Jae‐Kwang Yoo

Exosomes are cell-secreted nano-sized vesicles which deliver diverse biological molecules for intercellular communication. Due to their therapeutic potential, exosomes have been engineered in numerous ways for efficient delivery of active pharmaceutical ingredients to various target organs, tissues, and cells. In vivo administered exosomes are normally delivered to the liver, spleen, kidney, lung, and gastrointestinal tract and show rapid clearance from the blood circulation after systemic injection. The biodistribution and pharmacokinetics (PK) of exosomes can be modulated by engineering various factors such as cellular origin and membrane protein composition of exosomes. Recent advances accentuate the potential of targeted delivery of engineered exosomes even to the most challenging organs including the central nervous system. Major breakthroughs have been made related to various imaging techniques for monitoring in vivo biodistribution and PK of exosomes, as well as exosomal surface engineering technologies for inducing targetability. For inducing targeted delivery, therapeutic exosomes can be engineered to express various targeting moieties via direct modification methods such as chemically modifying exosomal surfaces with covalent/non-covalent bonds, or via indirect modification methods by genetically engineering exosome-producing cells. In this review, we describe the current knowledge of biodistribution and PK of exosomes, factors determining the targetability and organotropism of exosomes, and imaging technologies to monitor in vivo administered exosomes. In addition, we highlight recent advances in strategies for inducing targeted delivery of exosomes to specific organs and cells.

The extracellular vesicles (EVs) research area has grown rapidly because of their pivotal roles in intercellular communications and maintaining homeostasis of individual organism. As a subtype of EVs, exosomes are made via unique biogenesis pathway and exhibit disparate functional and phenotypic characteristics. Functionally, exosomes transfer biological messages from donor cell to recipient cell, which makes exosomes as a novel therapeutic platform delivering therapeutic materials to the target tissue/cell. Currently, both academia and industry try to develop exosome platform-based therapeutics for disease management, some of which are already in clinical trials. In this review, we will discuss focusing on therapeutic values of exosomes, recent advances in therapeutic exosome platform development, and late development of exosome therapeutics in diverse therapeutic areas.