Redox-Responsive Drug Delivery for Small Interfering RNA (siRNA) Delivery

The therapeutic potential of small interfering RNA (siRNA) has gained significant attention due to its ability to silence specific genes, offering a promising approach to treating a wide range of diseases, including cancer, genetic disorders, and viral infections. However, the successful delivery of siRNA is hindered by its instability, rapid degradation, and challenges in crossing biological membranes. Redox-responsive drug delivery systems provide innovative solutions by leveraging intracellular redox gradients, particularly the high glutathione levels in the cytoplasm, to achieve controlled and targeted siRNA release. This chapter explores the design, development, and application of redox-responsive systems for siRNA delivery. Key topics include using disulfide bonds and other redox-sensitive linkers to enhance siRNA stability during systemic circulation and ensure its release in reductive environments. Advances in nanocarriers, such as liposomes, dendrimers, and polymeric nanoparticles, are discussed, highlighting their role in improving siRNA bioavailability and cellular uptake. The chapter also reviews preclinical and clinical progress in using redox-responsive systems for siRNA therapy, along with challenges and strategies for addressing off-target effects and large-scale production. By providing a comprehensive overview, this chapter aims to contribute to the development of efficient and safe siRNA-based therapeutics.