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Макаров, Владимир Игоревич

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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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  • Публикация
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    Effect of Photodynamic Therapy with the Photosensitizer Methylene Blue on Cerebral Endotheliocytes In Vitro
    (2024) Makarov, V. I.; Skobeltsin, A. S.; Averchuk, A. S.; Loschenov, V. B.; Макаров, Владимир Игоревич; Скобельцин, Алексей Сергеевич; Лощенов, Виктор Борисович
    Background: Microvessels in tumor tissue play a crucial role in meeting the metabolic needs of transformed cells, controlling the entry of xenobiotics into tumor tissue, and regulating local inflammation that promotes metastasis. Methylene blue has photosensitizing properties and can also affect dysfunctional mitochondria. Methods: The study was performed on the primary culture of CECs. The cells underwent photodynamic treatment through 660 nm laser irradiation at a power density of 300 mW/cm2. The MTT, TMRE, and TUNEL assays were used to assess the survival, redox metabolism, mitochondrial activity, and apoptosis of CECs. Additionally, the metabolic activity of cells was evaluated using FLIM by measuring the fluorescence lifetime of NADH and FAD. Results: When CECs were incubated with MB, there was an increase in mitochondrial activity that was dependent on the concentration of MB. Additionally, mitochondrial activity increased when the CECs were exposed to 660 nm laser irradiation at an energy dose of up to 5 J/cm2. Following PDT, a slight shift towards oxidative phosphorylation was observed. Conclusions: In vitro application of MB accumulation or laser irradiation causes a shift in the redox status of CECs towards increased reducing activity, without causing any cell damage. However, the combined action of PS and laser radiation has the opposite effect on the redox status of cells, resulting in an increase in the oxidized form of FAD.
  • Публикация
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    Spectral properties of crystalline aluminum phthalocyanine nanoparticles and the possibility of their use in biophotonics
    (2024) Makarov, V. I.; Pominova, D. V.; Ryabova, A. V.; Loschenov, V. B.; Макаров, Владимир Игоревич; Поминова, Дарья Вячеславовна; Рябова, Анастасия Владимировна; Лощенов, Виктор Борисович
  • Публикация
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    Fluorescence diagnostics and photodynamic therapy of grain crops pathogenic fungi
    (2020) Bikmukhametova, I. R.; Akhlyustina, E. V.; Pominova, D. V.; Ryabova, A. V.; Grachev, P. V.; Makarov, V. I.; Kartabaeva, B. B.; Ахлюстина, Екатерина Витальевна; Поминова, Дарья Вячеславовна; Рябова, Анастасия Владимировна; Макаров, Владимир Игоревич
    © 2020 IEEE.The studies show the dynamics of photosensitizers accumulation in various grain areas during germination and their photodynamic activity against pathogenic microflora (Fusarium, Bipolaris, Alternaria). Four photosensitizers (methylene blue, Chlorin E6, aluminum phthalocyanine in molecular- and nanoform) were used in the work. The accumulation level of methylene blue and aluminum phthalocyanine in molecular form in infected by Alternaria and Fusarium fungi grains was 4-5 times higher than in control on the 4th day. The possibility of pathogenic microflora inactivation using aluminum phthalocyanine was shown.
  • Публикация
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    Theranostic Properties of Crystalline Aluminum Phthalocyanine Nanoparticles as a Photosensitizer
    (2022) Makarov, V. I.; Pominova, D. V.; Ryabova, A. V.; Romanishkin, I. D.; Voitova, A. V.; Steiner, R. W.; Loschenov, V. B.; Макаров, Владимир Игоревич; Поминова, Дарья Вячеславовна; Рябова, Анастасия Владимировна; Лощенов, Виктор Борисович
    The study of phthalocyanines, known photosensitizers, for biomedical applications has been of high research interest for several decades. Of specific interest, nanophotosensitizers are crystalline aluminum phthalocyanine nanoparticles (AlPc NPs). In crystalline form, they are water-insoluble and atoxic, but upon contact with tumors, immune cells, or pathogenic microflora, they change their spectroscopic properties (acquire the ability to fluoresce and become phototoxic), which makes them upcoming agents for selective phototheranostics. Aqueous colloids of crystalline AlPc NPs with a hydrodynamic size of 104 В± 54 nm were obtained using ultrasonic dispersal and centrifugation. Intracellular accumulation and localization of AlPc were studied on HeLa and THP-1 cell cultures and macrophages (M0, M1, M2) by fluorescence microscopy. Crystallinity was assessed by XRD spectroscopy. Time-resolved spectroscopy was used to obtain characteristic fluorescence kinetics of AlPc NPs upon interaction with cell cultures. The photodynamic efficiency and fluorescence quantum yield of AlPc NPs in HeLa and THP-1 cells were evaluated. After entering the cells, AlPc NPs localized in lysosomes and fluorescence corresponding to individual AlPc molecules were observed, as well as destruction of lysosomes and a rapid decrease in fluorescence intensity during photodynamic action. The photodynamic efficiency of AlPc NPs in THP-1 cells was almost 1.8-fold that of the molecular form of AlPc (Photosens). A new mechanism for the occurrence of fluorescence and phototoxicity of AlPc NPs in interaction with cells is proposed.
