Abstract
Extracellular vesicles (EVs) are complex nanoparticles required for the intercellular transfer of diverse biological cargoes. Unlike synthetic nanoparticles, EVs may provide a natural platform for the enhanced targeting and functional transfer of therapeutics across complex and often impenetrable biological boundaries (e.g. the blood-brain barrier or the matrix of densely organised tumours). Consequently, there is considerable interest in utilising EVs as advanced drug delivery systems for the treatment of a range of challenging pathologies. Within the past decade, efforts have focused on providing standard minimal requirements for conducting basic EV research. However, no standard reporting framework has been established governing the therapeutic loading of EVs for drug delivery applications. The purpose of this review is to critically evaluate progress in the field, providing an initial set of guidelines that can be applied as a benchmark to enhance reproducibility and increase the likelihood of translational outcomes.
Highlights
Extracellular vesicles (EVs) are complex nanoparticles required for the intercellular transfer of diverse biological cargoes
The review details current methodologies applied for the loading of EVs (Table 1) and identifies an urgent need for the implementation of standardised reporting in the field. To assist with this endeavour, we provide the first basic framework outlining recommended reporting criteria for studies involving EV loading, which has been designed to supplement existing International Society for Extracellular Vesicles (ISEV) guidelines and position statements to enhance best practice in therapeutic EV science that help advance the field toward clinical application.[24,25]
This article calls for standardisation in the reporting of experimental parameters that could influence the exogenous loading of EVs and provides relevant guidelines (Table 2) that broadly cover the five principal stages employed in a standard EV loading protocol: 1) EV isolation, 2) EV characterisation, 3) EV loading, 4) assessment of loading and 5) the functional delivery of cargo
Summary
Extracellular vesicles (EVs) are complex nanoparticles required for the intercellular transfer of diverse biological cargoes. This increase has been most evident for the encapsulation of small RNAs [3,4,5,6] and chemotherapeutic drugs such as doxorubicin [7,8,9] Such advancements have considerable implications since they could provide a means of improving the penetration of approved chemotherapeutics within the densely packed extracellular matrix of solid tumours, where a recent metaanalysis has highlighted that only 0.7% penetration is achieved using conventional synthetic nanoparticle systems.[10] The emergence of EV DDS has considerable implications for the delivery of high molecular weight biological drugs such as proteins, peptides or RNA therapies, which account for over 93% of net drug spending at a global level.[11] These therapies are currently administered parenterally, with short plasma half-lives and poor patient compliance often resulting from the required frequency of administration. These include: Variations in EV starting material – typically assessed by total protein concentration, sample volume or particle number
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
