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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Dymova M. A., Malysheva D. O., Popova V. K., Dmitrienko E. V., Endutkin A. V., Drokov D. V., Mukhanov V. S., Byvakina A. A., Kochneva G. V., Artyushenko P. V., Shchugoreva I. A., Rogova A. V., Tomilin F. N., Kichkailo A. S., Richter V. A., Kuligina E. V.
Заглавие : Characterizing aptamer interaction with the oncolytic virus VV-GMCSF-Lact
Колич.характеристики :14 с
Место публикации : Molecules. - 2024. - Vol. 29, Is. 4. - Ст.848. - ISSN 14203049 (eISSN), DOI 10.3390/molecules29040848
Примечания : Cited References: 46. - This study was supported by the Russian Science Foundation grant No. 22-64-00041, available online: https://rscf.ru/en/project/22-64-00041/ (accessed on 6 February 2024). This work was supported by the Russian state-funded project for ICBFM SB RAS (grant number 121030200173-6)
Аннотация: Aptamers are currently being investigated for their potential to improve virotherapy. They offer several advantages, including the ability to prevent the aggregation of viral particles, enhance target specificity, and protect against the neutralizing effects of antibodies. The purpose of this study was to comprehensively investigate an aptamer capable of enhancing virotherapy. This involved characterizing the previously selected aptamer for vaccinia virus (VACV), evaluating the aggregation and molecular interaction of the optimized aptamers with the recombinant oncolytic virus VV-GMCSF-Lact, and estimating their immunoshielding properties in the presence of human blood serum. We chose one optimized aptamer, NV14t_56, with the highest affinity to the virus from the pool of several truncated aptamers and built its 3D model. The NV14t_56 remained stable in human blood serum for 1 h and bound to VV-GMCSF-Lact in the micromolar range (Kd ≈ 0.35 μM). Based on dynamic light scattering data, it has been demonstrated that aptamers surround viral particles and inhibit aggregate formation. In the presence of serum, the hydrodynamic diameter (by intensity) of the aptamer–virus complex did not change. Microscale thermophoresis (MST) experiments showed that NV14t_56 binds with virus (EC50 = 1.487 × 109 PFU/mL). The analysis of the amplitudes of MST curves reveals that the components of the serum bind to the aptamer–virus complex without disrupting it. In vitro experiments demonstrated the efficacy of VV-GMCSF-Lact in conjunction with the aptamer when exposed to human blood serum in the absence of neutralizing antibodies (Nabs). Thus, NV14t_56 has the ability to inhibit virus aggregation, allowing VV-GMCSF-Lact to maintain its effectiveness throughout the storage period and subsequent use. When employing aptamers as protective agents for oncolytic viruses, the presence of neutralizing antibodies should be taken into account.
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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Bashmakova E. E., Kudryavtsev A. N., Tupikin A. E., Kabilov M. R., Sokolov A. Е., Frank L. A.
Заглавие : Bioluminescent aptamer-based microassay for detection of melanoma inhibitory activity protein (MIA)
Место публикации : Anal. Methods. - 2024. - Article in press. - ISSN 17599660 (ISSN), DOI 10.1039/D4AY00706A. - ISSN 17599679 (eISSN)
Примечания : Cited References: 23
Аннотация: Melanoma inhibitory activity protein (MIA) does obviously offer the potential to reveal clinical manifestations of melanoma. Despite a pressing need for effective diagnosis of this highly fatal disease, there are no clinically approved MIA detection ELISA kits available. A recommended MIA threshold has not yet been defined, mostly by reason of variability in immunoglobulins' affinity and stability, the difference in sample preparation and assay conditions. Here we present a pair of high-affinity DNA aptamers developed as an alternative recognition and binding element for MIA detection. Their stability and reproducible synthesis are expected to ensure this analysis under standard conditions. The devised aptamer-based solid-phase microassay of model standard and control human sera involves luciferase NLuc as a highly sensitive reporter. Bioluminescence dependence on MIA concentration ranges in a linear manner from 2.5 to 250 ng mL−1, providing a MIA detection limit of 1.67 ± 0.57 ng mL−1.
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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Poolsup S., Zaripov E., Huttmann N., Minic Z., Artyushenko P. V., Shchugoreva I. A., Tomilin F. N., Kichkailo A. S., Berezovski M. V.
