A DNA nanocomplex with bifunctions of reactive oxygen species scavenging and gene silencing for synergistic repair of myocardial infarction

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 in vivo 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.