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Деев, Сергей Михайлович

Организационные подразделения

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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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Сергей Михайлович

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Теперь показываю 1 - 10 из 54

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Long-Term Fate of Magnetic Particles in Mice: A Comprehensive Study
(2021) Yaremenko, A. V.; Yuryev, M. V.; Cherkasov, V. R.; Nikitin, M. P.; Zelepukin, I. V.; Ivanov, I. N.; Deyev, S. M.; Nikitin, P. I.; Деев, Сергей Михайлович; Никитин, Петр Иванович
© 2021 American Chemical Society.Safe application of nanoparticles in medicine requires full understanding of their pharmacokinetics including catabolism in the organism. However, information about nanoparticle degradation is still scanty due to difficulty of long-term measurements by invasive techniques. Here, we describe a magnetic spectral approach for in vivo monitoring of magnetic particle (MP) degradation. The method noninvasiveness has allowed performing of a broad comprehensive study of the 1-year fate of 17 types of iron oxide particles. We show a long-lasting influence of five parameters on the MP degradation half-life: dose, hydrodynamic size, ζ-potential, surface coating, and internal architecture. We observed a slowdown in MP biotransformation with an increase of the injected dose and faster degradation of the particles of a small hydrodynamic size. A comparison of six types of 100 nm particles coated by different hydrophilic polymer shells has shown that the slowest (t1/2 = 38 ± 6 days) and the fastest (t1/2 = 15 ± 4 days) degradations were achieved with a polyethylene glycol and polyglucuronic acid coatings, respectively. The most significant influence on the MP degradation was due to the internal architecture of the particles as the coverage of magnetic cores with a solid 39 nm polystyrene layer slowed down the half-life of the core-shell MPs from 48 days to more than 1 year. The revealed deeper insights into the particle degradation in vivo may facilitate rational design of nano- and microparticles with predictable long-term fate in vivo.
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In vivo blockade of mononuclear phagocyte system with solid nanoparticles: Efficiency and affecting factors
(2021) Mirkasymov, A. B.; Nikitin, M. P.; Zelepukin, I. V.; Nikitin, P. I.; Deyev, S. M.; Никитин, Петр Иванович; Деев, Сергей Михайлович
© 2020 Elsevier B.V.Smart nanomaterials, contrast nanoparticles and drug nanocarriers of advanced targeting architecture were designed for various biomedical applications. Most of such agents demonstrate poor pharmacokinetics in vivo due to rapid elimination from the bloodstream by cells of the mononuclear phagocyte system (MPS). One of the promising methods to prolong blood circulation of the nanoparticles without their modification is MPS blockade. The method temporarily decreases macrophage endocytosis in response to uptake of a low-toxic non-functional material. The effect of different factors on the efficiency of macrophage blockade in vivo induced by solid nanomaterials has been studied here. Those include: blocker nanoparticle size, ζ-potential, surface coating, dose, mice strain, presence of tumor or inflammation. We found that the blocker particle coating type had the strongest effect on MPS blockade efficiency, which allowed to prolong functional particle blood circulation half-life 18 times. The mechanisms capable of regulation of the MPS blockade have been demonstrated, which can promote application of this phenomenon in medicine for improving delivery of diagnostic and therapeutic nanomaterials.
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Comparison of pharmacokinetics and biodistribution of laser-synthesized plasmonic Au and TiN nanoparticles
(2021) Tselikov, G. I.; Al-Kattan, A.; Bailly, A. -L.; Correard, F.; Popov, A. A.; Zelepukin, I. V.; Tikhonowski, G. V.; Popova-Kuznetsova, E. A.; Klimentov, S. M.; Deyev, S. M.; Kabashin, A. V.; Попов, Антон Александрович; Тихоновский, Глеб Валерьевич; Попова-Кузнецова, Елена Алефтиновна; Климентов, Сергей Михайлович; Деев, Сергей Михайлович; Кабашин, Андрей Викторович
© 2021 Institute of Physics Publishing. All rights reserved.Plasmonic nanostructures offer wide range of diagnostic and therapeutic functionalities for biomedical applications. Gold nanoparticles (Au NPs) present one of the most explored nanomaterial in this field, while titanium nitride nanoparticles (TiN NPs) is a new promising nanomaterial with superior plasmonic properties for biomedicine. However conventional chemical techniques for the synthesis of these nanomaterials cannot always match stringent requirements for toxicity levels and surface conditioning. Laser-synthesized Au and TiN NPs offer exceptional purity (no contamination by by-products or ligands) and unusual surface chemistry. Therefore, these NPs present a viable alternative to chemically synthesized counterparts. This work presents comparative analysis of pharmacokinetics and biodistribution of laser-synthesized 20 nm Au and TiN NPs under intravenous administration in mice model. Our data show that Au NPs and bare TiN NPs are rapidly eliminated from the blood circulation and accumulate preferentially in liver and spleen, while coating of TiN NPs by hydrophilic polymer polyethylene glycol (PEG) significantly prolongates blood circulation time and improves delivery of the NPs to tumor. We finally discuss potential applications of laser synthesized Au NPs in SERS, SEIRA and electrocatalysis, while TiN nanoparticles are considered as promising agents for photothermal therapy and photoacoustic imaging.
