Early assessment and treatment of ventricular remodeling in vivo via a targeted ultrasonic molecular probe loaded with oxygen and cholecystokinin.

Abstract

Early identification and treatment of ventricular remodeling (VR) are crucial for delaying the progression of heart failure after myocardial infarction. This study aims to develop a dual-responsive phase-shift molecular probe loaded with a cholecystokinin octapeptide (CCK-8) and oxygen, which will provide a new integrated scheme for the assessment and treatment of VR. Biocompatible phospholipid shells were utilized to encapsulate CCK-8 and perfluoropentane (PFP), an efficient oxygen carrier. Surface modification involves reactive oxygen species (ROS)-responsive thioketal (TK) bonds and anti-ICAM-1 antibodies to create CCK-8 and oxygen-carrying phase-shift nanoparticles (PFP-O₂-CCK8@lipid/TK-ICAM1 Ab nanoparticles, POC@L/TI NPs). These nanoparticles were designed for coronary artery endothelial cell targeting and responsiveness to dual stimuli. The results demonstrated that delayed myocardial contrast-enhanced echocardiography (DMCE) provided dynamic VR monitoring, with contrast intensity values showing a negative correlation with cardiac function parameter changes. POC@L/TI NPs significantly improved cardiac structural and functional parameters in rats with myocardial infarction and reperfusion and delayed the progression of heart failure by increasing tissue oxygenation, reducing the inflammatory response, inhibiting fibrotic scar formation and preventing myocardial cell apoptosis. This innovative approach combines supersaturated oxygen therapy with the multitarget therapeutic effect of CCK-8 and dynamic monitoring via DMCE to offer an integrated strategy for early detection and comprehensive VR treatment.