The treatment of myocardial infarction (MI) is hindered by a vicious cycle of the accumulation of reactive oxygen species (ROS) and overexpression of apoptotic factors. Implementing a co-delivery drug system that regulates the expression of ROS and apoptotic factors remains a critical challenge. Herein, we report a DNA nanocomplex that achieves the synergistic repair of MI injury by ROS scavenging and the attenuation of apoptotic factors expression. The DNA nanocomplex integrates a multitude of peroxidase-like nano-enzymes and gene drugs by precise molecular recognition and cascade hybridization chain reaction of two hairpin DNA monomers. The nano-enzyme, G-quadruplex with hemin intercalation, functions as glutathione peroxidase to scavenge excess ROS for alleviating the microenvironmental deterioration; the gene drug, miRNA-21, is responsible for silencing the expression of apoptotic-related factor PDCD4, to regulate metabolic dysfunction. Meanwhile, the design of adenosine triphosphate (ATP) aptamer in DNA nanocomplex facilitates the controlled release of miRNA-21 in cells. By combining the functions of ROS scavenging and apoptosis factor inhibition, DNA nanocomplex effectively alleviates the myocardial cell damage under hypoxia, achieving enhanced therapeutic effect for MI. This work provides a new strategy of disrupting the vicious cycle of metabolic dysfunction and microenvironmental deterioration at the infarcted area for MI treatment.

中文翻译：

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具有活性氧清除和基因沉默双重功能的DNA纳米复合物协同修复心肌梗死

活性氧（ROS）积累和凋亡因子过度表达的恶性循环阻碍了心肌梗死（MI）的治疗。实施调节 ROS 和凋亡因子表达的共同递送药物系统仍然是一个严峻的挑战。在此，我们报道了一种DNA纳米复合物，它通过ROS清除和凋亡因子表达的减弱实现了MI损伤的协同修复。 DNA纳米复合物通过两个发夹DNA单体的精确分子识别和级联杂交链式反应，整合了多种过氧化物酶类纳米酶和基因药物。嵌入氯化血红素的纳米酶G-四联体，作为谷胱甘肽过氧化物酶清除多余的ROS，缓解微环境恶化；基因药物miRNA-21负责沉默凋亡相关因子PDCD4的表达，从而调节代谢功能障碍。同时，DNA纳米复合物中三磷酸腺苷（ATP）适体的设计有利于细胞内miRNA-21的受控释放。 DNA纳米复合物通过结合ROS清除和凋亡因子抑制的功能，有效减轻缺氧下的心肌细胞损伤，从而增强心肌梗死的治疗效果。这项工作为心肌梗塞治疗提供了一种打破梗死区代谢功能障碍和微环境恶化的恶性循环的新策略。