Emerging Plant-Derived Exosome-Like Particles Reveal Key Therapeutic Benefits. A Comprehensive Review of Evidence

Jia Chi,1,* Xubo Wang,1,* Yanrui Song,1 Jiazhi Wang,1 Lin Guo,1 Rui Wang,2,3 Guangzhi Wang1 1Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, 116023, People’s Republic of China; 2Department of Oncology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430065, People’s Republic of China; 3Department of Oncology, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, 430061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rui Wang, Department of Oncology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430065, People’s Republic of China, Email [email protected] Guangzhi Wang, Department of General Surgery, The Second Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian, Liaoning, 116023, People’s Republic of China, Tel +86-411-84671291-5277, Email [email protected]: Plant-derived exosome-like nanoparticles (PELNs) are lipid bilayer-enclosed nanoscale vesicles isolated from plant cells, harboring a diverse cargo such as RNAs, proteins, lipids, and biologically active constituents. Increasing evidence indicates that PELNs can efficiently enter mammalian cells through multiple uptake pathways, including phagocytosis, clathrin/caveolin-mediated endocytosis, and macropinocytosis. In recent years, they have emerged as highly promising nanocarriers for targeted drug delivery, disease diagnosis, and therapeutic intervention. This review provides a systematic overview of the therapeutic applications of PELNs across various diseases and the signaling mechanisms involved, while briefly outlining their isolation and characterization to provide essential research background. Despite remarkable advancements, the field still has several challenges, including protocol standardization, precise marker identification, biological stability, and refinement of targeted delivery strategies. Nevertheless, owing to their intrinsic properties, such as low cytotoxicity, high biocompatibility, inherent targeting capacity, minimal immunogenicity, and surface modifiability, PELNs hold considerable promise as next-generation delivery vectors. Future investigations will likely focus on refining manufacturing processes, elucidating PELN-associated molecular mechanisms, and engineering more advanced delivery systems designed for clinical translation.Keywords: plant-derived exosome-like nanoparticles, extracellular vesicles, drug delivery, signal transduction pathways, therapeutic applications