Precision inflammation targeting via myeloperoxidase mediated antioxidant melanin nanomedicines for chronic inflammation therapy.

Chronic inflammation represents a great threat to human health, yet the lack of site-specific therapies often leads to suboptimal efficacy and serious side effects. Here we report an inflammatory targeting strategy leveraging myeloperoxidase (MPO), a well-established pathological marker elevated in inflamed tissues, mediated accumulation of melanin nanomedicines (MNMs) in inflammatory tissues. We demonstrate that MPO mediates the precise targeting of MNMs to inflammatory tissues. MNMs treatment significantly improved survival rate of hepatopulmonary syndrome (HPS) rat model compared with the standard antioxidant N-acetylcysteine (NAC) and the Tumor Necrosis Factor-α (TNF-α) monoclonal antibody Infliximab. Meanwhile, this strategy also demonstrated robust therapeutic efficacy in the mouse model of chronic inflammatory bowel disease (IBD), highlighting its broad potential for managing chronic inflammatory conditions. The MNM platform is amenable to the loading of additional therapeutic agents for synergistic effects. Our work establishes an MPO-mediated nanomedicine targeting strategy that may serve as a blueprint for developing next-generation precision anti-inflammatory therapies.