Glucosamine-Modified Reduction-Responsive Polymeric Micelles for Liver Cancer Therapy

Abstract

In this work, glucose transporter-1 (GLUT-1) and glutathione (GSH) over-expression in liver cancer was utilized to design a reduction-responsive and active targeting drug delivery system AG-PEG-SS-PCL (APSP) for the delivery of sorafenib (SF). The SF-APSP micelles were prepared using the thin film hydration method and characterized by various techniques. In vitro release experiments showed that the cumulative release of SF-APSP micelles in the simulated tumor microenvironment (pH 7.4 with GSH) reached 94.76 ± 1.78% at 48 h, while it was only 20.32 ± 1.67% in the normal physiological environment (pH 7.4 without GSH). The in vitro study revealed that glucosamine (AG) enhanced the antitumor effects of SF, and SF-APSP micelles inhibited proliferation by targeting HepG2 cells and suppressing cyclin D1 expression. The in vivo antitumor efficacy study further confirmed that the SF-APSP micelles had excellent antitumor effects and better tolerance against nude mouse with HepG2 cells than other treatment groups. All in all, these results indicated that SF-APSP micelles could be a promising drug delivery system for anti-hepatoma treatment.

Hypermethylation of GSTM5 and its effect on oxidation in myelodysplastic syndrome

“…GSH has other effects, particularly on cancer cells. For instance, elevated GSH levels enhance proliferation in HepG2 cells [36] and promote metastasis of B16 melanoma cells [37]. These findings highlight the impact of intracellular GSH concentration on cancer cell function and its crucial role in determining cancer characteristics.…”

Recent Advances in Nanotechnology-Based Targeted Delivery Systems of Active Constituents in Natural Medicines for Cancer Treatment

“…Therefore, GLUT is abundantly expressed on the surface of tumor cells [148,149]. Recently, the design and development of tumor cells-targeted nano-preparation in virtue of GLUT-mediated endocytosis has become a hot research topic [149][150][151]. As modifying glucose with alkyl groups can enhance the affinity of glucose to GLUT, researchers used n-octyl-β-D-glucopyranosideis as a targeting ligand to modify liposomes loaded with dihydroartemisinin [151].…”