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Folic acid-mediated re-shuttling of ferritin receptor specificity towards a selective delivery of highly cytotoxic nickel(II) coordination compounds
B. Tesarova, M. Charousova, S. Dostalova, A. Bienko, P. Kopel, R. Kruszyński, D. Hynek, P. Michalek, T. Eckschlager, M. Stiborova, V. Adam, Z. Heger,
International journal of biological macromolecules.
2019 ;
126 (-) :
1099-1111.
[pub] 20181231
Language English Country Netherlands
Document type Journal Article
Persistent link
https://www.medvik.cz/link/bmc19027938
- MeSH
- Apoptosis drug effects MeSH
- Biocompatible Materials pharmacology MeSH
- Cell Death drug effects MeSH
- Clone Cells MeSH
- Endocytosis drug effects MeSH
- Ferritins metabolism MeSH
- Coordination Complexes chemical synthesis chemistry pharmacology MeSH
- Folic Acid pharmacology MeSH
- Humans MeSH
- Ligands MeSH
- Cell Line, Tumor MeSH
- Nickel pharmacology MeSH
- Cell Movement drug effects MeSH
- Cell Proliferation drug effects MeSH
- Iron-Binding Proteins metabolism MeSH
- Receptors, Cell Surface metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Metal-based coordination compounds, including the well-known cytostatic drug cisplatin, are widely used in the anticancer therapy. Generally, they exhibit high cytotoxicity not only towards malignant cells, but also towards non-malignant cells, which represents main problem of their clinical use. Herein, we describe the synthesis, characterization and biological testing of three trinuclear nickel(II) coordination compounds. Central nickel atoms are bridged by trithiocyanurate anion and coordinated by triamine and bis-benzimidazoles, respectively. To delineate a potential usage in anticancer therapy, we encapsulated the most cytotoxic complex into biomacromolecular protein cage apoferritin (FRT), forming FRTNi. FRT encapsulation markedly decreased the hemotoxicity of free Ni compounds. Despite FRTNi can be internalized through passive targeting by enhanced permeability and retention effect, we further introduced active targeting utilizing folate receptor (FR) via folic acid (FA)-modified FRT (FRTNiFA). Using breast cancer cell lines T-47D (FR+), MCF-7 (FR-) and non-malignant mammary gland derived cell line HBL-100 (FR-), we show pronounced FR-dependent internalization of FRTNiFA. Overall, we demonstrate that the FRT macromolecular nanocarrier provides a very low off-target toxicity, which could enable the use of highly toxic Ni compounds in cancer nanomedicine.
References provided by Crossref.org
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- $a Tesarova, Barbora $u Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic; Central European Institute of Technology, Brno University of Technology, Purkynova 656/123, CZ-612 00 Brno, Czech Republic.
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- $a Metal-based coordination compounds, including the well-known cytostatic drug cisplatin, are widely used in the anticancer therapy. Generally, they exhibit high cytotoxicity not only towards malignant cells, but also towards non-malignant cells, which represents main problem of their clinical use. Herein, we describe the synthesis, characterization and biological testing of three trinuclear nickel(II) coordination compounds. Central nickel atoms are bridged by trithiocyanurate anion and coordinated by triamine and bis-benzimidazoles, respectively. To delineate a potential usage in anticancer therapy, we encapsulated the most cytotoxic complex into biomacromolecular protein cage apoferritin (FRT), forming FRTNi. FRT encapsulation markedly decreased the hemotoxicity of free Ni compounds. Despite FRTNi can be internalized through passive targeting by enhanced permeability and retention effect, we further introduced active targeting utilizing folate receptor (FR) via folic acid (FA)-modified FRT (FRTNiFA). Using breast cancer cell lines T-47D (FR+), MCF-7 (FR-) and non-malignant mammary gland derived cell line HBL-100 (FR-), we show pronounced FR-dependent internalization of FRTNiFA. Overall, we demonstrate that the FRT macromolecular nanocarrier provides a very low off-target toxicity, which could enable the use of highly toxic Ni compounds in cancer nanomedicine.
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- $a Charousova, Marketa $u Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic; Central European Institute of Technology, Brno University of Technology, Purkynova 656/123, CZ-612 00 Brno, Czech Republic.
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- $a Dostalova, Simona $u Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic; Central European Institute of Technology, Brno University of Technology, Purkynova 656/123, CZ-612 00 Brno, Czech Republic.
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- $a Bienko, Alina $u Faculty of Chemistry, University of Wroclaw, 14 F. Joliot - Curie, PL-50-383 Wroclaw, Poland.
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- $a Kopel, Pavel $u Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic; Central European Institute of Technology, Brno University of Technology, Purkynova 656/123, CZ-612 00 Brno, Czech Republic.
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