Dark Matter: Developing a Nanoantioxidant-Based Therapeutic System for AMD
Detailed Non-Technical Summary
In Aim 1, we will focus on the antioxidative activity of ceria-coated melanin nanoparticles (CMNPs) in scavenging against multiple primary and secondary reactive oxide and nitrogen species (RONS), and demonstrate cytotoxicity and treatment efficacy using RONS-induced mouse primary retinal pigmented epithelial (mRPE) cells. In Aim 2, we will demonstrate that CMNPs ensure a long-term sustained release of antioxidants for neutralizing oxidative stress, and relieve pathological damages in an Nrf2-/- -CNV of new dry and a wet AMD-like mouse model through a single-dose intravitreal administration.
This work provides a strategy of combining melanin nanoparticles with traditional cerium oxide nanoparticles (ceria) for the treatment of AMD. The designed ceria-coated melanin nanoparticles (CMNPs) provide a powerful treatment option for oxidative stress-induced pathogenesis such as AMD by taking advantage of inherent antioxidant ability of melanin and ceria to create a unique synergistic approach. Our strategy will ensure the autoregenerative properties and more efficacious antioxidant activities of CMNPs for sustained therapy as robust reactive oxide and nitrogen species scavengers.
This novel strategy is designed to overcome both forms of wet and dry AMD. Our findings will add a new, potentially powerful treatment option for patients with AMD, and be used in treatments for several other diseases, such as neurodegenerative disorders and diabetic retinopathy, which have oxidative stress in common and are challenged by current standard approaches. The designed ceria-coated melanin nanoparticles (CMNPs) could function as an alternative to natural melanin in RPE cells, providing insight into future directions as a novel approach to overcome dysfunction of melanin.