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Targeted nanomedicines for applications in preclinical cancer models
стр.5-13
Marchio Serena, Bussolino Federico
Despite substantial advancements in cancer management, a considerable proportion of patients cannot yet be cured. Strategies to address this open medical need are actively pursued and include two main approaches: 1) optimizing diagnostic protocols to detect tumors at early stages, and 2) designing personalized therapies to increase efficiency and selectivity of clinical interventions. Our recent work has been directed to a rationally-designed implementation of both approaches. Particularly, we have contributed to the development of nanomedicines that can be targeted to diseased tissues for theranostic purposes in preclinical models of human cancers. Such modular nanoscale systems proved to be versatile platforms to combine imaging and drug delivery for applications in the oncological field and could be a basis for future improvements.
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A novel spheroid model for preclinical intercellular nanophotosensitizer-mediated tumor study
стр.14-20
Maklygina YuS, Romanishkin ID, Ryabova AV, Yakavets IV, Bolotin L, Loschenov VB
Aluminum phthalocyanine nanoparticles (NP AlPc) possess the features that make them a promising photosensitizer. In particular, AlPc NPs do not fluoresce in free nanoform, fluoresce weakly in normal tissue, strongly in tumors and very strongly in macrophages. Also, such particles fluoresce and become phototoxic when contacting certain biocomponents. The type of biocomponents that bind to AlPc NPS defines intensity, lifetime, and spectral distribution of the fluorescence. This study aimed to investigate the peculiarities of nanophotosensitizer capturing in 3D models of cell cultures. The data obtained demonstrate that AlPc NPs are captured by cells inside the spheroid in the course of the first hour, as the fluorescent signal's growth shows. Having analyzed the fluctuations of the fluorescence signal of AlPc NPs inside a spheroid, we have also discovered that the cellular 3D models are heterogeneous. Laser irradiation (two-photon excitation at λ = 780/390 nm) resulted in photobleaching of fluorescence, which is probably associated with AlPc NP deactivation. Thus, the created model comprised of a 3D cell culture and AlPc NPs provides a better insight into metabolic processes in cells than monolayer 2D cell cultures. Besides, the model allows to evaluate the photodynamic effect depending on phenotypic properties of various areas in the heterogeneous 3D-structure.
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Magnetic resonance imaging for predicting personalized antitumor nanomedicine efficacy
стр.21-24
Naumenko VA, Garanina AS, Vodopyanov SS, Nikitin AA, Prelovskaya AO, Demikhov EI, Abakumov MA, Majouga AG, Chekhonin VP
Magnetic resonance imaging (MRI) is widely used to diagnose cancer and study patterns and effectiveness of nanocarrier delivery of anticancer drugs. Accumulation of nanoparticles in a tumor varies widely in a given population; it is also highly dependent on biological factors, which remain largely unstudied. In recent years, there was developed a hypothesis that suggests that MRI can be used to predict response to nanoformulations-based anticancer therapy since it provides data on accumulation of MRI contrast agents in the tumor. Pilot tests prove feasibility of the approach based on this hypothesis, however, there is a number of conceptual and technical problems and limitations that hamper its introduction into the routine clinical practice. This article discusses the advantages and disadvantages of methods to stratify tumors by level of nanoparticles accumulation. Further research in this field would facilitate development of effective algorithms of personalized treatment with anticancer drugs delivered by nanoparticles.
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Molecular origin of surface-enhanced Raman spectra of E. coli suspensions excited at 532 and 785 nm using silver nanoparticle sols as SERS substrates
стр.25-32
Durovich EA, Evtushenko EG, Senko OV, Stepanov NA, Efremenko EN, Eremenko AV, Kurochkin IN
Research into the molecular origin of surface-enhanced Raman spectra (SERS) of bacteria is a crucial step in assessing the future of SERS-based discrimination and identification of bacteria in clinical analysis, food quality control, etc. Previous studies have revealed that at 785 nm excitation wavelength SERS of bacterial cells placed on a solid surface functionalized with in-situ grown aggregated gold nanoparticles covered with SiO originate from a mixture of 6 purine derivatives (adenine, guanine, AMP, hypoxanthine, xanthine, and uric acid) that are released by the cells into the medium. The aim of the present work was to investigate whether such interpretation is possible with a different class of SERS substrates: silver nanoparticle sols at excitation wavelengths of 785 and 532 nm. The suspension of the Escherichia coli DH5α strain was used as a model bacterium. Sols of silver nanoparticles were obtained by reducing silver nitrate in the presence of alkaline hydroxylamine hydrochloride. Number-weighted mean hydrodynamic diameter of the particles was 43±2 nm. We confirm that at both excitation wavelengths the spectra can be best described as a superposition of 4 purine derivatives: adenine, guanine, hypoxanthine, and xanthine. Importantly, we have discovered that 1) the spectra of the purine mixture are characteristic of viable cells only; 2) due to the variations in the concentrations of purine metabolites released by the cells into the surrounding medium the spectra of a bacterial strain can vary significantly when a silver nanoparticle sol is used as a SERS substrate.
