Beyond drug delivery: nanoparticles as active modulators of immunometabolism for treating inflammatory diseases

Immunometabolism is central to chronic inflammatory diseases, with metabolic reprogramming including dysregulated glycolysis, mitochondrial dysfunction and excessive reactive oxygen species (ROS) production driving pathology in conditions like inflammatory bowel disease (IBD), rheumatoid arthritis and psoriasis. Although metabolic regulators hold therapeutic promise, their efficacy is limited by poor site-specific delivery and bioavailability. Nanotechnology-based platforms (e.g. liposomes, polymeric nanoparticles (NPs), nanoemulsions and metal NPs) address these barriers by enhancing bioavailability and forming a protein corona that modulates NP uptake by macrophages and T cells, directly influencing metabolic fate. Advanced organelle-targeting strategies such as mitochondria-directed liposomes and lysosome-responsive polymers enable precise metabolic rescue by restoring mitochondrial respiration or modulating nutrient-sensing pathways. By targeting key metabolic nodes including HIF-1α, mTOR and AMPK, nanocarriers actively shift immune cells from pro-inflammatory glycolysis towards anti-inflammatory oxidative phosphorylation, minimising toxicity and restoring immune homeostasis. Thus, nanocarriers function not as passive delivery vehicles but as sophisticated immunometabolism modulators. Despite progress, a comprehensive review bridging nanomaterial design and metabolic intervention remains lacking. This review addresses that gap by highlighting nanoscale phenomena such as stimulus-responsive release, membrane perturbation and organelle-specific targeting.