Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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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.

Received: 2018-11-29

Published online: 2018-12-31

DOI: 10.24075/brsmu.2018.090

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VIEWS 3582

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 188Re (188Re-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 188Re-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.

Received: 2018-09-12

Published online: 2018-12-31

DOI: 10.24075/brsmu.2018.089

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VIEWS 3485

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 SiO2 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.

Received: 2018-08-15

Published online: 2018-12-31

DOI: 10.24075/brsmu.2018.088

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VIEWS 4143

Meerovich GA, Akhlyustina EV, Tiganova IG, Makarova EA, Philipova NI, Romanishkin ID, Alekseeva NV, Lukianets 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.

Received: 2018-08-31

Published online: 2018-12-31

DOI: 10.24075/brsmu.2018.087

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VIEWS 4278

Naumenko VA, Garanina AS, Vodopyanov SS, Nikitin AA, Prelovskaya AO, Demihov EI, Abakumov MA, Majouga AM, 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.

Received: 2018-08-30

Published online: 2018-12-31

DOI: 10.24075/brsmu.2018.086

Comments 0

VIEWS 3474

Nizamov TR, Garanina AS, Uvarova VI, Naumenko VA, Shchetinin 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 efficiency 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 the 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 efficiently at early incubation stages in comparison with nanospheres, but the difference is insignificant.

Received: 2018-08-28

Published online: 2018-12-31

DOI: 10.24075/brsmu.2018.085

Comments 0

VIEWS 3696

Zhang C, Morozova AYu, Baklaushev VP, Gubsky IL, Melnikov PA, Gabashvily AN, Wang G, Li L, Wu H, Wang X, 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 • 105 to 1 • 106, 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 • 105 to 1 • 106, 1 • 106 cells were proved to be the best dose.

Received: 2018-08-26

Published online: 2018-12-31

DOI: 10.24075/brsmu.2018.084

Comments 0

VIEWS 3673

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.

Received: 2018-08-26

Published online: 2018-12-30

DOI: 10.24075/brsmu.2018.083

Comments 0

VIEWS 3381