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Accumulating evidence has redefined IDD as an immune-mediated disorder characterized by the breakdown of immune privilege, infiltration of immune cells, and chronic sterile inflammation driven by innate immune pathways including NF-\u03baB and the NLRP3 inflammasome. Current management strategies, including conservative care and surgery, primarily alleviate symptoms but fail to halt disease progression, while biological therapies are often costly. There is a pressing need for effective, accessible interventions. Plant-derived extracellular vesicle-like nanoparticles (PELNs) present a promising alternative. Rich in bioactive components, PELNs have demonstrated pleiotropic benefits in various diseases by exerting anti-inflammatory, antioxidant, and extracellular matrix (ECM)-enhancing activities, and by inhibiting multiple modes of programmed cell death, including apoptosis, pyroptosis, and ferroptosis. Notably, these nanoparticles act as multi-targeted immunomodulators capable of reshaping the local immune microenvironment\u2014suppressing pro-inflammatory cytokine cascades and dampening inflammasome activation, and shifting macrophage polarization from a pro-inflammatory M1 to a tissue-repair M2 phenotype. These multi-targeted mechanisms align closely with the complex pathophysiology of IDD. Although the direct application of PELNs for IDD remains largely unexplored, their mechanistic profile and inherent advantages position them as a novel and compelling therapeutic candidate to prevent or delay IDD. By targeting the core immunopathological drivers of disc degeneration, PELNs offer a unique opportunity to restore immune homeostasis within this otherwise privileged niche.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1871902","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:38:58Z","timestamp":1785389938000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Plant-derived extracellular vesicle-like nanoparticles: an emerging immunomodulatory strategy for intervertebral disc degeneration"],"prefix":"10.3389","volume":"17","author":[{"given":"Taobo","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Orthopedics, First Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]},{"name":"Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases","place":["Dalian, 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