Edible source-derived exosome-like nanoparticles for hepatocellular carcinoma: mechanisms, engineering strategies, and translational challenges

Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality, and the development of safer and more effective delivery systems remains an important goal. Exosome-like nanoparticles (ELNs) from edible and medicinal sources, including medicinal plants and mammalian milk, have shown gastrointestinal stability, systemic absorption, hepatic enrichment, or therapeutic activity in selected preclinical models. However, these properties are source-, preparation-, route-, and model-dependent and should not be generalized to all edible ELNs. This structured narrative review critically evaluates evidence relevant to HCC by distinguishing: (i) direct anti-HCC studies; (ii) liver disease and gut-liver axis studies indirectly relevant to HCC prevention; and (iii) non-HCC cancer studies that provide mechanistic or engineering insights. We discuss apoptosis, cell-cycle regulation, ferroptosis, immune and gut-liver axis modulation, as well as biomimetic targeting, stimuli-responsive delivery, and theranostic applications. Particular attention is paid to context-dependent pro-metastatic signals reported for bovine milk-derived extracellular vesicles, critical quality attributes, scalable manufacturing, food-drug interactions, and regulatory uncertainty. Current evidence supports edible ELNs as promising but early-stage preclinical platforms; clinical translation for HCC will require standardized characterization, clinically relevant disease models, reproducible manufacturing, and prospective safety evaluation.