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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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

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VIEWS 5178

Maklygina YuS, Romanishkin ID, Ryabova AV, Yakavec 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.

Received: 2018-06-26

Published online: 2018-12-30

DOI: 10.24075/brsmu.2018.079

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VIEWS 5133

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 (25Mg, 43Ca, 60Co, 67Zn, …) — 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-C60 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.

Received: 2018-06-27

Published online: 2018-12-30

DOI: 10.24075/brsmu.2018.078

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VIEWS 4712

Goodilin EA, Semenova AA, Eremina OE, Brazhe NA, Goodilinа 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.

Received: 2018-07-20

Published online: 2018-12-26

DOI: 10.24075/brsmu.2018.077

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VIEWS 5024

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 reduction 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 interaction. 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 synthe-sized nanoparticles find in pharmacology and medicine.

Received: 2018-06-27

Published online: 2018-12-25

DOI: 10.24075/brsmu.2018.076

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VIEWS 4775

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.

Received: 2018-06-27

Published online: 2018-12-25

DOI: 10.24075/brsmu.2018.075

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VIEWS 4819

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).

Received: 2018-12-03

Published online: 2018-12-25

DOI: 10.24075/brsmu.2018.074

Comments 0

VIEWS 4697

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 CuInS2 and AgInS2. In this study, biodistribution and biocompatibility of QDs based on the AgInS2 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 • 10–7 to 4 • 10–6 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.

Received: 2018-07-28

Published online: 2018-12-24

DOI: 10.24075/brsmu.2018.073

Comments 0

VIEWS 4765