“…In the pathological setting, many EVs are playing the role of villains, exacerbating the hostile environment of the disease. For example, in a mouse model of TBI, EVs are significantly increased in the peripheral blood, and highly express pro-coagulant TFs on their surface and carry various inflammatory mediators, such as inflammatory vesicles, to amplify the inflammatory response, leading to lung epithelial cell death and blood-gas barrier disruption, and even affecting coagulation [ 70 ], In addition, brain-derived EVs activate leukocytes and platelets in the induction of systemic coagulation disorders after TBI and inflammation [ 71 , 72 ]; in epileptic mechanisms, it was found that epileptogenic neuron-derived EVs carrying miR-181c-5p reduced glutamate uptake capacity of astrocytes and promoted susceptibility to epilepsy [ 73 ]. Therefore, before selecting EVs as drug carriers, the source of EVs and the physiological and pathological environment of the animal model must be considered; EVs from different sources have different biological functions and targeting sites, which will affect the efficiency of drug delivery.…”