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- Title
An application of p-sulfonatocalix[6]arenes to attenuate cardiotoxicity of mitoxantrone in vitro: preparation, characterization and evaluation.
- Authors
Yu, Xuan; Wang, Meng; Wang, Huimin; Ren, Xiaoliang; Jiang, Miaomiao; Zhu, Yan; Zhang, Deqin
- Abstract
Objectives: 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. Methods: 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. Key findings: 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. Conclusions: 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. Graphical Abstract
- Subjects
CARDIOTOXICITY; PROTON magnetic resonance; AROMATIC compounds; NUCLEAR magnetic resonance; MITOXANTRONE; MITOCHONDRIAL membranes
- Publication
Journal of Pharmacy & Pharmacology, 2022, Vol 74, Issue 1, p41
- ISSN
0022-3573
- Publication type
Academic Journal
- DOI
10.1093/jpp/rgab154