Journal Article

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

Zhang, Yu-Bo, Zhang, Huan-Tian, Hu, Liu-Bing, Chen, Qi, Zhang, Guan-Yan, Dong, Pei-Na, Peng, Yuan-Shu, Shen, Si, Wang, Zhi-Guo, Xu, Yi-Xian, Zhong, Qian, Zeng, Rong, Wang, Jing-Hao, Wang, Hao

2025

Overview

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. Graphical Abstract

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Animal models / Animals / Anti-Inflammatory Agents - pharmacology / Apolipoprotein E / Apoptosis / Apoptosis - drug effects / Apoptotic cell-derived microvesicles / Arteriosclerosis / Atherosclerosis / Atherosclerosis - drug therapy / Atherosclerosis - metabolism / Atherosclerosis - pathology / Biodistribution / Biotechnology / CC chemokine receptors / Cell activation / Chemistry / Chemistry and Materials Science / Chronic inflammation / Colchicine / Colchicine - chemistry / Colchicine - pharmacology / Cytokines / Cytotoxicity / Disease / Disease Progression / Flow cytometry / Foam Cells - drug effects / Foam Cells - metabolism / Humans / Immunomodulation / Inflammation / Inflammatory diseases / Macrophages / Male / Mice / Mice, Inbred C57BL / Microscopy / Molecular Medicine / Nanoparticles / Nanotechnology / NF-kappa B - metabolism / NF-κB protein / Particle size / Phagocytes / Phosphatidylserine / Phosphatidylserines - chemistry / Receptors, CCR7 - metabolism / Signal transduction / Signal Transduction - drug effects / Toxicity