Drug-eluting stents are the most commonly employed method to control post-angioplasty restenosis. Unfortunately, they exacerbate life-threatening stent thrombosis because of endothelium damage caused by both drug and stenting. To solve this major medical problem, an endothelium-protective and stent-free anti-restenotic method is highly desirable. Here we have generated a biomimetic intravenous delivery system using dendritic polymer-based nanoclusters, which were coated with platelet membranes for targeting to the injured arterial wall where restenosis occurs. These nanoclusters were loaded with an endothelium-protective epigenetic inhibitor (JQ1) or an endothelium-toxic status quo drug (rapamycin), and compared for their ability to mitigate restenosis without hindering the process of re-endothelialization. Fluorescence imaging of Cy5-tagged biomimetic nanoclusters indicated their robust homing to injured, but not uninjured arteries. Two weeks after angioplasty, compared to no-drug control, both rapamycin- and JQ1-loaded biomimetic nanoclusters substantially reduced (by >60%) neointimal hyperplasia, the primary cause of restenosis. However, whereas the rapamycin formulation impaired the endothelial re-coverage of the denuded inner arterial wall, the JQ1 formulation preserved endothelial recovery. In summary, we have created an endothelium-protective anti-restenotic system with biomimetic nanoclusters containing an epigenetic inhibitor. This system warrants further development for a non-thrombogenic and stent-free method for clinical applications.

药物洗脱支架是控制血管成形术后再狭窄最常用的方法。不幸的是，由于药物和支架置入引起的内皮损伤，它们加剧了危及生命的支架血栓形成。为了解决这一重大医疗问题，一种内皮保护和无支架抗-再狭窄方法是非常可取的。在这里，我们使用基于树突状聚合物的纳米团簇生成了一种仿生静脉给药系统，该纳米团簇涂有血小板膜，用于靶向发生再狭窄的受伤动脉壁。这些纳米簇装载了一种内皮保护性表观遗传抑制剂（JQ1）或一种内皮毒性现状药物（雷帕霉素），并比较了它们在不阻碍再内皮化过程的情况下减轻再狭窄的能力。Cy5 标记的仿生纳米簇的荧光成像表明它们对受伤的动脉有很强的归巢能力，但不是未受伤的动脉。血管成形术后两周，与无药物对照相比，装载雷帕霉素和 JQ1 的仿生纳米簇均显着减少（>60%）新内膜增生，这是再狭窄的主要原因。然而，雷帕霉素制剂损害了裸露的内动脉壁的内皮再覆盖，而 JQ1 制剂保留了内皮恢复。总之，我们创造了一种内皮保护剂具有包含表观遗传抑制剂的仿生纳米簇的抗再狭窄系统。该系统值得进一步开发用于临床应用的非血栓形成和无支架方法。