Cerium oxide nanoparticles for enhanced healing of diabetic foot ulcers

One of the main complications of diabetes is diabetic foot ulcers (DFUs), which have a substantial global impact on morbidity, medical expenses, and lower limb amputations. A complicated microenvironment-characterized by bacterial infections, chronic inflammation, oxidative stress, and poor angiogenesis impedes the healing process of DFUs. Cerium oxide nanoparticles (CeO₂ nanoparticles), owing to their antibacterial, anti-inflammatory, and antioxidant properties, have emerged as a promising treatment. These nanoparticles can scavenge reactive oxygen species (ROS), reduce inflammation, and stimulate tissue regeneration by modulating macrophage polarization and promoting angiogenesis. However, limitations such as poor biocompatibility, aggregation, and dose-dependent toxicity hinder their clinical application. Recent advances in coating strategies-including polymeric, natural biomolecule, and hybrid coatings have improved the stability, targeting, and controlled release of CeO₂ nanoparticles. This review discusses the design, therapeutic mechanisms, and safety considerations of coated CeO₂ nanoparticles in DFU treatment, with emphasis on combination therapies and smart-responsive coatings. Clinical translation challenges and future research directions are also addressed.