Small molecule-assisted assembly of multifunctional ceria nanozymes for synergistic treatment of atherosclerosis

Abstract Considering that intravascular reactive oxygen species (ROS) and inflammation are two characteristic features of the atherosclerotic microenvironment, developing an appropriate strategy to treat atherosclerosis by synergistically regulating ROS and inflammation has attracted widespread attention. Herein, a special molecule, zoledronic acid, containing imidazole and bisphosphonate groups, was selected for the first time to assist the assembly of cerium ions and produce functionalized ceria-zoledronic acid nanocomposites (CZ NCs). It not only serves as a new carrier for different kinds of drugs (e.g. probucol, PB) but also exerts an efficient multienzyme activity to achieve collaborative therapy. More importantly, platelet membrane-coated biomimetic nanoplatform (PCZ@PB NCs) specifically accumulate at inflammatory atherosclerotic lesions, synergistically regulate ROS levels and inflammation, and efficiently inhibit foam cell formation. This novel assembly method can also be applied in the treatment of many other diseases associated with oxidative stress and inflammation.