Antitumor effect and metabonomics of niclosamide micelles

Polymer micelles now have promising applications in the treatment of cancer, increasing the water solubility and bioavailability of drugs. Previous studies have found that micelles of niclosamide have good anti‐liver cancer effect. In view of the poor water solubility of niclosamide (NIC), we decided to prepare niclosamide micelles. However, its therapeutic mechanism is not clear, so this paper conducted a preliminary study on its vitro anti‐tumour mechanism and metabonomics to find out its impact. It was found that the drug‐loaded micelles (PEG(2K)‐FIbu/NIC) had an inhibitory effect on HepG2 cells. Moreover, it can promote apoptosis of HepG2 cells and block S and G2/M phase of cell cycle. The plasma and liver metabolomics of mice in normal group, model group and administration group were studied by UPLC‐MS and (1)H‐NMR. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS‐DA) were used to process the data and find the relevant metabolites. metaboanalyst 5.0 was used to integrate the relevant metabolites to find the main related metabolic pathways. Thus, the anti‐tumour mechanism of PEG(2K)‐FIbu/NIC was analysed. Fifty‐one biomarkers were detected in plasma, and 43 biomarkers were detected in liver. After comprehensive biomarker and metabolic pathway analysis, it was found that PEG(2K)‐FIbu/NIC micelles could affect the changes of many metabolites, mainly affecting amino acid metabolism. This article is an in‐depth study based on the published Preparation and pharmacodynamics of niclosamide micelles (DOI: 10.1016/j.jddst.2021.103088).