Two copper(II) compounds derived from tetrazole carboxylates for chemodynamic therapy against hepatocellular carcinoma cells

Xinya Shi; Yulan Gu; Chuandan Wan; Xin Jiang; Lei Shen; Litao Tan; Yujie Zhong; Dengfeng Zou

doi:10.3389/fchem.2022.915247

Two copper(II) compounds derived from tetrazole carboxylates for chemodynamic therapy against hepatocellular carcinoma cells

Front Chem. 2022 Aug 29:10:915247. doi: 10.3389/fchem.2022.915247. eCollection 2022.

Authors

Xinya Shi¹, Yulan Gu¹, Chuandan Wan², Xin Jiang³, Lei Shen⁴, Litao Tan⁴, Yujie Zhong⁴, Dengfeng Zou³

Affiliations

¹ Changshu No. 2 People's Hospital, Changshu, Jiangsu, China.
² Central Laboratory of Changshu Medical Examination Institute, Changshu, China.
³ School of Pharmacy, Guilin Medical University, Guilin, China.
⁴ Department of Materials Engineering, Changshu Institute of Technology, Changshu, China.

Abstract

Two Cu(II) compounds based on tetrazole-carboxylate ligands, [Cu(phtza)₂(H₂O)₂]∙3H₂O (1) and [Cu(atzipa)₂]∙2H₂O (2) (phtza = 2,2'-(5,5'-(1,3-phenylene)bis(2H-tetrazole-5,2-diyl))diacetate, atzipa = 3-(5-amino-1H-tetrazol-1-yl)isopropanoic anion), were designed and synthesized by hydrothermal reactions. The X-ray diffraction results show that the two compounds show two-dimensional (2D) layer structures. Nanoprecipitation with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)_-2000] (DSPE-PEG_-2000) contributes to the formation of the nanoparticles (NPs) with excellent water dispersity. In vitro study indicates that the two NPs exert considerable cytotoxicity toward human hepatocellular carcinoma cells (HepG2 and Huh7) with low half-maximal inhibitory concentration (IC₅₀). However, the cytotoxicity of such NPs is negligible in normal cells (HL-7702). The cytotoxicity of these NPs was also investigated by the flow cytometry and Calcein-AM/PI (live/dead) co-stained experiments. The results promise the great potential of these NPs for chemodynamic therapy against cancer cells.

Keywords: Cu(II); chemodynamic therapy; human hepatocellular carcinoma cells; in vitro; tetrazole carboxylate.