Extracellular Vesicles as Promising Carriers in Drug Delivery: Considerations from a Cell Biologist’s Perspective

SIMPLE SUMMARY: Extracellular vesicles are promising nanocarriers of active pharmaceutical ingredients in precision medicine. However, to develop safe and effective extracellular vesicles-based therapies, it is crucial to gain fundamental knowledge on key cell biology mechanisms governing the extracellular vesicles-mediated cell-cell exchange of macromolecules. In this review, we present five aspects we believe are worth taking into account before considering extracellular vesicles as candidate vectors of pharmaceutical ingredients in cell-free therapies. ABSTRACT: The use of extracellular vesicles as cell-free therapy is a promising approach currently investigated in several disease models. The intrinsic capacity of extracellular vesicles to encapsulate macromolecules within their lipid bilayer membrane-bound lumen is a characteristic exploited in drug delivery to transport active pharmaceutical ingredients. Besides their role as biological nanocarriers, extracellular vesicles have a specific tropism towards target cells, which is a key aspect in precision medicine. However, the little knowledge of the mechanisms governing the release of a cargo macromolecule in recipient cells and the Good Manufacturing Practice (GMP) grade scale-up manufacturing of extracellular vesicles are currently slowing their application as drug delivery nanocarriers. In this review, we summarize, from a cell biologist’s perspective, the main evidence supporting the role of extracellular vesicles as promising carriers in drug delivery, and we report five key considerations that merit further investigation before translating Extracellular Vesicles (EVs) to clinical applications.