Therapeutic effects of a new selenium-sorafenib nanocomplex in liver and tumor in a TAA-induced HCC model.

Abstract

OBJECTIVE: The objective of this work was to develop and study the therapeutic properties of a nanocomplex based on selenium nanoparticles, an important microelement, and sorafenib, a known anticancer drug, on a model of hepatocellular carcinoma in mice. This nanocomplex combines the anticancer activity of selenium and sorafenib, which significantly increases its effectiveness in the treatment of HCC METHODS: A nanocomplex of selenium and sorafenib (SeSo) was obtained by laser ablation. To test the physicochemical properties of the nanocomplex, absorption spectrometry, dynamic light scattering, fluorimetry and electron microscopy were used. In the course of the work, real-time PCR was used to screen the mRNA expression levels of more than 40 genes encoding key markers of various signaling cascades associated with HCC, separately in the liver and tumor. Western blotting was used to test the reliability of real-time PCR. To assess the tumor size and the liver size and weight of mice, morphometric and statistical analyses were used. RESULTS: Based on the results of a large-scale analysis of the expression of a large number of genes, the advantages of SeSo over the well-known drug sorafenib were revealed and the molecular mechanisms of its therapeutic effect were established. CONCLUSIONS: SeSo is a multikinase inhibitor, which significantly inhibits tumor growth. SeSo differentially regulates anti-cancer processes in tumor tissue and simultaneously triggers regenerative therapeutic processes in the liver itself.