Quantitative visualization of myocardial ischemia- reperfusion-induced cardiac lesions via ferroptosis

Myocardial ischemia-reperfusion (MI/R) injury is a complication in vascular reperfusion therapy for MI, occurring in approximately 60% of patients. Ferroptosis is an important process in the development of MI/R cardiac lesions. Transferrin receptor 1 (TfR1), a marker of ferroptosis, corresponds to the changes in MI/R cardiac lesions and is expected to be a biomarker for detecting MI/R-induced ferroptosis. However, the noninvasive in vivo visualization of ferroptosis in MI/R is a big challenge. Thus, this study aimed to develop a novel multimodal imaging platform to identify markers of MI/R cardiac lesions in vivo through targeting TfR1. Methods: Magnetic particle imaging (MPI) modality for ferroptosis based on superparamagnetic cubic -iron oxide nanoparticles (SCIO NPs), named feMPI, has been developed. FeMPI used TfR1 as a typical biomarker. The feMPI probe (SCIO-ICG-CRT-CPPs NPs, CCI NPs) consists of SCIO NPs, TfR1-targeting peptides (CRT), cell -penetrating peptides (CPPs), and indocyanine green (ICG). The specificity and sensitivity of CCI NPs in the MI/R mouse model were evaluated by MPI, magnetic resonance imaging (MRI), and near -infrared (NIR) fluorescent imaging. Results: The intensity of the MPI signal correlates linearly with the percentage of infarct area in MI/R stained by TTC, enabling a quantitative assessment of the extent of cardiac lesions. Notably, these findings are consistent with the standard clinical biochemical indicators in MI/R within the first 24 h. FeMPI detects cardiac injury approximately 48 h prior to the current clinical imaging detection methods of MI/R. Conclusion: The feMPI strategy can be a powerful tool for studying the process of MI/R-induced ferroptosis in vivo, providing clues for molecular imaging and drug development of ferroptosis-related treatments.