Biomimetic membrane-coated nanoparticles for targeted synergistic therapy of homocysteine-induced atherosclerosis: Dual modulation of cholesterol efflux and reactive oxygen species scavenging

作者：Hanshuang Ding, Yi Liu, Tongtong Xia, Huiping Zhang, Yinju Hao, Bin Liu, Yideng Jiang · 发表于：Materials Today Bio · 年份：2025 · DOI：10.1016/j.mtbio.2025.101938 · 被引用次数：6 · 研究领域：Cholesterol and Lipid Metabolism、Lipoproteins and Cardiovascular Health、Cardiovascular Disease and Adiposity

Pharmacological intervention represents the most prevalent strategy for managing hyperhomocysteinemia- induced atherosclerosis (AS). However, conventional drugs are often hampered by the liver first-pass effect and limited targeted efficacy. To address these challenges, we exploited the cholesterol efflux-promoting effects of Atorvastatin and reactive oxygen species (ROS)-scavenging capacity of Astragaloside IV in plaque macrophages to innovatively develop a biomimetic membrane-modified targeted nanomaterials. This biomimetic membrane grants the nanodrug immune evasion capabilities, while hyaluronic acid ensures precise targeting to plaque sites. In vitro studies revealed that these nanomaterials can accurately target the CD44 receptor, which is highly expressed in macrophages within plaques. More importantly, the sustained and stable release of the nanomedicine could promote cholesterol efflux and reduce lipid deposition by activating the LXRα -mediated ABCG1, ABCA1/SR-B1 signaling pathway. Meanwhile, this nanomedicine could activate Parkin-mediated autophagy, ameliorate damaged mitochondria and inhibit the production of ROS. In vivo studies demonstrated that the nanomaterials significantly enhanced its half-life in the bloodstream and exhibited remarkable biological safety in the ApoE -/- mouse model. These findings indicate that this biomimetic nanomaterial possesses a potential capability to safeguard against the advancement of AS.