Cationic Solid Lipid Nanoparticles as Non Viral Vectors for the Inhibition of Hepatocellular Carcinoma Growth by RNA Interference

Hepatocellular carcinoma (HCC) is one of the most important cause of cancer deaths worldwide. Gene therapy represents a novel approach for treating HCC. A safe and efficient gene delivery method, by using viral or non-viral vectors, is a crucial factor for a successful HCC gene therapy. Among non-viral vectors, cationic solid lipid nanoparticles (cSLN) possess advantageous features as biocompatibility and transfection efficiency.
In this study, cSLN were prepared, characterized and complexed with a plasmid (shNUPR1) able to inhibit the expression of the NUPR1 gene, which is involved in HCC growth and chemoresistance. The particles resulted biocompatible, as confirmed by hemolysis and cytotoxicity assays, and able to protect the shNUPR1 plasmid from degradation by DNase I. We also demonstrated, carrying out transfection and immunofluorescence studies, that the particles efficiently delivered the shNUPR1 plasmid into HCC cells, determining downregulation of NUPR1-regulated genes and NUPR1 protein expression.
These results suggest that the obtained cSLN could be proposed for further in vivo studies as novel transfection vectors for HCC gene therapy, having showed in vitro excellent transfection efficiency and biocompatibility.