Exosome engineering: Current progress in cargo loading and targeted delivery

Exosomes, a class of small bilayer vesicles derived from virtually all eukaryotic cells, have been exploited as a promising natural delivery platform due to their low toxicity, excellent structural stability, nanoscale size, cargo loading ability, and editable surface structure. To load therapeutic or diagnostic cargos (drugs, nucleic acids, proteins, peptides, and nanomaterials) into exosomes, multiple techniques have been developed, such as incubating cargos with exosomes or exosome-secreting cells, transfection, physical treatments (sonication, electroporation, extrusion, freeze-thaw, surfactant treatment, and dialysis), and in situ synthesis. Moreover, homing-molecules with high receptor binding affinity, acidic milieu responsiveness, or magnetic properties have been assembled on exosomal surface by transfection or chemical modification, conferring the targeting capacity to exosomes. In this review, we summarize the biogenesis, contents and functions of natural exosomes, and provide a comprehensive discussion for the strategies of exosomal cargo loading and membrane modification for targeted delivery.