Персона: Попова-Кузнецова, Елена Алефтиновна
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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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Елена Алефтиновна
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- ПубликацияТолько метаданныеEffect of Oxygen on Colloidal Stability of Titanium Nitride Nanoparticles Synthesized by Laser Ablation in Liquids(2021) Tikhonowski, G. V.; Popova-Kuznetsova, E. A.; Aleshchenko, Y. A.; Klimentov, S. M.; Kabashin, A. V.; Popov, A. A.; Тихоновский, Глеб Валерьевич; Попова-Кузнецова, Елена Алефтиновна; Алещенко, Юрий Анатольевич; Климентов, Сергей Михайлович; Кабашин, Андрей Викторович; Попов, Антон Александрович© 2021, Allerton Press, Inc.Abstract: The effect of oxygen existing in an ablation medium during synthesis of titanium nitride (TiN) nanoparticles (NPs) by pulsed laser ablation in liquid (PLAL) on colloidal stability of obtained solutions was studied. It was shown that an increase in the oxygen content both incorporated in liquid molecules and in the form of dissolved gas increases the colloidal stability of synthesized NPs. The results obtained extend the range of available methods for developing new nanomaterials due to control of colloidal stability of laser-synthesized NPs.
- 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.
- ПубликацияТолько метаданныеColloidal samarium oxide nanoparticles prepared by femtosecond laser ablation and fragmentation for nuclear nanomedicine(2020) Duflot, V. R.; Popova-Kuznetsova, E.; Tikhonowski, G.; Popov, A. A.; Deyev, S. M.; Klimentov, S. M.; Zavestovskaya, I. N.; 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© 2020 SPIE.Nanotechnology promises a major improvement of efficacy of nuclear medicine by targeted delivery of radioactive agents to tumors, but this approach still needs novel efficient nanoformulations to maximize diagnostic and therapeutic functions. Here, we present a two-step method of laser ablation and fragmentation in water to produce non-radioactive 152Sm-enriched samarium oxide nanoparticles (Sm NPs), which can be converted to radioactive form of 153Sm beta-emitters by neutron capture reaction. We found that laser ablation in deionized water leads to the formation of NPs having diverse morphology and broad size dispersion. To improve size characteristics of formed NPs, we applied additional femtosecond laser fragmentation step, which made possible a good control of mean NPs size under a drastic narrowing of size dispersion, and the spherical shape of formed NPs. Obtained colloidal solutions of Sm NPs were stable for several weeks after the synthesis. The formed NPs present a very promising object for nuclear nanomedicine.
- ПубликацияТолько метаданныеComparison 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.
- ПубликацияТолько метаданныеLaser-ablative synthesis of stable size-tunable Bi nanoparticles and their functionalization for radiotherapy applications(2021) Tikhonowski, G. V.; Popov, A. A.; Popova-Kuznetsova, E. A.; Klimentov, S. M.; Prasad, P. N.; Kabashin, A. V.; Тихоновский, Глеб Валерьевич; Попов, Антон Александрович; Попова-Кузнецова, Елена Алефтиновна; Климентов, Сергей Михайлович; Кабашин, Андрей Викторович© 2021 Institute of Physics Publishing. All rights reserved.Nanoformulations of high-Z elements can improve therapeutic outcome in radiotherapy-based treatment of tumors, but current nanomedicine implementations in radiotherapy still need biocompatible, non-toxic nano-agents exhibiting low polydispersity and high colloidal stability. Here, we elaborate methods of femtosecond (fs) laser ablation in water and organic solvents to fabricate stable aqueous colloidal solutions of ultrapure elemental Bi nanoparticles (NPs) and characterize them. We show that fs laser ablation of Bi target leads to the formation of spherical elemental Bi NPs having 25 nm mean size and wide size-dispersion. NPs prepared in water undergo fast conversion into 400-500 nm flake-like nanosheets, while NPs prepared in acetone demonstrate a high colloidal stability. We then employ methods of fs laser fragmentation to control mean size and size dispersion of Bi NPs. Stable aqueous solution of Bi NPs suitable for biomedical applications can be obtained by coating with Pluronic® F-127. We finally show that surface modification of Bi NPs increases its colloidal stability in phosphate buffer saline (PBS) solution by more than 6 fold. Exempt of any toxic synthetic by-products, laser-ablated Bi NPs present a novel appealing nanoplatform for image-guided combination photo- and radiotherapy.
- 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.
