Ultrasound-triggered targeted delivery of engineered ADSCs-derived exosomes with high SDF-1α levels to promote cardiac repair following myocardial infarction.

Myocardial Infarction (MI) is still a leading cause of mortality, and current treatments primarily focus on symptom alleviation and blood flow restoration, with limited capacity for myocardial repair. Exosomes, key mediators of intercellular communication, have demonstrated potential to promote myocardial regeneration but exhibit limited cardiac-targeting efficiency due to rapid accumulation in other organs. To overcome this limitation, we designed targeted nanobubbles (TNBCD81-cRGD) loaded with exosomes derived from adipose-derived stem cells (ADSCs) in this study. These ADSCs were genetically modified through viral transfection to secrete exosomes with high expression of stromal cell-derived factor 1α (SDF-1α), which was upregulated in the infarcted region and promotes stem cell homing via the SDF-1α-CXCR4 axis. The nanobubbles, modified with anti-CD81 antibodies and cRGD, enabled efficient targeting of ischemic myocardium under Low-Intensity Pulsed Ultrasound (LIPUS) irradiation. Our study demonstrated that the combination of targeted nanobubbles, ADSC-derived exosomes with high SDF-1α expression, and LIPUS irradiation enhanced exosome retention in the heart, improved therapeutic efficacy, and promoted myocardial repair. This approach holds potential for advancing exosome-based therapies in myocardial infarction treatment.