Given the complex pathogenesis of skin diseases, current treatments are not always adequate or suitable for all patients. This highlights the necessity for a multi-target therapeutic nanoplatform. Owing to their intrinsic biological functions, exosomes have emerged as a promising transdermal drug delivery system. However, native exosomes face bottlenecks in drug loading efficiency, tissue specificity, and scalability. This article aims to review the advances in engineered exosomes, focusing on cargo engineering, surface engineering, and manufacturing engineering. We outline the methods and strategies deployed for encapsulating functional molecules into exosomes or remodeling vesicle interface properties, with particular attention to the advantages and disadvantages of different technologies employed for engineering exosomes. Through rational design, exosomes can be engineered to achieved precise targeting, controlled delivery, combination therapeutic effects, and scalable production. They exhibit therapeutic potential in refractory skin diseases, including psoriasis, atopic dermatitis, scleroderma, chronic wounds, and skin malignancies, but there are still challenges regarding clinical standardization and quality control. Overall, engineered exosomes represent a new type of nanotherapeutic platform in the field of transdermal drug delivery. Exosome-based drug formulations have the potential to serve as delivery vehicles with more predictable and reproducible therapeutic effects.
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