Lu Wang, Xinkui Zhang, Haotao Su, Xiang Long, Chengming Dai, Bihui Cao, Linjiang Han, Yuliang Zhou, Yufeng Deng, Changjiang Yu, Tucheng Sun, Zerui Chen, Ping Zhu, Shuoji Zhu, Yeneng Dai, Qi Zhao, Nanbo Liu
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.