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Barnase*Barstar-guided two-step targeting approach for drug delivery to tumor cells in vivo
(2021) Shramova, E. I.; Shilova, M. V.; Ryabova, A. V.; Dzhalilova, D. S.; Deyev, S.; Деев, Сергей Михайлович
© 2021 Elsevier B.V.For precise ligation of a targeting and cytotoxic moiety, the use of Barnase-Barstar pair as a molecular glue is proposed for the first time. Targeting was mediated through the use of a scaffold protein DARPin_9–29 specific for the human epidermal receptor 2 (HER2) antigen that is highly expressed on some types of cancer and Barnase*Barstar native bacterial proteins interacted with each other with Kd 10−14 M. The approach proposed consists of prelabeling a target tumor with hybrid protein DARPin-Barnase prior to administration of cytotoxic component-loaded liposomes that have Barstar covalently attached to their surface. Based on in vivo bioimaging we have proven that DARPin-based Barnase*Barstar-mediated pretargeting possesses precise tumor-targeting capability as well as antitumor activity leading to apparent tumor-growth inhibition of primary tumors and distant metastases in experimental animals. The results obtained indicate that the new system combining DARPin and Barnase*Barstar can be useful both for the drug development and for monitoring the response to treatment in vivo in preclinical studies.
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Synthesis of bismuth-based coordination polymer for biomedical applications
(2021) Belyaev, I. B.; Zelepukin, I. V.; Popov, A. A.; Kabashin, A. V.; Deyev, S. M.; Попов, Антон Александрович; Кабашин, Андрей Викторович; Деев, Сергей Михайлович
© 2021 Institute of Physics Publishing. All rights reserved.Metal organic frameworks (MOFs) are of great interest for biomedicine due to their high loading capacity of various drugs, dyes, and other small molecules. In vivo application of MOFs requires small sizes of nanoparticles and their high colloidal stability. Here we designed the first nano-sized MOFs composed of bismuth and trimesic acid by a rapid microwave-assisted solvothermal method. After coating of the prepared nanoparticles with polyacrylic acid they show improved colloidal stability in aqueous solutions. These particles have 2.2 times higher X-ray attenuation ability than a clinically used BaSO4 agent. Also, they demonstrate high loading efficiency for organic dyes: 35.5 % w/w for Rose bengal and 17.9 % w/w for Rhodamine B.
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DARPin_9-29-targeted gold nanorods selectively suppress her2-positive tumor growth in mice
(2021) Proshkina, G. M.; Shramova, E. I.; Shilova, M. V.; Ryabova, A. V.; Zelepukin, I. V.; Shipunova, V. O.; Deyev, S. M.; Деев, Сергей Михайлович
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.Near-infrared phototherapy has great therapeutic potential for cancer treatment. How-ever, for efficient application, in vivo photothermal agents should demonstrate excellent stability in blood and targeted delivery to pathological tissue. Here, we demonstrated that stable bovine serum albumin-coated gold mini nanorods conjugated to a HER2-specific designed ankyrin repeat protein, DARPin_9-29, selectively accumulate in HER2-positive xenograft tumors in mice and lead to a strong reduction in the tumor size when being illuminated with near-infrared light. The results pave the way for the development of novel DARPin-based targeted photothermal therapy of cancer.
