We developed a biomimetic approach for targeted treatment of cardiovascular disease, which is mediated by a yeast-derived microcapsule (YC). Different positively charged nanoprobes and nanotherapies can be efficiently packaged into YC via electrostatic force-driven spontaneous deposition. These nanoparticle-loaded YCs may be rapidly endocytosed by macrophages and maintained in cells for up to one week. After oral delivery of YCs containing fluorescent nanoprobes, their accumulation in aortic plaques and macrophages was observed in apolipoprotein E-deficient (ApoE−/−) mice with established atherosclerotic lesions. This YC-mediated atherosclerotic targeting was realized by transcytotic absorption in the gastrointestinal tract via M cells in Peyer's patches, followed by subsequent endocytosis in resident monocytes/macrophages, and final translocation through recruitment to diseased sites via the lymphatic system. Correspondingly, oral delivery of assembled anti-atherosclerotic nanotherapies packaged in YCs afforded notably potentiated efficacies in ApoE−/− mice. These findings demonstrated that this Trojan horse-like YC mediated nanomedicinal approach may be employed to orally deliver a diverse array of therapies for the management of atherosclerosis and other vascular disorders.

中文翻译：

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装载自组装纳米疗法的仿生酵母微胶囊用于心血管疾病的靶向治疗

我们开发了一种靶向治疗心血管疾病的仿生方法，该方法由酵母微胶囊 (YC) 介导。不同的带正电荷的纳米探针和纳米疗法可以通过静电力驱动的自发沉积有效地封装到 YC 中。这些载有纳米颗粒的 YCs 可能会被巨噬细胞迅速内吞并在细胞中维持长达一周。在口服递送含有荧光纳米探针的 YCs 后，在载脂蛋白 E 缺陷（ApoE-/-）小鼠中观察到它们在主动脉斑块和巨噬细胞中的积累，这些小鼠已出现动脉粥样硬化病变。这种 YC 介导的动脉粥样硬化靶向是通过在胃肠道中通过 Peyer 斑块中的 M 细胞进行胞吞吸收，然后在常驻单核细胞/巨噬细胞中进行内吞来实现的，并通过淋巴系统募集到患病部位而最终易位。相应地，包装在 YC 中的组装抗动脉粥样硬化纳米疗法的口服给药在 ApoE-/- 小鼠中提供了显着增强的功效。这些发现表明，这种类似特洛伊木马的 YC 介导的纳米医学方法可用于口服提供多种治疗动脉粥样硬化和其他血管疾病的疗法。