Atom-Efficient Cerium-Based Molecular Cages as Biocompatible Reactive Oxygen Scavengers

The development of reactive oxygen species (ROS)-scavenging materials for biomedical applications has been constrained by the difficulty associated with achieving simultaneously broad-spectrum scavenging efficiency and acceptable biosafety. To date, ceria/nanoceria systems have been explored for this purpose; however, they suffer from limited cerium-atom utilization. Inspired by the atom-economy concept of single-atom catalysis, we report a cerium-based molecular-cage strategy for treating oxidative stress-driven atherosclerosis (AS). It involves mixed-valent cerium ions (Ce³⁺/Ce⁴⁺) that are stably confined within tailored molecular cages and that mimic the cooperation between oxygen vacancies and cerium redox cycling in CeO₂. This endows the four representative cages of this study with an ability to scavenge superoxide anion (O₂•^-), hydrogen peroxide (H₂O₂), and hydroxyl radical (•OH). Their catalytic function can be readily modulated through the ROS-responsive release of the molecular cages at local lesion sites. This capability was found to alleviate oxidative stress and associated inflammation, as inferred from the finding that a lead cerium cage incorporated into a biocompatible nanoparticle reduces the progression of AS in a mouse model. A reduction in plaque lipid deposition, macrophage accumulation, necrotic core formation, and MMP-9-associated matrix was seen.