Заглавие : Discovery of DNA aptamers targeting SARS-CoV-2 nucleocapsid protein and protein-binding epitopes for label-free COVID-19 diagnostics
Место публикации : Mol. Ther. Nucleic Acids. - 2023. - Vol. 31. - P.731-743. - ISSN 21622531 (eISSN), DOI 10.1016/j.omtn.2023.02.010
Примечания : Cited References: 74. - M.V.B. thanks the Canadian Institutes of Health Research grant OV1-170353 for providing financial support. Molecular modeling and docking were supported by a grant from the Russian Science Foundation (project number 21-73-20240) for A.S.K. S.P. is thankful to Dr. Bob Dass, Dylan Tanner, and Dr. Degang Liu, Sartorius for generously providing excellent technical training and consumable support for binding assay on BLI, and Aldo Jordan for assisting with creating the figures. The authors also thank John L. Holmes’s mass spectrometry facility for providing access to perform nLC-MS/MS. Lastly, the authors thank the JCSS Joint Super Computer Center of the Russian Academy of Sciences for providing supercomputers for computer simulations
Аннотация: The spread of COVID-19 has affected billions of people across the globe, and the diagnosis of viral infection still needs improvement. Because of high immunogenicity and abundant expression during viral infection, SARS-CoV-2 nucleocapsid (N) protein could be an important diagnostic marker. This study aimed to develop a label-free optical aptasensor fabricated with a novel single-stranded DNA aptamer to detect the N protein. The N-binding aptamers selected using asymmetric-emulsion PCR-SELEX and their binding affinity and cross-reactivity were characterized by biolayer interferometry. The tNSP3 aptamer (44 nt) was identified to bind the N protein of wild type and Delta and Omicron variants with high affinity (KD in the range of 0.6–3.5 nM). Utilizing tNSP3 to detect the N protein spiked in human saliva evinced the potential of this aptamer with a limit of detection of 4.5 nM. Mass spectrometry analysis was performed along with molecular dynamics simulation to obtain an insight into how tNSP3 binds to the N protein. The identified epitope peptides are localized within the RNA-binding domain and C terminus of the N protein. Hence, we confirmed the performance of this aptamer as an analytical tool for COVID-19 diagnosis.
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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Semina P. N., Isaev I. L., Komogortsev S. V., Klyuchantsev A. B., Kostyukov A. S., Blagodatova A. V., Khrennikov D. E., Kichkailo A. S., Zamay T. N., Lapin I. N., Sokolov A. Е., Polyutov S. P., Karpov S. V.
Заглавие : Towards understanding the triggering of the malignant cell death in high-efficiency magneto-mechanical anticancer therapy
Место публикации : J. Phys. D. - 2023. - Vol. 56, Is. 6. - Ст.065401. - ISSN 00223727 (ISSN), DOI 10.1088/1361-6463/acb0dd. - ISSN 13616463 (eISSN)
Примечания : Cited References: 146. - P N S, A S K, D E K, S P P, S V K acknowledge the support by the Ministry of Science and High Education of Russian Federation (Project No. FSRZ-2020-0008). Experimental analyses were funded by the Ministry of Science and Higher Education of the Russian Federation (Project FWES-2022-0005) – A S K, T N Z. The authors thank Dr S V Saikova for providing the TEM image in figure (b)
Аннотация: The paper discusses schemes for the implementation of magneto-mechanical anticancer therapy and the most probable scenarios of damaging mechanical eﬀects on the membranes of malignant cells by targeted magnetic nanoparticles selectively bound to membrane mechanoreceptors employing aptamers. The conditions for selective triggering of the malignant cell apoptosis in a low-frequency non-heating alternating magnetic ﬁeld, corresponding to the exceeding threshold value of the force acting on the membrane and its mechanoreceptors, are established using a nanoparticle dynamic simulation. The requirements for the functionality of magnetic nanoparticles and their suitability for biomedical applications are analysed. Attention is paid to the possibility of the formation of magnetite nanoparticle aggregates in an external magnetic ﬁeld and their localization near tumor cell membranes. It is shown that the scenario involving the process of aggregation of magnetite nanoparticles provides a suﬃcient magneto-mechanical impact to achieve a therapeutic eﬀect. A possible explanation for the experimentally established fact of successful application of magneto-mechanical therapy using magnetite nanoparticles is presented, in which complete suppression of the Ehrlich carcinoma in an alternating magnetic ﬁeld as a response to a magnetome-chanical stimulus was demonstrated. This result conﬁrmed the possibility of using the method for high eﬃciency treatment of malignant neoplasms. The paper is provided with an extensive review of key publications and the state of art in this area.
