single-cell level. MNDs with a quasi-dipole three-layer structure (Au/Ni/Au) and DNA aptamer AS42 (AS42-MNDs) on the surface converted magnetic moment into mechanical and destroyed tumor cells. The effectiveness of MMM was analyzed on Ehrlich ascites carcinoma (EAC) cells in vitro and in vivo using sine and square-shaped AMF with frequencies from 1 to 50 Hz with 0.1 to 1 duty-cycle parameters. MMM with the “Nanoscalpel” in a sine-shaped 20 Hz AMF, a rectangular-shaped 10 Hz AMF, and a 0.5 duty cycle was the most effective. A sine-shaped field caused apoptosis, whereas a rectangular-shaped field caused necrosis. Four sessions of MMM with AS42-MNDs significantly reduced the number of cells in the tumor. In contrast, ascites tumors continued to grow in groups of mice and mice treated with MNDs with nonspecific oligonucleotide NO-MND. Thus, applying a “smart nanoscalpel” is practical for the microsurgery of malignant neoplasms.

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Держатели документа:
Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch, Russian Academy of Sciences, Krasnoyarsk 660036, Russia
Laboratory for Biomolecular and Medical Technologies, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk 660022, Russia
JSC «NPP «Radiosviaz», Krasnoyarsk 660021, Russia
Laboratory of Advanced Materials and Technology, Siberian Physical Technical Institute, Tomsk State University, Tomsk 634050, Russia
L.V. Kirensky Institute of Physics, Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk 660036, Russia
Institute of Automation and Control Processes (IACP), Far Eastern Branch of the Russian Academy of Science, Vladivostok 690041, Russia
Far Eastern Federal University, Vladivostok 690950, Russia
V.P. Astafiev Krasnoyarsk State Pedagogical University, Krasnoyarsk 660049, Russia

Доп.точки доступа:
Zamay, Tatiana; Zamay, Sergey; Luzan, Natalia; Fedotovskaya, Victoriya; Masyugin, Albert; Zelenov, F.; Koshmanova, Anastasia; Nikolaeva, Elena; Kirichenko, Daria; Veprintsev, Dmitry; Kolovskaya, Olga; Shchugoreva, Irina; Zamay, Galina; Lapin, I. N.; Lukyanenko, A. V.; Лукьяненко, Анна Витальевна; Borus, Andrey; Борус, Андрей Андреевич; Sukhachev, A. L.; Сухачев, Александр Леонидович; Volochaev, M. N.; Волочаев, Михаил Николаевич; Lukyanenko, Kirill; Shabanov, Alexandr; Zabluda, V. N.; Заблуда, Владимир Николаевич; Zhizhchenko, Alexey; Kuchmizhak, Aleksandr; Sokolov, A. Е.; Соколов, Алексей Эдуардович; Narodov, Andrey; Prokopenko, Vladimir; Galeev, Rinat; Svetlichnyi, Valery; Kichkailo, Anna
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10.

Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells / A. S. Kichkailo, A. A. Narodov, M. A. Komarova [et al.] // Mol. Ther. - Nucleic Acids. - 2023. - Vol. 32. - P. 267-288, DOI 10.1016/j.omtn.2023.03.015. - Cited References: 69. - The authors are grateful to all the patients and hospital staff participating in this research. We acknowledge the assistance of the AptamerLab LCC (www.aptamerlab.com) and personally Mr. Vasily Mezko for the aptamer 3D structure optimization and financial and technical support. The authors thank Mr. Alexey Kichkailo, Dr. Arkady B. Kogan, and Dr. Rinat G. Galeev for their general support. Mrs. Valentina L. Grigoreva, and Irina V. Gildebrand for the help with histological staining. Technical and instrumental support was provided by the Multiple-Access Center at Tomsk State University; the Krasnoyarsk Inter-District Ambulance Hospital, named after N.S. Karpovich; John L. Holmes Mass Spectrometry Facility at the University of Ottawa; Federal Siberian Research Clinical Centre under the Federal Medical Biological Agency; Shared Core Facilities of Molecular and Cell Technologies at Krasnoyarsk State Medical University and Krasnoyarsk Regional Centre for Collective Use at the Federal Research Centre “KSC SB RAS”. The confocal fluorescence microscopy research was carried out with the equipment of the Tomsk Regional Core Shared Research Facilities Center of the National Research Tomsk State University. The Center was supported by the Ministry of Science and Higher Education of the Russian Federation, grant no. 075-15-2021-693 (no. 13.RFC.21.0012). Acute toxicity studies were performed in a laboratory certified for preclinical studies, Laboratory of Biological Testing, Institute of Bioorganic Chemistry named after academics M.M. Shemyakin and Y.A. Ovchinnikov Russian Academy of Sciences. The authors are grateful to the Joint Super Computer Center of the Russian Academy of Sciences for providing supercomputers for computer simulations. Development of the glioma tumor model in immunosuppressed mice was supported by the Russian Science Foundation grant No. 22-64-00041 (M.A.D.), https://rscf.ru/en/project/22-64-00041/. Synthesis of 11C-aptamer and PET/CT visualization was funded by the Federal Medical Biological Agency; project 122041800132-2 (A.V.O.). Aptamer selection and their clinical applications were funded by the Ministry of Healthcare of the Russian Federation; project АААА-Б19-219090690032-5 (T.N.Z.). The Ministry of Science and Higher Education of the Russian Federation project FWES-2022-0005 (A.S.K.) supported aptamer characterization, molecular modelling, and in vivo experiments. Mass spectrometry analyses, DNA sequencing, and synthesis were supported by NSERC Discovery Grant (M.V.B.). We acknowledge the European Synchrotron Radiation Facility for SAXS experiments and thank Dr. Bart Van Laer for assistance in using a beamline BM29. SAXS measurements were supported by RFBR № 18-32-00478 for young scientists (R.V.M.). The synchrotron SEC-SAXS data for Gli-55 aptamer were also collected at beamline P12 operated by EMBL Hamburg at the PETRA III storage ring (DESY, Hamburg, Germany) . - ISSN 2162-2531
Аннотация: Here, we present DNA aptamers capable of specific binding to glial tumor cells in vitro, ex vivo, and in vivo for visualization diagnostics of central nervous system tumors. We selected the aptamers binding specifically to the postoperative human glial primary tumors and not to the healthy brain cells and meningioma, using a modified process of systematic evolution of ligands by exponential enrichment to cells; sequenced and analyzed ssDNA pools using bioinformatic tools and identified the best aptamers by their binding abilities; determined three-dimensional structures of lead aptamers (Gli-55 and Gli-233) with small-angle X-ray scattering and molecular modeling; isolated and identified molecular target proteins of the aptamers by mass spectrometry; the potential binding sites of Gli-233 to the target protein and the role of post-translational modifications were verified by molecular dynamics simulations. The anti-glioma aptamers Gli-233 and Gli-55 were used to detect circulating tumor cells in liquid biopsies. These aptamers were used for in situ, ex vivo tissue staining, histopathological analyses, and fluorescence-guided tumor and PET/CT tumor visualization in mice with xenotransplanted human astrocytoma. The aptamers did not show in vivo toxicity in the preclinical animal study. This study demonstrates the potential applications of aptamers for precise diagnostics and fluorescence-guided surgery of brain tumors.

