Research Progress of Grapefruit-derived Extracellular Vesicles in Anti-tumor Treatment

To date, the application of chemotherapy and gene therapy has improved the effectiveness and survival period of cancer patients. However, cancer remains a leading cause of death worldwide. Researchers have recognized the internal limitations of chemotherapy and gene therapy in anti-tumor treatment. Therefore, developing safe and effective delivery vehicles is crucial for overcoming the limitations. A variety of lipidstructured nano-vesicles, ranging from synthetic liposomes to biomimetic vehicles and natural membrane vesicles derived from mammalian cells, have been utilized as drug delivery systems (DDS) in anti-tumor treatment. However, due to factors such as yield, cost, safety, and ethical considerations, researchers are actively seeking optimal delivery vehicles. In recent years, there has been a growing interest in the research and therapeutic applications of plant-derived vesicles in anti-tumor treatment. Some plant-derived vesicles are known to have anti-tumor properties due to their unique bioactive compounds, and they can also serve as delivery vehicles of anti-tumor agents (e.g., drugs, siRNA, and functional exogenous proteins). Grapefruits, in particular, contain several phytochemicals, such as bergamottin, hesperidin, and naringenin, which contribute to their anti-tumor properties. Grapefruit-derived extracellular vesicles (GEVs) and the vesicles reassembled from their total lipids have demonstrated promise as both anti-tumor agents and as delivery systems for chemotherapy drugs and therapeutic genes in cancer research. This review will introduce the characteristics and anti-tumor properties of GEVs and their reassembled vesicles, as well as the research progress in anti-tumor treatment. Finally, we will discuss the challenges and prospects of GEVs and their reassembled vesicles in anti-tumor treatment.