- ПубликацияТолько метаданныеSynthesis of Titanium Nitride Nanoparticles by Pulsed Laser Ablation in Different Aqueous and Organic Solutions(2022) Tselikov, G. I.; Markeev, A. M.; Kabashin, A. V.; Popov, A. A.; Tikhonowski, G. V.; Shakhov, P. V.; Popova-Kuznetsova, E. A.; Romanov, R. I.; Klimentov, S. M.; Попов, Антон Александрович; Тихоновский, Глеб Валерьевич; Шахов, Павел Владимирович; Попова-Кузнецова, Елена Алефтиновна; Романов, Роман Иванович; Климентов, Сергей Михайлович© 2022 by the authors. Licensee MDPI, Basel, Switzerland.Owing to a strong photothermal response in the near-IR spectral range and very low toxicity, titanium nitride (TiN) nanoparticles (NPs) synthesized by pulsed laser ablation in liquids (PLAL) present a novel appealing object for photo-induced therapy of cancer, but the properties of these NPs still require detailed investigation. Here, we have elaborated methods of femtosecond laser ablation from the TiN target in a variety of liquid solutions, including acetonitrile, dimethyl-formamide, acetone, water, and H2O2, to synthesize TiN NPs and clarify the effect of liquid type on the composition and properties of the formed NPs. The ablation in all solvents led to the formation of spherical NPs with a mean size depending on the liquid type, while the composition of the NPs ranged from partly oxidized TiN to almost pure TiO2, which conditioned variations of plasmonic peak in the region of relative tissue transparency (670–700 nm). The degree of NP oxidation depended on the solvent, with much stronger oxidation for NPs prepared in aqueous solutions (especially in H2O2), while the ablation in organic solvents resulted in a partial formation of titanium carbides as by-products. The obtained results contribute to better understanding of the processes in reactive PLAL and can be used to design TiN NPs with desired properties for biomedical applications.
- ПубликацияТолько метаданныеLaser-ablative synthesis of nanomaterials for nuclear and radiative medicine applications(2022) Tikhonowski, G. V.; Popov, A. A.; Zelepukin, I.; Popova-Kuznetsova, E.; Dombrovska, Y.; Deyev, S. M.; Zavestovskaya, I. N.; Klimentov, S. M.; Prasad, P. N.; Kabashin, A. V.; Тихоновский, Глеб Валерьевич; Попов, Антон Александрович; Попова-Кузнецова, Елена Алефтиновна; Деев, Сергей Михайлович; Завестовская, Ирина Николаевна; Климентов, Сергей Михайлович; Кабашин, Андрей ВикторовичNewly emerging nanomaterials promise a major advancement of methods of nuclear and radiative medicine for cancer treatment, as they can be used as carriers of diagnostic or therapeutic radionuclides, contrast agents in nuclear imaging modalities (PET, SPECT) or sensitizers of radiative therapies (X-ray, ion beams, etc.). However, nanotechnology-based approaches have reported a limited success so far due to a lack of suitable functional nanoformulations, which are safe, non-toxic, excretable from the body and have favorable pharmacokinetics for effective accumulation in the tumor. As follows from the results of our on-going research activities, many of the above-stated problems can we solved by the employment of nanomaterials fabricated by clean laser-ablative synthesis. Here, we review our recent data on some promising nanomaterials, prepared by this method, including biodegradable silicon (Si) nanoparticles (NPs), Sm-152-enriched samarium oxide NPs, and elemental bismuth (Bi) NPs, which can be used either as carriers/agents in radionuclide therapy, or sensitizers in radiative diagnostics or therapy. Advantages of proposed approach include exceptional purity and flexibility in synthesizing of NPs of required physico-chemical parameters (controlled size, shape, composition, and surface conditioning of NPs). Advances in laser-ablative fabrication of novel nanomaterials open up avenues for future implementations of nuclear and radiative medicine approaches for safe and efficient theranostics of tumors and metastasis.
- ПубликацияТолько метаданныеLaser-ablative synthesis and photoheating characterization of TiN NPs for biomedical applications(2022) Popov, A. A.; Tikhonowski, G. V.; Popova-Kuznetsova, E. A.; Klimentov, S. M.; Kabashin, A. V.; Попов, Антон Александрович; Тихоновский, Глеб Валерьевич; Попова-Кузнецова, Елена Алефтиновна; Климентов, Сергей Михайлович; Кабашин, Андрей ВикторовичTitanium nitride (TiN) nanoparticles (NPs) prepared by methods of laser ablation in liquids present a novel object, which promises attractive biomedical applications. Here, we review our recent advances in the elaboration of femtosecond laser ablation technique from a TiN target in liquid medium (here, isopropanol) to maximize the efficiency of TiN NPs synthesis and optimize their characteristics. Our experiments showed that the synthesis productivity is dependent on lateral velocity of laser beam scanning during laser ablation with the achievement of productivity saturation at a certain relatively high velocity. The observed phenomenon was attributed to the interaction of laser pulses with cavitation bubbles generated during the ablation process. In addition, we assessed photo heating properties of the synthesized TiN NPs in the near-IR range. It was found that TiN NPs with sizes in 20-50 nm range have the highest heating rate and can be heated to maximal temperatures. As demonstrated by our recent tests in vitro and in vivo, this size range is optimal for biomedical applications, which promises successful applications of these nanoparticles in phototherapy and imaging modalities.