Atherosclerotic cardiovascular disease is the leading cause of mortality in the world. A driving feature of atherosclerotic plaque formation is dysfunctional efferocytosis. Because the “don’t eat me” molecule CD47 is upregulated in atherosclerotic plaque cores, CD47-blocking strategies can stimulate the efferocytic clearance of apoptotic cells and thereby help prevent the progression of plaque buildup. However, these therapies are generally costly and, in clinical and murine trials, they have resulted in side effects including anemia and reticulocytosis. Here, we developed and characterized an intracellular phagocytosis-stimulating treatment in the CD47-SIRPα pathway. We loaded a novel monocyte/macrophage-selective nanoparticle carrier system with a small molecule enzymatic inhibitor that is released in a pH-dependent manner to stimulate macrophage efferocytosis of apoptotic cell debris via the CD47-SIRPα signaling pathway. We demonstrated that single-walled carbon nanotubes (SWNTs) can selectively deliver tyrosine phosphatase inhibitor 1 (TPI) intracellularly to macrophages, which potently stimulates efferocytosis, and chemically characterized the nanocarrier. Thus, SWNT-delivered TPI can stimulate macrophage efferocytosis, with the potential to reduce or prevent atherosclerotic disease.

动脉粥样硬化性心血管疾病是世界上导致死亡的主要原因。动脉粥样硬化斑块形成的驱动特征是功能异常的红细胞增多。因为“不要吃我”分子CD47在动脉粥样硬化斑块核心中被上调，所以CD47阻断策略可以刺激凋亡细胞的胞浆清除，从而有助于防止斑块积聚的进行。然而，这些疗法通常是昂贵的，并且在临床和鼠类试验中，它们已经导致包括贫血和网织红细胞增多症的副作用。在这里，我们开发并表征了CD47-SIRPα途径中的细胞内吞噬刺激治疗。我们加载了一种新型的单核细胞/巨噬细胞选择性纳米颗粒载体系统，并带有一种小分子酶抑制剂，该酶抑制剂以pH依赖性方式释放，以通过CD47-SIRPα信号通路刺激凋亡细胞碎片的巨噬细胞流出。我们证明，单壁碳纳米管（SWNTs）可以选择性地在细胞内将酪氨酸磷酸酶抑制剂1（TPI）传递到巨噬细胞，从而有效刺激胞吞作用，并对纳米载体进行化学表征。因此，SWNT传递的TPI可以刺激巨噬细胞的胞吞作用，具有减少或预防动脉粥样硬化疾病的潜力。我们证明，单壁碳纳米管（SWNTs）可以选择性地在细胞内将酪氨酸磷酸酶抑制剂1（TPI）传递到巨噬细胞，从而有效刺激胞吞作用，并对纳米载体进行化学表征。因此，SWNT传递的TPI可以刺激巨噬细胞的胞吞作用，具有减少或预防动脉粥样硬化疾病的潜力。我们证明，单壁碳纳米管（SWNTs）可以选择性地在细胞内将酪氨酸磷酸酶抑制剂1（TPI）传递到巨噬细胞，从而有效刺激胞吞作用，并对纳米载体进行化学表征。因此，SWNT传递的TPI可以刺激巨噬细胞的胞吞作用，具有减少或预防动脉粥样硬化疾病的潜力。