RNA Interference and Nanotechnology: A Promising Alliance for Next Generation Cancer Therapeutics

Abstract

Cancer is a significant health hazard of the 21st century, and GLOBOCAN predicts increasing cancer incidence in the coming decades. Though several conventional treatment modalities exist, most of them end up causing off-target and debilitating effects, and drug resistance acquisition. Advances in our understanding of tumor molecular biology offer alternative strategies for precise, robust, and potentially less toxic treatment paradigms for circumventing the disease at the cellular and molecular level. Several deregulated molecules associated with tumorigenesis have been developed as targets in RNA interference (RNAi) based cancer therapeutics. RNAi, a post-transcriptional gene regulation mechanism, has significantly gained attention because of its precise multi-targeted gene silencing. Although the RNAi approach is favorable, the direct administration of small oligonucleotides has not been fruitful because of their inherent lower half-lives and instability in the biological systems. Moreover, the lack of an appropriate delivery system to the primary site of the tumor that helps determine the potency of the drug and its reach, has limited the effective medical utilization of these bio-drugs. Nanotechnology, with its unique characteristics of enhanced permeation and better tumor-targeting efficiency, offers promising solutions owing to the various possibilities and amenability for modifications of the nanoparticles to augment cancer therapeutics. Nanoparticles could be made multimodal, by designing and synthesizing multiple desired functionalities, often resulting in unique and potentially applicable biological structures. A small number of Phase I clinical trials with systemically administered siRNA molecules conjugated with nanoparticles have been completed and the results are promising, indicating that, these new combinatorial therapies can successfully and safely be used to inhibit target genes in cancer patients to alleviate some of the disease burden. In this review, we highlight different types of nano-based delivery strategies for engineering Nano-RNAi-based bio drugs. Furthermore, we have highlighted the insights gained from current research that are entering the preclinical evaluation and information about initial clinical developments, shaping the future for next generation cancer therapeutics.

The commonness in immune infiltration of rheumatoid arthritis and atherosclerosis: Screening for central targets via microarray data analysis

“…Nowadays, the main aspect of RNA therapeutics is RNA interference (RNAi). RNAi is an endogenous mechanism of mRNA silencing involving miRNA, and siRNA-based Interventions have revealed promising prospective in treatment of RA ( 93 , 94 ). Based on the MiRwalk database and TRRUST database, the TF-mRNA–miRNA regulatory network of hub genes was predicted and constructed and might provide the potential exploring clues for RNA therapeutics.…”

Dendrimers as Modifiers of Inorganic Nanoparticles for Therapeutic Delivery in Cancer

“…Dendrimers were used to encapsulate this pentapeptide to improve it delivery efficacy [ 90 , 91 ]. This resulted in the formulation of a DOX-encapsulated, LFC131-conjugated dendrimer to target the CXCR4 chemokine receptor and to prevent breast cancer from spreading to other organs [ 92 ].…”

Lab-to-Field Transition of RNA Spray Applications – How Far Are We?

“…Naked dsRNA showed effectiveness under lab conditions but had the potential for instability when sprayed in fields, where it could be degraded by UV radiation or washed off by rain. To circumvent this, several studies, inspired by human RNAi therapy research (Swaminathan et al, 2021), attempted to increase stability and durability by establishing protective envelops around dsRNAs and siRNAs (Pugsley et al, 2021;Yan et al, 2021). In mammals, the delivery of siRNA therapeutics is mediated by liposome encapsulation (Liu and Huang, 2021;Zabel et al, 2021).…”