Challenges for the Development of Extracellular Vesicle-Based Nucleic Acid Medicines

Abstract

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.

Chemically Modified Extracellular Vesicles and Applications in Radiolabeling and Drug Delivery

“…This review has the merit of being the first collection of specific chemically modified studies of EVs, seldom encountered in either multiple original articles or reviews. Despite a strong focus on elucidating distinct aspects of these vesicles—such as biogenesis pathway and loading nucleic acid drug [ 50 , 51 ], interactions with cells [ 52 ], and different modification approach addressed for the design of personalized EVs as DDS [ 53 , 54 ]—there is still much work to be accomplished around integrating the multifaceted capabilities of EVs into DDS. Undoubtedly, the results of the studies gathered in this review demonstrate that manufacturing and administering EVs is feasible and safe, suggesting that the translation of EVs into a therapeutic platform may already be just beyond the horizon.…”

Origen, morfología y significancia clínica de microvesículas de tumor en cáncer gástrico

“…Se ha establecido que la hipoxia, puede estimular a las células a secretar más exosomas y vesículas extracelulares [30,31], que contienen citocinas proangiogénicas [30]. Las vesículas extracelulares que se originan a partir de células cancerosas, en condiciones hipóxicas, transportan directamente la FCEV o activan la vía de la FCEV en las CE, lo que conduce a la angiogénesis tumoral [31].…”

“…NF-κB pertenece a un grupo de factores de transcripción que forman homo y heterodímeros y además, aumentan o suprimen la expresión de muchos genes [83]. La activación de NF-κB ocurre en respuesta a varios estímulos, incluidos factores de crecimiento, citocinas, hormonas y compuestos microbianos y químicos, y conduce a la síntesis de factores proangiogénicos, como IL-1, IL-8, TNF, IL-6, VEGF, MMP-2 y MMP-9 [31]. Las vías de señalización asociadas con la activación de la angiogénesis, la invasión, la TEM y la metástasis, también incluyen ITGB1/FAK [84], Wnt/β-catenina [85], NF-κB-MMP-9/VEGF [86], ERK/PKA [11], y otras vías.…”

Transforming growth factor-β-induced secretion of extracellular vesicles from oral cancer cells evokes endothelial barrier instability via endothelial-mesenchymal transition

“…The uptake of EVs can reprogram recipient cells leading to changes in their phenotypes and functions [13]. Multiple groups have reported that EVs released from cancer cells promote tumor development by inducing EMT, which increases the invasive and migratory potentials of cancer cells [14][15][16][17].…”