The Anti-Proliferative Activity of Coordination Compound-Based ZnO Nanoparticles as a Promising Agent Against Triple Negative Breast Cancer Cells

Hana Stepankova; Marcin Swiatkowski; Rafal Kruszynski; Pavel Svec; Hana Michalkova; Vendula Smolikova; Andrea Ridoskova; Zbynek Splichal; Petr Michalek; Lukas Richtera; Pavel Kopel; Vojtech Adam; Zbynek Heger; Simona Rex

doi:10.2147/IJN.S304902

The Anti-Proliferative Activity of Coordination Compound-Based ZnO Nanoparticles as a Promising Agent Against Triple Negative Breast Cancer Cells

Int J Nanomedicine. 2021 Jul 1:16:4431-4449. doi: 10.2147/IJN.S304902. eCollection 2021.

Authors

Hana Stepankova^{1

2}, Marcin Swiatkowski³, Rafal Kruszynski³, Pavel Svec¹, Hana Michalkova¹, Vendula Smolikova^{1

2}, Andrea Ridoskova^{1

4}, Zbynek Splichal^{1

2}, Petr Michalek^{1

2}, Lukas Richtera^{1

2}, Pavel Kopel⁵, Vojtech Adam^{1

2}, Zbynek Heger^{1

2}, Simona Rex^{1

2}

Affiliations

¹ Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czechia.
² Central European Institute of Technology, Brno University of Technology, Brno, Czechia.
³ Institute of General and Ecological Chemistry, Lodz University of Technology, Lodz, Poland.
⁴ Central European Institute of Technology, Mendel University in Brno, Brno, Czechia.
⁵ Department of Inorganic Chemistry, Faculty of Science, Palacky University, Olomouc, Czechia.

Abstract

Purpose: The present study deals with the in vitro evaluation of the potential use of coordination compound-based zinc oxide (ZnO) nanoparticles (NPs) for the treatment of triple negative breast cancer cells (TNBrCa). As BrCa is one of the most prevalent cancer types and TNBrCa treatment is difficult due to poor prognosis and a high metastasis rate, finding a more reliable treatment option should be of the utmost interest.

Methods: Prepared by reacting zinc carboxylates (formate, acetate, propionate, butyrate, isobutyrate, valerate) and hexamethylenetetramine, 4 distinct coordination compounds were further subjected to two modes of conversion into ZnO NPs - ultrasonication with oleic acid or heating of pure precursors in an air atmosphere. After detailed characterization, the resulting ZnO NPs were subjected to in vitro testing of cytotoxicity toward TNBrCa and normal breast epithelial cells. Further, their biocompatibility was evaluated.

Results: The resulting ZnO NPs provide distinct morphological features, size, biocompatibility, and selective cytotoxicity toward TNBrCa cells. They internalize into two types of TNBrCa cells and imbalance their redox homeostasis, influencing their metabolism, morphology, and ultimately leading to their death via apoptosis or necrosis.

Conclusion: The crucial properties of ZnO NPs seem to be their morphology, size, and zinc content. The ZnO NPs with the most preferential values of all three properties show great promise for a future potential use in the therapy of TNBrCa.

Keywords: carboxylate; hexamethylenetetramine; nanoparticles; redox homeostasis imbalance; triple negative breast cancer; zinc oxide coordination compounds.

MeSH terms

Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Humans
Nanoparticles / chemistry*
Triple Negative Breast Neoplasms / pathology*
Zinc Oxide / chemistry*
Zinc Oxide / pharmacology*

Substances

Antineoplastic Agents
Zinc Oxide

Grants and funding

The synthesis and characterization of coordination compounds and ZnO nanoparticles, as well as crystallographic part of this work, was financed by funds allocated by the Ministry of Science and Higher Education (Poland) to the Institute of General and Ecological Chemistry, Lodz University of Technology. For testing of the in vitro effects of these nanoparticles, the financial support from ERDF “Multidisciplinary research to increase application potential of nanomaterials in agricultural practice” (No. CZ.02.1.01/0.0/0.0/16_025/0007314), ERC Starting Grant 759585 and the Czech Science Foundation (project no. 19-13766J) are gratefully acknowledged.