Cerium oxide caged metal chelator: anti-aggregation and anti-oxidation integrated H2O2-responsive controlled drug release for potential Alzheimer's disease treatment

Abstract

Metal ions play important roles in Aβ aggregate deposition and neurotoxicity which involves the formation of reactive oxygen species (ROS). Oxidative stress and metal dysregulation have been considered as therapeutic targets for AD. Herein, a novel double delivery platform has been presented by integrated anti-aggregation property of metal chelators and anti-oxidation property of CeO₂NPs in one system for Alzheimer's disease treatment. Compared with metal chelators or CeO₂NPs alone, a synergistic effect is observed in our H₂O₂-responsive controlled release system. So far, there is no report to use CeO₂NP as both capping and antioxidant agent for AD therapy. By taking advantage of good biocompatibility, high selectivity toward toxic metal ions, and their ability to cross the blood–brain barrier (BBB), the two-in-one bifunctional nanoparticles can effectively inhibit Aβ aggregate formation, decrease cellular ROS and protect cells from Aβ-related toxicity.