Reactive oxygen species-responsive hydrogel loaded with melatonin as a minimally invasive treatment for myocardial I/R injury.

Myocardial infarction (MI) poses a severe threat to human life, and timely reperfusion of ischemic myocardium stands as the most effective treatment approach. However, myocardial ischemia-reperfusion (I/R) could lead to the excessive generation of reactive oxygen species (ROS), worsening myocardial injury. In this investigation, an ROS-responsive injectable hydrogel encapsulating melatonin (MLT) was synthesized. This hydrogel could provide a controlled release of MLT, markedly enhancing its antioxidant, anti-inflammatory, anti-apoptotic, and autophagy-modulating effects, thereby significantly mitigating myocardial ischemia-reperfusion injury (MIRI). Moreover, this study proposes an injection method of ultrasound delivery, which offers significant advantages to MI patients without the necessity of thoracotomy. In conclusion, This ROS-responsive hydrogel loaded with MLT established the basis for minimally invasive treatment of myocardial I/R injury, which has considerable potential for the treatment of MIRI.