肝素
合作性
化学
共聚物
抗凝血酶
体内
抗凝剂
纳米颗粒
聚合物
组合化学
生物物理学
纳米技术
材料科学
生物化学
有机化学
外科
医学
生物技术
生物
作者
Qing Liu,Syed Tousif Ahmed,Zhuojun Meng,Sami Nummelin,Tekla Tammelin,Eero Kontturi,Renko de Vries,Mauri A. Kostiainen
出处
期刊:Biomacromolecules
[American Chemical Society]
日期:2023-01-04
卷期号:24 (2): 1014-1021
被引量:2
标识
DOI:10.1021/acs.biomac.2c01464
摘要
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-1 in plasma that is significantly below the therapeutic range (0.2-8 IU mL-1). Moreover, moderate cytocompatibility is demonstrated by in vitro cell studies. Therefore, such engineered protein copolymers present a promising alternative for neutralizing and sensing heparin, but further optimization is required for in vivo applications.
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