Liu Qing, Yang Shuo, Seitz Iris, Pistikou Anna-Maria Makri, de Greef Tom F A, Kostiainen Mauri A
Wenzhou Institute, University of Chinese Academy of Sciences (WIUCAS), Wenzhou, Zhejiang, 325001, China.
Biohybrid Materials, Department of Bioproducts and Biosystems, Aalto University, Espoo, 02150, Finland.
Small. 2023 Mar;19(13):e2201790. doi: 10.1002/smll.202201790. Epub 2022 May 15.
Heparin is a commonly applied blood anticoagulant agent in clinical use. After treatment, excess heparin needs to be removed to circumvent side effects and recover the blood-clotting cascade. Most existing heparin antidotes rely on direct heparin binding and complexation, yet selective compartmentalization and sequestration of heparin would be beneficial for safety and efficiency. However, such systems have remained elusive. Herein, a semipermeable protein-based microcompartment (proteinosome) is loaded with a highly positively charged chitosan derivative, which can induce electrostatics-driven internalization of anionic guest molecules inside the compartment. Chitosan-loaded proteinosomes are subsequently employed to capture heparin, and an excellent heparin-scavenging performance is demonstrated under physiologically relevant conditions. Both the highly positive scavenger and the polyelectrolyte complex are confined and shielded by the protein compartment in a time-dependent manner. Moreover, selective heparin-scavenging behavior over serum albumin is realized through adjusting the localized scavenger or surrounding salt concentrations at application-relevant circumstances. In vitro studies reveal that the cytotoxicity of the cationic scavenger and the produced polyelectrolyte complex is reduced by protocell shielding. Therefore, the proteinosome-based systems may present a novel polyelectrolyte-scavenging method for biomedical applications.
肝素是临床常用的血液抗凝剂。治疗后，需要去除多余的肝素以避免副作用并恢复凝血级联反应。现有的大多数肝素解毒剂依赖于直接的肝素结合和络合，然而肝素的选择性区室化和隔离对于安全性和效率将是有益的。然而，这样的系统仍然难以实现。在此，一种基于蛋白质的半透微区室（蛋白小体）装载了一种带高度正电荷的壳聚糖衍生物，它可以诱导阴离子客体分子在区室内通过静电作用驱动内化。随后使用装载壳聚糖的蛋白小体来捕获肝素，并在生理相关条件下展示了出色的肝素清除性能。高度带正电的清除剂和聚电解质复合物都以时间依赖性方式被蛋白质区室限制和屏蔽。此外，通过在应用相关情况下调节局部清除剂或周围盐浓度，实现了对血清白蛋白的选择性肝素清除行为。体外研究表明，原细胞屏蔽降低了阳离子清除剂和产生的聚电解质复合物的细胞毒性。因此，基于蛋白小体的系统可能为生物医学应用提供一种新型的聚电解质清除方法。
