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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
Jazyk angličtina Země Nizozemsko
Typ dokumentu časopisecké články
Perzistentní odkaz
https://www.medvik.cz/link/bmc19027938
- MeSH
- apoptóza účinky léků MeSH
- biokompatibilní materiály farmakologie MeSH
- buněčná smrt účinky léků MeSH
- buněčné klony MeSH
- endocytóza účinky léků MeSH
- ferritiny metabolismus MeSH
- komplexní sloučeniny chemická syntéza chemie farmakologie MeSH
- kyselina listová farmakologie MeSH
- lidé MeSH
- ligandy MeSH
- nádorové buněčné linie MeSH
- nikl farmakologie MeSH
- pohyb buněk účinky léků MeSH
- proliferace buněk účinky léků MeSH
- proteiny vázající železo metabolismus MeSH
- receptory buněčného povrchu metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články 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.
Citace poskytuje 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 Folic acid-mediated re-shuttling of ferritin receptor specificity towards a selective delivery of highly cytotoxic nickel(II) coordination compounds / $c B. Tesarova, M. Charousova, S. Dostalova, A. Bienko, P. Kopel, R. Kruszyński, D. Hynek, P. Michalek, T. Eckschlager, M. Stiborova, V. Adam, Z. Heger,
- 520 9_
- $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.
- 700 1_
- $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.
- 700 1_
- $a Bienko, Alina $u Faculty of Chemistry, University of Wroclaw, 14 F. Joliot - Curie, PL-50-383 Wroclaw, Poland.
- 700 1_
- $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.
- 700 1_
- $a Kruszyński, Rafał $u Department of X-ray Crystallography and Crystal Chemistry, Institute of General and Ecological Chemistry, Lodz University of Technology, Zeromskiego 116, PL-90-924 Lodz, Poland.
- 700 1_
- $a Hynek, David $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.
- 700 1_
- $a Michalek, Petr $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.
- 700 1_
- $a Eckschlager, Tomas $u Department of Pediatric Hematology and Oncology, s, Charles University and University Hospital Motol, V Uvalu 84/1, CZ-150 06 Prague 5, Czech Republic.
- 700 1_
- $a Stiborova, Marie $u Department of Biochemistry, Faculty of Science, Charles University, Hlavova 2030/8, CZ-128 43 Prague 2, Czech Republic.
- 700 1_
- $a Adam, Vojtech $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.
- 700 1_
- $a Heger, Zbynek $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. Electronic address: heger@mendelu.cz.
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