The immune system, one of the most important homeostatic organism systems, is actively involved in the protection against malignant tumors. The earliest sighs of immune homeostasis disorders should be invetigated at the cellular level, because of cell functional manifestations depend on the state of intracellular metabolic reactions. The study of lymphocyte NAD(P)-dependent dehydrogenases activity and peripheral blood neutrophils oxygen-dependent metabolism in patients with renal cellular carcinoma (RCC) showed a decrease in the intensity of ribose-5-phosphate and NADH-dependent synthetic processes, inhibition of terminal reactions of glycolysis. Altered activities of the studied enzymes favor an increase in outflow of intermediates of the Krebs cycle on the reaction of amino acid metabolism in peripheral blood lymphocytes. Radical nephrectomy was accompanied by increased activity of glycolysis. The basal level chemiluminescent of peripheral neutrophils of RCC patients response was higher both before and after operations. Stimulation of neutrophils by opsonized zymosan in vitro leads to increase in oxidative metabolism activity, most in 14 days after surgery period. Before and 30 days after surgery, adaptive metabolic capabilities of neutrophilic granulocytes decreased.

Cisplatin is an effective anticancer drug used to treat various types of cancer. The main disadvantage of the drug is its high toxicity. To reduce the toxic effect of cisplatin, we conjugated it with arabinogalactan, which is capable of forming soluble globules and bind poorly soluble pharmacological compounds by confining them inside spheroid globules. In this study, we compared the biological effect and mechanism of action of cisplatin and its complex with arabinogalactan (AG–Pt) on the growth of Ehrlich ascites carcinoma in vivo. It has been shown that the conjugates of arabinogalactan with cisplatin exerted a strong antitumor effect despite the fact that the dose of cisplatin in the composition of the conjugates was 10 times less than the standard dose. At the same time, the conjugates of arabinogalactan with cisplatin were virtually nontoxic. It has been established that the antitumor effect of cisplatin and its conjugates with arabinogalactan is due to the induction of apoptosis in tumor cells. It is assumed that a decrease in toxicity and an increase in the efficacy of cisplatin-arabinogalactan conjugates compared to pure cisplatin are associated with its more efficient accumulation in tumor cells.

We studied the effectiveness of using magnetic ferrihydrite nanoparticles of bacterial origin carrying ampicillin for local treatment of burn wounds in rats using a magnetic field. It was found that the use of these nanoparticles in combination with a magnetic field accelerated wound healing and reduced the titer of microorganisms in comparison with the corresponding parameters in the untreated animals and animals treated with nanoparticles or ampicillin alone.

We studied the distribution of ferrihydrite nanoparticles isolated from bacteria Klebsiella oxytoca in the whole body in vivo and in a cultured isolated organ (liver). The possibility of controlling these nanoparticles in the body using a magnetic field was assessed. One hour after intravenous injection of ferrihydrite nanoparticles to mice, their accumulation was observed in the liver, lungs, and kidneys. Experiment with cultured isolated rat liver showed that these nanoparticles can be controlled by a magnetic field and the influence of magnetic nanoparticles on the liver over 1 h does not lead to destruction of liver cells associated with the release of the marker enzyme AST. These results show the possibility of using magnetic nanoparticles as a system for controlled drug delivery in the body.

In this work, we investigated the NAD(P)-dependent dehydrogenase activity in different fields of the solid form of Ehrlich carcinoma. It was shown that there is a metabolic distinction between different fields of the solid tumor. In this way, there is a significant difference between the ascites and solid type of Ehrlich carcinoma. In the central area of the tested sample of tumor tissue, there is a high intensity of energetic metabolism and biosynthetic processes as opposed to the peripheral areas. Previously, we proposed the concept of nonspecific metabolic reaction of the cell in organism upon the influence of negative factors. In accordance with this concept, our results indicate the development of adaptation in the tumor cells in the central area of the tested sample.

The distribution in mice of intravenously injected modified nanodiamonds (MNDs) obtained by detonation synthesis was studied using electron paramagnetic resonance (EPR) spectrometry. It has been shown that 2.5 h after MND injection into the tail vein of mice, the nanoparticles accumulate mainly in the lungs and liver of animals; much smaller amounts of nanoparticles were found in the kidneys and heart. The presence of MNDs in the samples of blood, spleen, brain, and thigh muscles of mice was not detected within the sensitivity of the method used.

