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

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 develop new biomimetic membrane-modified nanomaterials with targeting capability. This biomimetic membrane grants the nanodrug immune evasion capability, while hyaluronic acid ensures precise targeting to plaque sites. studies revealed that the nanomaterials can accurately target the CD44 receptor, which is highly expressed on macrophages within plaques. More importantly, the sustained and stable release of the two drugs could promote cholesterol efflux and reduce lipid deposition by activating the LXRα-mediated ABCG1, ABCA1/SR-B1 signaling pathway. Meanwhile, these nanomaterials could activate Parkin-mediated autophagy, ameliorate damaged mitochondria and inhibit the production of ROS. 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 the biomimetic nanomaterials possess a potential capability to safeguard against the advancement of AS.