Engineered extracellular vesicles: From design strategies to therapeutic applications

Extracellular vesicles (EVs) are nanoscale, lipid bilayer-enclosed particles released by a wide range of cell types that facilitate intercellular communication by transporting bioactive cargoes such as proteins, lipids, and nucleic acids. Owing to their biocompatibility, low immunogenicity, and intrinsic tropism, EVs have been widely investigated as potential carriers for therapeutic delivery. However, the clinical translation of native EVs remains hindered by limited drug-loading efficiency, suboptimal targeting specificity, and persistent challenges in scalable manufacturing and robust standardization. Recent advances in bioengineering and nanotechnology have enabled the development of engineered EVs with enhanced therapeutic performance. Through direct modification or genetic engineering of parental cells, EVs can be customized to efficiently encapsulate therapeutic cargo, display targeting ligands, and respond to disease-specific microenvironments. These engineering strategies significantly improve drug delivery efficiency, tissue specificity, and biological functionality while maintaining structural integrity and biocompatibility. Engineered EVs have demonstrated great potential in diverse biomedical applications, including cancer, respiratory infectious diseases, neurological disorders, and autoimmune diseases. We highlight the advantages associated with EVs derived from different cellular sources and analyze how these unique properties influence their performance in diverse disease contexts, and discuss the key challenges and future opportunities for their clinical translation in precision medicine.