Plant-Derived Exosomes Deliver Theranostic Molecules to Target Cells

More specific targeted drug delivery systems with low immunogenicity and toxicity are expected to increase the efficacy of therapeutic molecules. The extracellular nanovesicles have been introduced as natural delivery systems for therapeutic molecules. More recently, considerable interest has emerged in plant-derived exosomes and their natural commitment to deliver molecules of various origins. Acridine Orange (AO) is an acidophilic dye with a strong tumoricidal action following excitation with a light source at 466 nm, but its clinical use is limited by the potential systemic toxicity. In this study we investigated the ability of exosomes from Citrus Sinensis to be successfully uploaded with AO (Exo-AO). We also studied the ability of the exosomes to be uploaded into target cells, as compared to the free molecules. We found that AO was efficiently uploaded into exosomes through electroporation. In fact, Exo-AO entered into the target cells significantly better than the free molecules, leading to both a marked intracellular AO delivery into target cells and an increase in the cytotoxic effect after excitation under a fluorescence microscope. This study shows a promising new approach for a more effective and less toxic drug delivery through the use of plant-derived extracellular nanovesicles.