Bioengineered extracellular vesicles escape lysosomal degradation and deliver Tet-PKM2 for macrophage immunometabolic reprogramming and periodontitis treatment.

ABSTRACT: Modulating macrophage phenotype and function via immunometabolic reprogramming represents a new therapeutic paradigm to combat chronic inflammatory diseases such as periodontitis. Tetrameric pyruvate kinase M2 (Tet-PKM2), a highly active metabolic enzyme involved in the flux of glucose-derived carbons into the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS), was found to be dramatically decreased in response to inflammation, rendering a potential immunometabolic target for developping new therapeutics. Hence, we report a large extracellular vesicle (LEV) that is bioengineered to intracellularly deliver Tet-PKM2 for the reprogramming of proinflammatory macrophages and the restoration of their aberrant immunometabolism. We engineered Tet-PKM2-enriched LEVs modified by t

SUBMITTER: Zhang WJ 

PROVIDER: S-EPMC12808913 | biostudies-literature | 2026 May

REPOSITORIES: biostudies-literature