Plant exosomes as multifunctional platforms for metabolic targeting and drug delivery in cancer therapy

Plant-based extracellular vesicles (Ph-EXs) represent an innovative new approach for targeting cancer, as they combine natural anti-cancer activity with an advanced ability to deliver drugs. Ph-EXs have direct killing activity against cancer cells through different mechanisms, including the initiation of apoptotic pathways, inhibition of cell growth signals, alteration of the metabolism of cancer cells, and overcoming the effects of drug resistance. Ph-EXs have the ability to alter immune cells' programming, modify cancer-associated fibroblasts, and change the composition of the microbiome, impacting the tumor microenvironment as well as contributing to tumor formation. Additionally, Ph-EXs can cross biological barriers (specifically across the blood-brain barrier) and, due to their lower costs in comparison with other anti-cancer drug delivery methods, present a feasible alternative to synthetics. Ph-EXs have been developed with many engineering efforts, including novel ways to load therapeutic agents onto exosomes as well as surface functionalization. There are several challenges associated with translating Ph-EXs into the clinical setting; these include: potential variability in effect depending on the botanicals they were extracted from, standardization of extraction and characterization methods, and regulatory obstacles for clinical implementation. This review identifies critical knowledge gaps and proposes priority research directions to advance Ph-EX-based platforms toward clinical use.