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

作者：Haiqin Yang, Mengcheng Guo, Qingran Guan, Lixue Zhang, Manqiang Liu, Haoyu Li, Guanyu Qiao, Qingbiao Yang, Meili Shen, Yapeng Li · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03232-1 · 被引用次数：12 · 研究领域：Nanoparticle-Based Drug Delivery、Nanoplatforms for cancer theranostics、Metal-Organic Frameworks: Synthesis and Applications

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.