Strontium Hexacyanoferrate Nanomedicine Alleviates Ischemic Cardiomyopathy by Regulating Pyroptosis

Abstract Ischemic cardiomyopathy remains high mortality and morbidity worldwide due to dysfunctional cell metabolism and programmed death of cardiomyocytes. Restoration of the blocked blood flows is a major therapeutic approach against ischemic cardiomyopathy, which, unfortunately, may cause the burst of oxidative species damaging tissues (ischemic/reperfusion injury, IR). Cardiac antioxidation and revascularization are two major therapeutic aims in treating cardiac IR as well as myocardial infarction (MI). In the present work, strontium hexacyanoferrate (SrHF) nanoparticles are synthesized for alleviating both the cardiac pathologies of MI and IR concurrently. SrHF features high antioxidative catalytic activity, mimicking superoxide dismutase and catalase in eliminating reactive oxygen species for cardiac protection. In vivo, investigation confirms that SrHF has significantly alleviated myocardial functional deterioration and enhanced cardiomyocyte survival. Mechanistic studies demonstrate that SrHF can effectively inhibit cardiac programmed pyroptosis and pathological remodeling through antioxidation and enhance angiogenesis by bioactive strontium ions. The present work provides a promising therapeutic strategy in treating ischemic cardiac pathologies, providing a fundamental basis for clinical translation and application toward cardiovascular diseases.