Персона: Поминова, Дарья Вячеславовна
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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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- ПубликацияТолько метаданныеPHOTODYNAMIC THERAPY WITH METHYLENE BLUE AND CHLORIN e6 PHOTOSENSITIZERS: STUDY ON EHRLICH CARCINOMA MICE MODEL ФОТОДИНАМИЧЕСКАЯ ТЕРАПИЯ С ФОТОСЕНСИБИЛИЗАТОРАМИ МЕТИЛЕНОВЫИ СИНИИ И ХЛОРИН е6: ИССЛЕДОВАНИЕ НА МЫШИНОИ МОДЕЛИ КАРЦИНОМЫ ЭРЛИХА(2024) Pominova, D. V.; Ryabova, A. V.; Skobeltsin, A. S.; Markova, I. V.; Romanishkin, I. D.; Поминова, Дарья Вячеславовна; Рябова, Анастасия ВладимировнаHypoxia negatively affcts the effctiveness of all types of anticancer therapy, in particular photodynamic therapy (PDT). In this regard, various approaches to overcome the limitations associated with hypoxia are widely discussed in the literature, one of them is the use of photosensitizers (PS) operating through the fist mechanism of the photodynamic reaction, such as methylene blue (MB). Previously, we have demonstrated that MB can have a positive effect on tumor oxygenation. In this work, we investigated the photodynamic activity of MB and a combination of MB with chlorin e6 on a tumor in vivo using a model of Ehrlich carcinoma. PDT was studied with the joint and separate administration of chlorin e6 and MB. The accumulation and localization of MB and its combination with chlorin e6 in vivo was assessed using video ‹?uorescence and spectroscopic methods, and the effect of laser exposure on accumulation was analyzed. After the PDT with chlorin e6, MB and a combination of MB with chlorin e6, a good therapeutic effect and a decrease in the tumor growth rate were observed compared to the control, especially in groups with PDT with MB and with the simultaneous administration of chlorin e6 and MB. The level of tumor oxygenation on days 3 and 5 after PDT was higher for groups with irradiation, the highest oxygenation on the 5th day after PDT was observed in the group with PDT only with MB. Phasor diagrams of tumors after PDT show a deviation from the metabolic trajectory and a shift towards a longer lifetimes compared to the control tumor, which indicates the presence of lipid peroxidation products. Thus, tumor regression after PDT is associated with the direct destruction of tumor cells under the in‹?uence of reactive oxygen species formed during PDT. Thus, the effectiveness of PDT with the combined use of MB and chlorin e6 has been demonstrated, and the main mechanisms of the antitumor effect of the combination of these PS have been studied.
- ПубликацияТолько метаданныеSPECTROSCOPIC STUDY OF METHYLENE BLUE IN VIVO: EFFECTS ON TISSUE OXYGENATION AND TUMOR METABOLISM СПЕКТРОСКОПИЧЕСКОЕ ИССЛЕДОВАНИЕ МЕТИЛЕНОВОГО СИНЕГО IN VIVO: ВЛИЯНИЕ НА ОКСИГЕНАЦИЮ ТКАНЕИ И ОПУХОЛЕВЫИ МЕТАБОЛИЗМ(2023) Pominova, D. V.; Ryabova, A. V.; Skobeltsin, A. S.; Markova, I. V.; Loschenov, V. B.; Поминова, Дарья Вячеславовна; Рябова, Анастасия Владимировна; Лощенов, Виктор Борисович
- ПубликацияОткрытый доступThe use of methylene blue to control the tumor oxygenation level(2024) Pominova, D.; Ryabova, A.; Skobeltsin, A.; Markova, I.; Поминова, Дарья Вячеславовна; Рябова, Анастасия Владимировна; Скобельцин, Алексей СергеевичHypoxia is a characteristic feature of many tumors. It promotes tumor proliferation, metastasis, and invasion and can reduce the effectiveness of many types of cancer treatment. The aim of this study was to investigate the pharmacokinetics of methylene blue (MB) and its impact on the tumor oxygenation level at mouse Lewis lung carcinoma (LLC) model using spectroscopic methods. The pharmacokinetics of MB were studied qualitatively and quantitatively using video