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Development of liposomal drug formulations: quality attributes and methods for quality control
стр.33-39
Melnikova EV, Goryachev DV, Chaplenko AA, Vodyakova MA, Sayfutdinova AR, Merkulov VA
The use of nanostructured components in drug manufacturing and, more specifically, targeted drug delivery has recently become a major trend in the pharmaceutical industry. Nanodrugs encompass a wide range of pharmaceutical agents containing dendrimers, nanocrystals, micelles, liposomes, and polymer nanoparticles. Liposomes are the most well-studied nanoparticles and effective drug carriers. However, the more complex their structure is, the more process controls are needed and the more quality attributes have to be monitored, including the chemical properties of the liposomal fraction such as the shape, size and charge of the nanoparticle, conjugation efficacy, and distribution of the active ingredient. We believe that quality control of key liposome characteristics should rely on dynamic and laser light scattering coupled with electrophoresis, differential scanning calorimetry, cryo-electron microscopy, nuclear magnetic resonance, laser diffraction analysis, and gel filtration chromatography.
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Lipidoid iron oxide nanoparticles are a platform for nucleic acid delivery to the liver
стр.40-48
Uvarova VI, Nizamov TR, Abakumov MA, Vodopyanov SS, Abakumova TO, Saltykova IV, Mogilnikov PS, Shchetinin IV, Majouga AG
Targeted delivery of antisense drugs is a promising technology which can provide a platform for the development of highly effective therapeuticals against a broad range of diseases. Insufficient stability of RNA in biological media coupled with hydrophilicity that prevents the molecule from penetrating cell membranes considerably limit RNA application in clinical practice. The aim of this work was to design a system for antisense drug delivery to liver hepatocytes using lipidoid magnetic nanoparticles (LNP). Nanocubes (NC) with average sizes of 16 and 27 nm were synthesized through decomposition of iron (III) oleate under high temperature conditions and functionalized with a cationic lipidoid С12-200. Magnetic NC demonstrated good MR-contrasting properties. Biodistribution of LNP was studied in vivo in BALB/c mice using the MR scanner. Additionally, liver sections obtained from the mice were subjected to histological examination. Nanoparticles of smaller size did not have a cytotoxic effect on HepG2 and Huh7 cell lines, whereas for larger NC, IC50 was 21.5 μg/ml and 126 μg/ml for HepG2 and Huh7 cells, respectively. Smaller particles tended to accumulate in hepatocytes. Bigger NC mainly accumulated in the spleen but also ended up in liver macrophages. This fact can be explained by a bigger hydrodynamic size of nanoparticles with a bigger magnetic core. Particles with smaller cores are a more effective platform for the delivery of antisense drugs to hepatocytes.
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Nanoparticles guided precise transplantation of varying numbers of mesenchymal stem cells into post-traumatic syrinx in spinal cord injury rat
стр.49-56
Zhang Chao, Morozova AY, Baklaushev VP, Gubsky IL, Melnikov PA, Gabashvily AN, Wang Guowen, Li Lili, Wu Haixiao, Wang Xin, Chekhonin VP
Spinal cord injury (SCI) is a traumatic injury to the spinal cord which is not a consequence of the disease. Mesenchymal stem cells (MSCs) have gradually become one of the most used stem cells in research and clinic trial. Based on the previous reports employed the cells ranged from 4 • 10 to 1 • 10, the present study was performed to figure out the best number of MSCs for transplantation of the chronic SCI. Magnetic nanoparticles were used for proving the precise transplantation strategy. Using magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), diffusion tensor tractography (DTT), and behavior testing evaluations, we focused the effect of varying numbers of MSCs on reducing lesion cavity and post-traumatic syrinx formation, suppressing glial scar formation, enhancing neuronal fibers remodeling, promoting axonal regeneration and sprouting, improving vascularization, ameliorating the neuronal factors expressional level, and function improvement. Magnetic nanoparticles were precisely transplanted into the post- traumatic syrinx (PTS). MSCs can restore function after chronic SCI through stimulating the regeneration and sprouting of the axons, reducing the formation of PTS. The effect of MSCs on PTS management and functional improvement post chronic SCI was cell number-dependent, and within the range of 4 • 10 to 1 • 10, 1 • 10 cells were proved to be the best dose.
