Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy

Abstract

RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient’s therapeutic response.

Polyethylenimine-based Magnetic Nanocomplexes Enhanced Cisplatin Toxicity on Ovarian Cancer Cells in Presence of Static Magnetic Field

“…Tseng et al, reported that CIS-incorporated gelatin nanocomplexes can be used for cancer chemotherapy (46). Lipid and polymer-based nanoparticles siRNA delivery systems are also developed by Mainini et al, to cancer therapy (47). Polymeric nanoparticles synthesized based on hostguest interaction between β-cyclodextrin and benzimidazole used for liver cancer-targeted therapy and its ability to induce cell apoptosis was found to be remarkable (48).…”

Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression

“…Although there are not any preclinical trials concerning circRNAs in clinical treatment for cancer, numerous studies and attempts to utilize siRNAs as therapeutics have been reported. 53 , 54 , 55 …”

Overcoming Barriers for siRNA Therapeutics: From Bench to Bedside

“…Many recent delivery vehicles have taken advantage of the change from extracellular to the endosomal environment. Among the many differences, the change in pH is often utilized for efficient endosomal disruption and further release of siRNA once inside the target cell [ 117 ]. Protonable cationic polymers have been shown to increase delivery efficiency due to their high buffering capacity [ 45 ].…”