Fe3O4-viral-like Mesoporous Silica Nanoparticle (Fe3O4-vMSN)-Sustained Release of Lenvatinib for Targeted Treatment of Hepatocellular Carcinoma.

BACKGROUND

Lenvatinib is an oral tyrosine kinase inhibitor that selectively inhibits receptors involved in tumor angiogenesis and tumor growth. It is an emerging first-line treatment agent for hepatocellular carcinoma (HCC). However, there is no intravenous administration of Lenvatinib.

AIMS: This study aimed to construct nanocomposites that can efficiently support Lenvatinib and target liver cancer tissues and cells.

OBJECTIVE

In this study, ferric oxide-viral-like mesoporous silica nanoparticles-folic acid (Fe3O4-vMSN-FA) nanocomposites loaded with Lenvatinib were constructed, and their antihepatocellular carcinoma effects were evaluated.

METHODS

The hydrothermal method was used to synthesize ferric oxide (Fe3O4). Ferric oxide- viral-like mesoporous silica nanoparticles (Fe3O4;-vMSN) were synthesized using a twophase method. Then, Fe3O4-vMSN was modified with folic acid (Fe3O4-vMSN-FA) to better target tumor cells.

RESULTS

The experimental data showed that Fe3O4-vMSN-FA nanocomposites were successfully synthesized and could be loaded with Lenvatinib (Len@ Fe3O4-vMSN-FA). Fe3O4-vMSN-FA had good stability and biocompatibility, and it can release the loaded Lenvatinib faster in an acidic environment (pH 5.5). CCK8 assay and flow cytometry showed that HepG2 cells in the Len@ Fe3O4-vMSN group had the lowest cell viability and the highest apoptosis rate, confirming the anticancer properties of Len@ Fe3O4-vMSN-FA in vitro. In addition, transwell experiments showed that the migration and invasion ability of HepG2 cells in the Len@ Fe3O4-vMSN-FA group were significantly inhibited. In vivo fluorescence imaging in mice confirmed the enhanced tumor-targeting ability of Fe3O4-vMSN-FA. The tumor volume of the Len@ Fe3O4-vMSN-FA group was significantly reduced, and there was no significant effect on body weight. Moreover, serum liver function index (ALT and AST) and HE staining showed that Len@ Fe3O4-vMSN-FA did not cause obvious damage to organ tissue.

CONCLUSION

Len@ Fe3O4-vMSN-FA has a good anti-liver cancer effect. Fe3O4-vMSN-FA can be used as an alternative platform for drug delivery, providing more options for cancer therapy.