Translational research : the journal of laboratory and clinical medicine
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Review
Peptide carriers to the rescue: overcoming the barriers to siRNA delivery for cancer treatment.
Cancer is a significant health concern worldwide and its clinical treatment presents many challenges. Consequently, much research effort has focused on the development of new anticancer drugs to combat this disease. One area of exploration, in particular, has been in the therapeutic application of RNA interference (RNAi). ⋯ Among these candidate drug delivery systems, peptides have shown great promise as siRNA carriers due to their varied physiochemical properties and functions, simple formulations, and flexibility in design. In this review, we will focus on distinguishing between the different classes of peptide carriers based on their functions, as well as summarize and discuss the various design strategies and advancements that have been made in circumventing the barriers to siRNA delivery for cancer treatment. Resolution of these challenges by peptide carriers will accelerate the translation of RNAi-based therapies to the clinic.
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RNA interference (RNAi) is a cellular mechanism for post-transcriptional gene regulation mediated by small interfering RNA (siRNA) and microRNA. siRNA-based therapy holds significant promise for the treatment of a wide-range of arthritic diseases. siRNA selectively suppresses the expression of a gene product and can thus achieve the specificity that is lacking in small molecule inhibitors. The potential use of siRNA-based therapy in arthritis, however, has not progressed to clinical trials despite ample evidence for efficacy in preclinical studies. ⋯ Herein, we review recent preclinical studies that use RNAi-based drug delivery systems to mitigate inflammation in models of rheumatoid arthritis and osteoarthritis. We discuss a self-assembling peptide-based nanostructure that demonstrates the potential of overcoming many of the critical barriers preventing the translation of this technology to the clinic.
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Liver fibrosis is a wound-healing process induced by chronic liver injuries, such as nonalcoholic steatohepatitis, hepatitis, alcohol abuse, and metal poisoning. The accumulation of excessive extracellular matrix (ECM) in the liver is a key characteristic of liver fibrosis. Activated hepatic stellate cells (HSCs) are the major producers of ECM and therefore play irreplaceably important roles during the progression of liver fibrosis. ⋯ Using RNA interference to downregulate these cytokines in activated HSCs is a promising strategy to reverse liver fibrosis. Meanwhile, microRNAs (miRNAs) have also been exploited for the treatment of liver fibrosis. This review focuses on the current siRNA- and miRNA-based liver fibrosis treatment strategies by targeting activated HSCs in the liver.
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Application of RNAi interference for type 1 diabetes (T1D) therapy bears tremendous potential. This review will discuss vehicles for oligonucleotide delivery, imaging modalities used for delivery monitoring, therapeutic targets, and different theranostic strategies that can be applied for T1D treatment.
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Small interfering RNA (siRNA) has an established and precise mode of action to achieve protein knockdown. With the ability to target any protein, it is very attractive as a potential therapeutic for a plethora of diseases driven by the (over)expression of certain proteins. Utilizing siRNA to understand and treat cancer, a disease largely driven by genetic aberration, is thus actively investigated. ⋯ In addition to cancer cells, the role of the tumor microenvironment has been increasingly appreciated. Components in the tumor microenvironment, particularly immune cells, and thus siRNA-based immunotherapy, are under extensive investigation. Lastly, multiple siRNAs with or without additional drugs can be codelivered on the same nanoparticle to the same target site of action, maximizing their potential synergy while limiting off-target toxicity.