Extracellular Vesicles: A Review of Their Therapeutic Potentials, Sources, Biodistribution, and Administration Routes

Xiaorong Su,1,* Hongxiang Wang,2,* Qiubai Li,3,4 Zhichao Chen1 1Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Hematology, Key Laboratory for Molecular Diagnosis of Hubei Province, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, People’s Republic of China; 3Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 4Hubei Engineering Research Center for Application of Extracellular Vesicle, Hubei University of Science and Technology, Xianning, 437100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhichao Chen, Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email [email protected] Qiubai Li, Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email [email protected]: Extracellular vesicles (EVs) participate in intercellular communication and play an essential role in physiological and pathological processes. In recent years, EVs have garnered significant attention as cell-free therapeutic alternatives, vectors for drug and gene delivery, biomarkers for disease diagnosis and prognosis, vaccine development, and nutraceuticals. The biodistribution of EVs critically influences their efficacy and toxicity. Therefore, this review aims to discuss the main factors influencing the biodistribution of unmodified EVs, highlighting their distribution patterns, advantages, limitations, and applications under different routes of administration. In addition, we provide a comprehensive discussion of the currently available sources of EVs and summarize the current status of the therapeutic potentials of EVs. By optimizing administration routes and selecting appropriate EV sources, we aim to offer valuable insights to enhance the delivery efficiency and therapeutic efficacy of EVs to target tissues.Keywords: extracellular vesicles, administration routes, biodistribution, drug delivery