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Gadolinium labelled nanoliposomes as the platform for MRI theranostics: in vitro safety study in liver cells and macrophages

P. Šimečková, F. Hubatka, J. Kotouček, P. Turánek Knötigová, J. Mašek, J. Slavík, O. Kováč, J. Neča, P. Kulich, D. Hrebík, J. Stráská, K. Pěnčíková, J. Procházková, P. Diviš, S. Macaulay, R. Mikulík, M. Raška, M. Machala, J. Turánek,

. 2020 ; 10 (1) : 4780. [pub] 20200316

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc20028378

Grant support
NV16-30299A MZ0 CEP Register

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.

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$a Gadolinium (Gd)-based contrast agents are extensively used for magnetic resonance imaging (MRI). Liposomes are potential nanocarrier-based biocompatible platforms for development of new generations of MRI diagnostics. Liposomes with Gd-complexes (Gd-lip) co-encapsulated with thrombolytic agents can serve both for imaging and treatment of various pathological states including stroke. In this study, we evaluated nanosafety of Gd-lip containing PE-DTPA chelating Gd+3 prepared by lipid film hydration method. We detected no cytotoxicity of Gd-lip in human liver cells including cancer HepG2, progenitor (non-differentiated) HepaRG, and differentiated HepaRG cells. Furthermore, no potential side effects of Gd-lip were found using a complex system including general biomarkers of toxicity, such as induction of early response genes, oxidative, heat shock and endoplasmic reticulum stress, DNA damage responses, induction of xenobiotic metabolizing enzymes, and changes in sphingolipid metabolism in differentiated HepaRG. Moreover, Gd-lip did not show pro-inflammatory effects, as assessed in an assay based on activation of inflammasome NLRP3 in a model of human macrophages, and release of eicosanoids from HepaRG cells. In conclusion, this in vitro study indicates potential in vivo safety of Gd-lip with respect to hepatotoxicity and immunopathology caused by inflammation.
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$a Hubatka, František $u Veterinary Research Institute, Brno, Czech Republic.
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$a Turánek Knötigová, Pavlína $u Veterinary Research Institute, Brno, Czech Republic.
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$a Kováč, Ondrej $u Veterinary Research Institute, Brno, Czech Republic.
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$a Neča, Jiří $u Veterinary Research Institute, Brno, Czech Republic.
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$a Kulich, Pavel $u Veterinary Research Institute, Brno, Czech Republic.
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$a Hrebík, Dominik $u Central European Institute of Technology CEITEC, Structural Virology, Masaryk University, Brno, Czech Republic.
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$a Stráská, Jana $u Regional Centre of Advanced Technologies and Materials, Palacký University, Olomouc, Czech Republic.
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$a Pěnčíková, Kateřina $u Veterinary Research Institute, Brno, Czech Republic.
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$a Procházková, Jiřina $u Veterinary Research Institute, Brno, Czech Republic.
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$a Diviš, Pavel $u Faculty of Chemistry, Technical University, Brno, Czech Republic.
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$a Macaulay, Stuart $u Malvern Instruments, Great Malvern, UK.
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$a Mikulík, Robert $u International Clinical Research Centre, St. Anne's University Hospital Brno, Brno, Czech Republic. Neurology Department, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic.
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$a Raška, Milan $u Veterinary Research Institute, Brno, Czech Republic. Department of Immunology, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic.
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$a Machala, Miroslav $u Veterinary Research Institute, Brno, Czech Republic. machala@vri.cz.
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