Applies Enzymatic Glycan Engineering to Functionalize and Tag Extracellular Vesicles
This method for modifying extracellular vesicles combines enzymatic glycan engineering with chemoselective functionalization to unlock applications such as targeted drug delivery. Extracellular vesicles are lipid bilayer-enclosed nanoparticles secreted by cells, acting as important messengers and substance transporters between cells. However, they must be modified to carry special molecular markers and functional cargos for practical application. Although many different modification methods exist, such as introducing lipophilic molecules to the vesicle’s membrane, they are difficult to control and often inadvertently influence the membrane structure or other properties of extracellular vesicles. Glycans or carbohydrates are prevalent and exposed on the surface of extracellular vesicles, rendering them ideal facilitators for modifying extracellular vesicles.
Researchers at the University of Florida have developed a method using enzymatic reactions to modify the surface glycans of extracellular vesicles. By introducing functionalized sugar residues, they can label carbohydrates on the surface of extracellular vesicles and enable the attachment of various molecules, including affinity and fluorescent tags, ligands, antigens, antibodies, and drugs.
Application
Functionalizing extracellular vesicles for biomedical applications such as immunotherapy and targeted drug delivery
Advantages
- Functionalizes the surface of extracellular vesicles, imbuing the vesicles with valuable properties such as fluorescent tagging and selective binding
- Attaches functional groups to extracellular vesicles, utilizing glycans that are found in large quantities on the surface of extracellular vesicles
- Modifies extracellular vesicles, whose inherent biocompatibility, stability, and ability to cross biological barriers render them widely applicable as biomedical vectors
Technology
The basic objective of extracellular vesicle engineering is attaching functional groups to the surface of the extracellular vesicles. These functional groups serve diverse purposes such as labeling vesicles with specific tags, ligands, and antibodies for targeted drug delivery or cancer immunotherapy. The glycans coating extracellular vesicles provides a straightforward method to functionalization via enzymatic glycan engineering. The glycans serve as the attachment point for functionalization owing to their abundance and excellent locations on the extracellular vesicle surface and their flexibility as the first link in the functional chain. Accordingly, an unnatural sugar residue with an azide is enzymatically attached to the natural sugar residue, facilitating further modification with various molecules for biological applications. The enzyme that enters this functionalization is a glycosyltransferase, which catalyzes the formation of covalent bonds between sugars, called glycosidic bonds. This enzyme proves especially wide-reaching in its ability to introduce useful unnatural sugar residues into the glycan chains.
Brochure
