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 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-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-synthesized TiN nanoparticles for biomedical applications: Evaluation of safety, biodistribution and pharmacokinetics(2021) Zelepukin, I. V.; Popov, A. A.; Shipunova, V. O.; Tikhonowski, G. V.; Mirkasymov, A. B.; Popova-Kuznetsova, E. A.; Klimentov, S. M.; Kabashin, A. V.; Deyev, S. M.; Попов, Антон Александрович; Тихоновский, Глеб Валерьевич; Попова-Кузнецова, Елена Алефтиновна; Климентов, Сергей Михайлович; Кабашин, Андрей Викторович; Деев, Сергей Михайлович© 2020 Elsevier B.V.Having plasmonic absorption within the biological transparency window, titanium nitride (TiN) nanoparticles (NPs) can potentially outperform gold counterparts in phototheranostic applications, but characteristics of available TiN NPs are still far from required parameters. Recently emerged laser-ablative synthesis opens up opportunities to match these parameters as it makes possible the production of ultrapure low size-dispersed spherical TiN NPs, capable of generating a strong phototherapy effect under 750–800 nm excitation. This study presents the first assessment of toxicity, biodistribution and pharmacokinetics of laser-synthesized TiN NPs. Tests in vitro using 8 cell lines from different tissues evidenced safety of both as-synthesized and PEG-coated NPs (TiN-PEG NPs). After systemic administration in mice, they mainly accumulated in liver and spleen, but did not cause any sign of toxicity or organ damage up to concentration of 6 mg kg−1, which was confirmed by the invariability of blood biochemical parameters, weight and hemotoxicity examination. The NPs demonstrated efficient passive accumulation in EMT6/P mammary tumor, while concentration of TiN-PEG NPs was 2.2-fold higher due to “stealth” effect yielding 7-times longer circulation in blood. The obtained results evidence high safety of laser-synthesized TiN NPs for biological systems, which promises a major advancement of phototheranostic modalities on their basis.
- ПубликацияОткрытый доступLaser-Synthesized Elemental Boron Nanoparticles for Efficient Boron Neutron Capture Therapy(2023) Zavestovskaya, I. N.; Zavestovskaya,I.N.; Babkova, J. S.; Zelepukin, I. V.; Tikhonowski, G. V.; Popov, A. A.; Klimentov, S. M.; Завестовская, Ирина Николаевна; Бабкова, Юлия Сергеевна; Тихоновский, Глеб Валерьевич; Попов, Антон Александрович; Климентов, Сергей Михайлович; Деев, Сергей МихайловичBoron neutron capture therapy (BNCT) is one of the most appealing radiotherapy modalities, whose localization can be further improved by the employment of boron-containing nanoformulations, but the fabrication of biologically friendly, water-dispersible nanoparticles (NPs) with high boron content and favorable physicochemical characteristics still presents a great challenge. Here, we explore the use of elemental boron (B) NPs (BNPs) fabricated using the methods of pulsed laser ablation in liquids as sensitizers of BNCT. Depending on the conditions of laser-ablative synthesis, the used NPs were amorphous (a-BNPs) or partially crystallized (pc-BNPs) with a mean size of 20 nm or 50 nm, respectively. Both types of BNPs were functionalized with polyethylene glycol polymer to improve colloidal stability and biocompatibility. The NPs did not initiate any toxicity effects up to concentrations of 500 Вµg/mL, based on the results of MTT and clonogenic assay tests. The cells with BNPs incubated at a 10B concentration of 40 Вµg/mL were then irradiated with a thermal neutron beam for 30 min. We found that the presence of BNPs led to a radical enhancement in cancer cell death, namely a drop in colony forming capacity of SW-620 cells down to 12.6% and 1.6% for a-BNPs and pc-BNPs, respectively, while the relevant colony-forming capacity for U87 cells dropped down to 17%. The effect of cell irradiation by neutron beam uniquely was negligible under these conditions. Finally, to estimate the dose and regimes of irradiation for future BNCT in vivo tests, we studied the biodistribution of boron under intratumoral administration of BNPs in immunodeficient SCID mice and recorded excellent retention of boron in tumors. The obtained data unambiguously evidenced the effect of a neutron therapy enhancement, which can be attributed to efficient BNP-mediated generation of О±-particles.
