CCR2-Engineered Macrophage Membrane-Coated Metal-Polyphenol Nanozyme to Enhance Antioxidation Activity for Inhibiting the Atherosclerotic Progression.

Abstract

Atherosclerosis (AS) is a prevalent chronic inflammatory disease characterized by excessive accumulation of reactive oxygen species (ROS) and persistent inflammation. Polyphenolic natural antioxidants possess strong ROS-scavenging properties. However, the poor targeting ability and rapid metabolism greatly limit their further clinical applications. To this end, a multifunctional biomimetic nanoplatform (CCR2@NPs) is developed by engineering macrophage membranes with the overexpressed C-C chemokine receptor 2 (CCR2) and subsequently enhances the target delivery to inflammatory lesions of AS via the C-C motif ligand 2 (CCL2)/CCR2 chemotactic signaling pathway for significantly improving drug bioavailability. In pathological local lesions, CCR2@NPs can effectively scavenge the excessive ROS, alleviate vascular injury, and finally inhibit AS progression. This strategy enables precise, synergistic therapy and offers new insights into the potential treatment approaches for AS.