Cardioprotection of Tetrahedral DNA Nanostructures in Myocardial Ischemia-Reperfusion Injury

Acute myocardial infarction, which can be extremely difficult to treat, is the worst deadly disease around the world. Reperfusion is expedient to reverse myocardial ischemia. However, during reperfusion, reactive oxygen species (ROS) produced by myocardial ischemia-reperfusion injury (MIRI) and further cell apoptosis are the most serious challenges to cardiomyocytes. Therefore, searching for reagents that can simultaneously reduce oxidative damage and MIRI-induced apoptosis is the pivotal strategy to rescue injured cardiomyocytes. Nevertheless, current cardioprotective drugs have some shortcomings, such as cardiotoxicity, inadequate intravenous administration, or immature technology. Previous studies have shown that tetrahedral DNA nanostructures (TDNs) have biological safety with promising anti-inflammatory and antioxidative potential. However, the progress that TDNs have made in the biological behavior of cardiomyocytes has not been explored. In this experiment, a cellular model of MIRI was first established. Then, confirmed by a series of experiments, our study indicates that TDNs can significantly decrease oxidative damage and apoptosis by limiting the overexpression of ROS, along with effecting the expression of apoptosis-related proteins. In addition, Western blot analysis demonstrated that TDNs could activate the Akt/Nrf2 signaling pathway to improve the myocardial injury induced by MIRI. Above all, the antioxidant and antiapoptotic capacities of TDNs make them a potential therapeutic drug for MIRI. This study provides new ideas and directions for more homogeneous diseases induced by oxidative damage.