Ceria Nanoparticles as Copper Chaperones that Activate SOD1 for Synergistic Antioxidant Therapy to Treat Ischemic Vascular Diseases.

All exogenous nanomaterials undergo rapid biotransformation once injected into body and fall short of executing the intended purpose. Here we report that copper-deposited ceria nanoparticles (CuCe NPs) exhibit enhanced antioxidant effects than pristine ceria nanoparticles as the released copper buffers the depletion of glutathione while providing the bioavailable copper as a cofactor for the antioxidant enzyme, superoxide dismutase 1. The upregulated intracellular antioxidants along with ceria nanoparticles synergistically scavenge reactive oxygen species and promote anti-inflammation and M2 polarization of macrophages by modulating STAT1 and STAT6. The therapeutic effect of CuCe NPs is demonstrated in ischemic vascular diseases (i.e., murine models of hindlimb ischemia and myocardial infarction) in which the copper-deposition affords increased perfusion and alleviation in tissue damages. The results provide rationale that metal oxide nanomaterials can be designed in a way to induce the upregulation of specific biological factors for optimal therapeutic performance. This article is protected by copyright. All rights reserved.