Preparation, Characterization and Multiple Biological Properties of Peptide-Modified Cerium Oxide Nanoparticles

Although cerium oxide nanoparticles are attracting much attention in the biomedical field due to their unique physicochemical and biological functions, the cerium oxide nanoparticles greatly suffer from several unmet physicochemical challenges, including loss of enzymatic activity during the storage, non-specific cellular uptake, off-target toxicities, etc. Herein, in order to improve the targeting property of cerium oxide nanoparticles, we first modified cerium oxide nanoparticles (CeO₂) with polyacrylic acid (PAA) and then conjugated with an endothelium-targeting peptide glycine-arginine-aspartic acid (cRGD) to construct CeO₂@PAA@RGD. The physiochemical characterization results showed that the surface modifications did not impact the intrinsic enzymatic properties of CeO₂, including catalase-like (CAT) and superoxide dismutase-like (SOD) activities. Moreover, the cellular assay data showed that CeO₂@PAA@RGD exhibited a good biocompatibility and a higher cellular uptake due to the presence of RGD targeting peptide on its surface. CeO₂@PAA@RGD effectively scavenged reactive oxygen species (ROS) to protect cells from oxidative-stress-induced damage. Additionally, it was found that the CeO₂@PAA@RGD converted the phenotype of macrophages from proinflammatory (M1) to anti-inflammatory (M2) phenotype, inhibiting the occurrence of inflammation. Furthermore, the CeO₂@PAA@RGD also promoted endothelial cell-mediated migration and angiogenesis. Collectively, our results successfully demonstrate the promising application of CeO₂@PAA@RGD in the future biomedical field.