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@article{2409389,
author = {Tesarova, Barbora and Charousova, Marketa and Dostalova, Simona and Bienko, Alina and Kopel, Pavel and Kruszynski, Rafal and Hynek, David and Michalek, Petr and Eckschlager, Tomas and Stiborova, Marie and Adam, Vojtech and Heger, Zbynek},
article_location = {AMSTERDAM},
article_number = {Apr},
doi = {http://dx.doi.org/10.1016/j.ijbiomac.2018.12.128},
keywords = {Active targeting; Biocompatibility; Cancer nanomedicine},
language = {eng},
issn = {0141-8130},
journal = {International journal of biological macromolecules},
title = {Folic acid-mediated re-shuttling of ferritin receptor specificity towards a selective delivery of highly cytotoxic nickel(II) coordination compounds},
url = {https://www.sciencedirect.com/science/article/pii/S0141813018350189?via%3Dihub},
volume = {126},
year = {2019}
}
TY - JOUR
ID - 2409389
AU - Tesarova, Barbora - Charousova, Marketa - Dostalova, Simona - Bienko, Alina - Kopel, Pavel - Kruszynski, Rafal - Hynek, David - Michalek, Petr - Eckschlager, Tomas - Stiborova, Marie - Adam, Vojtech - Heger, Zbynek
PY - 2019
TI - Folic acid-mediated re-shuttling of ferritin receptor specificity towards a selective delivery of highly cytotoxic nickel(II) coordination compounds
JF - International journal of biological macromolecules
VL - 126
IS - Apr
SP - 1099-1111
EP - 1099-1111
PB - Elsevier Science BV, Netherlands
SN - 01418130
KW - Active targeting
KW - Biocompatibility
KW - Cancer nanomedicine
UR - https://www.sciencedirect.com/science/article/pii/S0141813018350189?via%3Dihub
N2 - 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 nonmalignant 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. (C) 2018 Elsevier B.V. All rights reserved.
ER -
TESAROVA, Barbora, Marketa CHAROUSOVA, Simona DOSTALOVA, Alina BIENKO, Pavel KOPEL, Rafal KRUSZYNSKI, David HYNEK, Petr MICHALEK, Tomas ECKSCHLAGER, Marie STIBOROVA, Vojtech ADAM and Zbynek HEGER. Folic acid-mediated re-shuttling of ferritin receptor specificity towards a selective delivery of highly cytotoxic nickel(II) coordination compounds. \textit{International journal of biological macromolecules}. AMSTERDAM: Elsevier Science BV, Netherlands, 2019, vol.~126, Apr, p.~1099-1111. ISSN~0141-8130. Available from: https://dx.doi.org/10.1016/j.ijbiomac.2018.12.128.
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