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.
- MeSH
- diethylentriaminpentaacetát gadolinia * škodlivé účinky toxicita MeSH
- fibrinolytika MeSH
- fosfatidylethanolaminy * škodlivé účinky toxicita MeSH
- hepatocyty účinky léků MeSH
- inflamasomy MeSH
- kontrastní látky * MeSH
- kultivované buňky MeSH
- lidé MeSH
- liposomy * MeSH
- magnetická rezonanční tomografie * MeSH
- makrofágy účinky léků MeSH
- nanočástice MeSH
- nosiče léků * MeSH
- protein NLRP3 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- chronické selhání ledvin komplikace MeSH
- diethylentriaminpentaacetát gadolinia kontraindikace škodlivé účinky toxicita MeSH
- gadolinium škodlivé účinky toxicita MeSH
- kontrastní látky klasifikace kontraindikace škodlivé účinky MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- nefrogenní systémová fibróza chemicky indukované patologie prevence a kontrola MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- Check Tag
- lidé MeSH