Cationic SLN for siRNA and DNA plasmid delivery in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related deaths. For the treatment of HCC several drugs are under development, but the only one with proven survival benefit is sorafenib. This agent is a multikinase inhibitor that blocks Raf signaling and VEGF, PDGF and c-Kit. It has antiproliferative and antiangiogenic activity and delays tumor progression [1,2]. Moreover, systemic tumor-targeted gene delivery is attracting increasing attention as a promising alternative to conventional therapeutic strategies. At this purpose a large number of viral and non-viral vectors have been studied and applied as systems of stable transfection with low toxicity. Although cationic polymers and liposome are promising systems, solid lipid nanoparticles (SLN) have been recently proved to be a really useful vehicle for gene therapy [3,4]. The aim of this work was to design and to obtain cationic SLNs containing sorafenib capable of forming complexes with siRNA and DNA plasmid for the treatment of HCC, in order to combine the effects of drug and nucleic acids. The physical binding between cSLN and nucleic acids was confirmed by the study of complexes’ zeta potential values that became more positive as higher was the amount of cSLN and via the electrophoretic mobility of the samples in agarose gel 0.8%. Transfection studies on different tumor cell line are in progress.