Engineered extracellular vesicles for drug delivery in hepatocellular carcinoma

The high heterogeneity and immunosuppressive microenvironment of hepatocellular carcinoma (HCC) pose significant challenges to existing therapies. Extracellular vesicles (EVs) are natural nanocarriers with relatively low immunogenicity and intrinsic barrier-crossing capabilities, and they show potential as HCC biomarkers and therapeutic delivery vehicles. However, their clinical utility is severely hindered by low drug loading efficiency, poor targeting specificity, and a lack of scalable and standardized manufacturing protocols. This review briefly outlines the fundamental roles of EVs in HCC diagnosis, prognosis, and therapy, and then focuses on engineering strategies designed to overcome these inherent limitations. Furthermore, it critically evaluates the opportunities and barriers to the clinical translation of EV-based therapies for HCC, aiming to provide a translational framework for developing EVs into next-generation precision medicine platforms for HCC. This review integrates bioengineering advances with regulatory and clinical translation considerations. The available evidence suggests that the clinical future of engineered EVs depends less on maximal multifunctionality and more on scalable manufacturing, reproducible quality control, and clearly defined therapeutic mechanisms.