Extracellular vesicles: powerful candidates in nano-drug delivery systems

Extracellular vesicles (EVs), which are nanoparticles that are actively released by cells, contain a variety of biologically active substances, serve as significant mediators of intercellular communication, and participate in many processes, in health and pathologically. Compared with traditional nanodrug delivery systems (NDDSs), EVs have unique advantages due to their natural physiological properties, such as their biocompatibility, stability, ability to cross barriers, and inherent homing properties. A growing number of studies have reported that EVs deliver therapeutic proteins, small-molecule drugs, siRNAs, miRNAs, therapeutic proteins, and nanomaterials for targeted therapy in various diseases. However, due to the lack of standardized techniques for isolating, quantifying, and characterizing EVs; lower-than-anticipated drug loading efficiency; insufficient clinical production; and potential safety concerns, the practical application of EVs still faces many challenges. Here, we systematically review the current commonly used methods for isolating EVs, summarize the types and methods of loading therapeutic drugs into EVs, and discuss the latest progress in applying EVs as NDDs. Finally, we present the challenges that hinder the clinical application of EVs.