Extracellular Vesicles as Delivery Vehicles for Therapeutic Nucleic Acids in Cancer Gene Therapy: Progress and Challenges

Abstract

Extracellular vesicles (EVs) are nanoscale vesicles secreted by most types of cells as natural vehicles to transfer molecular information between cells. Due to their low toxicity and high biocompatibility, EVs have attracted increasing attention as drug delivery systems. Many studies have demonstrated that EV-loaded nucleic acids, including RNA-based nucleic acid drugs and CRISPR/Cas gene-editing systems, can alter gene expressions and functions of recipient cells for cancer gene therapy. Here in this review, we discuss the advantages and challenges of EV-based nucleic acid delivery systems in cancer therapy. We summarize the techniques and methods to increase EV yield, enhance nucleic acid loading efficiency, extend circulation time, and improve targeted delivery, as well as their applications in gene therapy and combination with other cancer therapies. Finally, we discuss the current status, challenges, and prospects of EVs as a therapeutic tool for the clinical application of nucleic acid drugs.

Production and Utility of Extracellular Vesicles with 3D Culture Methods

“…Various approaches are currently being explored to increase the yield and quality of exosome secretion, as well as their therapeutic and drug carrier properties, including 3D culture methods, stress inducing factors, genetically manipulating cells, exposing cells to physical stimulation, and chemically treating cells with drugs and other molecules. Additionally, it is also possible to engineer artificial EVs—EV-mimetic nanovesicles—which mimic natural EVs in morphology, size, and function ( Figure 2 ) [ 102 , 103 ].…”

The CRISPR/Cas9 System Delivered by Extracellular Vesicles

“…Meanwhile, the ability of EVs to carry information indicates that EVs can deliver cargoes for therapeutics [ 46 ]. Given the loading capacity of various biomacromolecules, ability to target specific cells, immunoregulation and ease of engineering, EVs can be an ideal vector for the delivery of therapeutic agents [ 47 ]. Furthermore, these beneficial characteristics of EVs are gradually being used in CRISPR/Cas9 delivery, which has potential for gene editing in vivo [ 48 ].…”

Extracellular Vesicles-Based Cell-Cell Communication in Melanoma: New Perspectives in Diagnostics and Therapy

“…EVs are notable candidates for therapeutic applications because they have a natural ability to carry biomolecules and they share several features with parental cells. The EVs of selected cell types are thought to be applied as therapeutic agents in immune therapy, vaccination trials, regenerative medicine, and drug delivery (for review [ 143 , 144 , 145 , 146 , 147 , 148 , 149 ]. For example, exosomes secreted by stem cells have wide regenerative potential, which could be utilized in several areas such as wound healing [ 150 , 151 ], muscle regeneration [ 152 ], or neuron regrowth after spinal cord injury [ 153 ].…”