Персона:
Деев, Сергей Михайлович

Организационные подразделения

Организационная единица

Инженерно-физический институт биомедицины

Цель ИФИБ и стратегия развития – это подготовка высококвалифицированных кадров на базе передовых исследований и разработок новых перспективных методов и материалов в области инженерно-физической биомедицины. Занятие лидерских позиций в биомедицинских технологиях XXI века и внедрение их в образовательный процесс, что отвечает решению практикоориентированной задачи мирового уровня – диагностике и терапии на клеточном уровне социально-значимых заболеваний человека.

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Деев

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Сергей Михайлович

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Теперь показываю 1 - 10 из 55

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HER2-Specific Targeted Toxin DARPin-LoPE: Immunogenicity and Antitumor Effect on Intraperitoneal Ovarian Cancer Xenograft Model
(2019) Sokolova, E. A.; Shilova, O. N.; Kiseleva, D. V.; Schulga, A. A.; Deyev, S. M.; Деев, Сергей Михайлович
High immunogenicity and systemic toxicity are the main obstacles limiting the clinical use of the therapeutic agents based on Pseudomonas aeruginosa exotoxin A. In this work, we studied the immunogenicity, general toxicity and antitumor effect of the targeted toxin DARPin-LoPE composed of HER2-specific DARPin and a low immunogenic exotoxin A fragment lacking immunodominant human B lymphocyte epitopes. The targeted toxin has been shown to effectively inhibit the growth of HER2-positive human ovarian carcinoma xenografts, while exhibiting low non-specific toxicity and side effects, such as vascular leak syndrome and liver tissue degradation, as well as low immunogenicity, as was shown by specific antibody titer. This represents prospects for its use as an agent for targeted therapy of HER2-positive tumors.
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Phase-Responsive Fourier Nanotransducers for Probing 2D Materials and Functional Interfaces
(2019) Kravets, V. G.; Wu, F.; Imaizumi, S.; Grigorenko, A. N.; Kabashin, A. V.; Shipunova, V. O.; Deyev, S. M.; Кабашин, Андрей Викторович; Деев, Сергей Михайлович
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Light scattered by an object contains plethora information about the object which is distributed evenly among all possible Fourier components of light observed in the far-field. There are some cases, however, where this information is accumulated in the light confined by the object and then encoded in just a few coherent optical beams. Here, Fourier nanotransducers based on 2D plasmonic metamaterials are introduced, which are capable of confining light in 2D plane contacting with a functional interface, gathering information about its properties, and then transmitting the information into discrete optical beams with amplified phase relations. It is shown that phase of light in such beams can be used for probing dynamic physical properties of 2D materials and performing bio/chemical sensing with unprecedented sensitivity. Using a Fourier transducer based on periodic gold nanostructures, ferroelectric response from a single atomic layer of MoS 2 is resolved and studied for the first time, as well as the detection of important antibiotic chloramphenicol at fg mL −1 level is demonstrated, which several orders of magnitude better than reported in the literature. The implementation of phase-responsive Fourier nanotransducers opens new avenues in exploration of emergent 2D structures and radical improvement of biosensing technology.
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Imaging‐guided therapy simultaneously targeting HER2 and EpCAM with trastuzumab and EpCAM‐directed toxin provides additive effect in Ovarian cancer model
(2021) Xu, T.; Vorobyeva, A.; Schulga, A.; Konovalova, E.; Deyev, S. M.; Деев, Сергей Михайлович
