Ameliorating Myocardial Infarction by Concurrent Pyroptosis Suppression and On-Demand Oxygen Production via Functionalized Nanocarrier.

The ideal treatment for myocardial infarction should address the critical issues of oxygen supply improvement in the infarcted area and prevention of myocardial cell death. Myocardial necrosis is a reversible process, but the challenge lies in mitigating the irreversible pyroptosis of cardiomyocytes, which significantly impedes the recovery of cardiac function. To tackle these complexities, here we have developed MnO2@INN@Alb (MIA) nanoparticles. MIA nanoparticles possess the unique ability to generate oxygen and release glibenclamide (INN) in response to the acidic and H2O2-rich environments present in the infarcted region. MIA plays a dual role by inhibiting the pyroptosis process of cardiomyocytes through the suppression of NLRP3 and by providing vital oxygen to alleviate hypoxia. The results shows that MIA can effectively reverse cardiomyocyte hypoxia, reduce infarct fibrosis, and aid in the reconstruction of myocardial vessels. Moreover, MIA demonstrates high biocompatibility, making it a promising avenue for the future of myocardial infarction improvement. We anticipate that MIA can pave the way for novel solutions and research paradigms in the field.