- ПубликацияОткрытый доступLaser-Ablative Synthesis of Silicon–Iron Composite Nanoparticles for Theranostic Applications(2023) Bubnov, A. A.; Belov, V. S.; Kargina, Yu. V.; Tikhonowski, G. V.; Popov, A. A.; Kharin, A. Yu.; Shestakov, M. V.; Klimentov, S. M.; Timoshenko, V. Y.; Белов, Владимир Сергеевич; Тихоновский, Глеб Валерьевич; Попов, Антон Александрович; Климентов, Сергей Михайлович; Тимошенко, Виктор ЮрьевичThe combination of photothermal and magnetic functionalities in one biocompatible nanoformulation forms an attractive basis for developing multifunctional agents for biomedical theranostics. Here, we report the fabrication of silicon-iron (Si-Fe) composite nanoparticles (NPs) for theranostic applications by using a method of femtosecond laser ablation in acetone from a mixed target combining silicon and iron. The NPs were then transferred to water for subsequent biological use. From structural analyses, it was shown that the formed Si-Fe NPs have a spherical shape and sizes ranging from 5 to 150 nm, with the presence of two characteristic maxima around 20 nm and 90 nm in the size distribution. They are mostly composed of silicon with the presence of a significant iron silicide content and iron oxide inclusions. Our studies also show that the NPs exhibit magnetic properties due to the presence of iron ions in their composition, which makes the formation of contrast in magnetic resonance imaging (MRI) possible, as it is verified by magnetic resonance relaxometry at the proton resonance frequency. In addition, the Si-Fe NPs are characterized by strong optical absorption in the window of relative transparency of bio-tissue (650-950 nm). Benefiting from such absorption, the Si-Fe NPs provide strong photoheating in their aqueous suspensions under continuous wave laser excitation at 808 nm. The NP-induced photoheating is described by a photothermal conversion efficiency of 33-42%, which is approximately 3.0-3.3 times larger than that for pure laser-synthesized Si NPs, and it is explained by the presence of iron silicide in the NP composition. Combining the strong photothermal effect and MRI functionality, the synthesized Si-Fe NPs promise a major advancement of modalities for cancer theranostics, including MRI-guided photothermal therapy and surgery.
- ПубликацияОткрытый доступBoron Nanoparticle-Enhanced Proton Therapy for Cancer Treatment(2023) Zavestovskaya, I. N.; Tikhonowski, G. V.; Savinov, M. S.; Shakhov, P. V.; Babkova, J. S.; Popov, A. A.; Klimentov, S. M.; Prasad, P. N.; Deyev, S. M.; Завестовская, Ирина Николаевна; Тихоновский, Глеб Валерьевич; Савинов, Максим Сергеевич; Шахов, Павел Владимирович; Бабкова, Юлия Сергеевна; Попов, Антон Александрович; Климентов, Сергей Михайлович; Деев, Сергей МихайловичProton therapy is one of the promising radiotherapy modalities for the treatment of deep-seated and unresectable tumors, and its efficiency can further be enhanced by using boron-containing substances. Here, we explore the use of elemental boron (B) nanoparticles (NPs) as sensitizers for proton therapy enhancement. Prepared by methods of pulsed laser ablation in water, the used B NPs had a mean size of 50 nm, while a subsequent functionalization of the NPs by polyethylene glycol improved their colloidal stability in buffers. Laser-synthesized B NPs were efficiently absorbed by MNNG/Hos human osteosarcoma cells and did not demonstrate any remarkable toxicity effects up to concentrations of 100 ppm, as followed from the results of the MTT and clonogenic assay tests. Then, we assessed the efficiency of B NPs as sensitizers of cancer cell death under irradiation by a 160.5 MeV proton beam. The irradiation of MNNG/Hos cells at a dose of 3 Gy in the presence of 80 and 100 ppm of B NPs led to a 2- and 2.7-fold decrease in the number of formed cell colonies compared to control samples irradiated in the absence of NPs. The obtained data unambiguously evidenced the effect of a strong proton therapy enhancement mediated by B NPs. We also found that the proton beam irradiation of B NPs leads to the generation of reactive oxygen species (ROS), which evidences a possible involvement of the non-nuclear mechanism of cancer cell death related to oxidative stress. Offering a series of advantages, including a passive targeting option and the possibility of additional theranostic functionalities based on the intrinsic properties of B NPs (e.g., photothermal therapy or neutron boron capture therapy), the proposed concept promises a major advancement in proton beam-based cancer treatment.