Advanced RNA-based immunotherapies have been widely investigated in recent years, due to their ability to regulate immune system response via RNA interference. Specifically, the use of siRNA to selectively modulate gene expression in activated immune cells represents a promising strategy; however, several challenges remain. Targeted siRNA delivery to activated immune cells is the key to obtain sequence-specific gene silencing, but since nucleic acids in their free form are rapidly degraded by nucleases present in extracellular matrices, have poor pharmacokinetics and hardly pass cellular membranes, carrier systems are required. Suitable carriers that have been extensively investigated are cationic lipids and cationic polymers due to their ability to encapsulate negatively charged nucleic acids through electrostatic interaction.