Effective and safe hemodialysis is essential for patients with acute kidney injury and chronic renal failures. However, the development of effective anticoagulant agents with safe antidotes for use during hemodialysis has proven challenging. Here, we describe DNA origami-based assemblies that enable the inhibition of thrombin activity and thrombus formation. Two different thrombin-binding aptamers decorated DNA origami initiates protein recognition and inhibition, exhibiting enhanced anticoagulation in human plasma, fresh whole blood and a murine model. In a dialyzer-containing extracorporeal circuit that mimicked clinical hemodialysis, the origami-based aptamer nanoarray effectively prevented thrombosis formation. Oligonucleotides containing sequences complementary to the thrombin-binding aptamers can efficiently neutralize the anticoagulant effects. The nanoarray is safe and immunologically inert in healthy mice, eliciting no detectable changes in liver and kidney functions or serum cytokine concentration. This DNA origami-based nanoagent represents a promising anticoagulant platform for the hemodialysis treatment of renal diseases.

有效和安全的血液透析对患有急性肾损伤和慢性肾功能衰竭的患者至关重要。然而，已经证明开发具有安全解毒剂的有效抗凝剂以用于血液透析的过程具有挑战性。在这里，我们描述基于DNA折纸的程序集，可以抑制凝血酶活性和血栓形成。两种不同的凝血酶结合适体修饰了DNA折纸，从而开始了蛋白质的识别和抑制作用，在人血浆，新鲜全血和小鼠模型中表现出增强的抗凝作用。在模拟临床血液透析的含有透析器的体外回路中，基于折纸的适体纳米阵列可有效防止血栓形成。含有与凝血酶结合的适体互补的序列的寡核苷酸可以有效地中和抗凝作用。纳米阵列在健康小鼠中是安全的和免疫惰性的，不会引起肝脏和肾脏功能或血清细胞因子浓度的可检测变化。这种基于DNA折纸的纳米剂代表了用于肾脏疾病的血液透析治疗的有前途的抗凝平台。