Liposomal Nanocarrier-Based Myocardial Targeting Enhances Bardoxolone Methyl Efficacy in Sepsis-Induced Cardiomyopathy Treatment

Sepsis-induced cardiomyopathy (SCM) is a severe complication characterized by acute myocardial dysfunction and reduced cardiac output, often leading to high mortality despite advances in critical care. Central to SCM progression is the dysregulation of inflammatory and oxidative stress pathways. Ferroptosis, a form of iron-dependent cell death, plays a crucial role in SCM pathogenesis. Bardoxolone methyl (BM) has shown potent antiferroptotic activity through dual modulation of oxidative stress and inflammation. However, its clinical application is limited by nonspecific tissue distribution and low bioavailability. Here, we show that a myocardial-targeting peptide-conjugated nanoplatform, PCM-modified liposomes (PCM-Lipo/BM), significantly enhances the targeted delivery of BM to myocardial cells. PCM-Lipo/BM treatment markedly increased BM uptake in myocardial cells, alleviated lipopolysaccharide (LPS)-induced myocardial injury, improved cardiac function metrics, and reduced inflammation and oxidative stress markers. Compared to BM or Lipo/BM alone, PCM-Lipo/BM exhibited superior efficacy in reducing TNF-α, IL-6, and IL-1β levels. These findings demonstrate that PCM-Lipo/BM effectively mitigates inflammatory responses and oxidative damage in myocardial cells, offering a promising precision medicine approach to SCM treatment. This study not only enhances our understanding of SCM pathogenesis but also proposes a therapeutic strategy that could be applied to other cardiovascular diseases characterized by similar pathological mechanisms.