%0 Journal Article %T Unignored intracellular journey and biomedical applications of extracellular vesicles. %A Zhao J %A Zhu W %A Mao Y %A Li X %A Ling G %A Luo C %A Zhang P %J Adv Drug Deliv Rev %V 0 %N 0 %D 2024 Jul 3 %M 38969268 %F 17.873 %R 10.1016/j.addr.2024.115388 %X The intracellular journey of extracellular vesicles (EVs) cannot be ignored in various biological pathological processes. In this review, the biogenesis, biological functions, uptake pathways, intracellular trafficking routes, and biomedical applications of EVs were highlighted. Endosomal escape is a unique mode of EVs release. When vesicles escape from endosomes, they avoid the fate of fusing with lysosomes and being degraded, thus having the opportunity to directly enter the cytoplasm or other organelles. This escape mechanism is crucial for EVs to deliver specific signals or substances. The intracellular trafficking of EVs after endosomal escape is a complex and significant biological process that involves the coordinated work of various cellular structures and molecules. Through the in-depth study of this process, the function and regulatory mechanism of EVs are fully understood, providing new dimensions for future biomedical diagnosis and treatment.