搭载于仿生酵母微囊上的AntagomiR-155通过抑制M1型巨噬细胞缓解动脉粥样硬化
AntagomiR-155 hitchhiking on biomimetic yeast microcapsules alleviate atherosclerosis by inhibiting M1-like macrophages.
摘要(中文译文)
动脉粥样硬化的进展由斑块巨噬细胞的可塑性驱动，因此抑制M1型巨噬细胞极化是一个有前景的治疗目标。尽管抑制M1型调节因子microRNA-155（miR-155）是一种可行策略，但其临床应用受到全身生物利用度不足和脱靶器官损伤的限制。在此，我们开发了YC/ANM-155，一种口服递送的仿生系统，利用酵母微胶囊（YC）将AntagomiR-155（ANM-155）特异性转运至主动脉斑块。与游离ANM-155相比，该靶向策略在减轻动脉粥样硬化负荷方面表现出更优的疗效。在机制上，该治疗抑制了局部miR-155表达，抑制了M1型巨噬细胞极化，并在病灶和全身水平下调了关键促炎细胞因子。补充的体外研究表明，抑制miR-155可减少M1型巨噬细胞极化并减弱炎症激活。该制剂在模拟胃肠道条件下表现出改善的稳定性，并在本实验条件下具有良好的生物安全性。总之，我们的研究结果表明，酵母介导的miRNA antagomir口服递送可能成为基于RNA的AS治疗的一种有前景的临床前策略，值得在更大规模的临床前模型中进行进一步评估。
Abstract
Atherosclerosis progression is driven by the plasticity of plaque macrophages, making the suppression of M1-like macrophage polarization a promising therapeutic goal. While inhibiting the M1-regulator microRNA-155 (miR-155) is a viable strategy, its clinical application is limited with inadequate systemic bioavailability and off-target organ damage. Herein, we developed YC/ANM-155, an orally delivered biomimetic system that utilizes yeast microcapsules (YC) to specifically transport AntagomiR-155 (ANM-155) to aortic plaques. This targeted strategy demonstrated superior efficacy compared to free ANM-155 in alleviating the atherosclerotic burden. Mechanistically, the treatment suppressed local miR-155 expression, inhibited M1-like macrophage polarization, and downregulated key pro-inflammatory cytokines at both the lesional and systemic levels. Complementary in vitro studies showed that miR-155 inhibition reduced M1-like macrophage polarization and attenuated inflammatory activation. The formulation showed improved stability under simulated gastrointestinal conditions and favorable biosafety under the present experimental settings. Collectively, our findings suggest that yeast-mediated oral delivery of miRNA antagomirs may serve as a promising preclinical strategy for RNA-based AS therapy and warrant further evaluation in larger-scale preclinical models.
如何引用
AMA
Ruilin Zhang, Ya Wu, Tao Kou, Yuhui Liu, Hao Chen, Runwen Li, et al. AntagomiR-155 hitchhiking on biomimetic yeast microcapsules alleviate atherosclerosis by inhibiting M1-like macrophages.. Materials today. Bio. 2026; doi:10.1016/j.mtbio.2026.103460.
APA
Ruilin Zhang, Ya Wu, Tao Kou, Yuhui Liu, Hao Chen, Runwen Li, et al (2026). AntagomiR-155 hitchhiking on biomimetic yeast microcapsules alleviate atherosclerosis by inhibiting M1-like macrophages.. Materials today. Bio. https://doi.org/10.1016/j.mtbio.2026.103460
GB/T 7714
Ruilin Zhang, Ya Wu, Tao Kou, Yuhui Liu, Hao Chen, Runwen Li, et al. AntagomiR-155 hitchhiking on biomimetic yeast microcapsules alleviate atherosclerosis by inhibiting M1-like macrophages.[J]. Materials today. Bio, 2026 doi:10.1016/j.mtbio.2026.103460.
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