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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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

Comments 0

VIEWS 5717

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 4622

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 5086

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 4950

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 4514

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.

Received: 2018-06-26

Published online: 2018-12-30

DOI: 10.24075/brsmu.2018.082

Comments 0

VIEWS 4585

Marchiò S, Bussolino F

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.

Received: 2018-06-29

Published online: 2018-12-30

DOI: 10.24075/brsmu.2018.081

Comments 0

VIEWS 4547

Uvarova VI, Nizamov TR, Abakumov MA, Vodopyanov SS, Abakumova TO, Saltykova IV, Mogilnikov PS, Shchetinin IV, Majouga AM

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.

Received: 2018-06-26

Published online: 2018-12-30

DOI: 10.24075/brsmu.2018.080

Comments 0

VIEWS 5137