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Promising methods for noninvasive medical diagnosis based on the use of nanoparticles: surface-enhanced Raman spectroscopy in the study of cells, cell organelles and neurotransmitter metabolism markers
стр.57-67
Goodilin EA, Semenova AA, Eremina OE, Brazhe NA, Goodilina EA, Danzanova TYu, Maksimov GV, Veselova IA
Application of advances in nanomedicine and materials science to medical diagnostics is a promising area of research. Surface-enhanced Raman spectroscopy (SERS) is an innovative analytical method that exploits noble metal nanoparticles to noninvasively study cells, cell organelles and protein molecules. Below, we summarize the literature on the methods for early clinical diagnosis of some neurodegenerative and neuroendocrine diseases. We discuss the specifics, advantages and limitations of different diagnostic techniques based on the use of low- and high molecular weight biomarkers. We talk about the prospects of optical methods for rapid diagnosis of neurotransmitter metabolism disorders. Special attention is paid to new approaches to devising optical systems that expand the analytical potential of SERS, the tool that demonstrates remarkable sensitivity, selectivity and reproducibility of the results in determining target analytes in complex biological matrices.
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Towards a computational prediction for the tumor selective accumulation of paramagnetic nanoparticles in retinoblastoma cells
стр.68-73
Johansen RJ, Bukhvostov AA, Ermakov KV, Kuznetsov DA
Retinoblastoma is a malignant growth affecting retina. An original combination of modified Non-Markov and Gompertzian computational approaches is proven of being a reliable tool for prediction of tumor selective accumulation of the bivalent metal isotopes (Mg, Ca, Co, Zn, …) - releasing nanoparticles in human retinoblastoma cells. This mathematical model operates with a starting point of the discriminative drug uptake caused by a gap-like distinction between the neighboring malignant and normal cell proliferation rates. This takes into account both pharmacokinetic and pharmacodynamic peculiarities of PMC16, fullerene-C based nanoparticles, known for their unique capabilities for a cancer-targeted delivery of paramagnetic metal isotopes followed by an essential chemotherapeutic effect. Being dependent on a tumor growth rate but not on the neoplasm steady state mass, a randomized level of drug accumulation in retinoblastoma cells has been formalized as a predictive paradigm suitable to optimize an ongoing PMC16 preclinical research.
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Nanostructured photosensitizer based on a tetracationic derivative of bacteriochlorin for antibacterial photodynamic therapy
стр.74-78
Meerovich GA, Akhlyustina EV, Tiganova IG, Makarova EA, Philipova NI, Romanishkin ID, Alekseeva NV, Lukyanets EA, Romanova YuM, Loschenov VB
Making antibacterial PDT more effective is a task that calls for the development of photosensitizers (PS) based on polycationic synthetic bacteriochlorins and subsequent analysis of properties of such photosensitizers. This study aimed to explore photophysical and antibacterial properties of the nanostructured PS based on 3-Py4BSHp4Br4, tetracationic amphiphilic derivative of synthetic bacteriochlorin. The PS was solubilized in a 4% Kolliphor ELP to obtain its nanostructured dispersion. We researched the absorption and fluorescence spectra intensity and profiles, studying concentrations from 0.001 to 0.2 mM, and found that the aggregation level of the PS in question is low throughout the range investigated while the S. aureus (gram-positive) and P. aeruginosa and K. pneumoniae (gram-negative) PD inactivation effectiveness is high.
