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载氧酶驱动的双面血小板纳米马达用于溶栓药物靶向递送治疗血栓性疾病。

GOx-Powered Janus Platelet Nanomotors for Targeted Delivery of Thrombolytic Drugs in Treating Thrombotic Diseases.

机构信息

Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, People's Republic of China.

Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, People's Republic of China.

出版信息

ACS Biomater Sci Eng. 2023 Jul 10;9(7):4302-4310. doi: 10.1021/acsbiomaterials.3c00387. Epub 2023 Jun 12.

Abstract

Low efficiency of targeting and delivery toward the thrombus site poses challenges to using thrombolytic drugs. Inspired by the biomimetic system of platelet membranes (PMs) and glucose oxidase (GOx) modification technologies, we develop a novel GOx-powered Janus nanomotor by asymmetrically attaching the GOx to polymeric nanomotors coated with the PMs. Then the PM-coated nanomotors were conjugated with urokinase plasminogen activators (uPAs) on their surfaces. The PM-camouflaged design conferred excellent biocompatibility to the nanomotors and improved their targeting ability to thrombus. The Janus distribution of GOx also allows the uneven decomposition of glucose in biofluids to produce a chemophoretic motion, increasing the drug delivery efficiency of nanomotors. In addition, these nanomotors are located at the lesion site due to the mutual adhesion and aggregation of platelet membranes. Furthermore, thrombolysis effects of nanomotors are enhanced in static and dynamic thrombus as well as in mouse models. It is believed that the novel PM-coated enzyme-powered nanomotors represent a great value for thrombolysis treatment.

摘要

针对血栓部位的靶向和递送效率低下,给溶栓药物的应用带来了挑战。受血小板膜(PMs)仿生系统和葡萄糖氧化酶(GOx)修饰技术的启发,我们通过将 GOx 不对称地附着在涂有 PMs 的聚合物纳米马达上来开发一种新型的 GOx 驱动的 Janus 纳米马达。然后,将 PM 涂层纳米马达与表面上的尿激酶纤溶酶原激活剂(uPAs)连接。PM 伪装设计赋予纳米马达优异的生物相容性,并提高了它们对血栓的靶向能力。GOx 的 Janus 分布还允许生物流体中葡萄糖的不均匀分解产生趋化运动,从而提高纳米马达的药物递送效率。此外,由于血小板膜的相互粘附和聚集,这些纳米马达位于病变部位。此外,纳米马达在静态和动态血栓以及小鼠模型中的溶栓效果得到增强。相信新型 PM 涂层酶驱动纳米马达在溶栓治疗方面具有重要价值。

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