# Plant Extracellular Vesicles: Investigating Their Utilization as Beneficial Nutrients in Diet
## 5 Conclusions and Future Perspectives  
Extracellular vesicles play a key role in cell-signaling processes, in both intraspecies and interspecies communication. Besides mammalian cells, plants also produce and release vesicles rich in lipids, proteins, and nucleic acids that contribute to growth, response to environmental conditions, and defense against pathogens. Given the abundance of these natural molecules in diet, their role in regulating human body homeostasis has been widely investigated. Many efforts are underway to determine the most reliable method for isolating EVs, in terms of yield, purity, reproducibility, and cost-effectiveness. To date, differential ultracentrifugation is the method of choice concerning these parameters, although it has some limitations requiring expensive lab equipment and time-consuming. Aging and inflammation strictly depend on oxidative stress, and several molecules are important in preventing oxidation. In plants, a panoply of molecules with anti-oxidant properties are present, and the consumption of fruit is recommended in the diet. The lipid bilayer structure of plant-derived EVs protects powerful antioxidants in the vesicles that can be easily delivered. The antioxidant effect of P-EVs has great potential both in cosmetology and medicine. Moreover, P-EVs can be considered as ingredients in food with health benefits due to the possibility that plant-derived EVs can be taken up by intestinal epithelial cells and can exert beneficial healthy effects on the intestinal barrier (i.e., antioxidant protective properties), which in case of damage may lead to the pathogenesis of many chronic diseases. At the moment, P-EVs also represent an attractive alternative in nanosized drug delivery. P-EVs have the advantage over synthetic nanocarriers, such as liposomes and lipid nanoparticles, in that they can transport bioactive substances to the target site while being biocompatible, safe, and non-toxic. Issues about toxicity and immunogenicity, poor biodistribution, and costly production are the major limitations to the use of synthetic nanocarriers. Thus, the researchers have addressed their interest in the use of natural carriers, and several studies supported by ongoing clinical trials have supported mammalian-derived EVs as potential carriers. Unfortunately, the risk of immunogenicity, pathogen propagation, adverse genes or protein transmission renders the use of mammalian-derived EVs as very limited. In contrast to mammalian-derived EVs, plant-derived ones display important advantages: P-EVs do not harbor zoonotic or human pathogens [23], their natural provenance avoids adverse reactions; P-EVs are efficiently internalized by cells, are stable in the gastrointestinal environment, and specifically reach their target; and plants represent a cost-effective, sustainable and renewable resource for EVs [71]. Multiple studies have demonstrated the efficiency of P-EVs derived from grapefruit, ginger, bitter melon, and cabbage as carriers for paclitaxel, curcumin, doxorubicin, miRNA, methotrexate, fluorouracil, etc., as recently reviewed in [PERSON] et al. [11]. These properties are currently being exploited for the development of nanomedicine therapeutics. However, even with studies constantly emerging, the use of plant vesicles as therapeutic supplements requires further detailed analysis, in vivo studies, and clinical trials to better assess their long-term stability and effects. **Author Contributions:** [PERSON] and [PERSON] contributed to the conception of the manuscript. [PERSON] and [PERSON] wrote the first draft of the manuscript. [PERSON] and [PERSON] wrote sections of the manuscript and revised it critically. [PERSON] proofreads the manuscript. All authors have read and agreed to the published version of the manuscript. **Funding:** This research received no external funding. **Institutional Review Board Statement:** Not applicable. **Informed Consent Statement:** Not applicable. **Data Availability Statement:** Not applicable.