In Situ Lipoprotein‐seeking Dye for in Vivo Real‐Time Imaging of Lipid Dysregulation Diseases

ABSTRACT Lipoproteins, critical transporters of cholesterol and triglycerides, are essential to cardiovascular health and pathology. However, imaging probes that can specifically target endogenous lipoproteins in situ are lacking. This study introduces an innovative lipoprotein‐seeking near‐infrared‐II (NIR‐II) dye for in vivo imaging of lipid dysregulation diseases independent of immune interactions. This dye demonstrates high affinity and specificity for lipoproteins, enabling in situ selective lipoprotein‐seeking within the body, unaffected by other proteins. The lipoprotein‐seeking dynamics can be precisely modulated through rationally tuning hydrophilic moieties of dye structure. The lipoprotein‐seeking dye enables the real‐time high‐contrast detecting subtle biological changes associated with lipid metabolism disorders, successfully delineating the presence of fatty deposits in hepatic tissues and identifying the early formation of atherosclerotic plaques in cardiovascular systems. Notably, our dye can selectively image low density lipoprotein (LDL) without highlighting high density lipoprotein (HDL) through appropriate irradiation. The NIR‐II dye's ability to target lipoproteins and provide clear imaging could revolutionize the management of lipoprotein‐related conditions, facilitating earlier interventions and more personalized treatment strategies.