Abstract
Simple SummaryThe development of nucleic acid drugs has progressed in recent years, especially in the field of cancer therapy, where there has been considerable progress in the development of siRNA-, antisense oligonucleotide-, and miRNA-related drugs. Extracellular vesicles are expected to play a pivotal role as a drug delivery system for nucleic acid drugs. By conjugating EVs with proteins, antibodies, or chemical antibodies called aptamers that specifically bind to cancer, EVs can be effectively delivered to tumor tissues and cells. This review summarizes the latest findings, serving as a bridge to the clinical application of nucleic acid drugs in cancer therapy.Nucleic acid drugs, such as siRNAs, antisense oligonucleotides, and miRNAs, exert their therapeutic effects by causing genetic changes in cells. However, there are various limitations in their delivery to target organs and cells, making their application to cancer treatment difficult. Extracellular vesicles (EVs) are lipid bilayer particles that are released from most cells, are stable in the blood, and have low immunogenicity. Methods using EVs to deliver nucleic acid drugs to target organs are rapidly being developed that take advantage of these properties. There are two main methods for loading nucleic acid drugs into EVs. One is to genetically engineer the parent cell and load the target gene into the EV, and the other is to isolate EVs and then load them with the nucleic acid drug. Target organ delivery methods include passive targeting using the enhanced permeation and retention effect of EVs and active targeting in which EVs are modified with antibodies, peptides, or aptamers to enhance their accumulation in tumors. In this review, we summarize the advantages of EVs as a drug delivery system for nucleic acid drugs, the methods of loading nucleic acid drugs into EVs, and the targeting of EVs to target organs.
Highlights
Extracellular vesicles (EVs) are phospholipid bilayer membranous vesicles and are generated by almost all types of mammalian cells as a cell-to-cell communication tool [1].EVs carry various nucleic acids, proteins, and lipids inherited from the cell of origin
Pre-secretion loading is a method for transfecting target genes into parent cells, which increases the target gene expression in the cell, leading to the target gene being loaded into EVs
When vesicular stomatitis virus G protein (VSV-G)-GFP11 and AGO2-GFP1-10 plasmids and PTEN-induced kinase 1 (PINK1) shRNA were transfected into 293T cells, PINK1 shRNA was loaded into EVs isolated from culture supernatants
Summary
Extracellular vesicles (EVs) are phospholipid bilayer membranous vesicles and are generated by almost all types of mammalian cells as a cell-to-cell communication tool [1]. Most nucleic acid drugs are taken up by the liver, which has a discontinuous sinusoidal endothelium and is a hyperperfused organ [28], and when administered intravenously, these drugs can lose their organ-targeting properties To improve their delivery into cells, chemical modification of RNAs and their encapsulation in liposomes have been attempted, but some of the compounds have resulted in undesirable consequences, such as loss of biological activity [29] and toxicity [30]. The bilayer membrane and nanoscale size of EVs protect their cargo from destruction by complement and macrophages, extending their circulating half-life and improving their biological activity [35]. By applying biological and chemical modifications to the lipid bilayer, artificial liposomes and EVs can Cancers 2021, 13, x FOR PEER REVIEW.
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