Nanoparticles of antiferromagnetically ordered materials acquire the uncompensated magnetic moment caused by defects and surface effects. A bright example of such a nano-antiferromagnet is nanoferrihydrite consisting of particles 2–5 nm in size, the magnetic moment of which amounts to hundreds of Bohr magnetons per particle. We present a brief review of the studies on magnetic properties of ferrihydrite produced by bacteria. Special attention is focused on the aspects of possible biomedical applications of this material, i.e., the particle elimination, toxicity, and possible use for targeted drug delivery.

В модельных экспериментах in vitro установлена применимость метода ЭПР-спектрометрии для детекции модифицированных наноалмазов (МНА) в крови и гомогенатах органов мышей. В образцах биоматериалов, содержащих МНА, зарегистрировали характерный сигнал (g = 2,003, H 10 Гс), интенсивность которого линейно возрастала с ростом концентрации наночастиц в диапазоне 1,6-200 мкг МНА на 1 мл образца. Методом ЭПР в биоматериалах выявили наличие собственных парамагнитных центров, сигналы которых накладывались на сигнал МНА. Интенсивность этих сигналов была незначительной, что позволило регистрировать МНА методом ЭПР-спектрометрии с необходимой точностью. Полученные результаты открывают перспективы для использования метода ЭПР в исследованиях фармакокинетики и фармакодинамики МНА в организме экспериментальных животных.

In this work, we investigated the activity of the key NAD(P)-dependent dehydrogenases associated with macrophage tumors in mice with Ehrlich ascites carcinoma. It was shown that cancer grow is associated with the development of conditions in macrophages leading to a decrease in the substrate flow intensity in the tricarboxylic acid cycle, deceleration of oxidative deamination of L-glutamate, NADP regeneration, and a decrease in the antioxidant defense efficiency. There results are consistent with our recent concept on the nonspecific metabolic reaction of cells to extreme exposures.

In model experiments in vitro, the applicability of the EPR spectrometry method for the detection of modified nanodiamonds (MNDs) in blood and homogenates of mouse organs has been established. A characteristic signal (g = 2.003, ΔH ≈ 10 G) is observed in the samples of biomaterials containing MNDs, the intensity of which increases linearly with the concentration of nanoparticles in the range of 1.6–200 μg MNDs per 1 mL of the sample. The EPR method in biomaterials reveals the presence of intrinsic paramagnetic centers, signals from which are superimposed on the signal from the MNDs. However, the intensity of these signals is small, which makes it possible to register the MNDs using EPR spectrometry with the necessary accuracy. The data obtained open up the prospects of using the EPR method for studies of the interorgan distribution, accumulation, and elimination of MNDs during their intravenous injection into experimental animals.

We studied antitumor properties of modified detonation nanodiamonds loaded with doxorubicin on in vivo model of Ehrlich ascites carcinoma. The type of tumor development and morphological characteristics of the liver, kidneys, and spleen were evaluated in experimental animals. Modified nanodiamonds injected intraperitoneally produced no antitumor effect on Ehrlich carcinoma. However, doxorubicin did not lose antitumor activity after sorption on modified nanodiamonds.

This work summarizes the authors’ recent investigations into metabolic changes in blood lymphocytes, cancer cells, and hepatocytes during tumor growth from mice with Ehrlich ascites carcinoma. These results were compared with the metabolic changes in hepatocytes from rats after hyperthermia and in lymphocytes from patients with different diseases. It was shown that the extreme conditions induced metabolic changes that were independent of the cell type or the nature of the extreme factor. These changes characterized the metabolic mechanisms of cell adaptation and disadaptation. The concept of the “nonspecific metabolic reaction” of cells to extreme exposures had been introduced.

Suspension of magnetic nanoparticles (0.7 g/liter) obtained from Klebsiella oxytoca culture was injected intraperitoneally (1 ml), intramuscularly (in the hip; 100 μl), and subcutaneously (200 μl) or administered orally instead of drinking water for 2 days. The presence of magnetic nanoparticles was evaluated detected by MRI in 15 min and 2 h after injections and in 1 and 2 days after the beginning of oral consumption of the suspension. Magnetic nanoparticles were eliminated from the site of intramuscular and intraperitoneal injections and after oral consumption. The period of elimination after intramuscular and intraperitoneal injections did not exceed 2 h, while after oral consumption it corresponded to the time of gastrointestinal tract contents evacuation.