Bioinspired yeast microcapsules loaded with self-assembled nanotherapies for targeted treatment of cardiovascular disease

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.