Персона: Завестовская, Ирина Николаевна
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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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Ирина Николаевна
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- 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 доступNuclear nanomedicine using Si nanoparticles as safe and effective carriers of 188 Re radionuclide for cancer therapy(2019) Tischenko, V. K.; Mikhailovskaya, A. A.; Popov, A. A.; Tselikov, G.; Petriev, V. M.; Deyev, S. M.; Timoshenko, V. Y.; Prasad, P. N.; Zavestovskaya, I. N.; Kabashin, A. V.; Деев, Сергей Михайлович; Тимошенко, Виктор Юрьевич; Завестовская, Ирина Николаевна; Кабашин, Андрей Викторович© 2019, The Author(s). Nuclear nanomedicine, with its targeting ability and heavily loading capacity, along with its enhanced retention to avoid rapid clearance as faced with molecular radiopharmaceuticals, provides unique opportunities to treat tumors and metastasis. Despite these promises, this field has seen limited activities, primarily because of a lack of suitable nanocarriers, which are safe, excretable and have favorable pharmacokinetics to efficiently deliver and retain radionuclides in a tumor. Here, we introduce biodegradable laser-synthesized Si nanoparticles having round shape, controllable low-dispersion size, and being free of any toxic impurities, as highly suitable carriers of therapeutic 188 Re radionuclide. The conjugation of the polyethylene glycol-coated Si nanoparticles with radioactive 188 Re takes merely 1 hour, compared to its half-life of 17 hours. When intravenously administered in a Wistar rat model, the conjugates demonstrate free circulation in the blood stream to reach all organs and target tumors, which is radically in contrast with that of the 188 Re salt that mostly accumulates in the thyroid gland. We also show that the nanoparticles ensure excellent retention of 188 Re in tumor, not possible with the salt, which enables one to maximize the therapeutic effect, as well as exhibit a complete time-delayed conjugate bioelimination. Finally, our tests on rat survival demonstrate excellent therapeutic effect (72% survival compared to 0% of the control group). Combined with a series of imaging and therapeutic functionalities based on unique intrinsic properties of Si nanoparticles, the proposed biodegradable complex promises a major advancement in nuclear nanomedicine.
- ПубликацияОткрытый доступBioprotective properties of nano-diamond composition at intragastric introduction to rats(2020) Lomteva, N. A.; Kondratenko, E. I.; Kasimova, S. K.; Gordeev, S. K.; Alykova, A. F.; Zavestovskaya, I. N.; Завестовская, Ирина Николаевна© Published under licence by IOP Publishing Ltd.We studied a biocompatibility and a bioprotector property of nanodiamond composites on reduction of the toxic action to cadmium salt. The experimental animal intragastric received with the help of a probe activated carbon and nanodiamond composite. We researched the rate of spontaneous and ascorbate-dependent lipids peroxidation and the reference level of malonic dialdehyde in liver, thyroid and adrenal glands tissues. So this concentration of the nanopore material at intragastric entering did not led to difference of researched parameters of the lipid peroxidation. The solution of cadmium salt developed typical for it toxic action which expressed in increase intensity of the processes of POL in liver and thyroid gland tissues. The nanopore material developed the characteristic which screened the toxic action of cadmium chloride and it was more denominated on some parameters in comparison with the effect of the intragastric entering of the activated carbon.
- ПубликацияОткрытый доступNumerical Investigation of Ultrashort Laser-Ablative Synthesis of Metal Nanoparticles in Liquids Using the Atomistic-Continuum Model(2020) Izgin, T.; Veiko, V. P.; Rethfeld, B.; Garcia, M. E.; Ivanov, D. S.; Maiorov, A. N.; Dombrovska, Y. I.; Zavestovskaya, I. N.; Klimentov, S. M.; Иванов, Дмитрий Сергеевич; Майоров, Алексей Николаевич; Завестовская, Ирина Николаевна; Климентов, Сергей МихайловичWe present a framework based on the atomistic continuum model, combining the Molecular Dynamics (MD) and Two Temperature Model (TTM) approaches, to characterize the growth of metal nanoparticles (NPs) under ultrashort laser ablation from a solid target in water ambient. The model is capable of addressing the kinetics of fast non-equilibrium laser-induced phase transition processes at atomic resolution, while in continuum it accounts for the effect of free carriers, playing a determinant role during short laser pulse interaction processes with metals. The results of our simulations clarify possible mechanisms, which can be responsible for the observed experimental data, including the presence of two populations of NPs, having a small (5-15 nm) and larger (tens of nm) mean size. The formed NPs are of importance for a variety of applications in energy, catalysis and healthcare.
