MPI quantification of magnetically labeled extracellular vesicles in mouse heart following myocardial infarction

This study aims to develop magnetically labeled iPSC-derived extracellular vesicles (magneto-EVs) for MRI/MPI and myocardial repair in a theranostic manner. Using optimized electroporation and purification protocols, we prepared magneto-EVs with high SuperSPIO20 loading efficiency (1.77 ng Fe/10? EVs) and well-preserved therapeutic effects. In vitro MPI results reveal that the detectability of magneto-EVs is ~1 × 109 EVs/mL. In vivo MPI shows that MPI can detect magneto-iPSC-EVs injected intramyocardially in mouse hearts for up to 7 days following myocardial infarction. MPI quantification showed that 32% of injected EVs remained in the heart after 24 hours, with a further ~50% decrease by day 7, indicating progressive clearance or biodegradation of magneto-EVs from the injected site. Despite this low retention and rapid clearance, magneto-EVs led to significant improvement in left ventricular ejection fraction (37.3% increase) and scar formation (61.0% reduction). This theranostic EV imaging platform enables quantitative MPI monitoring of EV delivery and predicting therapeutic outcomes.