Co-Delivery of Renal Clearable Cerium Complex and Synergistic Antioxidant Iron Complex for Treating Sepsis

The mononuclear phagocytic system clears the circulating inorganic nanomaterials from the bloodstream, which raises concerns about the chronic toxicity of the accumulated metal species. A better understanding of the behavior of each metal after systemic injection is thus required for clinical translations. This study investigates the significance of the metal-ligand interaction on the accumulation of cerium and demonstrates that only the form in which cerium is coordinated to a multidentate chelator with a strong binding affinity does not accumulate in major organs. Specifically, cerium complexed with diethylenetriamine pentaacetic acid (DTPA) forms renally excretable nanoparticles in vivo to circumvent the leaching of cerium ions, whereas weakly coordinated cerium-based nanomaterials produce insoluble precipitates upon encountering physiological phosphate anions. Ceria-based renally cle…