Abstract
Myocardial ischemia-reperfusion injury (MIRI), a frequent complication in acute myocardial infarction (AMI) treatment, arises from complex mechanisms including oxidative stress, inflammation, and mitochondrial dysfunction, which impair myocardial repair and recovery. Current therapies for MIRI offer limited efficacy and raise safety concerns, highlighting the need for innovative and precise treatment strategies in cardiovascular research. Ultrasound-targeted microbubble destruction (UTMD) is a promising therapeutic approach that enhances drug delivery precision to the myocardium. By utilizing ultrasound cavitation and nanodrug delivery, UTMD overcomes microvascular barriers, significantly improving drug bioavailability and therapeutic outcomes. It has demonstrated potential in modulating the hypoxia-inducible factor-1α/vascular endothelial growth factor (HIF-1α/VEGF) pathway to promote angiogenesis and enhance myocardial perfusion. In addition, it inhibits NOD-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing inflammatory responses and protecting the myocardium from reperfusion damage. The integration of radiomics and artificial intelligence (AI) further advances MIRI diagnosis and treatment. Real-time monitoring of myocardial blood flow and microcirculatory perfusion, combined with AI-driven image analysis, enables accurate assessment of myocardial injury and therapeutic efficacy, supporting personalized and precise therapy. Moreover, multi-omics technologies-such as single-cell RNA sequencing, proteomics, and metabolomics-combined with UTMD provide deeper insights into its therapeutic mechanisms, laying a robust foundation for clinical translation. This review summarizes recent progress in UTMD-based therapies for MIRI, emphasizing their roles in angiogenesis, immune regulation, precision diagnostics, and multi-omics analysis. It highlights new perspectives for future research and clinical applications in the management of MIRI.