An application of p-sulfonatocalix[6]arenes to attenuate cardiotoxicity of mitoxantrone in vitro: preparation, characterization and evaluation.

Abstract

In this study, p-sulfonatocalix[6]arenes (SCA6) was proposed to construct a host-guest complexation to carry mitoxantrone (MIT) to maintain its anti-proliferation effect on HepG2 cells as well as to attenuate cardiotoxicity on H9C2 cells as a nano-size drug delivery system. SCA6 binding to MIT evidenced through competitive fluorescence titration method. The complex was characterized using UV-visible, Fourier transform infrared, and proton nuclear magnetic resonance (1H-NMR) spectroscopies and differential scanning calorimetry analysis. The cytotoxicity was examined by a cell counting kit-8 assay on six cells. High content analysis, cell apoptosis and cell cycle experiments were measured to investigate the mechanism of detoxification in H9C2. The host-guest complexation was formed with a stoichiometry ratio of 1:1. Cytotoxicity study demonstrated that MIT/SCA6 complex could improve the cell viability on H9C2, MCF-7, A549, Hek293 and L02 cells and remained cytotoxicity effect on HepG2 cells. High content analysis showed that MIT/SCA6 complex could enhance the cell viability, mitochondrial mass and mitochondrial membrane potential and ameliorate the nuclear swelling on H9C2 cells. Moreover, the complex were arrested in G0/G1 phase of the cell cycle and same with MIT, while the detoxication was attributed to reducing early apoptosis. The host-guest complexation between SCA6 and MIT had the ability to attenuate cardiotoxicity and provided a potential strategy for the application of soluble calixarenes in chemotherapy.