Targeted nanomedicine for ischemic cardiomyopathy

Ischemic cardiomyopathy remains a leading cause of morbidity and mortality worldwide. The therapeutic efficacy of conventional pharmacological interventions is constrained by poor bioavailability, limited myocardial targeting capacity, and systemic adverse effects. Nanomedicine has emerged as a promising strategy to overcome these limitations by enhancing drug stability, prolonging blood circulation time, and enabling precise delivery to diseased tissues. In the setting of ischemic cardiomyopathy, active targeting approaches-particularly those functionalized with tannic acid and cardiac-targeting peptides-have been extensively investigated to boost the delivery efficiency of therapeutic agents and halt disease progression. Moreover, the ischemic microenvironment (IME), characterized by inflammation, redox imbalance, and enzymatic dysregulation, not only drives pathological progression but also creates unique opportunities for site-specific therapeutic intervention. Systematic comprehension and evaluation of these targeting strategies are critical to advancing the clinical translation of myocardium-targeted nanomedicines. In this review, we summarize recent advances in myocardium-targeted nanotherapeutic strategies, with a special focus on tannic acid-based systems, cardiac-targeting peptides, reductive microenvironment-responsive platforms, and enzyme-responsive delivery approaches. We also discuss the current limitations and future perspectives of such strategies, aiming to offer insights into the rational design and clinical development of next-generation therapeutics for ischemic cardiomyopathy.