Liposome–extracellular vesicle hybrid nanocarriers: design principles, interfacial properties and translational perspectives

Liposome-extracellular vesicle (EV) hybrid nanocarriers have emerged as a versatile strategy to integrate the physicochemical tunability of synthetic liposomes with the biological functionality of EV membranes. However, a materials-oriented understanding of how membrane fusion alters supramolecular organization and interfacial behavior remains insufficient. Despite extensive reports of enhanced drug loading, cellular uptake and therapeutic efficacy, systematic understanding of how membrane fusion alters interfacial properties and subsequent biological responses remains limited. Fusion-induced changes in lipid organization, membrane rigidity and protein distribution may significantly affect colloidal stability, receptor-mediated interactions and immune compatibility. This review provides a comprehensive overview of contemporary engineering strategies for liposome-EV hybrid systems, emphasizing the core design principles that govern their structural integrity, functional performance, and safety. By correlating membrane architecture with nano-bio interfacial dynamics, we propose a multidimensional evaluation framework that bridges physicochemical characteristics with biological outcomes. Ultimately, this analysis seeks to provide a roadmap for the rational engineering of hybrid vesicles, ensuring their enhanced clinical and translational relevance.