A paradigm of endothelium-protective and stent-free anti-restenotic therapy using biomimetic nanoclusters

作者：Wang Bowen; Chen Guojun; Urabe Go; Xie Ruosen; Wang Yuyuan; Shi Xudong; Guo Lian Wang^*; Gong Shaoqin^*; Kent K Craig^*

来源：Biomaterials, 2018, 178: 293-301.

DOI：10.1016/j.biomaterials.2018.06.025

• Biomimetic nanoclusters
• Endothelium-protective
• JQ1
• Rapamycin
• Re-endothelialization

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 (AI) 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.

• 出版日期2018-9
• 单位河北医科大学