Wydział Chemii

Barbora Tesarova

Marketa Charousova

Simona Dostalova

Alina Bieńko

Pavel Kopel

Rafał Kruszyński

David Hynek

Petr Michalek

Tomas Eckschlager

Marie Stiborova

Vojtech Adam

Zbynek Heger

2019

International Journal of Biological Macromolecules

126

1099-1111

10.1016/j.ijbiomac.2018.12.128

Naukowa

Angielski

Artykuł

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

Active targeting, Biocompatibility, Cancer nanomedicine

https://doi.org/10.1016/j.ijbiomac.2018.12.128

http://www.elsevier.com