From Uptake to Therapeutic Function in Engineered Exosome Delivery Systems.

Engineered exosomes are increasingly recognized as promising vehicles for precision drug delivery. Genetic display, chemical modification, physical loading, and hybrid vesicle construction have expanded their applications, while introducing additional variables to the interpretation of delivery outcomes. Because engineering can alter vesicle properties, receptor engagement, endocytic routing, intracellular trafficking, and functional readouts, tissue accumulation or cellular uptake alone is insufficient to define effective delivery. This review traces engineered exosome delivery from cellular uptake to therapeutic function, covering engineering strategies, targeting validation, endocytic routing, intracellular fate, and functional readouts. We further discuss the strengths and limitations of commonly used evaluation methods. Across biomedical applications, we emphasize that delivery evidence should be judged according to cargo type, site of action, disease model, and therapeutic mechanism. By linking engineering design, assay selection, and evidence strength, this review supports a more careful interpretation of engineered exosome delivery.