Engineering hybrid and synthetic extracellular vesicles for emerging biomedical applications

Naturally secreted extracellular vesicles (EVs) have attracted considerable interest as next-generation theranostic platforms because of their intrinsic biocompatibility, membrane complexity, and intercellular communication capabilities. However, their broader biomedical and translational applications remain limited by low production yields, heterogeneous quality, high manufacturing costs, and limited controllability in functional engineering. This mini-review highlights how hybrid and synthetic EV platforms are being developed to overcome these intrinsic barriers through scalable manufacturing and rational membrane engineering. We summarize emerging strategies for EV surface functionalization, including chemical modification, bioorthogonal conjugation, and metabolic engineering, which enable the modular installation of targeting ligands, imaging probes, and therapeutic moieties. We further discuss membrane-camouflaged nanosystems, in which engineered single or hybrid membranes are combined with functional nanomaterials to create multifunctional biomimetic nanoparticles with enhanced performance. These advances have broadened the potential applications of EV-based systems in drug delivery, cancer theranostics, immunotherapy, and other biomedical fields.