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Pavlína Šimečková, František Hubatka, Jan Kotouček, Pavlína Turánek Knötigová, Josef Mašek, Josef Slavík, Ondrej Kováč, Jiří Neča, Pavel Kulich, Dominik Hrebík, Jana Stráská, Kateřina Pěnčíková, Jiřina Procházková, Pavel Diviš, Stuart Macaulay, Robert Mikulík, Milan Raška, Miroslav Machala & Jaroslav Turánek
Original Title
Gadolinium labelled nanoliposomes as the platform for MRI theranostics: in vitro safety study in liver cells and macrophages
Type
journal article in Web of Science
Language
English
Original Abstract
Gadolinium (Gd)–based contrast agents are extensively used for magnetic resonance imaging (MRI). Liposomes are potential nanocarrier–based biocompatible platforms for development of new generations of MRI diagnostics. Liposomes with Gd–complexes (Gd–lip) co–encapsulated with thrombolytic agents can serve both for imaging and treatment of various pathological states including stroke. In this study, we evaluated nanosafety of Gd–lip containing PE-DTPA chelating Gd+3 prepared by lipid film hydration method. We detected no cytotoxicity of Gd–lip in human liver cells including cancer HepG2, progenitor (non–differentiated) HepaRG, and differentiated HepaRG cells. Furthermore, no potential side effects of Gd–lip were found using a complex system including general biomarkers of toxicity, such as induction of early response genes, oxidative, heat shock and endoplasmic reticulum stress, DNA damage responses, induction of xenobiotic metabolizing enzymes, and changes in sphingolipid metabolism in differentiated HepaRG. Moreover, Gd–lip did not show pro–inflammatory effects, as assessed in an assay based on activation of inflammasome NLRP3 in a model of human macrophages, and release of eicosanoids from HepaRG cells. In conclusion, this in vitro study indicates potential in vivo safety of Gd–lip with respect to hepatotoxicity and immunopathology caused by inflammation.
Keywords
gadolinium, nanoliposomes
Authors
Released
16. 3. 2020
ISBN
2045-2322
Periodical
Scientific Reports
Year of study
10
Number
4780
State
United Kingdom of Great Britain and Northern Ireland
Pages from
1
Pages to
13
Pages count
URL
https://www.nature.com/articles/s41598-020-60284-z.pdf
BibTex
@article{BUT163205, author="Jaroslav {Turánek} and Pavel {Diviš}", title="Gadolinium labelled nanoliposomes as the platform for MRI theranostics: in vitro safety study in liver cells and macrophages", journal="Scientific Reports", year="2020", volume="10", number="4780", pages="1--13", doi="10.1038/s41598-020-60284-z", issn="2045-2322", url="https://www.nature.com/articles/s41598-020-60284-z.pdf" }