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.Efficient treatment of disseminated ovarian cancer (OC) is challenging due to its heterogeneity and chemoresistance. Overexpression of human epidermal growth factor receptor 2 (HER2) and epithelial cell adhesion molecule (EpCAM) in approx. 30% and 70% of ovarian cancers, respectively, allows for co‐targeted treatment. The clinical efficacy of the monoclonal antibody trastuzumab in patients with HER2‐positive breast, gastric and gastroesophageal cancers makes it readily available as the HER2‐targeting component. As the EpCAM‐targeting component, we investigated the designed ankyrin repeat protein (DARPin) Ec1 fused to a truncated variant of Pseudomonas exotoxin A with reduced immunogenicity and low general toxicity (LoPE). Ec1‐LoPE was radiolabeled, evaluated in ovarian cancer cells in vitro and its biodistribution and tumor-targeting properties were studied in vivo. The therapeutic efficacy of Ec1‐LoPE alone and in combination with trastuzumab was studied in mice bearing EpCAM‐ and HER2‐expressing SKOV3 xenografts. SPECT/CT imaging enabled visualization of EpCAM and HER2 expression in the tumors. Co‐treatment using Ec1‐LoPE and trastuzumab was more effective at reducing tumor growth and prolonged the median survival of mice compared with mice in the control and monotherapy groups. Repeated administration of Ec1‐LoPE was well tolerated without signs of hepatic or kidney toxicity. Co‐treatment with trastuzumab and Ec1‐LoPE might be a potential therapeutic strategy for HER2‐ and EpCAM‐positive OC.
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Comparative Evaluation of Engineered Polypeptide Scaffolds in HER2-Targeting Magnetic Nanocarrier Delivery
(2021) Kolesnikova, O. A.; Kotelnikova, P. A.; Soloviev, V. D.; Proshkina, G. M.; Shipunova, V. O.; Popov, A. A.; Deyev, S. M.; Попов, Антон Александрович; Деев, Сергей Михайлович
© 2021 The Authors. Published by American Chemical Society.Targeted drug delivery is one of the most intriguing and challenging issues in modern biomedicine. For active targeting, full-size IgG molecules (150 kDa) are usually used. Recent studies have revealed that small artificial polypeptide scaffolds such as DARPins (14 kDa) and affibodies (8 kDa) are much more promising tools for drug delivery due to their small size, artificial nature, low immunogenicity, and many other properties. However, there is no comparative information on the targeting abilities of scaffold polypeptides, which should be taken into account when developing drug delivery systems (DDSs). The present work is the first comprehensive study on the comparison of the effectiveness of different HER2-targeting proteins within the architecture of nanoparticles. Namely, we synthesized trimodal nanoparticles: magnetic, fluorescent, and directed toward HER2 oncomarker on cancer cells. The magnetic particles (MPs) were covalently modified with (i) full-size IgG, 150 kDa, (ii) DARPin_G3, 14 kDa, and (iii) affibody ZHER2:342, 8 kDa. We showed that the number of DARPin_G3 and affibody ZHER2:342 molecules conjugated to the nanoparticle surface are 10 and 40 times higher, respectively, than the corresponding value for trastuzumab. Using the methods of magnetic particle quantification (MPQ)-cytometry and confocal microscopy, we showed that all types of the obtained magnetic conjugates specifically labeled HER2-overexpressing cells. Namely, we demonstrated that particle binding to HER2-positive cells is 1113 ± 39 fg/cell for MP*trastuzumab, 1431 ± 186 fg/cell for MP*ZHER2:342, and 625±21 fg/cell for MP*DARPin_G3, which are 2.77, 2.75, and 2.30 times higher than the corresponding values for control HER2-negative cells. Thus, we showed that the smallest HER2-recognizing polypeptide affibody ZHER2:342 is more effective in terms of specificity and selectivity in nanoparticle-mediated cell labeling.
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Plga nanoparticles decorated with anti-her2 affibody for targeted delivery and photoinduced cell death
(2021) Nikitin, M. P.; Shipunova, V. O.; Sogomonyan, A. S.; Zelepukin, I. V.; Deyev, S. M.; Согомонян, Анна Самвеловна; Деев, Сергей Михайлович
