Unlocking the potential of Extracellular Vesicles: from single molecules to novel therapeutics
As part of normal homeostasis, cells release different types of small-sized membrane vesicles to traffic analytes across membranes, communicate with other cells and remove unwanted cell content. These vesicles can range in size from 30nm to 1,000nm and are collectively known as Extracellular Vesicles (EVs).
EVs can be found in circulating blood, serum (1) and in most biological fluids. In recent years, it has been shown that EVs are able to interfere with biological functions, stimulating the growth of EV research particularly in their characterisation as a novel class of therapeutics, with the limelight on drug delivery and diagnostics (2).
EVs are ideal candidates for developing and testing new drug delivery methods. In this piece, we explore the growth of the EV-mediated drug delivery sector and the tools available to exhaustively characterise EVs and their cargoes. Recent advances in EV research are technology-driven, with a particular focus on high sensitivity imaging methods, such as single-molecule localisation microscopy. These technologies support engineering of EVs and enable the better understanding of EV-mediated drug delivery.
Different subtypes of extracellular vesicles
EVs are highly stable membrane-enclosed particles that act as carriers of active molecules like RNA, DNA, proteins, metabolites and lipids, which can either be membrane-bound or enclosed within vesicles. Once secreted, EVs can mediate intercellular signalling, modulate stroma tissue or even regulate inflammatory and immune responses by trafficking to local or distant targets and governing various biological functions.
Circulating EVs are considered small long-distance signalling units travelling around the human body with the ability to cross biological barriers. They have different characteristics according to the cell type releasing them, and cargoes are reflective of the producer cell. Released EVs also have distinctive composition in pathological conditions. This makes EVs appealing in early disease diagnostics and biomarker development tools and their use in targeted drug delivery to tackle diseases, including cancer or neuronal disorders.
For many years, EVs have been classified according to their size and origin as exosomes (nanoscalesized, of endocytic origin), microvesicles/microparticles (various sizes, shed from the plasma membrane), apoptotic bodies and Golgi vesicles. However, after the 2019 International Society for Extracellular Vesicles (ISEV) annual conference in Kyoto, Japan, a statement issued by the society endorsed the use of the generic term extracellular vesicles (EV) for particles naturally released from the cell, delimited by a lipid bilayer and without a functional replicating nucleus (3).....
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