Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, United States.
Nanotechnology Characterization Lab., Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, Maryland 21702, United States.
Nano Lett. 2022 Jul 27;22(14):5961-5972. doi: 10.1021/acs.nanolett.2c02019. Epub 2022 Jul 5.
The unbalanced coagulation of blood is a life-threatening event that requires accurate and timely treatment. We introduce a user-friendly biomolecular platform based on modular RNA-DNA anticoagulant fibers programmed for reversible extracellular communication with thrombin and subsequent control of anticoagulation via a "kill-switch" mechanism that restores hemostasis. To demonstrate the potential of this reconfigurable technology, we designed and tested a set of anticoagulant fibers that carry different thrombin-binding aptamers. All fibers are immunoquiescent, as confirmed in freshly collected human peripheral blood mononuclear cells. To assess interindividual variability, the anticoagulation is confirmed in the blood of human donors from the U.S. and Brazil. The anticoagulant fibers reveal superior anticoagulant activity and prolonged renal clearance in comparison to free aptamers. Finally, we confirm the efficacy of the "kill-switch" mechanism in murine and porcine models.
血液的失衡凝结是一种危及生命的事件，需要准确和及时的治疗。我们引入了一个基于模块化 RNA-DNA 抗凝纤维的用户友好型生物分子平台，该平台经过编程可与凝血酶进行可逆的细胞外通讯，并通过“致死开关”机制来控制抗凝，从而恢复止血功能。为了展示这种可重构技术的潜力，我们设计并测试了一组携带不同凝血酶结合适体的抗凝纤维。所有纤维都具有免疫惰性，这在新鲜采集的人类外周血单核细胞中得到了证实。为了评估个体间的可变性，我们在美国和巴西的人类供体血液中确认了抗凝效果。与游离适体相比，抗凝纤维显示出更高的抗凝活性和更长的肾脏清除率。最后，我们在小鼠和猪模型中证实了“致死开关”机制的有效性。
