School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
Faculty of Robot Science and Engineering, Northeastern University, Shenyang, China.
J Cell Mol Med. 2022 Sep;26(18):4814-4824. doi: 10.1111/jcmm.17509. Epub 2022 Aug 3.
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 -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 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 -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 -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).
聚合物胶束在癌症治疗中具有广阔的应用前景，可提高药物的水溶性和生物利用度。先前的研究发现，硝唑尼特胶束具有良好的抗肝癌作用。鉴于硝唑尼特（NIC）的水溶性差，我们决定制备硝唑尼特胶束。然而，其治疗机制尚不清楚，因此本文对其体外抗肿瘤机制和代谢组学进行了初步研究，以了解其影响。结果表明，载药胶束（PEG-FIbu/NIC）对 HepG2 细胞具有抑制作用。此外，它可以促进 HepG2 细胞凋亡，并阻断细胞周期的 S 和 G2/M 期。通过 UPLC-MS 和 1H-NMR 研究正常组、模型组和给药组小鼠的血浆和肝脏代谢组学。采用主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）对数据进行处理，寻找相关代谢物。metaboanalyst 5.0 用于整合相关代谢物，寻找主要相关代谢途径。从而分析了 PEG-FIbu/NIC 的抗肿瘤机制。在血浆中检测到 51 种生物标志物，在肝脏中检测到 43 种生物标志物。经过综合生物标志物和代谢途径分析，发现 PEG-FIbu/NIC 胶束可以影响许多代谢物的变化，主要影响氨基酸代谢。本文是基于已发表的文章《硝唑尼特胶束的制备及药效学研究》（DOI: 10.1016/j.jddst.2021.103088）的深入研究。
