Nano-formulated siRNA-based therapeutic approaches for cancer therapy

Abstract

RNAi is a remarkable treatment strategy to knock down gene overexpression in a variety of disorders, including cancers. RNAi processes allow siRNAs to detect and degrade a homologous mRNA sequence in the cell. However, the limited potential of siRNA delivery to target cells, poor cellular uptake, off-target effect, and their breakdown by serum nucleases in systemic circulation are limiting factors for their therapeutic applications. Over the past few years, siRNA drugs are undergoing a period of clinical translation. Therefore, this review mainly highlights the state-of-the-art of nanocarriers for delivering siRNA cargos and their coadministration with anticancer drugs, along with their applications in cancer treatment. Besides, molecular manifestations, challenges in the delivery of siRNA, design, and development of siRNA-based delivery systems, merits, and demerits of different nanocarriers have been discussed. The endosomal trapping of siRNA is a major difficulty for most delivery strategies, influencing the therapeutic effect. To address this issue various approaches for siRNA release including pH-responsive release, membrane fusion, proton sponge effect, and photochemical disruption have been discussed. Finally, the current status of siRNA therapeutics in clinical trials is explored, providing a systematic and comprehensive overview of siRNA-based therapeutics for effective cancer treatment.