数字农科院2.0

Non-lethal sonodynamic therapy-engineered foam cell exosomes reprograms endothelial immunometabolic crosstalk to stabilize atherosclerotic plaques

文献类型： 外文期刊

作者： Li, Yu;Yang, Zhiqiang;Ma, Xueyuan;Fu, Pengbin;Zhang, Lihong;Gao, Penghao;Wang, Yifan;Chen, Zhihao;Tian, Ye;Yang, Yang

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关键词： （3-0-3）Sonodynamic therapy;Atherosclerosis exosomes;Immunometabolic reprogramming;miR-17-5p/ABCA1-TIMP2 axis;Foam cell-endothelial crosstalk

期刊名称： INTERNATIONAL IMMUNOPHARMACOLOGY

ISSN： 1567-5769

年卷期： 2025 年 167 卷

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收录情况： SCIE（2025版）

摘要： Objective: While non-lethal sonodynamic therapy (NL-SDT) demonstrates therapeutic potential for atherosclerosis, its immunomodulatory mechanisms via exosomal signaling remain unexplored. This study investigates how SDT-engineered foam cell exosomes orchestrate plaque stabilization through coordinated immunometabolic reprogramming of endothelial inflammation and matrix dynamics. Methods: Atherosclerotic apolipoprotein E-deficient mice received NL-SDT with GW4869-mediated exosome blockade to confirm SDT-exosome axis dependency. Exosomes from bone marrow-derived foam cells were isolated, sequenced, and functionally validated via miR-17-5p gain/loss-of-function experiments. Dual-luciferase reporter assays confirmed miR-17-5p targeting of ABCA1 (cholesterol metabolism) and TIMP2 (inflammatory matrix regulation). Endothelial cholesterol efflux (using BODIPY-cholesterol) and MMP2/MMP9 levels were quantified. Results: SDT-engineered foam cell exosomes showed endothelial tropism, delivering anti-inflammatory miR-17-5p suppression. Through miR-17-5p downregulation, SDT-engineered exosomes activated ABCA1-dependent cholesterol efflux and enhanced TIMP2-mediated MMP inhibition. Conclusion: We identify SDT-engineered exosomes as novel immunotherapeutic vectors that synchronize metabolic detoxification and immune resolution in atherosclerotic plaques. Mechanistically distinct from direct exosome therapies, SDT amplifies endogenous exosome production while engineering cargo specificity, offering a tunable, lesion-targeted strategy.

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