Biodistribution of Exosomes and Engineering Strategies for Targeted Delivery of Therapeutic Exosomes

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. Researchers from ILIAS Biologics 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, they highlight recent advances in strategies for inducing targeted delivery of exosomes to specific organs and cells.

Targeting and biodistribution/PK analysis strategies of exosome therapeutics

Targeting of exosomes to specific organs or cells could be achieved via modification of the composition of exosomal membrane proteins including tetraspanins and integrins. Exosomal surface engineering by displaying targeting peptides conjugated with exosomal membrane-associated domains such as lysosome-associated membrane glycoprotein 2b (Lamp2b) or C1C2 domain of lactadherin (LA) is another approach for active tissue targeting. Both glycan and lipid compositions of exosomal membrane also contribute to the biodistribution of administered exosomes. Biodistribution/PK analysis of administered exosomes can be conducted via various exosome labeling methods (i.e., bioluminescence, fluorescence, and radio isotope-labeling methods)