- ПубликацияОткрытый доступBiodistribution ex vivo of 213 Bi-KHEDP - A promising boneseeking agent for targeted alpha therapy(2019) Tishchenko, V. K.; Stepchenkova, E. D.; Ivanov, S. A.; Kaprin, A. D.; Petriev, V. M.; Zavestovskaya, I. N.; Завестовская, Ирина Николаевна© 2019 Published under licence by IOP Publishing Ltd. Alpha-emitters are increasingly used for targeted alpha therapy because of their emission of high linear energy transfer (LET) particles with a relative short path length. Bismuth-213 ( 213 Bi, T 1/2 = 46 min) is one of the most suitable radiation sources for medical applications. In the present work the biodistribution of 213 Bi-monopotassium salt of 1-hydroxyethylidene diphosphonic acid ( 213 Bi-KHEDP) in intact mice was studied. It was shown that bones uptake of 213 Bi-KHEDP were higher than in the most soft tissue organs throughout the study. The bone-to-soft tissue ratios for 213 Bi-KHEDP were higher than the corresponding data for 213 BiCl 5 . Among the soft tissue organs, only kidneys had a high uptake of Bi-KHEDP and free 213 Bi. In conclusion, 213 Bi-KHEDP had a strong and selective bone affinity, indicating that this complex could be useful to deliver alpha-particle radiation to primary bone cancer and skeletal metastases.
- ПубликацияОткрытый доступBiological evaluation of histidine and tryptophan labeled with gallium-68 as potential tumor imaging agents(2019) Tishchenko, V. K.; Mikhailovskaya, A. A.; Kuzenkova, K. A.; Kaprin, A. D.; Petriev, V. M.; Zavestovskaya, I. N.; Завестовская, Ирина Николаевна© 2019 Published under licence by IOP Publishing Ltd. Radiolabeled with gallium-68 amino acids can be interesting and promising probes for tumor imaging using positron emission tomography (PET). Radiolabeled amino acids target the increased amino acid transport in cancer cells compared with normal tissues. In this study we labeled two amino acids histidine and tryptophan with 68 Ga, investigated its biodistribution in Wistar rats with subcutaneously transplanted cholangioma RS-1 by gamma counting and compared them with 68 GaCl 3 . The accumulation of 68 Ga-histidine in tumor tissue increased approximately 6 fold from 0.11±0.04 %ID/g at 5 min post injection (p.i.) to 0.67±0.07 %ID/g at 3 h p.i. The amount of 68 Ga-tryptophan in tumor was also risen 2.4 fold from 0.34±0.18 %ID/g to 0.80±0.06 %ID/g at 5 min and 3 h p.i., respectively. In contrast, the uptake of 68 GaCl 3 decreased throughout the study from 0.34±0.07 %ID/g to 0.13±0.04 %ID/g. The uptake and retention of 68 Ga-histidine and 68 Ga-tryptophan in non-target organs, except kidney and femur, were higher than those of 68 GaCl 3 . In conclusion, the obtained results suggest that 68 Ga-histidine and 68 Ga-tryptophan could serve as potential new PET tracers for tumor imaging.
- ПубликацияОткрытый доступMorphophysiological changes in the intact surface of rat skin under the application of silicon and gold nanoparticles(2019) Kondratenko, E. I.; Lomteva, N. A.; Kasimova, S. K.; Yakovenkova, L. A.; Timoshenko, V. Yu.; Alykova, A. F.; Zavestovskaya, I. N.; Тимошенко, Виктор Юрьевич; Завестовская, Ирина Николаевна© Published under licence by IOP Publishing Ltd.The effect of a course application of suspension of porous silicon and gold nanoparticles on the skin of female rats on the level of free radical oxidation and catalase activity in the skin homogenate was studied. MesoPSi samples were formed using the standard method of electrochemical etching of p-type c-Si wafers with a surface orientation of (100) and a specific resistance of 1-5 mOm x cm in a solution of hydrofluoric acid and ethanol (HF (50%): C2H5OH = 1: 1) at an etching current density of 60 mA / cm2 for 1 hour (45 minutes-hour). After this, mesoPSi films were separated from the silicon substrate by a short-term increase in the current density to 600 mA / cm2. Aqueous suspensions of porous silicon nanoparticles with sizes of the order of 100 nm were obtained by mechanical grinding of mesoporous silicon films in water. Aqueous suspensions of gold nanoparticles with an average size of 30-50 nm were obtained by laser ablation of gold targets in deionized water. A suspension of silicon and gold nanoparticles in physiological saline at a concentration of 0.2 mg / ml was applied once a day in the form of a thin layer on a shaved area of the skin of animals (interscapular region) and left to dry completely. Applications were carried out for 10 days. The studied silicon and gold nanoparticles did not change the initial content of malondialdehyde and catalase activity in the skin tissue but contributed to the activation of the rate of spontaneous lipid peroxidation.
