Advances in hybrid exosome-liposome nanoparticles for enhanced cancer therapy.

Exosomes, endogenous nanoscale vesicles secreted by various cell types, have emerged as promising natural carriers for therapeutic delivery due to their excellent biocompatibility, low immunogenicity, prolonged systemic circulation, and intrinsic ability to cross the blood-brain barrier (BBB). They can encapsulate diverse bioactive molecules-including nucleic acids, proteins, and small-molecule drugs-showing great potential in cancer therapy. However, their clinical translation remains hindered by low production yield and limited drug-loading capacity. To overcome these limitations, engineered approaches such as exosome-liposome fusion have been developed. This strategy integrates the biological targeting and membrane stability of exosomes with the tunable physicochemical properties of liposomes, resulting in hybrid exosome-liposome nanoparticles (HELNs) that exhibit improved stability, loading efficiency, and therapeutic performance. This review systematically summarizes the biological characteristics of exosomes from different cellular origins, current methodologies for HELNs fabrication, and their recent advances in drug delivery, gene therapy, and immunotherapy. Finally, the review highlights key advantages of this hybrid strategy for cancer theranostics and discusses ongoing challenges and future perspectives for large-scale production and clinical translation.