Manipulating the Production and Activity of Extracellular Vesicles as Delivery Carriers through Regulation of the External Environment: A Review

Extracellular vesicles (EVs) are emerging as drug nanocarriers that hold immense potential. However, the low yield and insufficient targeting as well as activity of natural EVs are important issues that future industrialization has to face. The engineering of EVs is an effective method to ameliorate these problems, but the applications are limited, forced by manufacturing costs and safety issues. Recent studies have shown that the biogenesis and molecular composition of EVs are very sensitive to the extracellular environment of parental cells, which is a novel and efficient strategy to enhance EV production and biological function. Therefore, this review summarizes the impact of the external environment, including cultural conditions, physical stimulation and molecular interference, on the production, biological activity and physiological properties of EVs. This regulating method not only causes less damage to parental cells and EVs but also is simpler and more convenient to operate. Additionally, we discuss the potential for therapeutic applications leveraging metabolic modulation to control extracellular vesicle production and function. It is significant to promote the large-scale production and clinical application of EVs.