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Gold nanoparticles in the diagnosis and treatment of cancer
стр.79-85
Kurapov PB, Bakhtenko EYu
Due to chemical stability, low toxicity, and relative simplicity of synthesis/modification techniques, gold nanoparticles (NP) enjoy a wide range of biomedical applications, including in vitro diagnostics, targeted drug delivery, contrast-enhanced radiation therapy, and photothermal therapy. The high ratio of the gold NP surface area to their volume facilitates design of complex nanoplatforms for various therapeutic and diagnostic purposes. Unique electrical and optical properties of gold NP known as surface plasmon resonance assist medical diagnosis. In this work we look at the basic methods for gold NP synthesis and modification, including the so-called green chemistry, talk about the pharmacological aspects of their application and highlight their potential as diagnostic agents. We believe that due to their unique properties, gold-based nanoplatforms for targeted drug delivery and theranostics have indisputable advantages over other nanoparticles.
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Hydroxyapatite and porphyrin-fullerene nanoparticles for diagnostic and therapeutic delivery of paramagnetic ions and radionuclides
стр.86-93
Orlova MA, Nikolaev AL, Trofimova TP, Orlov AP, Severin AV, Kalmykov SN
Nanoparticles for drug delivery are the subject of extensive research. Importantly, they can transform in size during synthesis or actual use, thereby changing their cytotoxic properties. The aim of the present work was to study the tendency of [67Zn] porphyrin-fullerene nanoparticles (BFNP) to aggregate over time and to compare the properties of hydroxyapatite (HAP) nanoparticles obtained through 3 different techniques. We found that aggregation of BFNP nanoparticles does not affect their function but attenuates their cytotoxicity against leukemia cells. We were also able to obtain HAP nanoparticles with programmable properties (such as size, shape or the capacity to adsorb metal ions, ligands and chemical complexes) through enzymatic synthesis by varying its conditions. The synthesized HAP nanoparticles contain short-lived isotopes of zinc and copper (in the form of ions and complexes with pyrimidine or thiazine derivatives). These tumoricidal components (a radionuclide and a ligand or a complex) determine the diagnostic and therapeutic potential of the obtained radiopharmaceutical agents.
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ZAIS-based colloidal QDs as fluorescent labels for theranostics: physical properties, biodistribution and biocompatibility
стр.94-101
Istomina MS, Pechnikova NA, Korolev DV, Pochkayeva EI, Mazing DS, Galagudza MM, Moshnikov VA, Shlyakhto EV
In recent years there has been an increase in interest in the use of colloidal quantum dots (QDs) in biology and medicine. In particular, QDs can be a perspective nanoscale object for theranostics, in which due to the specific accumulation of drug-loaded QDs in the pathological focus, its simultaneous visualization and targeted therapeutic influence occur. One of the serious limitations of the use of QDs in medicine is their potential toxicity, especially when the nanocrystal material contains elements such as cadmium or plumbum. Therefore, it is promising to develop labels based on QDs of relatively less toxic semiconductors of group I-III-VI, such as CuInS and AgInS. In this study, biodistribution and biocompatibility of QDs based on the AgInS compound with a ZnS shell (ZAIS) are considered. In the study of biodistribution, the accumulation of QDs in organs such as liver, lungs, heart and kidneys was revealed. It was shown that QDs in the dose range from 2 • 10 to 4 • 10 M/L at intravenous administration in rats does not have a significant effect on body mass dynamics and basic hematological parameters for 30 days. Thus, ZAIS QDs can be used to visualize tissues and organs in various pathological processes, and immobilization of the drugs on their surface will allow to approach their application for theranostics.
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Nanoprticles of metals and their inorganic compounds obtained through interphase and redox-transmetalation interaction: application in medicine and pharmacology
стр.102-106
Vorobyova SA, Rzheussky SE
Synthesis of nanoparticles of metals and their compounds with given morphology and dispersity for use in medicine, pharmacology, microelectronics, as well as subsequent research of their properties, is one of the current problems in the field of preparative inorganic chemistry. Interphase synthesis and redox-transmetalation interaction are as promising as the traditional precipitation from aqueous solutions, but not as researched. This study presents the results of a physicochemical analysis of nanoparticles of metals and their compounds obtained through chemical precipitation from aqueous solutions, interphase and redox-transmetalation interactions. Data describing the influence of phase composition and dispersity of copper and copper oxide (II) nanoparticles on their antimicrobial properties, as well as the results of researching the possibility to use magnetite magnetic fluids for mesenchymal stem cells marking, illustrate the application options synthesized nanoparticles find in pharmacology and medicine.
