Engineered exosome-mimetic nanoparticles improve liver function in aged mice

In aged mice, systemic treatment with engineered exosome-mimetic lipid nanoparticles revitalized baseline liver function. Researchers developed the controllable nanotherapeutic to address the manufacturing bottlenecks and batch heterogeneity common to natural mesenchymal stem cell-derived exosomes. The synthetic platform employed a microfluidic procedure to standardize a ten-component core containing three master-regulatory microRNAs and seven functional proteins. In vitro and in vivo evaluations showed the nanoparticles had favorable biosafety, rapid hepatic internalization, and immunological inertness. Mechanistically, the therapy modulated collapsed mitochondrial energy networks, attenuated the senescence-associated secretory phenotype, and reduced age-related fibrotic architectures. The particles also remodeled the liver immune microenvironment, shifting macrophage populations toward a pro-resolving M2-like state and attenuating chronic inflammaging.