Synthesis and Search for the Most Effective Cytotoxic Nanocomplex Based on Selenium and Sorafenib Nanoparticles Against Hepatocellular Carcinoma In Vitro

Developing targeted nanoplatforms for the selective destruction of hepatocellular carcinoma cells with minimal damage to healthy parenchyma is a priority in modern oncopharmacology. Nanoselenium is a promising agent for creating such systems; however, it requires vector modification to prevent nonspecific toxicity. Therefore, the aim of this study was to create new nanocomplexes containing selenium nanoparticles of medium size (50 and 100 nm) doped with sorafenib and the cyclic peptide cRGDfC to enhance the selectivity of cytotoxic effects against three different liver cancer cell lines. A comparative study of the physicochemical properties and selectivity of the biological effects of these nanocomplexes and their peptide-free analogs on cell viability and death patterns, as well as wound healing activity, was conducted. Modification of nanocomplexes with the cRGDfC peptide significantly enhanced their cytotoxic effect in solid hepatocarcinoma models MH-22a and Hepa 1–6 at low concentrations. For the H22 ascites cell line, the nanocomplex size was the determining factor in MTT cytotoxicity, while the B16-F10 melanoma cell line demonstrated resistance, confirming the narrow hepatospecificity of the developed nanocomplex design. Thus, the newly synthesized nanocomplexes containing the cRGDfC peptide provide an optimal combination of biological safety for normal cells and high cytotoxic activity against liver cancer within the studied concentration range.