fluorescence imaging and fluorescence spectroscopy. The degree of hemoglobin oxygenation in vivo was examined by calculating hemoglobin optical absorption from the measured diffuse reflectance spectra. The distribution of MB fluorescence and the lifetime of NADH were analyzed using laser scanning microscopy and fluorescence lifetime imaging microscopy (FLIM) to assess cellular metabolism. After intravenous administration of MB at 10ў??20 mg/kg, it quickly transitioned in the tumor to a colorless leucomethylene blue, with maximum accumulation in the tumor occurring after 5ў??10 minutes. A concentration of 10 mg/kg resulted in a relative increase of the tumor oxygenation level for small tumors (volume 50ў??75 mm3) and normal tissue 120 minutes after the introduction of MB. A shift in tumor metabolism towards oxidative phosphorylation (according to the lifetime of the NADH coenzyme) was measured using FLIM method after intravenous administration of 10 mg/kg of MB. Intravenous administration of MB at 20 mg/kg results in a long-term decrease in oxygenation, which persisted for at least 120 minutes after the administration and did not return to its initial level. Administration of MB at 10 mg/kg shown to increase tumor oxygenation level, potentially leading to more effective antitumor therapy. However, at higher doses (20 mg/kg), MB may cause long-term decrease in oxygenation.
- ПубликацияОткрытый доступSPECTROSCOPIC STUDY OF METHYLENE BLUE PHOTOPHYSICAL PROPERTIES IN BIOLOGICAL MEDIA СПЕКТРОСКОПИЧЕСКОЕ ИССЛЕДОВАНИЕ ФОТОФИЗИЧЕСКИХ СВОИСТВ МЕТИЛЕНОВОГО СИНЕГО В БИОЛОГИЧЕСКИХ СРЕДАХ(2023) Pominova, D. V.; Ryabova, A. V.; Markova, I. V.; Akhlyustina, E. V.; Skobeltsin, A. S.; Поминова, Дарья Вячеславовна; Рябова, Анастасия Владимировна; Ахлюстина, Екатерина Витальевна; Скобельцин, Алексей СергеевичA spectroscopic study of the photophysical properties of methylene blue (MB) in aqueous solutions was carried out. Absorption and fluorescence spectra as well as fluorescence lifetime were recorded. The concentration dependence of the intensity and shape of the spectra allowed establishing the ranges of MB concentrations for in vitro and in vivo studies at which aggregation is not observed (up to 0.01 mM, which corresponds to 3.2 mg/kg). Studies of photodegradation in biological media showed that photobleaching of more than 80% in plasma and culture media is observed already at a dose of 5 J/cm2 , while in water at this concentration and dose photobleaching is not yet observed, and at a dose of 50 J/cm2 photobleaching of MB is about 30%. It was found that in media containing proteins and having an alkaline pH, photobleaching occurs significantly faster than in neutral aqueous media. The ionic strength of the solution has no effect on the photobleaching rate. Such photobleaching is caused by the photodegradation of MB rather than the transition to the leucoform.The efficiency of singlet oxygen generation and photodynamic activity were evaluated in vitro. In the investigated range of MB concentrations, the efficiency of singlet oxygen generation is rather low, because positively charged MB binds to negatively charged cell membranes, which leads to a change in the type of photodynamic reaction. The emergence of other reactive oxygen species (ROS), different from singlet oxygen, in cells has been demonstrated. The generation of ROS and the low quantum yield of singlet oxygen generation indicate the tendency of MB to provide the type I photosensitization mechanism (electron transfer with the formation of semi-reduced and semi-oxidized MB+ radicals) rather than to the type II mechanism (energy transfer to oxygen with the formation of singlet oxygen) in biological media and in vivo.