The effect of enhanced permeability and retention is often not sufficient for highly effective cancer therapy with nanoparticles, and the development of active targeted drug delivery systems based on nanoparticles is probably the main direction of modern cancer medicine. To meet the challenge, we developed polymer PLGA nanoparticles loaded with fluorescent photosensitive xanthene dye, Rose Bengal, and decorated with HER2-recognizing artificial scaffold protein, af-fibody ZHER2:342. The obtained 170 nm PLGA nanoparticles possess both fluorescent and photosensitive properties. Namely, under irradiation with the green light of 540 nm nanoparticles, they produced reactive oxygen species leading to cancer cell death. The chemical conjugation of PLGA with anti-HER2 affibody resulted in the selective binding of nanoparticles only to HER2-overexpressing cancer cells. HER2 is a receptor tyrosine kinase that belongs to the EGFR/ERbB family and is overexpressed in 30% of breast cancers, thus serving as a clinically relevant oncomarker. However, the standard targeting molecules such as full-size antibodies possess serious drawbacks, such as high immunogenicity and the need for mammalian cell production. We believe that the developed affibody-decorated targeted photosensitive PLGA nanoparticles will provide new solutions for ongoing problems in cancer diagnostics and treatment, as well in cancer theranostics.
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Laser-Synthesized Germanium Nanoparticles as Biodegradable Material for Near-Infrared Photoacoustic Imaging and Cancer Phototherapy
(2024) Belyaev, I. B.; Zelepukin, I. V.; Kotelnikova, P. A.; Tikhonowski, G. V.; Popov, A. A.; Kopylov, A. N.; Deyev, S. M.; Тихоновский, Глеб Валерьевич; Попов, Антон Александрович; Копылов, Алексей Николаевич; Деев, Сергей Михайлович
Abstract Biodegradable nanomaterials can significantly improve the safety profile of nanomedicine. Germanium nanoparticles (Ge NPs) with a safe biodegradation pathway are developed as efficient photothermal converters for biomedical applications. Ge NPs synthesized by femtosecondў??laser ablation in liquids rapidly dissolve in physiologicalў??like environment through the oxidation mechanism. The biodegradation of Ge nanoparticles is preserved in tumor cells in vitro and in normal tissues in mice with a halfў??life as short as 3.5 days. Biocompatibility of Ge NPs is confirmed in vivo by hematological, biochemical, and histological analyses. Strong optical absorption of Ge in the nearў??infrared spectral range enables photothermal treatment of engrafted tumors in vivo, following intravenous injection of Ge NPs. The photothermal therapy results in a 3.9ў??fold reduction of the EMT6/P adenocarcinoma tumor growth with significant prolongation of the mice survival. Excellent massў??extinction of Ge NPs (7.9 L g ў??1 cm ў??1 at 808 nm) enables photoacoustic imaging of bones and tumors, following intravenous and intratumoral administrations of the nanomaterial. As such, strongly absorbing nearў??infraredў??light biodegradable Ge nanomaterial holds promise for advanced theranostics.
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Label-free methods of multiparametric surface plasmon resonance and MPQ-cytometry for quantitative real-time measurements of targeted magnetic nanoparticles complexation with living cancer cells
(2021) Shipunova, V. O.; Nikitin, M. P.; Belova, M. M.; Deyev, S. M.; Деев, Сергей Михайлович
Most of the methods used today for investigation of nanoparticle binding to living cells imply a quantitative or qualitative analysis and do not provide information on the binding dynamics. To meet the challenge, we show here for the first time that the interaction of metal nanoparticles with eukaryotic cells in the flow system in dynamics can be studied by the method of multiparametric surface plasmon resonance. To this aim, we obtained a spectrum of colloidally stable targeted magnetite nanoparticles modified by phytolectins (SBA, WGA, ConA) of different specificity to monosaccharides (GalNAc, GlcNAc, and Man, respectively), and studied the interaction of these conjugates with human epidermoid carcinoma A431 cells. We showed that multiparametric surface plasmon resonance can be effectively used as a label-free method to study the process of dynamic mass transfer in the nanoparticle*cell system in the fluid cell. We show that not only the commonly used parameter in such systems, the angle of