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Климентов, Сергей Михайлович

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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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2023 - 20242
11
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Автор: Popov, A. A. × Тема: Boron Neutron Capture Therapy ×

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    Boron 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 Николаевна
    Boron-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.
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    Laser-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 Михайлович
    Boron 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.