Plant vs mammal extracellular vesicles: new tools in therapeutic drug delivery

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The illustration reports the extracellular vesicle production from multiple biological substrates, including both animal- and plant-derived cells. After isolation and purification, EVs must be thoroughly characterised using physical, chemical, and biological approaches, a critical prerequisite for their therapeutic application. Once characterised, EVs can be functionalised by loading them with specific bioactive molecules. • Extracellular vesicles (EVs) are highly promising carriers for drug delivery. • EVs, naturally released by cells, can be classified into different types based on their origin, size and content. • Animal-derived EVs have been deeply characterised while Plant-derived EVs are gaining attention for properties in therapeutic applications. Extracellular vesicles (EVs) are highly promising biological carriers, due to their potential for drug delivery and their involvement in multiple cellular processes. These vesicles, released by cells into the extracellular space, can be classified into different types based on their origin, size, and molecular content. While animal-derived EVs have been extensively studied and characterised, recent research has highlighted the growing interest in plant-derived EVs, which present unique properties that could offer novel advantages in therapeutic applications. This review aims to provide an overview of similarities and differences between animal and plant-derived EVs, focusing on their structural and functional characteristics. Additionally, we report various methods used for the isolation and characterisation of these vesicles, to provide a comprehensive summary, highlighting the main challenges and opportunities of each experimental option. Moreover, the present work explores the most used techniques for loading bioactive molecules into EVs, transforming them from natural biological entities into innovative drug delivery systems. The ability to encapsulate drugs, small RNA molecules, or proteins within EVs opens up new frontiers for the targeted treatment of diseases, with particular emphasis on overcoming barriers related to drug bioavailability and specificity. Finally, this review stresses the importance of ongoing research in the extracellular vesicles field, from both animal and plant origins, given their adaptable properties to multiple pharmaceutical purposes. Plant-derived EVsoffer a sustainable and economic alternative, together with the better characterised mammalian vesicles, showing the potential to strongly improve the drug delivery strategy in the near future.

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