Applications of Cell Surface Engineering in Extracellular Vesicles

Extracellular vesicles, including exosomes, shuttle proteins and genetic information between cells and are recently regarded as a promising class of nanoparticles for biomedical applications. They are lipid-protein bilayer vesicular constructs secreted to the extracellular spaces by cells. All cells secrete extracellular vesicles as a regular biological process that appears to be conserved throughout the evolution. In the recent decades, extracellular vesicles have gained an important stand as vehicles enabling cell-to-cell transport and communication. Owing to the rich molecular cargo of extracellular vesicles and documented role in cellular communication, extracellular vesicles have been exploited as a versatile agent in the biomedical field.

Fig.1 The surface functionalization capsule. (Rayamajhi, 2020)

Applications of Cell Surface Engineered Extracellular Vesicles

• Targeted drug delivery

The surface molecules anchored on exosomes from different cell sources vary, which endows them with selectivity for specific recipient cells. Surface engineering aims to increase the local concentration of exosomes at the diseased site, thereby reducing toxicity and side effects and maximizing therapeutic efficacy. Therefore, surface engineering is widely used in targeted drug delivery. Indeed exosome surface molecules have been engineered to enhance the efficiency and sensitivity of the exosome-based delivery system. For instance, in one study, tumor targeting was facilitated by engineering the immature dendritic cells (imDCs) to express a well-characterized exosomal membrane protein (Lamp2b) fused to αv integrin-specific iRGD peptide (CRGDKGPDC). The results suggest that exosomes modified by targeting ligands can be used therapeutically for the delivery of doxorubicin to tumors, thus having great potential value for clinical applications.

Fig.2 Approaches for engineering exosomes displaying targeting ligands. (Liang, 2021)

• Tracking/imaging for diagnosis purpose

Imaging of extracellular vesicles, including exosomes, is a rapidly developing field that first of all allows diagnosis, monitoring, and prediction of cancer. The surface-modified exosomes have been effectively used to determine their in vivo biodistribution by performing exosome tracking studies. Tracking/imaging of exosomes in vivo helps in determining their applicability as site-specific delivery vehicles, their role in intercellular communication and their half-life. The data could help the researchers to optimize exosome-based formulation strategy at an early stage thereby reducing time, cost, and resources associated with the entire production process.

Biodistribution studies can be carried out by using exogenously or endogenously labeled exosomes. The selection of exosome imaging approaches, such as in vivo imaging system, microscopy, flow cytometry (FC), immunohistochemistry (IHC) and magnetic resonance, depend upon the labeling approach and the objective of each study. Optical imaging and radiolabelling are widely used techniques for carrying out imaging/trackin of exosomes. All of these techniques possess a distinct advantage that can be used as a criteria for the selection of labeling method depending on the purpose.

Extracellular vesicles can be functionalized with exogenous imaging and targeting moiety that allows for the target specificity and the real-time tracking of extracellular vesicles for diagnostic and therapeutic applications. Owing to the exosome’s strong correlation with disease progression, collecting exosomes from patients and amplifying the signal from the exosome cargo could enable new liquid biopsies. A promising strategy to develop personalized therapeutic carriers is through surface engineering the exosomes and hijacking their inherent messenger system. Creative Biolabs has organized a staff of outstanding scientists who have engaged in extracellular vesicle surface engineering research and project development for many years. Different strategies have been explored for extracellular vesicle surface engineering, including genetic engineering, covalent modification, non-covalent modification. If you are interested in our extracellular vesicles surface engineering service, please don't hesitate to contact us for more detailed information.

References

1. Rayamajhi, S.; Aryal, S. Surface functionalization strategies of extracellular vesicles. Journal of Materials Chemistry B. 2020, 8(21):4552-69.
2. Liang, Y.; et al. Engineering exosomes for targeted drug delivery. THERANOSTICS. 2021, 11(7):3183-95.