AT1R-mediated NIR-II/PA imaging-guided iCM exosome therapy for myocardial ischemia revascularization.

Abstract

Ischemic heart disease remains a leading cause of global mortality, primarily driven by myocardial infarction and subsequent ischemia-reperfusion injury (MI/RI) following coronary artery occlusion. This highlights a critical unmet clinical need for integrated strategies that enable both timely intervention during the acute phase and precise postinjury assessment of myocardial damage. Here, we report a theranostic platform based on a dual-modality near-infrared II fluorescence and photoacoustic imaging probe targeting the angiotensin II type 1 receptor (AT1R). The system is coloaded with losartan and exosomes derived from induced pluripotent stem cell-derived cardiomyocytes (iCMs), enabling noninvasive, high-resolution visualization and evaluation of myocardial injury. Under imaging guidance, this platform allows spatially precise delivery of therapeutics, thereby integrating the antifibrotic and anti-inflammatory effects of AT1R blockade with the regenerative paracrine signaling mediated by iCM-derived exosomes. The synergistic therapeutic efficacy of this system was systematically validated in established mouse and rat models of MI/RI, demonstrating enhanced angiogenesis, attenuation of fibrosis, and improved cardiac functional recovery. Collectively, this study establishes a multifunctional platform that integrates diagnosis and therapy, providing a promising strategy for the precise management of MI/RI.