Targeted suppression of CCR7/NF-κB signaling by apoptotic body-inspired colchicine nanovesicles halts atherosclerotic progression

作者：Qi Chen, Yi Peng, Qian Zhong, Yubo Zhang, Liubing Hu, Ge Zhang, Yixian Xu, Peina Dong, Si Shen, Jing‐Hao Wang, Zhiguo Wang, Huan‐Tian Zhang, Rong Zeng, Hao Wang · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03840-x · 被引用次数：2 · 研究领域：Inflammasome and immune disorders、Immune cells in cancer、Phagocytosis and Immune Regulation

Atherosclerosis (AS) is a chronic inflammatory disorder characterized by foam cell formation and persistent inflammation as central pathological drivers. Although colchicine (Col) exhibits potent anti-inflammatory activities, its clinical application is limited by a narrow therapeutic window. In the present study, we developed phosphatidylserine-exposing nanovesicles (Col@PSVs) that leverage the innate phagocytic capacity of macrophage-derived foam cells by presenting surface “eat-me” signals, thereby enabling targeted immune modulation. The synergistic collaboration between Col and PSVs allows low-dose Col to retain robust anti-inflammatory efficacy while mitigating dose-dependent toxicity. Mechanistically, Col@PSVs potently suppress CCR7-mediated NF-κB signaling activation in foam cells, leading to a marked downregulation of pro-inflammatory cytokine and disruption of inflammatory cascades. In ApoE−/− AS mouse models, Col@PSVs treatment significantly improved plaque stability and attenuated disease progression. These findings highlight the pivotal role of the CCR7/NF-κB signaling pathway in AS-associated inflammation and present a translational nanotherapeutic strategy with the potential to overcome the clinical limitations of Col.