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Application of nanoscale polymer colloid carriers for targeted delivery of the brain-derived neurotrophic factor through the blood-brain barrier in experimental parkinsonism
стр.107-112
Kapitonova MYu, Alyautdin RN, Wan-Syazli RWAL, Nor-Ashikin MNK, Ahmad A, Norita S, Dydykin SS
Parkinson disease is one of the common age-related motor neurodegenerative diseases, in which dopamine neurons degeneration is considered to be pathognomic for the development of motor disfunction. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which is considered to be a key regulator of neuronal plasticity. BDNF, being a large molecule, does not pass through the blood-brain barrier (BBB). Synthetic polymer nanoparticles (NP), covered by surfactant, provide the phenomenon of “Trojan hoarse” and enable BDNF to penetrate into the brain tissue. For modelling of parkinsonism we used an intraperitoneal (i.p.) injection of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which was injected to the C57BL/6 mice with subsequest treatment with normal saline (group 1), BDNF (group 2), nanoparticulate BDNF (group 3) and surfactant-coated nanoparticulate BDNF (group 4). After 90 min, 24 hours, 72 hours and 7 days manifestations of parkinsonism were evaluated using behavioural tests of open field, rota-rod, assessment of the tremor, length of the body and pace. At the end of experiment the brain was sampled for histological evaluation of changes in the striatum and midbrain and concentration of BDNF in the brain tissues. The results of the experiments demonstrated that nanoparticulate BDNF covered with surfactant significanltly reduced rigidity of the skeletal muscles, oligokinesia and tremor, and also significantly increased BDNF concentration in the brain tissues.
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Experimental study of dendrimer-based nanoparticles with RGD-peptide for anticancer radionuclide therapy
стр.113-119
Stukalov YuV, Grigorieva EYu, Smirnova AV, Lipengolts AA, Kubasova IYu, Pozdniakova NV, Lukashina MI
Radionuclide therapy (RNT) is an effective modality for treating multiple metastases in patients with cancer. The list of malignancies that can be managed with RNT expands with the arrival of novel tumoritropic radiopharmaceuticals (RP). A versatile delivery platform capable of carrying various therapeutic and diagnostic radionuclides, as well as vector molecules needed to achieve sufficient specificity to tumor cells and ensure therapeutic efficacy may hold great promise for radiation therapy. The aim of this work was to assess the performance of a delivery system based on the original dendrimer. The dendrimer demonstrated low toxicity in mice (LD50 was 779 ± 111 mg/kg). To study the specificity of the dendrimer to tumor cells and its therapeutic efficacy, we used a nanostructure (NS) composed of the dendrimer itself, the RGD peptide and Re (Re-NS). Lewis lung carcinoma LLC1 was used as a tumor model. The biodistribution analysis revealed that the compound effectively accumulated in the tumor demonstrating a tumor-to-normal ratio >1 (relative to healthy organs and tissues) and retention time of at least 6 hours. Injections of 185 MBq/kg Re-NS caused a statistically significant inhibition of tumor growth ( p < 0.05) by day 7 following the injection (Т/С = 5%), which remained stable for 6 days. Our findings suggest that the proposed dendrimer is a promising platform for RP delivery.
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Poly(3-hydroxyalkanoate)-based drug formulations: the microand nanostructure
стр.120-124
Bonartsev AP, Bonartseva GA, Voinova VV, Kirpichnikov MP, Shaitan KV
Biodegradable and biocompatible polymers referred to as polyhydroxyalkanoates (PHAs) are extensively used in the production of pharmaceutical drugs to ensure sustained release, targeted delivery, reduced toxicity, and increased stability of the drug substance. Although the pharmaceutical industry ordinarily exploits chemically synthesized PHAs, bioengineered polymers are also starting to enjoy growing interest. This article focuses on the research and development of drug formulations based on natural PHAs that act as auxiliary substances for antibacterial, anti-inflammatory, anticancer, and hormonal medications, as well as pain killers, and discusses the association between their properties and the micro/nano structure of the synthetic drug. The problems associated with the poor performance of active components in traditional dosage forms can be overcome in PHAs-based formulations.
