Targeting Extracellular Vesicles to Dendritic Cells and Macrophages

Abstract

Targeting protein therapeutics to specific cells and tissues is a major challenge in modern medicine. Improving the specificity of protein therapeutic delivery will significantly enhance efficiency in drug development. One of the promising tools for protein delivery is extracellular vesicles (EVs) that are enveloped by a complex lipid bilayer. EVs are secreted by almost all cell types and possess significant advantages: biocompatibility, stability, and the ability to penetrate the bloodbrain barrier. Overexpression of the vesicular stomatitis virus protein G (VSV-G) was shown to promote EV formation by the producer cell. We have developed an EV-based system for targeted delivery of protein cargoes to antigen-presenting cells (APCs). In this study, we show that attachment of a recombinant llama nanobody -CD206 to the N-terminus of a truncated VSV-G increases the selectivity of EV cargo delivery mainly to APCs. These results highlight the outstanding technological and biomedical potential of EV-based delivery systems for correcting the immune response in patients with autoimmune, viral, and oncological diseases.

Strategies for Engineering of Extracellular Vesicles

“…The authors demonstrated that the attachment of a recombinant llama nanobody α-CD206 to the N-terminus of the truncated VSV-G glycoprotein increased the selectivity of EV cargo delivery, mainly to APCs. This strategy is supposed to be used in the development of drugs for the correction of the immune response in patients with autoimmune, viral, and oncological diseases [37].…”

Extracellular Vesicles in Amyotrophic Lateral Sclerosis

“…Some studies have shown that EVs are taken up by any cell to which they are exposed [ 41 , 43 ]. However, EV uptake can also be a highly specific process requiring the expression of specific surface markers and ligands [ 44 , 45 , 46 ].…”