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
- Názvy látek
- diethylentriaminpentaacetát gadolinia * MeSH
- fibrinolytika MeSH
- fosfatidylethanolaminy * MeSH
- gadolinium phosphatidylethanolamine-DTPA MeSH Prohlížeč
- inflamasomy MeSH
- kontrastní látky * MeSH
- liposomy * MeSH
- NLRP3 protein, human MeSH Prohlížeč
- nosiče léků * MeSH
- protein NLRP3 MeSH
Recently we described a novel, nontoxic, natural ether phospholipid with selective antitumor activity, 1-0-alkyl-2-acyl-sn-glycero-3-phospho-(N-acyl)ethanolamine, i.e., plasmanyl-(N-acyl)ethanolamine (PNAE), isolated from ischemic tissue of chick embryo. The chemical structure of PNAE has been confirmed by partial synthesis. The semisynthetic preparation PNAE(s), 1-0-octadecyl-2-oleoyl-sn-glycero-3-phospho-(N-palmitoyl)ethanolamine, exhibited tumoricidal activity against human tumor cells T24 and mouse sarcoma cells Mcll as well as in vivo against murine sarcomas S-180 and Mcll. PNAE(s) selectively destroyed tumor cell membranes as has been demonstrated by scanning electron microscopy. The antitumor activity of PNAE(s) in vitro and in vivo was significantly enhanced by Ca2+ ions. These results may be explained by selective damage of tumor cell membranes by PNAE(s), increasing also the tumor cell membrane permeability for exogenous Ca2+ ions and altering the intracellular calcium homeostasis in tumor cells. By increased concentration of Ca2+ in tumor cell cytosol selective damage and lysis of tumor cells was induced. The combined use of parenteral administration of PNAE(s) and peroral doses of calcium gluconate may provide a new approach to enhancement of antitumor activity of PNAE(s) by Ca2+ in a very selective and nontoxic antitumor therapy.
- MeSH
- buněčné dělení účinky léků MeSH
- buněčné linie MeSH
- DNA nádorová biosyntéza účinky léků MeSH
- experimentální sarkom farmakoterapie MeSH
- fibrosarkom farmakoterapie MeSH
- fosfatidylethanolaminy terapeutické užití toxicita MeSH
- inbrední kmeny myší MeSH
- lékové interakce MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- protinádorové látky terapeutické užití toxicita MeSH
- sarkom 180 farmakoterapie MeSH
- screeningové testy protinádorových léčiv MeSH
- synergismus léků MeSH
- thymidin metabolismus MeSH
- vápník terapeutické užití toxicita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 1-O-octadecyl-2-oleoyl-sn-glycero-3-phospho-(N-palmitoyl)ethanolamine MeSH Prohlížeč
- DNA nádorová MeSH
- fosfatidylethanolaminy MeSH
- protinádorové látky MeSH
- thymidin MeSH
- vápník MeSH
