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WIREs Nanomed Nanobiotechnol
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Imaging as a tool to accelerate the translation of extracellular vesicle‐based therapies for central nervous system diseases

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Abstract Extracellular vesicles (EVs) are natural and diverse lipid bilayer‐enclosed particles originating from various cellular components and containing an abundance of cargoes. Due to their unique properties, EVs have gained considerable interest as therapeutic agents for a variety of diseases, including central nervous system (CNS) disorders. Their therapeutic value depends on cell origin but can be further enhanced by enrichment of cargo when used as drug carriers. Therefore, there has been significant effort directed toward introducing them to clinical practice. However, it is essential to avoid the failures we have seen with whole‐cell therapy, in particular for the treatment of the CNS. Successful launching of clinical studies is contingent upon the understanding of the biodistribution of EVs, including their uptake and clearance from organs and specific homing into the region of interest. A multitude of noninvasive imaging methods has been explored in vitro to investigate the spatio‐temporal dynamics of EVs administered in vivo. However, only a few studies have been performed to track the delivery of EVs, especially delivery to the brain, which is the most therapeutically challenging organ. We focus here on the use of advanced imaging techniques as an essential tool to facilitate the acceleration of clinical translation of EV‐based therapeutics, especially in the CNS arena. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging
Biogenesis of exosomes and microvesicles (MVs). Exosomes originate from the multivesicular bodies (MVBs). A MVB can fuse with a lysosome for degradation or with the plasma membrane to release the intraluminal vesicles into the extracellular space, at that stage called exosomes. Exosomes are rich in nucleic acids, lipids, and proteins. MVs are larger than exosomes and are produced by outward budding of the plasma membrane. Their cargoes are mainly composed of plasma membrane components. ESCRT, Endosomal Sorting Complex Required for Transport
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A clinical perspective on intra‐arterial delivery of Extracellular vesicles (EVs) to the brain for precise targeting. Modern imaging can visualize the biodistribution of EVs after injection. The advanced real‐time image‐guided drug delivery system should be an indispensable tool for advancing EVs treatment, allowing for their precise targeting. PET‐MR further enables quantification and mapping biodistribution of injected EVs with anatomic information at the target region
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Strategies to label Extracellular vesicles (EVs) for in vivo imaging. Optical reporter proteins or fluorescent dyes are solely suitable for preclinical use. Radionuclides and contrast agents have the potential for clinical applications. Rluc, Renilla luciferase; GFP, green fluorescent protein; GION, gold‐iron oxide nanoparticles; Gluc, Gaussia princeps luciferase; GNP, gold nanoparticles; SPION, superparamagnetic iron oxide nanoparticle; USPION, ultrasmall superparamagnetic iron oxide nanoparticle
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Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease

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