RNAi-based combination therapies

Abstract Cancer is a major global health issue, and the clinical outcome of cancer treatment has remained poor for many years. Numerous therapeutic strategies have been implemented in an effort to overcome cancer progression. RNA-interfering (RNAi) molecules are potent and versatile means for regulating and exploring gene expression. RNAi can be used to silence specific cancer genes upon which tumor cells are dependent and could act in combination with anticancer medications to improve the cancer treatment. However, the clinical use of RNAi technology for cancer treatment has been hindered due to enzymatic instability, limited cellular uptake, nuclease degradation, inability to escape from the endosomes, and poor pharmacokinetic profiles. To address these issues and to codeliver different anticancer drugs, a number of specially designed nanocarrier-based drug delivery strategies have been utilized, and significant evolution has been made in this area. This chapter provides an overview of RNAi, as well as the barriers and challenges associated with RNAi delivery, and discusses the application of various nanocarriers, including liposomes, polymeric, and inorganic nanoparticles in the formulation of these agents with special focus on the combination of conventional anticancer drugs with RNAi.