Ischemic Area‐Targeting and Self‐Monitoring Nanoprobes Ameliorate Myocardial Ischemia/Reperfusion Injury by Scavenging ROS and Counteracting Cardiac Inflammation

Abstract Precise and effective management of myocardial ischemia/reperfusion injury (MIRI) is still a formidable challenge in clinical practice. Additionally, real‐time monitoring of drug aggregation in the MIRI region remains an open question. Herein, a drug delivery system, hesperadin and ICG assembled in PLGA‐Se‐Se‐PEG‐IMTP (HI@PSeP‐IMTP), is designed to deliver hesperadin and ICG to the MIRI region for in vivo optical imaging tracking and to ameliorate MIRI. The peak aggregation of nanoprobes in the MIRI region is monitored by near‐infrared fluorescence and photoacoustic imaging. The maximal fluorescence and photoacoustic signals of the HI@PSeP‐IMTP group in the MIRI region rise ≈32% and 40% respectively compared with that of HI@PSeP group. Moreover, HI@PSeP‐IMTP effectively mitigates MIRI due to a synergistic integration of diselenide bonds and hesperadin, which can eliminate ROS and suppress cardiac inflammation. Specifically, the expression levels of p‐CaMKII, p‐IκBα, and p65 in the MIRI region in the HI@PSeP‐IMTP group demonstrate a reduction of 30%, 46%, and 42% respectively compared to that of the PBS group. Collectively, HI@PSeP‐IMTP provides new insights into the development of drugs integrating diagnosis and treatment for MIRI.