Abstract
Pancreatic cancer (PC) is one of the leading causes of death and is the fourth most malignant tumor in men. The epigenetic and genetic alterations appear to be responsible for development of PC. Small interfering RNA (siRNA) is a powerful genetic tool that can bind to its target and reduce expression level of a specific gene. The various critical genes involved in PC progression can be effectively targeted using diverse siRNAs. Moreover, siRNAs can enhance efficacy of chemotherapy and radiotherapy in inhibiting PC progression. However, siRNAs suffer from different off target effects and their degradation by enzymes in serum can diminish their potential in gene silencing. Loading siRNAs on nanoparticles can effectively protect them against degradation and can inhibit off target actions by facilitating targeted delivery. This can lead to enhanced efficacy of siRNAs in PC therapy. Moreover, different kinds of nanoparticles such as polymeric nanoparticles, lipid nanoparticles and metal nanostructures have been applied for optimal delivery of siRNAs that are discussed in this article. This review also reveals that how naked siRNAs and their delivery systems can be exploited in treatment of PC and as siRNAs are currently being applied in clinical trials, significant progress can be made by translating the current findings into the clinical settings.
Highlights
Despite advances in various treatment modalities, pancreatic cancer (PC) still remains an incurable disease
An experiment has only investigated role of Small interfering RNA (siRNA) in cancer immunotherapy and as immune evasion is a common phenomenon in Pancreatic cancer (PC) [176], more studies are required to show how such genetic tools can be employed in PC treatment and activating anti-tumor immunity
To suppress PC growth and viability, siRNAs have been developed for down-regulating the various tumorpromoting factors including Precursor of nerve growth factor (proNGF), Receptor-associated protein 80 (RAP80), NUF2, SnoN, Hypoxia inducible factor-1α (HIF-1α), COX-2 and Nek2
Summary
Despite advances in various treatment modalities, pancreatic cancer (PC) still remains an incurable disease. Genetic tools such as CRISPR/Cas and small interfering RNA (siRNA), despite their ability to facilitate gene silencing and inhibit cancer progression are unable to completely kill cancer cells [16,17,18,19] This is due to presence of some limitations including their off-targeting feature, their degradation in blood circulation and other impediments such as blood-brain barrier (BBB) and blood-tumor barrier (BTB) [20,21,22,23,24]. Various kinds of nanostructures including micelles, liposomes, carbon-based nanomaterials and dendrimers among others have been used for delivery of siRNAs and in promoting their potential for gene down-regulation in PC treatment These topics are discussed in the current review article.
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