Adaptive bioactivable nanosystems for synergistic myocardial infarction therapy using traditional pharmaceutics

Heart failure resulting from myocardial infarction (MI) is a leading global health concern. Current revascularization therapies cannot fully restore the infarcted myocardium or prevent maladaptive ventricular remodeling. Traditional Chinese medicine with its multitarget regulation and favorable biosafety shows a promising therapeutic potential. Tanshinone IIA (TIIA) and formononetin (FM), two bioactive compounds derived from Salvia miltiorrhiza and Astragalus membranaceus, respectively, exhibit antioxidant, anti-inflammatory, and proangiogenic effects. Herein, a neutrophil-targeted nanomedicine (TF-5NP) was developed to deliver TIIA and FM to the infarcted myocardium for mitigating oxidative damage and promoting angiogenesis. TF-5NP was synthesized by coassembling bis-5-hydroxytryptamine-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-carboxylic acid with cholesterol and lipid 1,2-distearoyl-sn-glycero-3-phosphoglycerol, which binds to troponin in the infarcted myocardium. This nanomedicine reduces inflammation and cardiomyocyte damage and improves cardiac function in porcine MI models, with therapeutic effects lasting for ∼28 d. These findings suggest that TF-5NP use is a promising approach for treating post-MI maladaptive remodeling and heart failure.