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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Kolovskaya O. S., Zyuzyukina A. V., Dassie, Justin P., Zamay G. S., Zamay T. N., Boyakova N. V., Khorzhevskii V. A., Kirichenko D. A., Lapin I. N., Shchugoreva I. A., Artyushenko P. V., Tomilin F. N., Veprintsev D. V., Glazyrin Yu. E., Minic, Zoran, Bozhenko V. K., Kudinova E. A., Kiseleva Ya. Y., Krat A. V., Slepov E. V., Bukatin A. S., Zukov R. A., Shesternya P. A., Berezovski M. V., Giangrande P. H., Kichkailo A. S.
Заглавие : Monitoring of breast cancer progression via aptamer-based detection of circulating tumor cells in clinical blood samples
Место публикации : Front. Mol. Biosci. - 2023. - Vol. 10. - Ст.1184285. - ISSN 2296889X (eISSN), DOI 10.3389/fmolb.2023.1184285
Примечания : Cited References: 37. - CTCs isolation method development and clinical sample analyses were supported by the Ministry of Healthcare of Russian Federation project REYC-2023-0012. The Ministry of Science and Higher Education of the Russian Federation project FWES-2022-0005 supported aptamer characterization, molecular modeling. MDA-231/LUC cells were from R. Domann (Jenkin et al. Breast Cancer Research, 2005). Technical and instrumental support was provided by the 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)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 Vasily Mezko for the technical support. The authors thank Valentina L. Grigoreva, and Irina V. Gildebrand for the help with СTC staining
Аннотация: Introduction: Breast cancer (BC) diagnostics lack noninvasive methods and procedures for screening and monitoring disease dynamics. Admitted CellSearch® is used for fluid biopsy and capture of circulating tumor cells of only epithelial origin. Here we describe an RNA aptamer (MDA231) for detecting BC cells in clinical samples, including blood. The MDA231 aptamer was originally selected against triple-negative breast cancer cell line MDA-MB-231 using cell-SELEX. Methods: The aptamer structure in solution was predicted using mFold program and molecular dynamic simulations. The affinity and specificity of the evolved aptamers were evaluated by flow cytometry and laser scanning microscopy on clinical tissues from breast cancer patients. CTCs were isolated form the patients’ blood using the developed method of aptamer-based magnetic separation. Breast cancer origin of CTCs was confirmed by cytological, RT-qPCR and Immunocytochemical analyses. Results: MDA231 can specifically recognize breast cancer cells in surgically resected tissues from patients with different molecular subtypes: triple-negative, Luminal A, and Luminal B, but not in benign tumors, lung cancer, glial tumor and healthy epithelial from lungs and breast. This RNA aptamer can identify cancer cells in complex cellular environments, including tumor biopsies (e.g., tumor tissues vs. margins) and clinical blood samples (e.g., circulating tumor cells). Breast cancer origin of the aptamer-based magnetically separated CTCs has been proved by immunocytochemistry and mammaglobin mRNA expression. Discussion: We suggest a simple, minimally-invasive breast cancer diagnostic method based on non-epithelial MDA231 aptamer-specific magnetic isolation of circulating tumor cells. Isolated cells are intact and can be utilized for molecular diagnostics purposes.
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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Stolyar S. V., Li O. A., Nikolaeva E. D., Vorotynov A. M., Velikanov D. A., Knyazev Yu. V., Bayukov O. A., Iskhakov R. S., Kryukova O. V., Pyankov V. F., Volochaev M. N., Mokhov A. A.
