Posted by Atherosclerosis (AS) has been considered a systemic disease characterized by the excessive generation of reactive oxygen species (ROS) and the accumulation of lipids within arterial walls. To increase ROS scavenging and cholesterol efflux, a ROS-responsive biomimetic nanoparticle drug delivery system (AtPCT/AM) was fabricated for the first time. Polypropylene glycol (PPG)-substituted hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared and ended with adamantane moieties and ROS cleavable tannic acid (TA), respectively, to form AtPCT. Thereafter, atorvastatin (ATV) was loaded into AtPCT via a self-assembly process to fabricate AtPCT/A nanoparticle. Macrophage membranes (MMs) were subsequently functionalized onto the surface of AtPCT/A (abbreviated as AtPCT/AM) to achieve active targetability via the homing effect. Following intravenous administration, AtPCT/AM demonstrated targeted accumulation within AS plaques and mediated ROS-triggered release of TA and HP-β-CD. TA scavenged ROS, while HP-β-CD precisely bound excess cholesterol to increase cholesterol efflux. Together with ATV-driven systemic lipid modulation, this engineered nano-delivery system significantly promoted plaque regression and attenuated AS progression, which provided a potential strategy for the treatment of AS.
Xiaofang Li, Min Liu, Jingwen Jia, Han Yang, Guanxin Zhao, Siyi Liu, Jingya Xiu, Dan Li, Jiulong Zhang, Xiuli Zhao (2025) Construction of multifunctional biomimetic nanocarriers for the treatment of atherosclerosis via precise cholesterol removal and ROS scavenging. Chemical Engineering Journal 525, 170455. https://doi.org/10.1016/j.cej.2025.170455