Vincenza Tinnirello

In the last years, the field of nanomedicine and drug delivery has grown exponentially, providing new platforms to carry therapeutic agents into the target sites. Extracellular vesicles (EVs) are ready-to-use, biocompatible, and non-toxic nanoparticles that are revolutionizing the field of drug delivery. EVs are involved in cell–cell communication and mediate many physiological and pathological processes by transferring their bioactive cargo to target cells. Recently, nanovesicles from plants (PDNVs) are raising the interest of the scientific community due to their high yield and biocompatibility. This study aims to evaluate whether PDNVs may be used as drug delivery systems. We isolated and characterized nanovesicles from tangerine juice (TNVs) that were comparable to mammalian EVs in size and morphology. TNVs carry the traditional EV marker HSP70 and, as demonstrated by metabolomic analysis, contain flavonoids, organic acids, and limonoids. TNVs were loaded with DDHD1-siRNA through electroporation, obtaining a loading efficiency of 13%. We found that the DDHD1-siRNA complex TNVs were able to deliver DDHD1-siRNA to human colorectal cancer cells, inhibiting the target expression by about 60%. This study represents a proof of concept for the use of PDNVs as vehicles of RNA interference (RNAi) toward mammalian cells.

The scientific community has become increasingly interested in plant-derived nanoparticles (PDNPs) over the past ten years. Given that they possess all the benefits of a drug carrier, including non-toxicity, low immunogenicity, and a lipid bilayer that protects its content, PDNPs are a viable model for the design of innovative delivery systems. In this review, a summary of the prerequisites for mammalian extracellular vesicles to serve as delivery vehicles will be given. After that, we will concentrate on providing a thorough overview of the studies investigating the interactions of plant-derived nanoparticles with mammalian systems as well as the loading strategies for encapsulating therapeutic molecules. Finally, the existing challenges in establishing PDNPs as reliable biological delivery systems will be emphasized.