Персона: Попов, Антон Александрович
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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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Антон Александрович
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- ПубликацияОткрытый доступComparative 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.
- ПубликацияОткрытый доступLocalized infrared radiation-induced hyperthermia sensitized by laser-ablated silicon nanoparticles for phototherapy applications(2020) Oleshchenko, V. A.; Karpukhina, O. V.; Bezotosnyi, V. V.; Kharin, A. Y.; Alykova, A. F.; Karpov, N. V.; Popov, A. A.; Klimentov, S. M.; Zavestovskaya, I. N.; Kabashin, A. V.; Timoshenko, V. Y.; Попов, Антон Александрович; Климентов, Сергей Михайлович; Завестовская, Ирина Николаевна; Кабашин, Андрей Викторович; Тимошенко, Виктор Юрьевич© 2020 Elsevier B.V.Silicon (Si) nanoparticles (NPs) synthesized by methods of laser ablation in water are explored as sensitizers of photothermal therapy under a laser excitation in the window of relative tissue transparency. Based on theoretical calculations and experimental data, it is shown that the NPs can be heated up to temperatures above 42–50 °C by laser diode irradiation at 808 nm in continuous wave (CW) and quasi-continuous wave (QCW) regimes. Profiting from the laser-induced heating, a high efficiency Si-NPs as sensitizers of the hyperthermia of cells in Paramecium Caudatum model is demonstrated. The QCW regime is found to be more efficient, leading to complete cell destruction even under relatively mild laser irradiation conditions. The obtained data evidence a great potential in using laser-ablated Si-NPs as sensitizers of photohyperthermia in antibacterial or cancer therapy applications.
- ПубликацияОткрытый доступLaser-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 МихайловичAbstract 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.
- ПубликацияТолько метаданныеBismuth Nanoparticles Increase Effectiveness of Proton Therapy of Ehrlich Carcinoma(2024) Filimonova, M. V.; Popov, A. A.; Ivanov, S. A.; Koryakin, S. N.; Попов, Антон Александрович
- ПубликацияТолько метаданныеCytotoxicity of Laser-Synthesized Nanoparticles of Elemental Bismuth(2024) Shakhov, P. V.; Tikhonowski, G. V.; Popov, A. A.; Iliasov, A. R.; Lebedev, A. A.; Klimentov, S. M.; Шахов, Павел Владимирович; Тихоновский, Глеб Валерьевич; Попов, Антон Александрович; Илясов, Артём Романович; Лебедев, Анатолий Алексеевич; Климентов, Сергей Михайлович
- ПубликацияТолько метаданныеLaser-Ablative Engineering of ZrN-Based Nanoparticles for Photothermal Therapy and SERS-Based Biological Imaging(2024) Pastukhov, A. I.; Babkova, J. S.; Zelepukin, I. V.; Popov, A. A.; Klimentov, S. M.; Prasad, P. N.; Deyev, S. M.; Бабкова, Юлия Сергеевна; Попов, Антон Александрович; Климентов, Сергей Михайлович; Деев, Сергей Михайлович
- ПубликацияТолько метаданныеBoron Nanoparticle-Enhanced Proton Therapy: Molecular Mechanisms of Tumor Cell Sensitization(2024) Popov, A. L.; Kolmanovich, D. D.; Chukavin, N. N.; Zelepukin, I. V.; Tikhonowski, G. V.; Popov, A. A.; Klimentov, S. M.; Deyev, S. M.; Zavestovskaya, I. N.; Тихоновский, Глеб Валерьевич; Попов, Антон Александрович; Климентов, Сергей Михайлович; Деев, Сергей Михайлович; Завестовская, Ирина НиколаевнаBoron-enhanced proton therapy has recently appeared as a promising approach to increase the efficiency of proton therapy on tumor cells, and this modality can further be improved by the use of boron nanoparticles (B NPs) as local sensitizers to achieve enhanced and targeted therapeutic outcomes. However, the mechanisms of tumor cell elimination under boron-enhanced proton therapy still require clarification. Here, we explore possible molecular mechanisms responsible for the enhancement of therapeutic outcomes under boron NP-enhanced proton therapy. Spherical B NPs with a mode size of 25 nm were prepared by methods of pulsed laser ablation in water, followed by their coating by polyethylene glycol to improve their colloidal stability in buffers. Then, we assessed the efficiency of B NPs as sensitizers of cancer cell killing under irradiation with a 160.5 MeV proton beam. Our experiments showed that the combined effect of B NPs and proton irradiation induces an increased level of superoxide anion radical generation, which leads to the depolarization of mitochondria, a drop in their membrane mitochondrial potential, and the development of apoptosis. A comprehensive gene expression analysis (via RT-PCR) confirmed increased overexpression of 52 genes (out of 87 studied) involved in the cell redox status and oxidative stress, compared to 12 genes in the cells irradiated without B NPs. Other possible mechanisms responsible for the B NPs-induced radiosensitizing effect, including one related to the generation of alpha particles, are discussed. The obtained results give a better insight into the processes involved in the boron-induced enhancement of proton therapy and enable one to optimize parameters of proton therapy in order to maximize therapeutic outcomes.
