Longevity & AgingEngineered Vesicles Reprogram Macrophage Metabolism to Fight Chronic Inflammation
Researchers engineered large extracellular vesicles (LEVs) loaded with tetrameric pyruvate kinase M2 (Tet-PKM2) and coated with tannic acid to enable lysosomal escape in macrophages. In periodontitis patients, Tet-PKM2 was found to be dramatically reduced, correlating with aberrant glycolytic metabolism. The tannic acid coating enabled pH-responsive lysosomal disruption so the enzyme cargo reached the cytoplasm intact. In LPS-activated macrophages, treated vesicles restored TCA cycle activity, boosted mitochondrial oxidative phosphorylation, reduced pro-inflammatory cytokines, and shifted cells toward anti-inflammatory M2 phenotypes. In a mouse ligature-induced periodontitis model, the vesicles reduced bone loss and promoted periodontal tissue regeneration, demonstrating a new immunometabolic reprogramming strategy for chronic inflammatory disease.