- ПубликацияОткрытый доступThe influence of chemical structure of phosphonic acids labeled with gallium-68 on their pharmacokinetic properties in animals(2020) Tishchenko, V. K.; Mikhailovskaya, A. A.; Stepchenkova, E. D.; Kuzenkova, K. A.; Petriev, V. M.; Postnov, A. A.; Zavestovskaya, I. N.; Завестовская, Ирина Николаевна© Published under licence by IOP Publishing Ltd.68 Ga-labeled phosphonates are of great interest due to their possibility to serve promising agents in nuclear medicine for bone tissue PET imaging. It is known that multidentate aminophosphonate ligands could form much stable chelates with different radiometals as compared to diphosphonates. In this work we studied the pharmacokinetic properties of 68Ga-labeled complexes with two, four and five phosphonate groups (68Ga-HEDP, 68Ga-EDTMP, and 68Ga-DTPMP, respectively) in normal Wistar rats after intravenous administration. It was shown that the structure of phosphonates had a great influence on the biodistribution of 68Ga-HEDP, 68Ga-EDTMP, and 68Ga-DTPMP. Complexes with higher number of aminomethylenephosphonate groups (68Ga-EDTMP and 68Ga-DTPMP) had higher bone uptake than diphosphonate 68Ga-HEDP. In blood 68Ga-HEDP had lower activity than 68Ga-EDTMP and 68Ga-DTPMP, indicating poor stability of diphosphonate-based complex. In other soft organs and tissues 68Ga-EDTMP and 68Ga-DTPMP uptake was slightly lower as compared with 68Ga-HEDP. In conclusion, 68Ga-EDTMP and 68Ga-DTPMP have the potential to be suitable radiotracers for bone tissue PET imaging.
- ПубликацияОткрытый доступPulse duration and wavelength effects of laser ablation on the oxidation, hydrolysis, and aging of aluminum nanoparticles in water(2019) Zhang, K.; Ganeev, R. A.; Boltaev, G. S.; Krishnendu, P. S.; Ivanov, D. S.; Zavestovskaya, I. N.; Иванов, Дмитрий Сергеевич; Завестовская, Ирина Николаевна© 2019 by the authors. Licensee MDPI, Basel, Switzerland.We analyzed the formation of the aluminum (Al) nanoparticles (NPs) with triangular shape obtained by ablating Al bulk in liquid using pulses with different durations (5 ns, 200 ps, and 30 fs) and wavelengths (355 nm, 800 nm, and 1064 nm). We report three stages of synthesis and aging of Al NPs: Formation, transformation, and stable stage. The NPs prepared by different pulses are almost identical at the initial stage. The effects of duration and wavelength of the ablation pulses on the aging of NPs are revealed. Pulse duration is determined to be essential for morphological transformation of NPs, while pulse wavelength strongly influences particle sizes. NPs produced by ultra-short pulses have smaller sizes and narrow size distribution. We demonstrate that oxidation and hydrolysis of Al in water are the results of ablation for all pulse durations and wavelengths, which also strongly modify the preferable reaction path of NPs in water, thus affecting the composition and morphology of triangle NPs. The results of modeling of the NPs generation in water due to a 50 ps laser pulse interacting with a thick Al target are presented. Water-based effects in the formation of NPs, their evolution, and solidification are considered from the mechanical and thermophysical points of view. The detailed analysis of the modeling results allowed for determination of the main mechanism responsible for the ablation process followed by the NPs formation.
- 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.