Differential fates of biomolecules delivered to target cells via extracellular vesicles

Significance Extracellular vesicle (EV)-mediated transfer of macromolecules may play a key role in cellular communication and may have utility in directed molecular therapies. In addition, the EV packaged biomolecules in serum may have potential for diagnosing cancer and determining its likelihood of metastasis. EVs are heterogeneous and there are many outstanding questions associated with biogenesis, uptake, and the fate of transferred molecules in recipient cells. In fact, the function, characterization, and even the nomenclature of EVs are being refined. Here we aimed to improve the functional characterization of EVs, and observed that only microvesicles (MVs), but not exosomes, can functionally transfer loaded reporter molecules to recipient cells, largely by delivering plasmid DNA. Our data show that exosomes and MVs are structurally and functionally distinct.