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    Synthesis Strategy of Tetrapyrrolic Photosensitizers for Their Practical Application in Photodynamic Therapy
    (2022) Koifman, O. I.; Ageeva, T. A.; Kuzmina, N. S.; Ryabova, A. V.; Pominova, D. V.; Makarov, V. I.; Loschenov, V. B.; Рябова, Анастасия Владимировна; Поминова, Дарья Вячеславовна; Макаров, Владимир Игоревич; Лощенов, Виктор Борисович
  • Публикация
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    The effect of photodynamic therapy on gram-positive and gram-negative bacteria of the oral mucosa in children with disabilities
    (2022) Kashtanova, M. S.; Morozova, N. S.; Kozlitina, Y. A.; Tatulyan, A. R.; Makarov, V. I.; Макаров, Владимир Игоревич
    © 2022, Dynasty Publishing House. All rights reserved.This literature review on the antibacterial photodynamic therapy (aPDT) use in dentistry, its latest achievements, prospects and effectiveness in children with disabilities. The treatment methods using in modern clinical practice often turn out to be insuffi-ciently effective, and the steady development of periodontal pathologies is determined in all social groups of the population, and especially in such children. They cannot independently carry out the rational oral care, and the oral cavity hygienic condition deteriorates, which means that the problem of the prevention and treatment of dental diseases in such children is an urgent task of the modern dentistry. The bacterial microflora composition of the oral cavity plays the special role in the periodontal disease development, and the structure of bacterial cell walls affects the effectiveness of aPDT. The article provides the information about the microbiological composition prevailing in the oral cavity in periodontal diseases, reflects the structural features of gram-positive and gram-negative bacteria, which have a significant impact on the photosensitizer penetration and the further procedure effectiveness. Various photosensitizer groups and sources for their excitation are also investigated. Various methods of the application and the latest approaches in the treatment of periodontal diseases with PDT in children with disabilities are described. APDT with various photosensitizers is considered as the most promising alternative approach to the periodontal disease elimination.
  • Публикация
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    УСТРОЙСТВО ДЛЯ ОЦЕНКИ СОСТАВА ИММУНОКОМПЕТЕНТНЫХ КЛЕТОК В ОПУХОЛЕВОЙ ТКАНИ СПЕКТРАЛЬНО-ФЛУОРЕСЦЕНТНЫМИ МЕТОДАМИ С ПРИМЕНЕНИЕМ ФОТОСЕНСИБИЛИЗАТОРА НА ОСНОВЕ ХЛОРИНА Е6
    (Федеральное государственное бюджетное учреждение науки Федеральный исследовательский центр "Институт общей физики им. А.М. Прохорова Российской академии наук", 2022) Лощенов, В. Б.; Рябова, А. В.; Макаров, В. И.; Романишкин, И. Д.; Макаров, Владимир Игоревич; Лощенов, Виктор Борисович; Рябова, Анастасия Владимировна
    Изобретение относится к области медицинской техники, а более конкретно к лазерно-спектроскопической технике для контроля состояния биологических тканей. Устройство содержит импульсный лазер, возбуждающий флуоресценцию накопившегося в биологической ткани фотосенсибилизатора, систему определения и анализа кинетических характеристик флуоресцентного излучения и систему отображения информации, систему приема флуоресцентного излучения, которая дополнительно содержит многоволоконный оптический зонд для доставки возбуждающего лазерного излучения к исследуемому образцу и передачи обратно рассеянного лазерного и флуоресцентного излучения на вход системы регистрации излучения флуоресценции, систему регистрации излучения флуоресценции, которая дополнительно содержит систему оптических фильтров и полихроматор для спектрального разложения регистрируемых лазерного и флуоресцентного излучения, поступающих через оптоволоконный кабель на вход полихроматора, в спектрально разложенную полосу на оптическом выходе полихроматора, электронно-оптический преобразователь с фотокатодом, системой временной развертки в направлении, перпендикулярном спектрально разложенной полосе флуоресцентного сигнала, и люминесцентным экраном на выходе, CCD-камеру для регистрации картины, отображаемой на люминесцентном экране на выходе ЭОП, выход CCD-камеры связан с входом системы определения и анализа кинетических характеристик флуоресцентного излучения, устройство дополнительно содержит последовательно соединенные блок для суммирования экспоненциальных характеристических функций кинетики флуоресценции хлорина е6 в моноцитах ТНР-1, макрофагах М0, M1, М2 с регулируемыми весовыми коэффициентами и итерационной подгонки суммы к кинетическим характеристикам излучения фотосенсибилизатора путем вариации весовых коэффициентов, блок анализа и обработки весовых коэффициентов для получения из их соотношения информации о количественном содержании моноцитов ТНР-1, макрофагов М0, M1, М2, выход которого соединен с входом блока отображения информации персонального компьютера. Устройство позволяет реализовать неинвазивный способ оценки направления развития опухолевого процесса, быстро получить комплексную оценку состояния ткани во время проведения хирургической операции или сеанса лазерно-индуцированной терапии для своевременной коррекции терапевтического или хирургического лечения. 1 ил.
