College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.
West China Hospital, Department of Nephrology, Sichuan University, Chengdu, 610041, China.
Colloids Surf B Biointerfaces. 2018 Apr 1;164:316-323. doi: 10.1016/j.colsurfb.2018.01.050. Epub 2018 Feb 2.
Heparin-based anticoagulant drugs are widely used for the prevention of blood clotting during extracorporeal circuit (bloodlines or cassette system) and surgical procedures as well as for the treatment of thromboembolic events. However, these anticoagulants are associated with bleeding risks that demand continuous monitoring and neutralization with antidotes. We explore the possibility of utilizing anticoagulants for blood clotting prevention, then removing them before transfusing the blood back to body, thus avoid bleeding risks. Here, we report on the strength of a strategy to solve problems with bleeding risks by rationally designing and using superparamagnetic iron oxide nanoparticles (SPIONs) with layer-by-layer self-assembled heparin. The morphology of these SPIONs was investigated by using dynamic light scattering and transmission electron microscopy. In vitro assays demonstrated superior efficacy and safety profiles and significantly mitigated conventional heparin-induced bleeding risks. In addition, the in vivo assay in a model animal (dog) proved that it is possible to use magnetic anticoagulant (MAC) in blood purification. The new magnetic anticoagulant drugs may benefit patients undergoing high-risk surgical procedures and may overcome anticoagulant-related bleeding problems to a great extent.
基于肝素的抗凝药物被广泛用于体外循环（血液管路或盒式系统）和外科手术中预防血液凝固，以及治疗血栓栓塞事件。然而，这些抗凝剂与出血风险相关，需要持续监测并使用解毒剂中和。我们探索了在将血液输回体内之前使用抗凝剂预防血液凝固，然后去除它们的可能性，从而避免出血风险。在这里，我们报告了通过合理设计和使用具有层层自组装肝素的超顺磁性氧化铁纳米粒子（SPION）来解决出血风险问题的策略的有效性。通过动态光散射和透射电子显微镜研究了这些 SPION 的形态。体外试验表明，该策略具有优异的疗效和安全性，并显著减轻了常规肝素引起的出血风险。此外，在犬模型动物中的体内试验证明，在血液净化中使用磁性抗凝剂（MAC）是可行的。新型磁性抗凝药物可能使接受高风险手术的患者受益，并在很大程度上克服与抗凝相关的出血问题。
