Strontium Prussian blue Promotes cardiac energy metabolism to alleviate Doxorubicin-Induced cardiotoxicity

Abstract

The anthracycline doxorubicin (DOX) is an effective clinical drug for tumor chemotherapy, but its lethal cardiotoxicity limits its clinical applicability. Medical protection against DOX-induced cardiotoxicity and progressive heart failure remains challenging. Here, we present a feasible strategy in which polyvinylpyrrolidone, strontium, and ferricyanide are integrated to form self-assembled strontium Prussian blue (SrPB) to prevent DOX-induced cardiomyotoxicity effectively. The in vitro and in vivo results showed that SrPB significantly improved cardiomyocyte survival and cardiac function in the DOX-challenged murine model. Mechanistically, mitochondrial function analysis revealed that DOX-induced mitochondrial damage by increasing the amount of mitochondrial reactive oxygen species (mtROS) and decreasing the energy metabolism. SrPB administration effectively improved mitochondrial energy metabolism by scavenging mtROS and improving the intermediate products of glycolysis and glycoxidation. Together, our findings provide an intriguing paradigm for targeting mitochondrial energy metabolism to inhibit DOX-induced cardiotoxicity and demonstrate the therapeutic potential of SrPB for further clinical application.