ROS-responsive simvastatin nano-prodrug based on tertiary amine-oxide zwitterionic polymer for atherosclerotic therapy

Abstract

Abstract Atherosclerosis (AS) is a major cause of cardiovascular disease and is characterized by high levels of reactive oxygen species (ROS) and lipid deposition. This study utilized ROS-responsive oxalate bonds to conjugate simvastatin (SV) and tertiary amine-oxide zwitterionic polymer (OPDH), resulting in the design of a ROS-responsive simvastatin nano-prodrug (OPDH-SV). In vitro experiments have proved that OPDH-SV has excellent stability and low toxicity, can effectively reduce intracellular ROS and lipid levels, and inhibit foam cells formation. In addition, OPDH-SV is able to achieve cell-to-cell transmission through the cell’s “endocytosis-efflux” mechanism and target mitochondria. In vivo experiments further confirmed the long-term circulation, targeted enrichment, and reduction of ROS and lipid levels of OPDH-SV in vivo. In summary, OPDH-SV has good biosafety and excellent in vivo therapeutic effect, and is expected to become a new type of anti-atherosclerotic nano-prodrug. Graphical Abstract Schematic diagram of OPDH-SV for the treatment of atherosclerotic plaques

Keywords

• Atherosclerosis
• Nano-Prodrug
• Active transcytosis
• Long-acting circulation
• ROS response