Chapter 12 - Hyaluronic Acid as an Emerging Technology Platform for Silencing RNA Delivery

Abstract

For cancer treatment, there are several gene therapies involved like silencing RNA (siRNA), micro RNA, short hairpin RNA, etc. out of which, siRNAs promise to show significant progress in pharmacotherapy, including considerable expansion of the druggable target space and the possibility of treating cancer. However, stability in serum, off-target effects, and endosomal degradation are the major issues that need urgent attention. In the current case scenario, there has been an increased inclination toward the utility of hyaluronic acid (HA) (a glycosaminoglycan biopolymer) as a novel biomedical modality owing to its discrete properties like biodegradability, biocompatibility, aqueous solubility, viscoelasticity, and nonimmunogenicity. It has been well established that cluster differentiating 44 receptors (CD44), are overexpressed in a variety of solid tumors, such as pancreatic, breast, and lung cancer. More interestingly, HA has been reported to be used as a marker for distinguishing cancerous cells, as it acts as a primary substrate for CD44. Hence, this has granted a different notion of utilizing HA to develop various nanoplatforms (polymeric nanoparticles, liposomes, dendrimers) for the delivery of siRNA. Thus this chapter expounds on HA and HA hybridized nanoplatforms for siRNA delivery and discusses the emerging potential of using HA as a targeting agent due to its CD44 receptor specificity.