Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 28, Issue 9, Pages 743-750Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612828666220113161712
Keywords
Intrahepatic cholangiocarcinoma; H-MnO2-FA; Lenvatinib; proliferation; apoptosis; Raf-1MEK1; 2-ERK1; 2
Categories
Funding
- National Natural Science Foundation of China [81803895]
Ask authors/readers for more resources
In this study, a Lenvatinib@H-MnO2-FA drug delivery system was successfully synthesized, which effectively inhibited ICC cell proliferation and promoted apoptosis. This system shows promise as a drug delivery nano-vehicle.
Background: To investigate the effects of the Lenvatinib@H-MnO2-FA administration system on the proliferation and apoptosis of Intrahepatic cholangiocarcinoma (ICC) and the underlying molecular mechanism. Materials and Methods: In this research, hollow MnO2 (H-MnO2) was synthesized via the modified Stober method, and H-MnO2 was modified with polyethylene glycol-bis (Amine) (NH2-PEG-NH2) and folic acid (FA) to obtain H-MnO2-PEG-FA (H-MnO2-FA). Lenvatinib was coated in the hollow cavity of H-MnO2-PEG-FA to further form a nanometre drug-carrying system (Lenvatinib@H-MnO2-PEG-FA). Lenvatinib@H-MnO2-FA was characterized through transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FT-IR) was used to verify that Lenvatinib was loaded on nanoparticles. Functionally, confocal laser scanning microscopy (CLSM), 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed to determine the effect of Lenvatinib@H-MnO2-FA on the proliferation and apoptosis of ICC cells (9810 cells). Finally, the protein levels of Raf-1MEK1/2-ERK1/2 signalling pathway components were detected through Western blotting analysis. Results: We successfully synthesised a Lenvatinib@H-MnO2-PEG-FA administration system. The resulting nanomaterials had excellent biological stability and improved targeting effects. Functionally, Lenvatinib@H-MnO2-FA inhibited the proliferation of 9810 cells. The Bcl-2 protein level was significantly downregulated, and the caspase-3 protein level was significantly upregulated, indicating that Lenvatinib@H-MnO2-PEG- FA promoted the apoptosis of 9810 cells. Mechanistically, Lenvatinib@H-MnO2-FA increased the phosphorylation levels of Raf, MEK1/2, and ERK1/2. Conclusion: H-MnO2-FA can more effectively deliver Lenvatinib to inhibit proliferation and promote apoptosis in ICC, which could be the promising drug delivery nano-vehicles for delivery drugs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available