Enabling topical and long-term anti-radical properties for percutaneous coronary intervention-related complications by incorporating TEMPOL into electrospun nanofibers

负载TEMPOL的静电纺丝纳米纤维实现PCI相关并发症治疗的局部长期抗自由基性能

Scavenging reactive oxygen species(ROS)by antioxidants has been demonstrated as the most effective strategy for preventing percutaneous coronary intervention(PCI)-related complications.However,topical and long-term delivery of ROS antioxidants to a specific vascular tissue is proven to be a great challenge.Herein,an ROS scavenger of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl(TEMPOL)is incorporated into electrospun nanofibers with a tunable loading amount to achieve its topical applicability and long-term antiradical capability.Biological functions of such TEMPOL-loaded electrospun membranes are evaluated by cell proliferation,ROS-scavenging capability,monocyte adhesion,cell migration,inflammatory molecule secretion and mRNA expression in vitro.After optimizing the loading amount of TEMPOL,such an electrospun membrane presents a superior ROS-scavenging and anti-inflammation performance for both endothelial cells and macrophages.The expression of endothelial prothrombogenic molecules and the migration of vascular smooth muscle cells(VSMCs)are also effectively inhibited.Thus,it is bravely predicted that the topical use of such a TEMPOL-loaded electrospun system will be a promising pathway for the anti-restenosis therapy,especially when used as a novel coating on stent for long-term and topical delivery of antioxidant drugs.

使用抗氧剂清除活性氧(ROS)被证实是应对经皮冠状动脉介入治疗(PCI)相关并发症的有效方法,但抗氧剂向特定组织的长期局部输送不易实现.本文将抗氧剂TEMPOL可控地负载入静电纺丝纳米纤维以实现其局部应用和长期抗自由基能力,制得TEMPOL负载薄膜的生物功能通过细胞增殖、ROS清除能力、单核细胞黏附、细胞迁移、炎症因子mRNA水平的表达及分泌等体外实验进行了表征.薄膜在优化TEMPOL负载量后,对内皮细胞和巨噬细胞表现出优异的清除ROS和抗炎症能力;同时有效抑制内皮细胞促血栓形成因子的表达和血管平滑肌细胞的迁移.因此,我们预测该TEMPOL负载电纺体系的局部使用,如用作长期局部输送抗氧化药物的血管支架涂层,可以有效治疗血管再狭窄和抑制血栓形成.