Engineering exosomes to target cancer metastasis

As a nanoscale subset of extracellular vehicles, exosomes represent a new pathway of intercellular communication by delivering cargos such as proteins and nucleic acids to recipient cells. Importantly, it has been well documented that exosome-mediated delivery of such cargo is involved in many pathological processes such as tumor progression, cancer metastasis, and development of drug resistance. Innately biocompatible and possessing ideal structural properties, exosomes offer distinct advantages for drug delivery over artificial nanoscale drug carriers. Vanderbilt University researchers summarize recent progress in methods for engineering exosomes including isolation techniques and exogenous cargo encapsulation, with a focus on applications of engineered exosomes to target cancer metastasis.

Illustration of exosome engineering through parental cells (upper) and post isolation (lower)

Parental cells can be genetically modified to express desirable therapeutic protein or nucleic acids. Drugs can be encapsulated inside parental cells simply by coincubation or electroporation. The exosome surface can be modified with imaging or therapeutic molecules by chemistry or other conjugation methods. Hydrophilic drugs can be encapsulated inside exosomes via simple co-incubation or electroporation while hydrophobic drugs are inserted into the hydrophobic core of the lipid bilayer membrane of exosomes.