Dark matter: Developing a new nanoantioxidant-based therapeutic system for the treatment of age-related macular degeneration

Excessive production of reactive oxygen and nitrogen species (RONS) leads to nonspecific inflammation and is a major cause of the pathogenesis of exudative and nonexudative forms of age-related macular degeneration (AMD). As a result, antioxidant therapy has been emerging as a promising means for the treatment and prevention of AMD. Nevertheless, antioxidant strategies have largely been unsuccessful for AMD treatment. Developing a more potent antioxidant that reaches its target, remains stable with specific RONS level regulation, and reduces treatment burdens would provide a foundation for the care and scientific understanding of using antioxidant therapies in AMD. To overcome these limitations, we developed a novel robust nanotechnology-mediated antioxidant strategy based on ceria-coated melanin-PEG nanoparticles (CMNPs) by taking advantage of their inherent antioxidant ability to autorenew cerium oxide nanoparticles (ceria) and their photoprotective role through scavenging a broad range of RONS of melanin. Our experiments demonstrate that CMNPs could relieve AMD-like pathology with long-term improvement and exhibited a significant synergistic effect in scavenging against multiple RONS compared to single-nanoantioxidant delivery. More importantly, CMNPs ensured autoregenerative properties, outperformed aflibercept, and relieved pathological damage in an AMD-like mouse model through a single-dose administration for up to three months. This study highlights a novel treatment targeted to preserve the RPE and photoreceptors in AMD as a monotherapy.