MPO Mediated Precise Inflammation Targeting of Antioxidant Melanin Nanomedicines as an Effective Therapeutic Strategy for Chronic Inflammation

Abstract Inflammation is the greatest threat to human health. Anti-inflammatory treatments are not always effective and can cause serious side effects. There is a critical need for anti-inflammatory drugs that are selective for inflammatory tissue over normal tissue, as well as for single inflammatory factor (or pathological factor) over broad-spectrum anti-inflammatories. Here we report a strategy for targeting inflammation by myeloperoxidase (MPO) mediated melanin nanomedicines (MNMs). Elevated MPO levels in blood and inflammatory tissues are significant pathological markers of numerous inflammatory diseases. We found for the first time that MPO could bind to MNMs with high specificity and mediate the specific entry of MNMs into inflammatory tissues. MNMs were composed of eumelanin, a natural antioxidant substance in the human body that eliminates a variety of reactive oxygen species (ROS). MNMs inhibited oxidative stress damage mediated by a variety of inflammatory factors or pathology, breaking the vicious cycle of inflammation and oxidative stress in inflammatory tissues. With hepatopulmonary syndrome (HPS, a complex inflammatory syndrome driven by multiple pathological factors) as an example, the powerful anti-inflammatory therapeutic effect of this strategy was verified, which could significantly inhibit the progression of HPS. This highly targeted strategy can serve as a blueprint for the development of other highly specific targeted anti-inflammatory treatments.