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The use of iron oxide magnetic nanospheres and nanocubes for targeted doxorubicin delivery into 4T1 mouse breast carcinoma cells
стр.125-133
Nizamov TR, Garanina AS, Uvarova VI, Naumenko VA, Schetinin IV, Savchenko AG
Magnetic nanoparticles (MNP) are attracting increasing attention as promising materials for the treatment and diagnosis of cancer. The aim of this work was to explore the effect of the magnetic core shape of iron oxide nanoparticles (NP) on the efficacy of doxorubicin delivery into 4T1 cells. Nanospheres (NS) and nanocubes (NC) were synthesized by thermal decomposition of iron (III) oleate. This method of synthesis enables control over the NP shape and size. The NP were hydrophilized using Pluronic F-127. The obtained particles were doped with doxorubicin in a sodium phosphate buffer. The weight fractions of doxorubicin in the NS and NC were 15.22% and 15.44%, respectively. The IC50 of free doxorubicin was 1 μM. The IC50 of doxorubicin-loaded NS and NC were 6.4 μM and 5.5 μM, respectively. Unloaded NP did not exhibit any toxicity towards the cells at a studied range of concentrations between 1.77 mg/l and 227.2 mg/l. Free doxorubicin demonstrated more vigorous accumulation dynamics in 4T1 cells with a tendency to localize in cell nucleus, whereas doxorubicin loaded onto iron oxide NP was mainly accumulated in the vesicles surrounding the nucleus and was able to enter it only after being incubated with the cells for 2 h. We conclude that doxorubicin loaded onto cubic-shaped NP is delivered into the cell nucleus a little bit more effectively at early incubation stages in comparison with nanospheres, but the difference is insignificant.
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Enabling Technologies for the Preparation of Multifunctional “Bullets” for Nanomedicine
стр.134-143
Martina K, Serpe L, Cavalli R, Cravotto G
Recent advances in nanotechnology, including modern enabling techniques that can improve synthetic preparation and drug formulations, have opened up new frontiers in nanomedicine with the development of nanoscale carriers and assemblies. The use of delivery platforms has attracted attention over the past decade as researchers shift their focus away from the development of new drug candidates, and toward new means with which to deliver therapeutic and/or diagnostic agents. This work will explore a transdisciplinary approach for the production of a number of nanomaterials, nanocomplexes and nanobubbles and their application in a variety of potential biological and theranostic protocols. Particular attention will be paid to nanobubbles, stimuli responsive nanoparticles and cyclodextrin grafted nanosystems produced under non-conventional conditions, such as microwave and ultrasound irradiation. Besides nanoparticles preparation, ultrasound can also act as an enabling technology when activating sensitive nanobubbles and nanoparticles.
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Detecting reactive oxygen species in biological fluids by platinum nanoelectrode applying amperometric method
стр.144-149
Vaneev AN, Alova AV, Erofeev AS, Gorelkin PV, Aleksashkin AD, Beznos OV, Chesnokova NB, Kost OA, Majouga AM, Korchev Y, Klyachko NL
Reactive oxygen species (ROS) are vital metabolites in numerous biological functions. Disorders of cellular mechanisms can cause overproduction of ROS and, subsequently, oxidative damage to DNA, proteins, cells and tissues, which is associated with the pathogenesis of a number of neurodegenerative and inflammatory diseases. Development of highly sensitive, relatively simple and fast-to-implement innovative methods to detect oxidative stress requires understanding of how such disorders relate to the level of ROS. This research aimed to apply the biological fluids' ROS detection method we have developed (using the stable platinum nanoelectrode that allows assessing the level of hydrogen peroxide (HO) down to 1 μM) and determine the level of HO in lacrimal and intraocular fluids of rabbits, as well as to investigate how the level of HO changes under the influence of antioxidant therapy. The effect superoxide dismutase (SOD) nanoparticles produce on biological fluids' ROS level was shown. The level of H2O2 in lacrimal fluid increased 10 and 30 min after instillation of SOD nanoparticles. As for the intraocular fluid, HO concentration starts to grow only 30 min after instillation of SOD nanoparticles, which suggests that the they penetrate the internal structures of the eye gradually. The method seems to be of value in the context of eye diseases diagnosing and treatment.
