Репозиторий Университета

© 2020 Elsevier B.V. Magnetic hyperthermia (MH) is a perspective tool to treat the tumor while the magnetic material is delivered. The key problems in MH development is to ensure an effective local heating within cancer cell without overheating other cells. In order to do that one has to reach substantial local accumulation of magnetic nanoparticles (MNPs) and/or magnetically sensitive objects with advanced heat properties. Absorbing heat energy for destroying tumor cells can be generated only if there is sufficient amount of locally placed MNPs. In this work, we propose polyelectrolyte microcapsules modified with iron oxide nanoparticles as an approach to tie magnetic materials in high concentration locally. These microcapsules (about 3 microns in diameter) can be readily internalized by various cells. The human fibroblasts uptake of the microcapsules and cytotoxic effect upon the influence of alternating magnetic field (AMF) while magnetic capsules are inside the cells is under study in this work. The cytotoxicity of the magnetic microcapsules was compared with the cytotoxicity of the MNPs while free in the solution to evaluate the effect of bounding MNPs. A cytotoxic effect on cells was found in the case of preliminary incubation of fibroblasts with capsules while the AMF is applied. In the case of MNPs in an equivalent dose per mass of magnetic material, there was no cytotoxic effect noticed after the treatment with the field. It is noteworthy that during the treatment of cells with the AMF, the increase in temperature of the incubation medium was not registered. The morphological changes on fibroblasts were consistent with the data of the viability assessment. Thus, the synthesized capsules are shown as a means for local enhancement of magnetic hyperthermia in the treatment of tumor diseases.

© 2019 Elsevier B.V. Due to their unique optical properties upconversion nanoparticles (UCNPs) provide exceptionally high contrast for imaging of true nanoparticle distribution in excised human skin. It makes possible to show penetration of solid nanoparticles in skin treated with chemical enhancers. We demonstrated tracing upconversion nanoparticles in excised human skin by means of optical microscopy at the discrete particle level sensitivity to obtain their penetration profiles, which was validated by laser-ablation inductively-coupled-plasma mass-spectrometry. To demonstrate utilities of our method, UCNPs were coated with polymers, formulated in water and chemical enhancers, and applied on excised human skin mounted on Franz cells, followed by imaging using a custom-built laser-scanning microscope. To evaluate the toxicity impact on skin by polymer-coated UCNPs, we introduced a tissue engineering model of viable epidermis made of decellularized chick embryo skin seeded with keratinocytes. UCNPs formulated in water stopped in stratum corneum, whereas UCNPs formulated in ethanol-water solution crossed stratum corneum and reached viable epidermis – hence, the enhancement effect for solid nanoparticles was detected by optical microscopy. All polymer-coated UCNPs were found nontoxic within the accepted safety levels. The keratinocyte resilience to polyethyleneimine-coated UCNPs was surprising considering cytotoxicity of polyethyleneimine to two-dimensional cell cultures.

Copyright © 2018 American Chemical Society. Upconversion nanoparticles (UCNPs) coated with polyethylenimine (PEI) are popular background-free optical contrast probes and efficient drug and gene delivery agents attracting attention in science, industry, and medicine. Their unique optical properties are especially useful for subsurface nanotheranostics applications, in particular, in skin. However, high cytotoxicity of PEI limits safe use of UCNP@PEI, and this represents a major barrier for clinical translation of UCNP@PEI-based technologies. Our study aims to address this problem by exploring additional surface modifications to UCNP@PEI to create less toxic and functional nanotheranostic materials. We designed and synthesized six types of layered polymer coatings that envelop the original UCNP@PEI surface, five of which reduced the cytotoxicity to human skin keratinocytes under acute (24 h) and subacute (120 h) exposure. In parallel, we examined the photoluminescence spectra and lifetime of the surface-modified UCNP@PEI. To quantify their brightness, we developed original methodology to precisely measure the colloidal concentration to normalize the photoluminescence signal using a nondigesting mass spectrometry protocol. Our results, specified for the individual coatings, show that, despite decreasing the cytotoxicity, the external polymer coatings of UCNP@PEI quench the upconversion photoluminescence in biologically relevant aqueous environments. This trade-off between cytotoxicity and brightness for surface-coated UCNPs emphasizes the need for the combined assessment of the viability of normal cells exposed to the nanoparticles and the photophysical properties of postmodification UCNPs. We present an optimized methodology for rational surface design of UCNP@PEI in biologically relevant conditions, which is essential to facilitate the translation of such nanoparticles to the clinical applications.

© 2018 Wolters Kluwer Health, Inc. All rights reserved. This work presents the results of in-vitro biological activity studies of three novel anticancer agents, phosphonium salts based on the 3-hydroxypyridine scaffold, including one derivative of 4-deoxypyridoxine. Proliferation and viability of cells treated with these compounds was assessed by the colony formation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Effects of the compounds on apoptosis and cell cycle were studied by flow cytometry using annexin V-FITC/propidium iodide and propidium iodide staining, respectively. The influence of the compounds on mitochondrial membrane potential and intracellular reactive oxygen species was evaluated using tetramethyl rhodamine ethyl and DCFHA staining. Western blot analysis was used to study the changes in the expression of Bcl-xL, Bax, and caspase-3 apoptotic proteins. The treatment of ovarian adenocarcinoma cells OVCAR-4 with the tested compounds inhibited the growth and induced cell cycle arrest in the G1 phase. 3-Hydroxypyridine derivatives induced apoptosis by hyperexpression of Bax and caspase-3, whereas 4-deoxypyridoxine derivative induced cell death partly by reactive oxygen species generation and caspase-3 hyperexpression. These results indicate that the quaternary phosphonium salts studied represent potential therapeutic agents for the treatment of ovarian cancer.