Nanomaterials-Based siRNA Delivery: Routes of Administration, Hurdles and Role of Nanocarriers

Abstract

Ribonucleic acid interference (RNAi) is a potential alternative therapeutic approach to knock down the overexpression of genes in several disorders especially cancers with underlying genetic dysfunctions. For silencing of specific genes involved in cell cycle, small/short interfering ribonucleic acids (siRNAs) are being used clinically. The siRNA-based RNAi is more efficient, specific and safe antisense technology than other RNAi approaches. The route of siRNA administration for siRNA therapy depends on the targeted site. However, certain hurdles like poor stability of siRNA, saturation, off-target effect, immunogenicity, anatomical barriers and non-targeted delivery restrict the successful siRNA therapy. Thus, advancement of an effective, secure, and long-term delivery system is prerequisite to the medical utilization of siRNA. Polycationic nanocarriers mediated targeted delivery system is an ideal system to remove these hurdles and to increase the blood retention time and rate of intracellular permeability. In this chapter, we will mainly discuss the different biocompatible, biodegradable, non-toxic (organic, inorganic and hybrid) nanocarriers that encapsulate and shield the siRNA from the different harsh environment and provides the increased systemic siRNA delivery.

Design and In Vitro Evaluation of Novel Cationic Lipids for siRNA Delivery in Breast Cancer Cell Lines

“…Delivery of siRNAs into cells is very difficult since these are highly hydrophilic and polyvalent anionic midsized molecules. The major rate-limiting factor of siRNA's therapeutic activity is poor accumulation in the target tissue due to its easy degradation in blood by nucleases [ 25 ]. It is essential to find an efficient drug delivery system for siRNA-based drug development.…”

New paradigm in combination therapy of siRNA with chemotherapeutic drugs for effective cancer therapy

“…These bioengineered nanocarriers can act as effective therapeutic agents due to less toxicity, size, charge, and chemical modification capacities that protect the siRNA loaded nanocarriers from acid/enzymatic degradation and rapid elimination from local and systemic circulation. Studies have revealed the inefficiency of RNAi therapies is primarily due to inadequate delivery of siRNA, resulting in unfavorable immune response ( Sajid et al., 2020 ), ( Gupta, Rai, Jangid, Pooja, Kulhari ). So, extensive research is being conducted to obtain suitable siRNA conjugated nanocarriers having ideal characteristics like stability, biodegradability, biocompatibility that can o deliver siRNA at the target site without any immune responses (phagocytosis).…”

RNA Interference in Aquaculture: A Small Tool for Big Potential

“…Thus, the ideal diameter of the RNAi molecules should range from 20 to 100 nm. 38 When the RNAi molecules reach the target tissue, they will be hindered by the endothelial lining of tissues that have pores with sizes from 4.5 to 25 nm. 20,38 Even if the RNAi molecules bypass the nuclease activity in different body systems (e.g., digestive and respiratory), serum, and extracellular matrix, the negative charge and relatively large size could constrain its cellular uptake.…”

“…38 When the RNAi molecules reach the target tissue, they will be hindered by the endothelial lining of tissues that have pores with sizes from 4.5 to 25 nm. 20,38 Even if the RNAi molecules bypass the nuclease activity in different body systems (e.g., digestive and respiratory), serum, and extracellular matrix, the negative charge and relatively large size could constrain its cellular uptake. 38,39 In addition, endolysosomal compartments are another barrier that could degrade RNAi molecules by endosomal engulfing.…”