Development of Small Interfering RNA Loaded Cationic Lipid Nanoparticles for the Treatment of Liver Cancer with Elevated α-Fetoprotein Expression

α-Fetoprotein (AFP) is an oncogenic glycoprotein that is overexpressed in most patients with liver cancer. Moreover, it significantly affects tumorigenesis and progression, particularly by inhibiting programmed cell death or apoptosis. The treatment of liver cancer with chemotherapy is currently still in use, but its toxicity is a major concern. Alternatively, targeted therapy, especially small interfering RNA (siRNA)-based therapeutics that utilize siRNA to suppress target gene expression, is a promising cancer treatment approach that can help reduce such drawbacks. However, transporting siRNA into cells is a challenge due to its ease of degradation and limited cell membrane permeability. To overcome this limitation, we fabricated cationic lipid nanoparticles (cLNPs) to deliver <i>AFP-</i>targeted siRNA (siAFP) to AFP-producing liver cancer cells. Our results illustrated that these nanoparticles had a high capacity for siRNA encapsulation (>95%) and entered the cancer cells efficiently. Cell internalization of siAFP-loaded cLNPs resulted in the silencing of <i>AFP</i> mRNA expression and led to increased apoptotic cell death by inducing caspase-3/7 activity. This suggested that our cLNPs could be used as a powerful siRNA delivery carrier and siAFP-loaded cLNPs might be a useful strategy for treating liver cancer in the future.