J 2019

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

TESAROVA, Barbora, Marketa CHAROUSOVA, Simona DOSTALOVA, Alina BIENKO, Pavel KOPEL et. al.

Basic information

Original name

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

Authors

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

Edition

International journal of biological macromolecules, AMSTERDAM, Elsevier Science BV, Netherlands, 2019, 0141-8130

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.162

UT WoS

000460710000123

Keywords in English

Active targeting; Biocompatibility; Cancer nanomedicine

Tags

International impact, Reviewed
Změněno: 14/6/2024 10:01, Mgr. Eva Dubská

Abstract

V originále

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.

Links

90043, large research infrastructures
Name: CIISB