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Magnetic temperature-sensitive solid-lipid particles for targeting and killing tumor cells
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SYSNO ASEP 0524157 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Magnetic temperature-sensitive solid-lipid particles for targeting and killing tumor cells Author(s) Swietek, Malgorzata Anna (UMCH-V) RID, ORCID
Panchuk, R. (UA)
Skorokhyd, N. (UA)
Černoch, Peter (UMCH-V) RID, ORCID
Finiuk, N. (UA)
Klyuchivska, O. (UA)
Hrubý, Martin (UMCH-V) RID, ORCID
Molčan, M. (SK)
Berger, W. (AT)
Trousil, Jiří (UMCH-V) RID, ORCID
Stoika, R. (UA)
Horák, Daniel (UMCH-V) RID, ORCIDArticle number 205 Source Title Frontiers in Chemistry. - : Frontiers Media - ISSN 2296-2646
Roč. 8, 9 April (2020), s. 1-18Number of pages 18 s. Language eng - English Country CH - Switzerland Keywords magnetic ; temperature sensitive ; solid lipid particles Subject RIV CD - Macromolecular Chemistry OECD category Polymer science R&D Projects GA17-04918S GA ČR - Czech Science Foundation (CSF) GA18-07983S GA ČR - Czech Science Foundation (CSF) LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UMCH-V - RVO:61389013 UT WOS 000529903600001 EID SCOPUS 85083878443 DOI 10.3389/fchem.2020.00205 Annotation Magnetic and temperature-sensitive solid lipid particles (mag. SLPs) were prepared in the presence of oleic acid-coated iron oxide (IO-OA) nanoparticles with 1-tetradecanol and poly(ethylene oxide)-block-poly(ε-caprolactone) as lipid and stabilizing surfactant-like agents, respectively. The particles, typically ~850 nm in hydrodynamic size, showed heat dissipation under the applied alternating magnetic field. Cytotoxic activity of the mag.SLPs, non-magnetic SLPs, and iron oxide nanoparticles was compared concerning the mammalian cancer cell lines and their drug-resistant counterparts using trypan blue exclusion test and MTT assay. The mag.SLPs exhibited dose-dependent cytotoxicity against human leukemia cell lines growing in suspension (Jurkat and HL-60/wt), as well as the doxorubicin (Dox)- and vincristine-resistant HL-60 sublines. The mag.SLPs showed higher cytotoxicity toward drug-resistant sublines as compared to Dox. The human glioblastoma cell line U251 growing in a monolayer culture was also sensitive to mag.SLPs cytotoxicity. Staining of U251 cells with the fluorescent dyes Hoechst 33342 and propidium iodide (PI) revealed that mag.SLPs treatment resulted in an increased number of cells with condensed chromatin and/or fragmented nuclei as well as with blebbing of the plasma membranes. While the Hoechst 33342 staining of cell suggested the pro-apoptotic activity of the particles, the PI staining indicated the pro-necrotic changes in the target cells. These conclusions were confirmed by Western blot analysis of apoptosis-related proteins, study of DNA fragmentation (DNA laddering due to the inter-nucleosomal cleavage and DNA comets due to single strand breaks), as well as by FACS analysis of the patterns of cell cycle distribution (pre-G1 phase) and Annexin V/PI staining of the treated Jurkat cells. The induction of apoptosis or necrosis by the particles used to treat Jurkat cells depended on the dose of the particles. Production of the reactive oxygen species (ROS) was proposed as a potential mechanism of mag.SLPs-induced cytotoxicity. Accordingly, hydrogen peroxide and superoxide radical levels in mag.SLPs-treated Jurkat leukemic cells were increased by ~20–40 and ~70%, respectively. In contrast, the non-magnetic SLPs and neat iron oxides did not influence ROS levels significantly. Thus, the developed mag.SLPs can be used for effective killing of human tumor cells, including drug-resistant ones. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2021 Electronic address https://www.frontiersin.org/articles/10.3389/fchem.2020.00205/full
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