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 68

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Penetration efficiency of antitumor agents in ovarian cancer spheroids: The case of recombinant targeted toxin DARPin-LoPE and the chemotherapy drug, doxorubicin
(2019) Sokolova, E.; Kutova, O.; Grishina, A.; Pospelov, A.; Deyev, S.; Деев, Сергей Михайлович
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.The efficiency of delivering a therapeutic agent into a tumor is among the crucial factors determining the prospects for its clinical use. This problem is particularly acute in the case of targeted antitumor agents since many of them are high-molecular-weight compounds. In this work, the penetration of therapeutic agents of two distinct molecular weights into the spheroids of ovarian adenocarcinoma overexpressing human epidermal growth factor receptor 2 (HER2) was studied. It was shown that the low-molecular-weight chemotherapy drug, doxorubicin (~0.5 kDa), effectively penetrates through almost the entire depth of a 300 to 400 µm spheroid, while the penetration depth of the HER2-specific recombinant targeted toxin, DARPin-LoPE (~42 kDa), is only a few surface layers of cells and does not exceed 70 µm. The low penetration of the targeted toxin into spheroid was shown along with a significant decrease in its efficiency against the three-dimensional tumor spheroid as compared with the two-dimensional monolayer culture. The approaches to increasing the accumulation of agents in the tumor are presented and prospects of their use in order to improve the effectiveness of therapy are discussed.
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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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Indirect Radioiodination of DARPin G3 Using N-succinimidyl-Para-Iodobenzoate Improves the Contrast of HER2 Molecular Imaging
(2019) Vorobyeva, Anzhelika; Schulga, Alexey; Rinne, Sara S.; Gunther, Tyran; Deyev, Sergey; Деев, Сергей Михайлович
Radionuclide molecular imaging of human epidermal growth factor receptor 2 (HER2) in breast and gastroesophageal cancer might be used to stratify patients for HER2-targeted therapy as well as monitor treatment response and disease progression. Designed ankyrin repeat proteins (DARPins) are small engineered scaffold proteins with favorable properties for molecular imaging. Herein we compared two methods for labeling the anti-HER2 DARPin (HE)(3)-G3, direct and indirect radioiodination. We hypothesized that the use of N-succinimidyl-para-iodobenzoate (SPIB) for radioiodination would facilitate the clearance of radiometabolites and improve the contrast of imaging. Both radiolabeled (HE)(3)-G3 variants preserved their binding specificity and high affinity to HER2-expressing cells. The specificity of tumor targeting in vivo was also demonstrated. A biodistribution comparison of [I-125]I-(HE)(3)-G3 and [I-125]I-PIB-(HE)(3)-G3, in mice bearing HER2 expressing SKOV3 xenografts, showed rapid clearance of [I-125]I-PIB-(HE)(3)-G3 from normal organs and tissues and low accumulation of activity in organs with NaI-symporter expression. Both radiolabeled (HE)(3)-G3 variants had equal tumor uptake. Consequently, the indirect label provided higher tumor-to-blood and tumor-to-organ ratios compared with the direct label. Comparative Single Photon Emission Computed Tomography (SPECT)/CT imaging of HER2 expression in SKOV3 xenografts, using both radiolabeled DARPins, demonstrated the superior imaging contrast of the indirect label. Indirect radioiodination of (HE)(3)-G3 using SPIB could be further applied for SPECT and PET imaging with iodine-123 and iodine-124.
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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 plasmonic HfN-based nanoparticles as a novel multifunctional agent for photothermal therapy
(2024) Pastukhov, A. I.; Savinov, M. S.; Zelepukin, I. V.; Babkova, J. S.; Tikhonowski, G. V.; Popov, A. A.; Klimentov, S. M.; Zavestovskaya, I. N.; Deyev, S. M.; Kabashin, A. V.; Савинов, Максим Сергеевич; Тихоновский, Глеб Валерьевич; Попов, Антон Александрович; Климентов, Сергей Михайлович; Завестовская, Ирина Николаевна; Деев, Сергей Михайлович; Кабашин, Андрей Викторович
HfN nanoparticles exhibiting a tunable plasmonic feature in the near-IR were synthesized by laser ablation in liquids. A strong photothermal therapeutic effect yielding 100% cells death under 808 nm irradiation of nanoparticles was reported.
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Bismuth nanoparticles-enhanced proton therapy: Concept and biological assessment
(2024) Zavestovskaya, I. N.; Tikhonowski, G. V.; Savinov, M.; Shakhov, P. V.; Popov, A. A.; Klimentov, S. M.; Deyev, S. M.; Завестовская, Ирина Николаевна; Тихоновский, Глеб Валерьевич; Савинов, Максим Сергеевич; Шахов, Павел Владимирович; Попов, Антон Александрович; Климентов, Сергей Михайлович; Деев, Сергей Михайлович
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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.