Self‐Assembled Metal‐Polyphenol Colchicine Nanoparticles Targeting Oxidative Stress and Inflammation for Treatment of Atherosclerosis

Abstract Anti‐inflammatory colchicine therapy has emerged as a new era for atherosclerotic cardiovascular diseases. However, the therapeutic benefit of colchicine has not been clearly defined. Herein, we present a double coordination‐driven approach to fabricate a stable metal‐organic nano‐assembly of colchicine (COL‐TA‐Zn) by uniting the tropolone ring of colchicine (COL), phenolic groups of tannic acid (TA), and Zn 2+ ions. This design leverages the antioxidant and anti‐inflammatory properties of COL and TA to create a nanoscale platform capable of scavenging radicals and modulating inflammatory pathways. Through robust Zn 2+ coordination, the resulting COL‐TA‐Zn nanocomplexes exhibit enhanced stability under physiological conditions, ensuring efficient delivery and sustained bioactivity. In vitro assays confirm suppression of foam cell formation and multiple inflammatory mediators, suggesting significant potential for managing atherosclerosis by targeting both oxidative stress and inflammation. Intravenous administration of COL‐TA‐Zn in Apoe − / − mice significantly reduces atherosclerotic plaque area, MMP‐9, TNF‐α, and reactive oxygen species (ROS) levels, thereby illustrating its superior anti‐atherosclerotic efficacy compared to COL alone. These findings highlight the promise of the dual coordination‐driven nanoplatform in cardiovascular disease treatment.