Biohybrid Materials, Department of Bioproducts and Biosystems, Aalto University, Aalto00076, Finland.
Wenzhou Institute, University of Chinese Academy of Sciences (WIUCAS), Wenzhou325001, China.
Biomacromolecules. 2023 Feb 13;24(2):1014-1021. doi: 10.1021/acs.biomac.2c01464. Epub 2023 Jan 4.
Heparin is a widely applied anticoagulant agent. However, in clinical practice, it is of vital importance to reverse its anticoagulant effect to restore the blood-clotting cascade and circumvent side effects. Inspired by protein cages that can encapsulate and protect their cargo from surroundings, we utilize three designed protein copolymers to sequester heparin into inert nanoparticles. In our design, a silk-like sequence provides cooperativity between proteins, generating a multivalency effect that enhances the heparin-binding ability. Protein copolymers complex heparin into well-defined nanoparticles with diameters below 200 nm. We also develop a competitive fluorescent switch-on assay for heparin detection, with a detection limit of 0.01 IU mL in plasma that is significantly below the therapeutic range (0.2-8 IU mL). Moreover, moderate cytocompatibility is demonstrated by cell studies. Therefore, such engineered protein copolymers present a promising alternative for neutralizing and sensing heparin, but further optimization is required for applications.
肝素是一种广泛应用的抗凝剂。然而，在临床实践中，逆转其抗凝作用以恢复凝血级联并避免副作用至关重要。受能够包裹并保护其货物免受周围环境影响的蛋白质笼的启发，我们利用三种设计的蛋白质共聚物将肝素隔离到惰性纳米颗粒中。在我们的设计中，丝般的序列提供了蛋白质之间的协同作用，产生了多价效应，增强了肝素结合能力。蛋白质共聚物将肝素复合成直径小于 200nm 的明确定义的纳米颗粒。我们还开发了一种用于肝素检测的竞争性荧光开关分析方法，在血浆中的检测限为 0.01IU/mL，明显低于治疗范围（0.2-8IU/mL）。此外，细胞研究表明具有中等细胞相容性。因此，这种工程化的蛋白质共聚物为中和和检测肝素提供了一种有前途的替代方法，但需要进一步优化以应用。