Заглавие : Preparation and properties of magnetic composites γ-Fe2O3/SiO2/aptamer(FAS9) for magnetic resonance hyperthermia
Колич.характеристики :8 с
Место публикации : Phys. Met. Metallogr. - 2023. - Vol. 124, Is. 14. - P.1689-1696. - ISSN 0031918X (ISSN), DOI 10.1134/S0031918X23601439. - ISSN 15556190 (eISSN)
Примечания : Cited References: 27
Аннотация: Powders of maghemite γ-Fe2O3 with an average diameter of 8 nm, γ-Fe2O3/SiO2 composites with an agglomerate diameter of about 50 nm and a size of interspersed γ-Fe2O3 particles of 6 nm, and γ‑Fe2O3/SiO2/aptamer(FAS9) composites were synthesized by chemical deposition. Mössbauer spectra were measured, the static and dynamic magnetic properties of the powders were studied, and the coercive force was determined, which decreases from 14 Oe for γ-Fe2O3 powders to 3 Oe for the γ-Fe2O3/SiO2 composite. It is shown that the particle blocking temperature is close to room temperature. The increment of temperature of the powders was measured in the ferromagnetic resonance mode; the temperature of the Fe2O3/SiO2 composite (ΔT ≈ 16°C) turned out to be higher than that of the pure γ-Fe2O3 powder (ΔT ≈ 10°C). It has been experimentally shown that temperature increment ΔT is proportional to the square of the microwave field amplitude. It has been shown that the composition γ-Fe2O3/SiO2/aptamer FAS9 is able to effectively bind to tumor cells, and FMR hyperthermia leads to a decrease in the viability of tumor cells.
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Вид документа : Статья из сборника (однотомник)
Шифр издания :
Автор(ы) : Sokolov A. Е., Lukyanenko A. V., Zabluda V. N., Borus A. A., Zamay G. S., Zamay T. N., Luzan N., Zamay S. S.
Заглавие : Aptamer modified Au/Ni/Au nanodiscs for magnetomechanical cell surgery
Коллективы : International Baltic Conference on Magnetism, Балтийский федеральный университет им. И. Канта
Место публикации : V International Baltic Conference on Magnetism. IBCM: Book of abstracts. - 2023. - P.12
Примечания : Cited References: 3
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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Kostyukov A. S., Isaev I. L., Ershov A. E., Gerasimov V. S., Polyutov S. P., Karpov S. V.
Заглавие : Part II. Nanobubbles around plasmonic nanoparticles in terms of modern simulation modeling: what makes them kill the malignant cells?
Коллективы : Ministry of Science and High Education of Russian Federation [FSRZ-2020-0008]; RFBRRussian Foundation for Basic Research (RFBR); Krasnoyarsk Territory and Krasnoyarsk Regional Fund of Science [20-42-240003]
Место публикации : J. Phys. D. - 2022. - Vol. 55, Is. 17. - Ст.175402. - ISSN 0022-3727, DOI 10.1088/1361-6463/ac4c1f. - ISSN 1361-6463(eISSN)
Примечания : Cited References: 49. - The research was supported by the Ministry of Science and High Education of Russian Federation (Project No. FSRZ-2020-0008), and was funded by RFBR, Krasnoyarsk Territory and Krasnoyarsk Regional Fund of Science, Project No. 20-42-240003
Предметные рубрики: STRESS WAVES
LASER
MEMBRANE
DAMAGE
DEATH
LYSIS
Аннотация: We have established numerically the physical pattern and conditions for formation of nanosized bubbles in aqueous medium around biocompatible plasmonic nanoparticles (NPs) selectively bound to the membrane of the malignant cells by means of DNA-aptamers under the action of picosecond laser radiation. The results obtained are based on the finite volume method and hydrodynamic models underlying the ANSYS Fluent package with extended capabilities. We have found the main features and previously unknown dominant factors of the damage effect on the cell membrane at the moment of the bubble nucleation around the plasmonic NPs of different types taking into account the influence of the closely located membrane. Information on the kinetics of spatial distribution of pressure, temperature and the relative proportion of vapor in the 'nanoparticle-membrane-medium' system have been obtained. The attention is drawn to the advantages of using biocompatible, perfectly absorbing core–shell plasmonic NPs for anti-tumor therapy characterized by an increased mechanical effect on malignant cell membranes at lower laser radiation intensity and the spectral position of their plasmon resonance (λ = 700 nm) in the hemoglobin transparency range. This ensures penetration of laser radiation deep into tissues. The paper is provided with an extensive review of key publications and the state-of-art in this area.