  • Публикация
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    Optical spectral diagnostics of the oxygenation level in periodontal tissues and photodynamic therapy using methylene blue in children with cerebral palsy
    (2023) Morozova, N. S.; Kozlitina, Iu. A.; Makarov, V. I.; Loschenov, V. B.; Макаров, Владимир Игоревич; Лощенов, Виктор Борисович
    Dental diseases occur in children with cerebral palsy three times higher than in healthy children. Low values of the unstimulated salivation rate (andamp;lt;0.3 ml per minute), pH and buffer capacity, changes in enzyme activity and sialic acid concentration, as well as increased saliva osmolarity and total protein concentration, which indicates impaired hydration, are the factors in the development of a gingiva disease in case of cerebral palsy. This leads to increased bacterial agglutination and the formation of acquired pellicle and biofilm, leading to the formation of dental plaque. There is a tendency toward an increase in the concentration of hemoglobin and a decrease in the degree of hemoglobin oxygenation, as well as an increase in the generation of reactive oxygen and nitrogen species. Photodynamic therapy (PDT) with the use of photosensitizer methylene blue improves blood circulation and the degree of oxygenation in periodontal tissues, as well as eliminates a bacterial biofilm. Analysis of back diffuse reflection spectra makes it possible to conduct non-invasive monitoring determine tissue areas with a low level of hemoglobin oxygenation for precision photodynamic exposure. Aim To improve the effectiveness of phototheranostics methods using, namely PDT with simultaneous optical-spectral control, for the treatment of gingivitis in children with complex dental and somatic status (cerebral palsy). Methods The study involved 15 children (6-18 y.o.) with various forms of cerebral palsy, in particular, spastic diplegia and atonic-astatic form and with gingivitis. The degree of hemoglobin oxygenation was measured in tissues before PDT and on the 12th day. PDT was performed using laser radiation (О» = 660 nm) with a power density of 150 mW/cm 2 with a five-minute application of 0.01% MB. The total light dose was 45 В± 15 J/cm 2 . For statistical evaluation of the results, a paired Student s t-test was used. Results The paper presents the results of phototheranostics using methylene blue in children with cerebral palsy. An increase in the level of hemoglobin oxygenation from 50 to 67% ( p andamp;lt; 0.001) and a decrease in blood volume in the microcirculatory bed of periodontal tissues were shown. Conclusion Photodynamic therapy methods with application of methylene blue make it possible to assess the state of the gingival mucosa tissue diseases objectively in real time, and to provide effective targeted therapy for gingivitis in children with cerebral palsy. There is a prospect that they can become widely used clinical methods.
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    Devices and Methods for Dosimetry of Personalized Photodynamic Therapy of Tumors: A Review on Recent Trends
    (2024) Alekseeva, P.; Makarov, V.; Efendiev, K.; Loschenov, V.; Макаров, Владимир Игоревич; Эфендиев, Канамат Темботович; Лощенов, Виктор Борисович
    Significance: Despite the widespread use of photodynamic therapy in clinical practice, there is a lack of personalized methods for assessing the sufficiency of photodynamic exposure on tumors, depending on tissue parameters that change during light irradiation. This can lead to different treatment results. Aim: The objective of this article was to conduct a comprehensive review of devices and methods employed for the implicit dosimetric monitoring of personalized photodynamic therapy for tumors. Methods: The review included 88 peer-reviewed research articles published between January 2010 and April 2024 that employed implicit monitoring methods, such as fluorescence imaging and diffuse reflectance spectroscopy. Additionally, it encompassed computer modeling methods that are most often and successfully used in preclinical and clinical practice to predict treatment outcomes. The Internet search engine Google Scholar and the Scopus database were used to search the literature for relevant articles. Results: The review analyzed and compared the results of 88 peer-reviewed research articles presenting various methods of implicit dosimetry during photodynamic therapy. The most prominent wavelengths for PDT are in the visible and near-infrared spectral range such as 405, 630, 660, and 690 nm. Conclusions: The problem of developing an accurate, reliable, and easily implemented dosimetry method for photodynamic therapy remains a current problem, since determining the effective light dose for a specific tumor is a decisive factor in achieving a positive treatment outcome.