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 inhib-its 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 ad-ministration 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 anti-hepatocellular carcinoma effects were evaluated. Methods: The hydrothermal method was used to synthesize ferric oxide (Fe3O4). Ferric ox-ide-viral-like mesoporous silica nanoparticles (Fe3O4-vMSN) were synthesized using a two-phase 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 suc-cessfully 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 Len-vatinib 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 high-est 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 MSCs for drug delivery, providing more options for cancer therapy.