Dual‐Function Plant‐Derived Nanovesicles From Regenerated Cannabis sativa Roots for Immunotherapy and Vaccine Delivery

作者：Su Hyun Park, Han‐Gyu Choi, Zhun Li, Yun Hye Kim, Hyeon Jin Lee, Ki‐Won Shin, Hwa‐Jung Kim, Hyung‐Jun Kwon, Gimoon Seo, Jae Cheol Jeong, Young Bae Ryu, Woo Sik Kim · 发表于：Journal of Extracellular Vesicles · 年份：2025 · DOI：10.1002/jev2.70206 · 被引用次数：4 · 研究领域：Transgenic Plants and Applications、Immunotherapy and Immune Responses、Tryptophan and brain disorders

ABSTRACT Cannabis sativa is a medicinal plant that produces a diverse array of pharmacologically active metabolites, making it a valuable resource for pharmaceutical applications. In this study, an adventitious root (AR) culture system was established from C. sativa using two representative plant growth regulators—naphthaleneacetic acid (NAA; hereafter referred to as N‐ARs) and indole‐3‐butyric acid (IBA; hereafter referred to as I‐ARs) —from which plant‐derived nanovesicles (PDNVs) were subsequently isolated (hereafter N‐PDNVs and I‐PDNVs, respectively). The resulting N‐PDNVs and I‐PDNVs exhibited average diameters of 128 ± 2 and 124 ± 4 nm, respectively, with zeta potentials of −12.9 and −15.7 mV. Both PDNV types maintained structural integrity and colloidal stability under diverse external stress conditions, underscoring their physicochemical robustness. Metabolite profiling of PDNVs revealed 25 distinct metabolites. Functionally, I‐PDNVs markedly enhanced dendritic cell maturation through Toll‐like receptor 2 (TLR2)‐ and TLR4‐dependent pathways, promoted T cell proliferation and activation (notably IFN‐γ‐ and IL‐17A‐producing subsets), and increased natural killer (NK) cell activity compared with N‐PDNVs. In immunosuppressed and tumour‐bearing mouse models, I‐PDNVs further augmented NK cell, Th1 and cytotoxic T lymphocyte (CTL) responses, thereby confirming their superior potential as immunotherapeutic agents. Moreover, in immunized mouse models, OVA 257‐264 ‐encapsulated...