Advances in Extracellular Vesicle Nanotechnology for Precision Theranostics

Abstract

Extracellular vesicles (EVs) have increasingly been recognized as important cell surrogates influencing many pathophysiological processes, including cellular homeostasis, cancer progression, neurologic disease, and infectious disease. These behaviors enable EVs broad application prospects for clinical application in disease diagnosis and treatment. Many studies suggest that EVs are superior to conventional synthetic carriers in terms of drug delivery and circulating biomarkers for early disease diagnosis, opening up new frontiers for modern theranostics. Despite these clinical potential, EVs containing diverse cellular components, such as nucleic acids, proteins, and metabolites are highly heterogeneous and small size. The limitation of preparatory, engineering and analytical technologies for EVs poses technical barriers to clinical translation. This article aims at present a critical overview of emerging technologies in EVs field for biomedical applications and challenges involved in their clinic translations. The current methods for isolation and identification of EVs are discussed. Additionally, engineering strategies developed to enhance scalable production and improved cargo loading as well as tumor targeting are presented. The superior clinical potential of EVs, particularly in terms of different cell origins and their application in the next generation of diagnostic and treatment platforms, are clarified.

Hepatocyte-targeted delivery using oleanolic acid-loaded liposomes for enhanced hepatocellular carcinoma therapy

“…, JNK/p38, MAPK, and PI3K/Akt/mTOR), thereby inhibiting tumor metastasis. 46,47 EMT is a fundamental process that has been implicated in tumor progression. 48,49 Loss of E-cadherin and upregulation of N-cadherin and vimentin expressions are considered to be the major hallmarks of EMT.…”

“…It is well established that OA and its derivatives can block multiple processes of tumor cell invasion (e.g., adhesion, migration and matrix degradation) through the regulation of several signalling pathways (e.g., JNK/p38, MAPK, and PI3K/Akt/mTOR), thereby inhibiting tumor metastasis. 46,47 EMT is a fundamental process that has been implicated in tumor progression. 48,49 Loss of E-cadherin and upregulation of N-cadherin and vimentin expressions are considered to be the major hallmarks of EMT.…”

Extracellular vesicle-loaded hydrogels for tissue repair and regeneration

“…According to a survey conducted by ISEV at the end of 2015, ultracentrifugation is still the most common way to extract EVs [ 51 ]. This method obtains the required components mainly based on the difference in size and density of the components in the original solution [ 35 , 52 ]. However, it should be noted that the presence of fetal bovine serum in the cell culture supernatant may lead to contamination of EVs and affect their purity when ultracentrifugation is used [ 53 ].…”

CRISPR/Cas gene editing and delivery systems for cancer therapy

“…Extracellular vehicles (EVs) are another membrane‐based delivery vectors which are lipid bilayer vesicles secreted from almost all kinds of cells and released into the extracellular environment for transportation of cargos among cells including genetic information, proteins (Horodecka & Duchler, 2021; Li, Song, et al, 2022). At present, accumulating evidence has indicated EVs possess the ability of loading biomolecules and traveling across physiologic barriers to target specific cells or tissues (Dixson et al, 2023; Wu, Fu, et al, 2023). So EVs are recognized as the potential selective delivery vehicles for various cargoes including CRISPR/Cas systems (Wang, Wang, et al, 2023; Yan & Liang, 2022).…”