Isatis indigotica-derived exosome-like nanoparticles modulate macrophage polarization and inflammatory cytokine production through NF-κB inhibition

Exosome-like nanoparticles derived from Isatis indigotica (IID-ELNs) were isolated and characterized to assess their physicochemical properties and immunomodulatory functions. IID-ELNs exhibited a uniform cup-shaped nanoscale morphology, characteristic of lipid vesicles under transmission electron microscopy due to dehydration effects, and a relatively homogeneous size distribution as determined by nanoparticle tracking analysis. Macrophages efficiently internalized IID-ELNs, which suppressed lipopolysaccharide-induced M1 polarization, decreasing iNOS and TNF-α expression while increasing Arg1 and IL-10 levels. Flow cytometry confirmed macrophage phenotypic reprogramming. In vivo, intra-articular administration of IID-ELNs in a murine osteoarthritis model reduced synovial inflammation and tissue damage without detectable toxicity in major organs. These results demonstrate that IID-ELNs act as bioactive nanomaterials capable of modulating macrophage polarization, highlighting their potential as natural nanoplatforms for inflammatory microenvironment regulation.