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.
Highlights
With the growing global burden and economic impact, cancer has become the most significant public health challenge of this century
Arising from a complex interplay of oncogenes and tumor suppressor genes, cancer is a collective manifestation of deregulated gene functions
In spite of the innovation of various approaches of therapeutic modalities like chemotherapy, radiotherapy, and immunotherapy to combat cancer, the fact that these strategies have encountered numerous limitations compelled the scientific world to go on a quest for a better treatment paradigm
Summary
With the growing global burden and economic impact, cancer has become the most significant public health challenge of this century. Add up to the challenges of onsite delivery of drugs using RNAi. The unique characteristics of nanoparticles have enabled researchers to successfully demonstrate them as efficient chaperones for the delivery of RNAi molecules to the primary site of the tumor. Nanoparticles usually exist as particulate dispersions or solid particles with sizes ranging between 10–1,000 nm (Nagal and Singlab, 2013) Their enhanced permeability and retention (EPR) effect, capacity to prevent RNAi molecules from undergoing enzymatic degradation, and transportation efficiency across the cell membrane make them a perfect carrier of RNAi molecules for targeted therapy (Xin et al, 2017). A small number of Phase I clinical trials with systemically administered ncRNA molecules conjugated with different nanoparticles as delivery vehicles are already complete, indicating that these new therapeutics can safely inhibit targeted gene products in patients with cancer. 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 RNAi-based therapeutics in cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
