Publication detail

Folic acid-mediated re-shuttling of ferritin receptor specificity towards a selective delivery of highly cytotoxic nickel(II) coordination compounds

TESAŘOVÁ, B. CHAROUSOVÁ, M. DOSTÁLOVÁ, S. BIEŃKO, A. KOPEL, P. KRUSZYŃSKI, R. HYNEK, D. MICHÁLEK, P. ECKSCHLAGER, T. STIBOROVÁ, M. ADAM, V. HEGER, Z.

Original Title

Folic acid-mediated re-shuttling of ferritin receptor specificity towards a selective delivery of highly cytotoxic nickel(II) coordination compounds

Type

journal article in Web of Science

Language

English

Original Abstract

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.

Keywords

Active targeting; Biocompatibility; Cancer nanomedicine

Authors

TESAŘOVÁ, B.; CHAROUSOVÁ, M.; DOSTÁLOVÁ, S.; BIEŃKO, A.; KOPEL, P.; KRUSZYŃSKI, R.; HYNEK, D.; MICHÁLEK, P.; ECKSCHLAGER, T.; STIBOROVÁ, M.; ADAM, V.; HEGER, Z.

Released

1. 4. 2019

ISBN

0141-8130

Periodical

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Year of study

126

Number

1

State

Kingdom of the Netherlands

Pages from

1099

Pages to

1111

Pages count

13

BibTex

@article{BUT156374,
  author="Barbora {Tesařová} and Markéta {Charousová} and Simona {Dostálová} and Alina {Bieńko} and Pavel {Kopel} and Rafał {Kruszyński} and David {Hynek} and Petr {Michálek} and Tomáš {Eckschlager} and Marie {Stiborová} and Vojtěch {Adam} and Zbyněk {Heger}",
  title="Folic acid-mediated re-shuttling of ferritin receptor specificity towards a selective delivery of highly cytotoxic nickel(II) coordination compounds",
  journal="INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES",
  year="2019",
  volume="126",
  number="1",
  pages="1099--1111",
  doi="10.1016/j.ijbiomac.2018.12.128",
  issn="0141-8130"
}