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Novel advanced nanotechnologies for nuclear medicine
(2021) Zavestovskaya, I. N.; Grigorieva, M.; Deyev, S. M.; Kabashin, A. V.; Завестовская, Ирина Николаевна; Григорьева, Мария Сергеевна; Деев, Сергей Михайлович; Кабашин, Андрей Викторович
Abstract Nuclear nanomedicine forms a new research field based on the synergy of nuclear medicine and nanotechnology and implying the use of nanomaterials as carriers of diagnostic or therapeutic radionuclides. Such an approach promises a series of advantages over classical methods of nuclear medicine, including an increased surface area-to-volume ratio, passive/active delivery, high loading capacity, large cross-section in interactions with biological tissues, and unique properties of nanomaterials that make possible many functionalities within one construct. In this short review article, we will highlight our recent achievements in the development of nuclear nanomedicine technologies, which promise the advancement of methods for cancer treatment.
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Flash drug release from nanoparticles accumulated in the targeted blood vessels facilitates the tumour treatment
(2022) Zelepukin, I. V.; Griaznova, O. Y.; Shevchenko, K. G.; Ivanov, A. V.; Baidyuk, E. V.; Serejnikova, N. B.; Volovetskiy, A. B.; Deyev, S. M.; Zvyagin, A. V.; Грязнова, Ольга Юрьевна; Деев, Сергей Михайлович
Tumour microenvironment hinders nanoparticle transport deep into the tissue precluding thorough treatment of solid tumours and metastatic nodes. We introduce an anticancer drug delivery concept termed FlaRE (Flash Release in Endothelium), which represents alternative to the existing approaches based on enhanced permeability and retention effect. This approach relies on enhanced drug-loaded nanocarrier accumulation in vessels of the target tumour or metastasised organ, followed by a rapid release of encapsulated drug within tens of minutes. It leads to a gradient-driven permeation of the drug to the target tissue. This pharmaceutical delivery approach is predicted by theoretical modelling and validated experimentally using rationally designed MIL-101(Fe) metal-organic frameworks. Doxorubicin-loaded MIL-101 nanoparticles get swiftly trapped in the vasculature of the metastasised lungs, disassemble in the blood vessels within 15 minutes and release drug, which rapidly impregnates the organ. A significant improvement of the therapeutic outcome is demonstrated in animal models of early and late-stage B16-F1 melanoma metastases with 11-fold and 4.3-fold decrease of pulmonary melanoma nodes, respectively. © 2022, The Author(s).
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Optoacoustic measurement of nanoparticle degradation in physiological media
(2022) Zelepukin, I. V.; Zvyagin, A. V.; Deyev, S. M.; Деев, Сергей Михайлович
Here we demonstrate application of optoacoustic technology for real-time measurement of inorganic nanoparticle degradation. We analysed kinetics of silicon nanoparticle dissolution in various physiological buffers. Silicon shows acceleration of degradation rate with the increase of pH and salt concentration. Screening dissolution rate of light-absorbing nanoparticles with optoacoustics can improve rational design of drug carriers for biomedical applications. © 2022 IEEE.
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Influence of magnetic nanoparticle biotransformation on contrasting efficiency and iron metabolism
(2022) Yaremenko, A. V.; Zelepukin, I. V.; Ivanov, I. N.; Deyev, S. M.; Nikitin, P. I.; Деев, Сергей Михайлович; Никитин, Петр Иванович
Magnetic nanoparticles are widely used in biomedicine for MRI imaging and anemia treatment. The aging of these nanomaterials in vivo may lead to gradual diminishing of their contrast properties and inducing toxicity. Here, we describe observation of the full lifecycle of 40-nm magnetic particles from their injection to the complete degradation in vivo and associated impact on the organism. We found that in 2 h the nanoparticles were eliminated from the bloodstream, but their initial biodistribution changed over time. In 1 week, a major part of the nanoparticles was transferred to the liver and spleen, where they degraded with a half-life of 21 days. MRI and a magnetic spectral approach revealed preservation of contrast in these organs for more than 1 month. The particle degradation led to the increased number of red blood cells and blood hemoglobin level due to released iron without causing any toxicity in tissues. We also observed an increase in gene expression level of Fe-associated proteins such as transferrin, DMT1, and ferroportin in the liver in response to the iron particle degradation. A deeper understanding of the organism response to the particle degradation can bring new directions to the field of MRI contrast agent design. © 2022, The Author(s).