Innovation of plant‐derived extracellular vesicles and interdisciplinary research: From discovery to biomedical applications

Abstract

Extracellular vesicles (EVs) are double‐membrane vesicular structures that can be secreted by nearly all living cells. These vesicles serve as “carriers” enabling the intercellular transport of membrane‐bound and soluble proteins, lipids, and RNA. Hence, EVs mediate the transfer of bioactive substances between different cells, playing a crucial role in intercellular communication. In particular, plant‐derived EVs (P‐EVs) have garnered significant attention in recent years due to their wide availability, excellent biocompatibility, inherent stability, low immunogenicity, and non‐toxicity. The potential of P‐EVs as natural therapeutic agents and drug delivery vehicles has been increasingly recognized, offering promising therapeutic avenues for various diseases. In this article, we first discuss the nomenclature of P‐EVs. We then review current strategies for their isolation and characterization as well as properties and biosafety profiles. Given the unique morphology and rich content of bioactive molecules present in these natural nanocarriers, we also summarize recent advances in the engineering and functional modification of P‐EVs, their application as delivery vehicles, and their therapeutic effects in disease models. Furthermore, we review the latest developments in patents and clinical research related to P‐EVs. Finally, we highlight the current limitations and challenges hindering the clinical translation of P‐EVs, including the need for improved isolation and purification methods, comprehensive physicochemical assessments, stringent quality control, safety assessments, delivery route optimization, and in‐depth pharmacodynamic and mechanistic analyses. We hope that this review will provide reference points and guidance for researchers in this field, thereby promoting further advances in P‐EVs research.