PDF(Pubmed)
Abstract：
Postoperative rehemorrhage following intracerebral hemorrhage surgery is intricately associated with a high mortality rate, yet there is now no effective clinical treatment. In this study, we developed a hemoglobin (Hb)-responsive in situ implantable DNA hydrogel comprising Hb aptamers cross-linked with two complementary chains and encapsulating deferoxamine mesylate (DFO). Functionally, the hydrogel generates signals upon postoperative rehemorrhage by capturing Hb, demonstrating a distinctive \"self-diagnosis\" capability. In addition, the ongoing capture of Hb mediates the gradual disintegration of the hydrogel, enabling the on-demand release of DFO without compromising physiological iron-dependent functions. This process achieves self-treatment by inhibiting the ferroptosis of neurocytes. In a collagenase and autologous blood injection model-induced mimic postoperative rehemorrhage model, the hydrogel exhibited a 5.58-fold increase in iron absorption efficiency, reducing hematoma size significantly (from 8.674 to 4.768 cubic millimeters). This innovative Hb-responsive DNA hydrogel not only offers a therapeutic intervention for postoperative rehemorrhage but also provides self-diagnosis feedback, holding notable promise for enhancing clinical outcomes.
摘要：
脑出血术后再出血与高死亡率密切相关。然而，现在没有有效的临床治疗方法。在这项研究中,我们开发了一种血红蛋白（Hb）响应的原位可植入DNA水凝胶，其包含与两条互补链交联的Hb适体，并封装了去铁胺甲磺酸酯（DFO）。功能上,水凝胶通过捕获Hb在术后再出血时产生信号，展示独特的“自我诊断”能力。此外,Hb的持续捕获介导了水凝胶的逐渐崩解，使DFO的按需释放而不损害生理铁依赖功能。该过程通过抑制神经细胞的铁性凋亡来实现自我治疗。在胶原酶和自体血注射模型诱导的模拟术后再出血模型中，水凝胶的铁吸收效率提高了5.58倍，显著减少血肿大小（从8.674至4.768立方毫米）。这种创新的Hb响应DNA水凝胶不仅为术后再出血提供治疗干预，还提供自我诊断反馈，在提高临床结果方面有着显著的希望。
