Recent advances in optimizing siRNA delivery to hepatocellular carcinoma cells

Hepatocellularcarcinoma (HCC), the primary form of liver cancer, is the second leading causeof cancer-related deaths worldwide. Current therapies have limited effectiveness,particularly in advanced stages of the disease, highlighting the need forinnovative treatment options. Small-interfering RNA(siRNA) molecules show great promise as a therapeutic solution since they caninhibit the expression of genes promoting HCC growth. Their cost-effective synthesis has further encouraged their potentialuse as novel drugs. However, siRNAs are vulnerable to degradation in biologicalenvironments, necessitating protective delivery systems. Additionally, targeteddelivery to HCC is critical for optimal efficacy and minimal undesired sideeffects. This review addresses the challenges associated with the delivery of siRNA toHCC, discussing and focusing on delivery systems based on lipid and polymeric nanoparticlesin publications from the past five years. Futurenanoparticles will need to effectively cross the vessel wall, migrate throughthe extracellular matrix and finally cross the HCC cell membrane. This may beachieved by optimizing nanoparticle size, the equipment of nanoparticles withHCC targeting moieties and loading nanoparticles with siRNAs againstHCC-specific oncogenes.