the minimum peak, theta(SPR), at the full angular spectrum, but also the intensity, I, of this peak, can be used to study the binding of targeted nanoparticles with living cells in dynamics. This is due to the contribution of metal nanoparticles to resonant absorption of incident electromagnetic radiation by free electrons at the interface between media with different refractive indices. To get the most relevant quantitative data on nanoparticle binding to the cell surface, we combined this assay with our original MPQ-cytometry method (Magnetic Particle Quantification based cytometry) precisely quantifying the nanoparticles in the static cell sample. By the combination of label-free plasmonic and magnetometry-based MPQ-cytometry methods, we showed that nanoparticles modified with agglutinin from soybeans, SBA, most efficiently (up to 4.2 +/- 0.1 pg/ cell) bind to epidermoid carcinoma cells with achieving a saturation at 12 min.
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MIL-53 (Al) metal-organic frameworks as potential drug carriers
(2021) Kolokolnikov, V. N.; Griaznova, O. Yu.; Zelepukin, I. V.; Tikhonowski, G. V.; Deyev, S. M.; Грязнова, Ольга Юрьевна; Тихоновский, Глеб Валерьевич; Деев, Сергей Михайлович
© 2021 Institute of Physics Publishing. All rights reserved.One of the challenges of the medicine is to improve the chemical stability of drugs and to prevent their premature biodegradation before reaching the therapeutic target. Various nanoparticles were used to solve this problem, but low drug loading efficiency limited their biomedical applications. Metal organic frameworks are promising candidates for drug delivery since they have extremely high surface area and regular porosity. In this study, we prepared high-crystalline MIL-53 frameworks based on aluminium and 2-aminoterephtalic acid by microwave-assisted synthesis and evaluated their properties as drug carriers. Drug loading of chemotherapeutic and diagnostic molecules of different nature riches value of 34% by particle weight, significantly higher than those of other reported solid nanoparticles. Therefore, our results make MIL-53 (Al) frameworks promising candidate for drug delivery.
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Targeted PLGA–Chitosan Nanoparticles for NIR-Triggered Phototherapy and Imaging of HER2-Positive Tumors
(2024) Kotelnikova, P. A.; Shipunova, V. O.; Deyev, S. M.; Деев, Сергей Михайлович
Targeted medicine uses the distinctive features of cancer cells to find and destroy tumors. We present human epidermal growth factor receptor 2 (HER2)-targeted PLGAвЂ“chitosan nanoparticles for cancer therapy and visualization. Loading with two near-infrared (NIR) dyes provides imaging in the NIR transparency window and phototherapy triggered by 808 nm light. Nile Blue (NB) is a biocompatible solvatochromic NIR dye that serves as an imaging agent. Laser irradiation of IR-780 dye leads to a temperature rise and the generation of reactive oxygen species (ROS). Resonance energy transfer between two dyes allows visualization of tumors in a wide range of visible and IR wavelengths. The combination of two NIR dyes enables the use of nanoparticles for diagnostics only or theranostics. Modification of poly(lactic-co-glycolic acid) (PLGA)вЂ“chitosan nanoparticles with trastuzumab provides an efficient nanoparticle uptake by tumor cells and promotes more than sixfold specificity towards HER2-positive cells, leading to a synergistic anticancer effect. We demonstrate optical imaging of the HER2-positive mouse mammary tumor and tumor-specific accumulation of PLGAвЂ“IR-780вЂ“NB nanoparticles in vivo after intravenous administration. We managed to achieve almost complete suppression of the proliferative activity of cells in vitro by irradiation with an 808 nm laser with a power of 0.27 W for 1 min at a concentration at which nanoparticles are nontoxic to cells in the dark.
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MPS blockade with liposomes controls pharmacokinetics of nanoparticles in a size-dependent manner
(2024) Belyaev, I. B.; Mirkasymov, A. B.; Rodionov, V. I.; Nikitin, P. I.; Deyev, S. M.; Никитин, Петр Иванович; Деев, Сергей Михайлович