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Держатели документа:
Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences,” 50 Akademgorodok, Krasnoyarsk 660036, Russia
Krasnoyarsk Inter-District Ambulance Hospital named after N.S. Karpovich, 17 Kurchatova, Krasnoyarsk 660062, Russia
Laboratory of Physics of Magnetic Phenomena, Kirensky Institute of Physics, 50/38 Akademgorodok, Krasnoyarsk 660036, Russia
Siberian Federal University, 79 Svobodny pr., Krasnoyarsk 660041, Russia
Department of Molecular Electronics, Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”, 50 Akademgorodok, Krasnoyarsk 660036, Russia
National Research Center Kurchatov Institute, 1 Akademika Kurchatova, Moscow 123182, Russia
Laboratory of Advanced Materials and Technology, Siberian Physical-Technical Institute of Tomsk State University, 36 Lenina, Tomsk 634050, Russia
Krasnoyarsk Regional Pathology-Anatomic Bureau, 3d Partizana Zheleznyaka, Krasnoyarsk 660022, Russia
Department of Chemistry, Lomonosov Moscow State University, 1/3 Leninskie gory, Moscow 119991, Russia
Department of Chemistry, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu, 702-701, South Korea
Nanoscience Center and Department of Chemistry, University of Jyväskylä, P.O. Box 35, Jyväskylä 40014, Finland
A.V. Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics” RAS, 59 Leninsky pr., Moscow, 119333, Russia
Federal Siberian Research Clinical Centre under the Federal Medical Biological Agency, Krasnoyarsk, Russia
Krasnoyarsk Regional Clinical Cancer Center, 16 1-ya Smolenskaya, Krasnoyarsk 660133, Russia
Institute of Chemistry and Chemical Technology SB RAS – The Branch of Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”, 660036 Krasnoyarsk, Russia
Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, Ontario K1N6N5, Canada
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 8 Lavrentyev Avenue, 630090 Novosibirsk, Russia

Доп.точки доступа:
Kichkailo, A. S.; Narodov, A. A.; Komarova, M. A.; Zamay, T. N.; Zamay, G. S.; Kolovskaya, O. S.; Erakhtin, E. E.; Glazyrin, Y. E.; Veprintsev, D. V.; Moryachkov, R. V.; Zabluda, V. N.; Заблуда, Владимир Николаевич; Shchugoreva, I.; Artyushenko, P.; Mironov, V. A.; Morozov, D. I.; Gorbushin, A. V.; Khorzhevskii, V. A.; Koshmanova, A. A.; Nikolaeva, E. D.; Grinev, I. P.; Voronkovskii, I. I.; Grek, D. S.; Belugin, K. V.; Volzhentsev, A. A.; Badmaev, O. N.; Luzan, N.; Lukyanenko, K. A.; Peters, G.; Lapin, I. N.; Лапин, И. Н.; Kirichenko, A. K.; Konarev, P. V.; Morozov, E. V; Mironov, G. G.; Gargaun, A.; Muharemagic, D.; Zamay, S. S.; Kochkina, E. V.; Dymova, M. A.; Smolyarova, T. E.; Sokolov, A. Е.; Соколов, Алексей Эдуардович; Modestov, A. A.; Tokarev, N. A.; Shepelevich, N.; Ozerskaya, A. V.; Chanchikova, N. G.; Krat, A. V.; Zukov, R. A.; Bakhtina, V. I.; Shnyakin, P. G.; Shesternya, P. A.; Svetlichnyi, V. A.; Petrova, M. M.; Artyukhov, I. P.; Tomilin, F. N.; Томилин, Феликс Николаевич; Berezovski, Maxim V.
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