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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Zamay T. N., Starkov A. K., Kolovskaya O. S., Zamay G. S., Veprintsev D. V., Luzan N., Nikolaeva E. D., Lukyanenko K. A., Artyushenko P. V., Shchugoreva I. A., Glazyrin Y. E., Koshmanova A. A., Krat A. V., Tereshina D. S., Zamay S. S., Pats Y. S., Zukov R. A., Tomilin F. N., Berezovski M. V., Kichkailo A. S.
Заглавие : Nucleic acid aptamers increase the anticancer efficiency and reduce the toxicity of cisplatin-arabinogalactan conjugates in vivo
Место публикации : Nucleic Acid Ther. - 2022. - Vol. 32, Is. 6. - P.497-506. - ISSN 21593337 (ISSN), DOI 10.1089/nat.2022.0024. - ISSN 21593345 (eISSN)
Примечания : Cited References: 42
Аннотация: Cisplatin is an effective drug for treating various cancer types. However, it is highly toxic for both healthy and tumor cells. Therefore, there is a need to reduce its therapeutic dose and increase targeted bioavailability. One of the ways to achieve this could be the coating of cisplatin with polysaccharides and specific carriers for targeted delivery. Nucleic acid aptamers could be used as carriers for the specific delivery of medicine to cancer cells. Cisplatin-arabinogalactan-aptamer (Cis-AG-Ap) conjugate was synthesized based on Cis-dichlorodiammineplatinum, Siberian larch arabinogalactan, and aptamer AS-42 specific to heat-shock proteins (HSP) 71?kDa (Hspa8) and HSP 90-beta (Hsp90ab1). The antitumor effect was estimated using ascites and metastatic Ehrlich tumor models. Cis-AG-Ap toxicity was assessed by blood biochemistry on healthy mice. Here, we demonstrated enhanced anticancer activity of Cis-AG-Ap and its specific accumulation in tumor foci. It was shown that targeted delivery allowed a 15-fold reduction in the therapeutic dose of cisplatin and its toxicity. Cis-AG-Ap sufficiently suppressed the growth of Ehrlich's ascites carcinoma, the mass and extent of tumor metastasis in vivo. Arabinogalactan and the aptamers promoted cisplatin efficiency by enhancing its bioavailability. The described strategy could be very promising for targeted anticancer therapy.
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10.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Shchugoreva I. A., Artyushenko P. V., Tomilin F. N., Morozov D. I., Mironov V. A., Moryachkov R. V., Kichkailo A. S.
Заглавие : Applying joint theoretical experimental research to aptamer modeling
Место публикации : Sib. Med. Rev. - 2021. - Vol. 2021, Is. 2. - P.105-106. - ISSN 18199496 (ISSN), DOI 10.20333/2500136-2021-2-105-106; Сиб. мед. обозрение
Примечания : Cited References: 4
Аннотация: The aim of the research. In this work we studied the structure of LC-18 DNA aptamer, which exhibits specific binding to lung adenocarcinoma cells. Obtain-ing the 3D structure of the aptamer is necessary for understanding the mechanism of binding of the aptamer to the target. Therefore, the aim of the research was modeling of the LC-18 aptamer spatial structure using combination of theoretical methods: DNA folding tools, quantum-chemical calculations and molecular dynamic simulations. Material and methods. The secondary structure of the LC-18 aptamer was predicted by using OligoAnalyzer and MFold online software under the conditions typical small-angle X-ray scattering (SAXS) experiment. The molecular modeling of the aptamer was carried out using the Avogadro program. For prediction of the structure two computational methods were used: quantum-mechanical method with third-order density-functional tight-binding (DFTB3) and molecular dynamics (MD) with force fields. Results. In this paper it was shown that molecular simulations can predict structures from the SAXS experiments. OligoAnalyzer and MFold web servers have been used to generate a set of several likely models. However, more accurate calculations have showed that these models do not predict the relative importance of isomers. Meanwhile, application of quantum-chemical and molecular dynamics calculations have showed reliable molecular structures which have a small deviations from the experimental SAXS curves. Conclusion. This study demonstrates the approach for modeling 3D structures of DNA-aptamers in solution using both experimental and theoretical meth-ods. It could be very helpful in designing more efficient aptamers based on results obtained from molecular simulations.
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