Milk-derived extracellular vesicles: nutritional significance, nano-delivery potential, and emerging therapeutic applications - an updated review

Milk-derived extracellular-vesicles (mEVs) have emerged as a promising natural nanocarriers for nutraceutical and therapeutic applications, owing to their rich cargo of bioactive proteins, lipids, microRNAs, and metabolites, coupled with their inherent biocompatibility and stability. Their unique ability to withstand gastrointestinal degradation and cross biological barriers, such as blood-brain-barrier, while eliciting minimal immunogenicity provide a distinct advantage over synthetic delivery systems. Furthermore, mEVs can also be engineered or enriched with functional molecules, enabling the targeted delivery of nutraceuticals, chemotherapeutic agents, anti-inflammatory compounds, and gene regulators. Growing evidence demonstrates their capacity to modulate immune functions, support gut integrity, mitigate oxidative stress, regulate inflammatory processes, and influence systemic metabolic and neurophysiological pathways. However, their translational potential, key challenges, including scale isolation, optimize cargo loading, and comprehensive functional characterization, still limit their broader application. This review summarizes the biological properties, isolation strategies, and therapeutic prospects of mEVs, emphasizing their dual role as nutrition component and precision delivery platforms. Additionally, this review enhances our understanding regarding the beneficial application of milk-EVs as a natural, nontoxic and efficient nutraceutical carrier for next-generation nutraceutical and biomedical innovations.