Near Infrared Light-Activatable Platelet-Mimicking NIR-II NO Nano-Prodrug for Precise Atherosclerosis Theranostics

Atherosclerosis is a chronic inflammatory disease that affects arteries and is the main cause of cardiovascular disease. Atherosclerotic plaque formation is usually asymptomatic and does not manifest until the occurrence of clinical events. Therefore, early diagnosis and treatment of atherosclerotic plaques is particularly important. Here, a series of NIR-II fluorescent dyes (RBT-NH) are developed for three photoresponsive NO prodrugs (RBT-NO), which can be controllably triggered by 808 nm laser to release NO and turn on the NIR-II emission in the clinical medicine "therapeutic window". Notably, RBT3-NO is selected for its exhibited high NO releasing efficiency and superior fluorescence signal enhancement. Subsequently, a platelet-mimicking nano-prodrug system (RBT3-NO-PEG@PM) is constructed by DSPE-mPEG_5k and platelet membrane (PM) for effectively targeted diagnosis and therapy of atherosclerosis in mice. The results indicate that this platelet-mimicking NO nano-prodrug system can reduce the accumulation of lipids at the sites of atherosclerotic plaques, improve the inflammatory response at the lesion sites, and promote endothelial cell migration, thereby slowing the progression of plaques.