Plant-Derived Extracellular Vesicles and Their Exciting Potential as the Future of Next-Generation Drug Delivery

Abstract

Plant cells release tiny membranous vesicles called extracellular vesicles (EVs), which are rich in lipids, proteins, nucleic acids, and pharmacologically active compounds. These plant-derived EVs (PDEVs) are safe and easily extractable and have been shown to have therapeutic effects against inflammation, cancer, bacteria, and aging. They have shown promise in preventing or treating colitis, cancer, alcoholic liver disease, and even COVID-19. PDEVs can also be used as natural carriers for small-molecule drugs and nucleic acids through various administration routes such as oral, transdermal, or injection. The unique advantages of PDEVs make them highly competitive in clinical applications and preventive healthcare products in the future. This review covers the latest methods for isolating and characterizing PDEVs, their applications in disease prevention and treatment, and their potential as a new drug carrier, with special attention to their commercial viability and toxicological profile, as the future of nanomedicine therapeutics. This review champions the formation of a new task force specializing in PDEVs to address a global need for rigor and standardization in PDEV research.

Tomato-fruit-derived extracellular vesicles inhibit Fusobacterium nucleatum via lipid-mediated mechanism

“…PDEV are regarded as safe and amenable to straightforward extraction, their preventive or therapeutic potential encompasses a wide spectrum. 43 Notably versatile, PDEV serve as carriers for small-molecule drugs and nucleic acids, amenable to diverse administration routes. The distinct advantages inherent to PDEV position them as compelling contenders for future clinical applications and proactive healthcare solutions.…”

“…The distinct advantages inherent to PDEV position them as compelling contenders for future clinical applications and proactive healthcare solutions. 43 This study into tomato-derived EV and their impact on gut health has indeed opened up new avenues for understanding the potential role of natural sources, such as edible plants, in modulating human health. The intricate interactions between PDEV and the gut microbiota offer a novel perspective on the connection between dietary components and microbiome dynamics, potentially reshaping how we perceive the influence of food on human well-being.…”

Edible Plant-Derived Extracellular Vesicles for Oral mRNA Vaccine Delivery

“…Nevertheless, the requirement for the stringent use of clean rooms under good manufacturing practice (GMP) conditions during the entire cell culture process, along with the required use of stringent sterile purification standards, are the major impediments to their use in clinical applications due to high cost and low productivity. Thus, for potential industrial use, the focus was turned to plant-derived EVs that due to already being present in nature are an extractive product and do not require cell culture [ 78 , 79 , 80 , 81 ]. Moreover, an additional cost reduction can be achieved through using the EVs purified from the juice of edible plants, such as orange juice, where EVs are particularly abundant.…”

“…The unique lipidic composition of plant-derived EV membranes confers high resistance to physical and chemical stresses. This makes them particularly suitable for engineering and drug loading for delivery purposes [ 79 ].…”

Engineered plant extracellular vesicles for natural delivery across physiological barriers

“…1 EVs can be divided into three categories based on production route and size: exosomes (50–150 nm), microvesicles (100–1000 nm), and apoptotic bodies (100–5000 nm). 2 EVs are mainly defined using the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines issued by the International Society for Extracellular Vesicles, given that there is no consensus on the specific surface markers of EVs. MISEV guidelines consider three main aspects: physical characteristics, biochemical components, and cell of origin.…”