- ПубликацияОткрытый доступСоздание композитов Bi@SiO2 со структурой ядро@оболочка на основе лазерно-синтезированных наночастиц Bi(2023) Скрибицкая, А. В.; Короткова, Н. А.; Котельникова, П. А.; Тихоновский, Г. В.; Попов, А. А.; Климентов, С. М.; Завестовская, И. Н.; Кабашин, А. В.; Завестовская, Ирина Николаевна; Кабашин, Андрей Викторович; Климентов, Сергей Михайлович; Попов, Антон Александрович; Скрибицкая, Ангелина Вячеславовна; Тихоновский, Глеб ВалерьевичРазработана методика получения нанокомпозитов по типу ядро@оболочка путём поверхностной модификации лазерно-синтезированных наночастиц (НЧ) висмута тетраэтоксисиланом с конечной структурной формулой Bi@SiO2. Показано, что покрытие НЧ Bi оболочкой из SiO2 приводит к образованию сферических наноформуляций с модой размерного распределения 250 – 300 нм. Разработанная методика, позволяющая создавать биосовместимые нанокомпозиты на основе Bi для сенсибилизации мультимодальной тераностики, является новой перспективной альтернативой традиционным методам.
- ПубликацияОткрытый доступLaser-ablative synthesis of stable aqueous solutions of elemental bismuth nanoparticles for multimodal theranostic applications(2020) Bulmahn, J. C.; Kuzmin, A.; Tikhonowski, G.; Popov, A. A.; Klimentov, S. M.; Kabashin, A. V.; Prasad, P. N.; Тихоновский, Глеб Валерьевич; Попов, Антон Александрович; Климентов, Сергей Михайлович; Кабашин, Андрей Викторович© 2020 by the authors. Licensee MDPI, Basel, Switzerland.Elemental bismuth (Bi) nanoparticles (NPs), with the high atomic density of the Bi nuclei, could serve as efficient targeted agents for cancer treatment, with applications such as contrast agents for computed tomography (CT) imaging, sensitizers for image-guided X-ray radiotherapy, and photothermal therapy. However, the synthesis of elemental Bi NPs suitable for biological applications is difficult using conventional chemical routes. Here, we explore the fabrication of ultrapure Bi-based nanomaterials by femtosecond laser ablation from a solid Bi target in ambient liquids and characterize them by a variety of techniques, including TEM, SEM, XRD, FTIR, Raman, and optical spectroscopy. We found that laser-ablative synthesis using an elemental Bi solid target leads to the formation of spherical Bi NPs having the mean size of 20–50 nm and a low size-dispersion. The NPs prepared in water experience a fast (within a few minutes) conversion into 400–500 nm flake-like nanosheets, composed of bismuth subcarbonates, (BiO)2 CO3 and (BiO)4 CO3 (OH)2, while the NPs prepared in acetone demonstrate high elemental stability. We introduce a procedure to obtain a stable aqueous solution of elemental Bi NPs suitable for biological applications, based on the coating of Bi NPs prepared in acetone with Pluronic® F68 and their subsequent transfer to water. We also show that the laser-synthesized elemental Bi NPs, due to their vanishing band gap, exhibit remarkable absorption in the infrared range, which can be used for the activation of photothermal therapy in the near IR-to-IR window with maximum optical transparency in biological media. Exempt of any toxic synthetic by-products, laser-ablated elemental Bi NPs present a novel appealing nanoplatform for combination image-guided photoradiotherapies.
- ПубликацияОткрытый доступLaser-ablative synthesis of isotope-enriched samarium oxide nanoparticles for nuclear nanomedicine(2020) Duflot, V.; Popova-Kuznetsova, E.; Tikhonowski, G.; Popov, A. A.; Deyev, S.; Klimentov, S.; Zavestovskaya, I.; Prasad, P. N.; Kabashin, A. V.; Попова-Кузнецова, Елена Алефтиновна; Тихоновский, Глеб Валерьевич; Попов, Антон Александрович; Деев, Сергей Михайлович; Климентов, Сергей Михайлович; Завестовская, Ирина Николаевна; Кабашин, Андрей Викторович© 2019 by the authors. Licensee MDPI, Basel, Switzerland.Nuclear nanomedicine is an emerging field, which utilizes nanoformulations of nuclear agents to increase their local concentration at targeted sites for a more effective nuclear therapy at a considerably reduced radiation dosage. This field needs the development of methods for controlled fabrication of nuclear agents carrying nanoparticles with low polydispersity and with high colloidal stability in aqueous dispersions. In this paper, we apply methods of femtosecond (fs) laser ablation in deionized water to fabricate stable aqueous dispersion of152Sm-enriched samarium oxide nanoparticles (NPs), which can capture neutrons to become153Sm beta-emitters for nuclear therapy. We show that direct ablation of a152Sm-enriched samarium oxide target leads to widely size-and shape-dispersed populations of NPs with low colloidal stability. However, by applying a second fs laser fragmentation step to the dispersion of initially formed colloids, we achieve full homogenization of NPs size characteristics, while keeping the same composition. We also demonstrate the possibility for wide-range tuning of the mean size of Sm-based NPs by varying laser energy during the ablation or fragmentation step. The final product presents dispersed solutions of samarium oxide NPs with relatively narrow size distribution, having spherical shape, a controlled mean size between 7 and 70 nm and high colloidal stability. The formed NPs can also be of importance for catalytic and biomedical applications.