Therapeutic Mesoporous Cerium Oxide Nanoparticles for Modulating Excessive Oxidative Stress as a Treatment for Age-Related Macular Degeneration

Age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, is characterized by progressive visual impairment caused by destructive changes in the photoreceptor and retinal pigment epithelial cells (RPEs). Since reactive oxygen species (ROS) and chronic inflammation in the retina are believed to be essential contributors to AMD pathogenesis, the regulation of the ROS and inflammation levels may be effective therapeutic targets. As cerium oxide nanoparticles (CeNPs) have attracted attention due to good ROS scavenging activities mimicking the enzymatic activity of superoxide dismutase (SOD) and catalase, many researchers have studied to confirm the therapeutic efficacy of the CeNPs and apply these to treat clinical diseases in the biomedical fields. In addition, mesoporous materials have recently been spotlighted as versatile drug carriers and catalysts due to their high surface area and pore volume, therefore, some studies have been reported on the development of various forms of mesoporous CeNPs (mCeNPs). However, most of the previous reports have been derived from hydrothermal methods with harsh conditions, such as high pressure and temperature, and mainly focused on catalytic ability for industrial use, rather than biomedical applications. To combine the advantages of CeNPs and mesoporous materials, mCeNPs are simply synthesized by using the chemical reaction with 1,1′-carbonyldiimidazole and imidazole in acetone without the need for heating and pressurization. The mCeNPs exhibiting mesoporous structures with a pore size of 2.3 nm show good ROS scavenging properties, suitable biocompatibility for human RPEs and Raw264.7 cells (murine macrophage cells), and cytoprotective effect on RPEs against the harmful effect of high H₂O₂, as well as additional anti-inflammatory effects. In addition, the mCeNPs were intravitreally administrated to a NaIO₃-induced AMD mouse model, and the mCeNP-treated group showed a partial salvage effect of at least 14 % in outer nuclear layer (ONL) thickness, indicating that mCeNPs protected RPEs from NaIO₃ injury by exerting a disease-preventive effect. In addition, the drug-carrying capacity of mCeNPs was demonstrated by loading indomethacin (IDM) as a model drug, and IDM-loaded mCeNPs exhibited an additional 17.3% reduction in interleukin-6 levels in vitro compared to the group treated with mCeNPs alone, suggesting that a synergistic anti-inflammatory effect when an additional drug is loaded onto mCeNPs, thereby enhancing their therapeutic potential. These findings suggest that mCeNP can be a therapeutic alternative or adjuvant for the treatment of AMD.