Organoid-Derived Extracellular Vesicles: From Biogenesis and Cargo Mechanisms Toward Therapeutic Applications.

Organoids are three-dimensional in vitro models that mimic the anatomical and functional complexity of biological tissues, evolving into a powerful platform for studying human development and disease. Organoid-derived extracellular vesicles have been revealed as important intercellular messengers within organoid systems. Participating in the transport of functional substances such as proteins, lipids, and nucleic acids, these lipid-coated nanometer-scale carriers play a role in regulating biological responses. Unlike extracellular vesicles derived from 2D culture, organoid-derived extracellular vesicles carry tissue-specific molecular information and offer unique advantages in terms of targeting precision and biocompatibility. Strategies for engineering organoid-derived extracellular vesicles-such as loading them with specific drugs, surface-modifying them with targeting ligands, or modulating the microenvironment governing vesicle secretion-are currently being extensively explored to enhance their therapeutic potential and targeting capabilities. At the same time, the specific genetic instructions carried by organoid-derived extracellular vesicles hold great promise for early disease diagnosis and prognosis assessment. However, urgent challenges remain, including the heterogeneity of organoids and their in vivo microenvironments, low efficiency in vesicle isolation and purification, and the lack of established standardized production and quality control systems. This paper focuses on two potential applications of organoid-derived extracellular vesicles: as novel therapeutic agents and as tools for improving disease models. It also explores their application prospects in targeted drug delivery, regenerative medicine, and biomarker identification, with the aim of providing insights and guidance for research on the use of organoid-derived extracellular vesicles as multifunctional platforms and carriers in precision medicine.