Stem Cell-derived Extracellular Vesicles: A Promising Nano Delivery Platform to the Brain?

A very important cause of the frustration with drug therapy for central nervous system (CNS) diseases is the failure of drug delivery. The blood–brain barrier (BBB) prevents most therapeutic molecules from entering the brain while maintaining CNS homeostasis. Scientists are keen to develop new brain drug delivery systems to solve this dilemma. Extracellular vesicles (EVs), as a class of naturally derived nanoscale vesicles, have been extensively studied in drug delivery due to their superior properties. This review will briefly present current brain drug delivery strategies, including invasive and non-invasive techniques that target the brain, and the application of nanocarriers developed for brain drug delivery in recent years, especially EVs. The cellular origin of EVs affects the surface protein, size, yield, luminal composition, and other properties of EVs, which are also crucial in determining whether EVs are useful as drug carriers. Stem cell-derived EVs, which inherit the properties of parental cells and avoid the drawbacks of cell therapy, have always been favored by researchers. Thus, in this review, we will focus on the application of stem cell-derived EVs for drug delivery in the CNS. Various nucleic acids, proteins, and small-molecule drugs are loaded into EVs with or without modification and undergo targeted delivery to the brain to achieve their therapeutic effects. In addition, the challenges facing the clinical application of EVs as drug carriers will also be discussed. The directions of future efforts may be to improve drug loading efficiency and precise targeting. Graphical Abstract