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The use of monoclonal antibodies in autoimmunity treatment
стр.150-154
Merzlyak EM, Syrko DS, Musatkina EA, Israelson MA
Recently, monoclonal antibodies (MA) have gained popularity as therapeutic agents for the treatment of autoimmune disorders. These antibodies target proinflammatory cytokines, as well as T and B cells potentially involved in the pathogenesis of such conditions. In the present work we attempt to give a systematic description of available therapeutic MA, highlight their key mechanisms of action and pinpoint their adverse effects. We believe that MA that are capable of recognizing and eliminating pathogenic T- and B-cell clones hold the most promise for medical application as biologics. Detection and identification of autoreactive lymphocyte clones is one of the most serious challenges of contemporary medicine.
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Chimeric antigen receptor expression in natural killer cell line NK-92 by transduction with lentiviral particles pseudotyped with the surface glycoproteins of the measles virus vaccine strain
стр.155-161
Kravchenko YE, Gagarinskaya DI, Frolova EI, Chumakov SP
Cancer immunotherapy with T-cells that carry chimeric antigen receptors is currently on cutting edge of modern oncology. Autotransplantation of T-lymphocytes with chimeric receptor specific for certain tumor antigen proves to be clinically effective, but costly. Linear carriers of chimeric antigen receptors based on natural killer NK-92 cell culture may be an affordable alternative, however, this culture is resistant to lentiviral transduction. Recently, lentiviral vectors, pseudotyped with surface glycoproteins of the measles virus vaccine strain, have recently been successfully applied for transduction of primary immune cells. The aim of the work was to assess the efficiency of transduction of NK-92 cells with lentivirus vectors, pseudotyped with measles F and H surface glycoproteins, as well as to establish optimal conditions for selection of NK-92 transduced with the chimeric receptor against CD20 and to evaluate the culture’s cytotoxic potential. The results showed that the maximum infectious titer is achieved using the H∆18 variant in combination with F∆30, and the use of the TBK1/IKKɛ inhibitor BX795 results in additional 3-fold increase in the infectious titer. CAR-expressing NK-92 were able to suppress the proliferation of CD20+ cell line Raji in lower effector-to-target ratios than unmodified NK-92.
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Modern Aneurysm Surgery: a pro-open surgery view
стр.162-167
Dubovoy AV, Bervitskiy AV, Spallone A
Modern management of intracranial aneurysms is matter of great debate between supporters of “traditional” microsurgical treatment and those of relatively new endovascular management. This paper briefly reports the experience of two experienced microvascular “traditional” neurosurgeons who shares the same management philosophy favouring open microsurgery in the modern era in which endovascular management is becoming fashionable. Difficult posterior circulation aneurysms are nowadays as a rule managed endovascularly, whilst anterior circulation aneurysms can be treated with both techniques, and MCA as well as distal ACA aneurysms are better treated microsurgically. Technical refinement and - hopefully- lower cost of endovascular devices will favour a trend of prevailing use of endovascular method in the future. However the need for well-prepared microvascular surgeon will always be there, and proper training of future generations of microvascular surgeons in a setting of decreasing number of patients and open surgical casuistics represents a big challenge for the neurosurgical community, to which an answer should be given.
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Identification of BRCA1/2 mutations in breast cancer patients by next-generation sequencing
стр.168-173
Stetsenko IF, Krasnenko AYu, Stanoevich US, Mescheryakov AA, Vorotnikov IK, Druzhilovskaya OS, Belova VA, Churov AV
Breast cancer is one of the most widespread forms of solid tumors. By analyzing the traits of breast cancer pathogenesis at the molecular level using modern genetic analysis techniques and at different stages of the disease new data can be obtained to be further utilized in clinical practice. Molecular profiling based on next-generation sequencing is being increasingly applied as a clinical test to select target drugs for treating breast cancer patients with tumors highly resistant to therapy. In this study, we performed targeted sequencing of BRCA1 and BRCA2 oncogenes. In the total of 66 DNA samples from patients with breast tumors, BRCA1/2 mutations were found in 39 patients. There were 78 unique genetic variants, including 30 mutations in BRCA1 and 48 mutations in BRCA2 . We identified 33 mutations affecting the sites of post-translational modification in proteins (PMT mutations).
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